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IMMUNOLOGY
9th edition
IMMUNOLOGY
David Male, BA, MA, PhD
Professor of Biology
Department of Life Sciences
The Open University
Milton Keynes, United Kingdom
R. Stokes Peebles, Jr., MD

Elizabeth and John Murray Professor of Medicine
Division of Allergy, Pulmonary, and Critical Care Medicine
Vanderbilt University School of Medicine
Nashville, Tennessee, United States
Victoria Male, BA, MA, PhD

Sir Henry Dale Fellow
Department of Metabolism
Digestion and Reproduction
Imperial College London
London, United Kingdom
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Copyright © 2021, 2013, 2006, 2001 by Elsevier Ltd.
First edition published by Gower Medical Publishing Ltd., 1985

Second Edition published by Gower Medical Publishing Ltd., 1989
Third Edition published by Mosby-Year Book Europe Ltd., 1993
Fourth Edition published by Mosby, an imprint of Times Mirror International Publishers, 1996
Fifth Edition published by Mosby, an imprint of Times Mirror International Publishers, 1998
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ISBN: 978-0-7020-7844-6
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PREFACE TO THE 9TH EDITION
This is the first edition of Immunology that has not included two elements that we consider essential for understanding basic
of our original editors, Ivan Roitt and Jonathan Brostoff. We and clinical immunology; the online version includes additional
would like to pay tribute to their foresight in developing this information at appropriate points (indicated by a symbol in
text, which was originally planned as a slide atlas of immuno- the margin), for readers who want to delve deeper. The critical
logy. They have steered the book through its eight previous edi- thinking sections that follow each chapter require an under-
tions, during which time the subject has advanced beyond all standing of the material presented and the implications in a lab-
recognition. In 1985 when the first edition was published, the oratory or clinical setting—they may be used as the basis of class
structure and function of antibodies were well known and discussion. Another important teaching tool is the summaries
MHC molecules had just been described, but how T cells which distil the key points of each chapter and are a solid basis
became activated was still a matter of conjecture and debate. for revision for exams.
Nowadays, antibodies have become key therapeutic agents, The contributors to this edition include many experts in dif-
not just for immunological conditions, but particularly for treat- ferent fields of immunology, with seven new contributors who
ment of cancer and the targeting of therapeutic agents. Cytokine- have brought their own expertise to individual chapters. We also
based treatments for many diseases are following closely behind. greatly appreciate the hard work of colleagues at Elsevier, par-
Hence, the subject of immunology impinges on diverse areas ticularly Trinity Hutton, Alex Mortimer and Karthikeyan
of clinical practice, as well as providing tools and important Murthy.
theoretical concepts for many of the biological sciences. Immunology bridges basic science and medicine and encom-
For this edition, and with two new editors, we have made passes genetics, cell biology and molecular biology. Advances in
a major reorganisation in the first half of the book, with innate biotechnology in the last 10 years have driven forward antibody-
immunity and cell-mediated immunity introduced first. based therapies. In the next 10 years we anticipate that under-
This rearrangement responds to our improved understanding standing of genetic diversity in the immune system will lead to
of these areas of immunology, and it also presents material advances in personalised medicine, while gene therapies are
in a more logical chronological order, since innate immune reac- becoming available to correct primary immunodeficiencies.
tions and lymphocyte activation precede antibody production. For the past century, immunology has fascinated and inspired
Despite these changes we have maintained the overall bal- some of the greatest scientific thinkers and Nobel prize winners.
ance of the text with the first two sections describing how the Most recently the prize for Medicine or Physiology was awarded
immune system works. Section three is concerned with immune to James Allison and Tasuko Honjo for advances in cancer
responses against pathogens—the primary function of the immunotherapy. We wish our readers well in their study of
immune system—and the final three sections deal with aspects immunology, a subject that continues to excite and surprise
of clinical immunology, including autoimmune disease, immu- us, and which underpins many areas of medicine and biomed-
nodeficiency, transplantation, tumour immunology and hyper- ical science.
sensitivity. All chapters have been fully updated with many new David Male
diagrams. R. Stokes Peebles, Jr.
We have followed the style of the 8th edition by including two Victoria Male
levels of detail in the text. The printed text includes those 2019
vii
CONTRIBUTORS
The editors would like to acknowledge and offer grateful thanks for the input of all previous editions’ contributors, without whom this
new edition would not have been possible.
Gregory J. Bancroft, BSc Hons, PhD David Isenberg, MD, FRCP, FAMS Luisa Martinez-Pomares, BSc, PhD
Professor Professor Associate Professor
Department of Infection Biology The Centre for Rheumatology Research, School of Life Sciences
Faculty of Infectious and Tropical Diseases Department of Medicine University of Nottingham
London School of Hygiene & Tropical University College London Nottingham, United Kingdom
Medicine London, United Kingdom
Bryan Paul Morgan, BSc, MBBCh, PhD,
Roy Jefferis, BSc, PhD, FRSC, CChem, FRCPath, MRCP
David Bending, BA, MA, PhD
MRCP, FRCPath, DSc Professor of Immunology
Institute of Immunology and
Emeritus Professor School of Medicine
Immunotherapy
Institute of Immunology & Immunotherapy Cardiff University
University of Birmingham
University of Birmingham Cardiff, United Kingdom
Birmingham, United Kingdom
Birmingham, United Kingdom
Persephone Borrow, BA, MA, PhD
Professor of Viral Immunology Thomas Kamradt, Dr. med. Luigi D. Notarangelo, MD
Nuffield Department of Clinical Medicine Professor Chief
University of Oxford Department of Immunology Laboratory of Clinical Immunology
Oxford, United Kingdom University Hospital Jena and Microbiology
Jena, Germany National Institute of Allergy and
Colin Casimir, BSc, PhD Infectious Diseases, National
Department of Natural Sciences Institutes of Health
Middlesex University Yasmin Khan, MD Bethesda, Maryland, United States
London, United Kingdom Assistant Professor of Pediatrics
Department of Pediatric Allergy,
Daniel Cook, MD, PhD Immunology, and Pulmonary Medicine R. Stokes Peebles, Jr., MD
Resident Physician Vanderbilt University Medical Center Elizabeth and John Murray
Department of Internal Medicine Nashville, Tennessee, United States Professor of Medicine
Vanderbilt University Medical Center Division of Allergy, Pulmonary,
Nashville, Tennessee, United States and Critical Care Medicine
Peter Maldwyn Lydyard, BSc, MSc, PhD, Vanderbilt University School of Medicine
FRCPath Nashville, Tennessee, United States
David P. D’Cruz, MD, FRCP Emeritus Professor
Consultant Rheumatologist University College London
The Louise Coote Lupus Unit Visiting Professor
Guy’s and St Thomas’ Hospitals Thomas A.E. Platts-Mills, MD,
University of Westminster PhD, FRS
London, United Kingdom London, United Kingdom Head, Asthma and Allergic Disease Center
Daniel Dulek, MD Department of Medicine
Assistant Professor Arti Mahto, BSc, MBBCh, MRCP, PhD University of Virginia
Department of Pediatric Infectious Diseases Department of Rheumatology Charlottesville, Virginia, United States
Vanderbilt University Medical Center University College Hospital,
Nashville, Tennessee, United States London, United Kingdom
Richard John Pleass, BSc, MSc, PhD
Professor
Hakimeh Ebrahimi-Nik, Doctorate of
David Male, BA, MA, PhD Department of Parasitology
Veterinary Medicine, PhD
Professor of Biology Liverpool School of Tropical Medicine
Postdoctoral Fellow
Department of Life Sciences Liverpool, Merseyside, United Kingdom
Department of Immunology
The Open University
UConn Health
Milton Keynes, United Kingdom
Farmington, Connecticut, United States
Nina Porakishvili, BSc, MSc, PhD
School of Life Sciences
Andrew George, MBE, MA, PhD, DSc, Victoria Male, BA, MA, PhD
University of Westminster
FRCPath, FHEA, FRSA, FRSB Sir Henry Dale Fellow
Emeritus Professor Department of Metabolism
Brunel University London Digestion and Reproduction
Uxbridge, United Kingdom Imperial College London
ix
x CONTRIBUTORS
Theo Rispens, PhD Pramod K. Srivastava, PhD, MD Gestur Vidarsson, BSc, MSc, PhD
Department of Immunopathology Professor of Immunology and Medicine Head of Laboratory
Sanquin Research, Amsterdam Director, Carole and Ray Neag Department of Experimental
Amsterdam, Netherlands Comprehensive Cancer Center and Immunohematology/Immunoglobulin
Department of Immunology Research Laboratory
University of Connecticut School of Medicine Sanquin Research
Farmington, Connecticut, United States Amsterdam, Netherlands
SECTION 1 The Immune System and Innate Immunity
1
Introduction to the Immune System
SUMMARY
• The immune system has evolved to protect us from pathogens. Intra- • Antigens are molecules that are recognized by receptors on B cells
cellular pathogens infect individual cells (e.g. viruses), whereas extracellular and T cells. B cells usually recognize intact antigen molecules, whereas T
pathogens divide outside cells in blood, tissues or the body cavities (e.g. many cells recognize antigen fragments displayed on the surface of the body’s
bacteria and parasites). These two kinds of pathogen require fundamentally own cells.
different immune responses. • An immune response occurs in two phases – antigen recognition and
• Phagocytes and lymphocytes are key mediators of immunity. Phago- antigen eradication. In the first phase, clonal selection involves recognition
cytes internalize pathogens and degrade them. Lymphocytes (B and T cells) of antigen by particular clones of lymphocytes, leading to expansion of specific
have receptors that recognize specific molecular components of pathogens clones of T and B cells and differentiation to effector and memory cells. In the
and have specialized functions. B cells make antibodies (effective against effector phase, these lymphocytes coordinate an immune response, which
extracellular pathogens), cytotoxic T lymphocytes (CTLs) kill virally infected eliminates the source of the antigen.
cells and helper T cells coordinate the immune response by direct cell–cell • Vaccination depends on the specificity and memory of adaptive
interactions and the release of cytokines. immunity. Vaccination is based on the key elements of adaptive immunity,
• Inflammation is a response to tissue damage. It allows antibodies, com- namely specificity and memory. Memory cells allow the immune system to
plement system molecules and leukocytes to enter the tissue at the site of mount a much stronger and more rapid response on a second encounter with
infection, resulting in phagocytosis and destruction of the pathogens. Lympho- antigen.
cytes are also required to recognize and to destroy infected cells in the tissues. • The immune system may fail (immunopathology). This can be a result of
• Specificity and memory are two essential features of adaptive immunodeficiency, hypersensitivity or dysregulation leading to autoimmune
immune responses. As a result, the adaptive arm of the immune system diseases.
(B and T lymphocytes) mounts a more effective response on second and sub- • Normal immune reactions can be inconvenient in modern medicine,
sequent encounters with a particular antigen. Non-adaptive (innate) immune for example blood transfusion reactions and graft rejection.
responses (mediated, for example, by complement and phagocytes) do not
alter on repeated exposure to an infectious agent.
The immune system is fundamental to survival, as it protects • It introduces the basic elements of the immune system and
the body from pathogens: viruses, bacteria and parasites that of immune responses, which are mediated principally by
cause disease. To do so, it has evolved a powerful collection white blood cells or leukocytes (from the Greek for white
of defence mechanisms to recognize and protect against poten- cell) and are detailed in Chapters 2–13.
tial invaders that would otherwise take advantage of the rich Over many millions of years, different types of immune
source of nutrients provided by the vertebrate host. At the same defence, appropriate to the infecting pathogens, have evolved
time it must differentiate between the individual’s own cells and in different groups of organisms. In this book, we concentrate
those of harmful invading organisms while not attacking the on the immune systems of mammals, especially humans.
beneficial commensal flora that inhabit the gut, skin and other Because mammals are warm-blooded and long-lived, their
tissues. immune systems have evolved particularly sophisticated sys-
This chapter provides an overview of the complex network tems for recognizing and destroying pathogens.
of processes that form the immune system of higher Many of the immune defences that have evolved in other
vertebrates: vertebrates (e.g. reptiles, amphibians) and other phyla (e.g.
• It illustrates how the components of the immune system fit sponges, worms, insects) are also present in some form in
together to allow students to grasp the big picture before mammals. Consequently the mammalian immune system con-
delving into the material in more depth in subsequent sists of multi-layered, interlocking defence mechanisms that
chapters. incorporate both ancient and recently evolved elements.
1
2 SECTION 1 The Immune System and Innate Immunity
leukocytes
other
cell lymphocytes phagocytes auxiliary cells
Innate mononuclear tissue

B cell T cell lymphoid phagocyte neutrophil eosinophil basophil mast cell platelets cells
cell
B T ILC
soluble antibodies cytokines complement inflammatory interferons

mediators mediators cytokines
Fig. 1.1 Components of the immune system The principal cells of the immune system and the mediators they
produce are shown. Neutrophils, eosinophils and basophils are collectively known as polymorphonuclear gran-
ulocytes (see Chapter 2). B cells and T cells have highly specific receptors for foreign material (antigens),
whereas innate lymphoid cells (ILCs) do not have the specific receptors. Cytotoxic describes the function of
different cells, including cytotoxic T lymphocytes (CTLs), natural killer (NK) cells (a type of ILC) and eosinophils.
Complement is made primarily by the liver, although there is some synthesis by mononuclear phagocytes. Note
that each cell produces and secretes only a particular set of cytokines or inflammatory mediators.
CELLS AND SOLUBLE MEDIATORS OF THE

N
IMMUNE SYSTEM
Cells of the Immune System
Immune responses are mediated by a variety of cells and the sol-
uble molecules that these cells secrete (Fig. 1.1). Although the
leukocytes are central to all immune responses, other cells in
the tissues also participate by signalling to the lymphocytes
and responding to the cytokines (soluble intercellular signalling
molecules) released by T cells and macrophages.
Phagocytes internalize antigens and pathogens and break

them down. The most important long-lived phagocytic cells
belong to the mononuclear phagocyte lineage (see
Chapter 5). These cells are all derived from bone marrow stem
cells and their function is to engulf particles, including infectious B
agents, internalize them and destroy them (Fig. 1.2). To do so,
mononuclear phagocytes have surface receptors that allow Fig. 1.3 Phagocytes internalize and kill invading organisms Electron
micrograph of a phagocyte from a tunicate (sea squirt) that has endocy-
them to recognize and bind to a wide variety of microbial
tosed three bacteria (B). N, Nucleus. (Courtesy Dr AF Rowley.)
phagosome forming lysosome damage and digestion

macromolecules. They can then internalize and kill the microor-
ganism (Fig. 1.3). The process of phagocytosis describes
the internalization (endocytosis) of large particles or microbes.
The primitive responses of phagocytes are highly effective and
people with genetic defects in phagocytic cells often succumb
release of to infections in infancy.
phagocytosis lysosome fusion To intercept pathogens, mononuclear phagocytes are strate-
microbial products
gically placed where they will encounter them. For example,
Fig. 1.2 Phagocytosis Phagocytes attach to microorganisms using cell the Kupffer cells of the liver line the sinusoids along which blood
surface receptors for microbial products or via adapter molecules. Pseu- flows, while the synovial A cells line the synovial cavity (Fig. 1.4).
dopods extend around the microorganism and fuse to form a phagosome.
Killing mechanisms are activated and lysosomes fuse with the phago-
Leukocytes of the mononuclear phagocyte lineage are called
somes, releasing digestive enzymes that break down the microbe. Undi- monocytes. These cells migrate from the blood into the tissues,
gested microbial products may be released to the outside. where they develop into tissue macrophages.
CHAPTER 1 Introduction to the Immune System 3
B cell is genetically programmed to express a surface receptor

which is specific for a particular antigen. If a B cell binds to
brain
its specific antigen and receives appropriate signals from T cells,
microglial cells it will multiply and differentiate into plasma cells, which pro-
duce large amounts of the secreted antibody (see Chapter 10).
Secreted antibody molecules are large glycoproteins found in
lung
alveolar the blood and tissue fluids. Because secreted antibody molecules
macrophages are a soluble version of the original receptor molecule (BCR),
liver splenic they bind to the same antigen that initially activated the B cells.
Kupffer cells macrophages Antibodies are an essential component of an immune response
blood kidney
and, when bound to their cognate antigens, they help phago-
monocytes mesangial cytes to take up antigens, a process called opsonization (from
lymph node phagocytes the Latin, opsono, ‘to prepare food’).
resident and There are several different types of T cell, and they have a
recirculating
macrophages variety of functions (Fig 1.5):
• TH1 cells (type-1 T helpers) interact with mononuclear
stem cell synovial phagocytes and help them destroy intracellular pathogens.
precursors in A cells • TH2 cells (type-2 T helpers) interact with B cells and help
bone marrow
them to divide, differentiate and make antibodies.
• TH17 cells are defined according to a cytokine they produce
(IL-17) and are involved in defence against microbes, partic-
ularly in mucosal tissues.
• Regulatory T cells, or Tregs, help to control the development
of immune responses and limit reactions against self tissues.
• CTLs (cytotoxic T lymphocytes), also called TC cells (cyto-
Fig. 1.4 Cells of the mononuclear phagocyte lineage Many organs
contain cells belonging to the mononuclear phagocyte lineage. These toxic T cells), are responsible for the destruction of host cells
cells are derived from blood monocytes and ultimately from stem cells that have become infected by viruses or other intracellular
in the bone marrow. pathogens.
In every case, the T cells recognize antigens present on the
Polymorphonuclear neutrophils (often just called neutro- surface of other cells using a specific receptor, the T cell antigen
phils or PMNs) are another important group of phagocytes. receptor (TCR) (see Chapter 6), which is quite distinct from,
Neutrophils constitute the majority of the blood leukocytes but related in structure to, the antigen receptor on B cells
and develop from the same early precursors as monocytes (BCR) (see Chapter 9). T cells generate their effects either by
and macrophages. Like monocytes, neutrophils migrate into tis- releasing soluble proteins, called cytokines, which signal to
sues, particularly at sites of inflammation. However, neutrophils other cells, or by direct cell–cell interactions.
are short-lived cells that phagocytose material, destroy it and
then die within a few days. Cytotoxic cells recognize and destroy other cells that have
become infected. Several cell types have the capacity to kill
B cells and T cells are responsible for the specific other cells should they become infected. Cytotoxic cells include
recognition of antigens. Adaptive immune responses are CTLs, natural killer (NK) cells and eosinophils (see Chapter 8).
mediated by a specialized group of leukocytes, the lymphocytes, Of these, the CTL is especially important, but other cell types
which include T and B lymphocytes (T cells and B cells) that may be active against particular types of infection.
specifically recognize foreign material or antigens. All lympho- All of these cell types damage their different targets by releas-
cytes are derived from bone marrow stem cells, but T cells then ing the contents of their intracellular granules close to them.
develop in the thymus, while B cells develop in the bone marrow Cytokines secreted by the cytotoxic cells, but not stored in gran-
(in adult mammals). ules, contribute to the damage.
These two classes of lymphocytes carry out very different NK cells have the capacity to recognize the surface changes
protective functions: that occur on a variety of tumour cells and virally infected cells.
• B cells are responsible for the production of antibodies that They use a different recognition system to the CTLs and are one
act against extracellular pathogens. member of the population of innate lymphoid cells (ILCs). Some
• T cells are mainly concerned with cellular immune responses NK cells are larger and more granular than T cells and were pre-
to intracellular pathogens, such as viruses. They also regulate viously referred to as large granular lymphocytes (LGLs).
the responses of B cells and the overall immune response. Eosinophils are a specialized group of leukocytes that have
B cells express specific antigen receptors on their cell surface the ability to engage and damage large extracellular parasites,
during their development and, when mature, secrete soluble such as schistosomes.
immunoglobulin molecules (also known as antibodies) into
the extracellular fluids. The B cell’s receptor for antigen Auxiliary cells control inflammation. The main purpose of
(BCR) is in fact a cell-surface form of its secreted antibody. Each inflammation is to attract leukocytes and the soluble mediators
Treg
TH1 T H2 TH17 CTL

NK
activation activation cytotoxicity

induction
antigen antigen
presentation presentation
B
macrophage inflammatory cells
virally infected cells
plasma cell antibody production
Fig. 1.5 Functions of different types of lymphocyte Macrophages present antigen to TH1 cells, which then
activate the macrophages to destroy phagocytosed pathogens. B cells present antigen to TH2 cells, which acti-
vate the B cells, causing them to divide and differentiate into antibody-secreting plasma cells. TH17 cells help to
protect mucosal surfaces by attracting and activating other leukocytes. Cytotoxic T lymphocytes (CTL) and nat-
ural killer cells (NK) recognize and destroy virally infected cells. Regulatory T cells (Treg) modulate activity of
other T-cell populations.
of immunity towards a site of infection. Inflammation is medi- Complement proteins mediate phagocytosis, control
ated by a variety of other cells, including basophils, mast cells inflammation and interact with antibodies in immune
and platelets. defence. The complement system, a key component of innate
Basophils and mast cells have granules that contain a variety immunity, is a group of about 20 serum proteins whose overall
of mediators, which induce inflammation in surrounding tissues function is to promote inflammation (Fig. 1.6) and clearance of
and are released when the cells are triggered. Basophils and mast microbes and damaged cells. The components interact with
cells can also synthesize and secrete a number of mediators that each other and with other elements of the immune system.
control the development of immune reactions. Mast cells lie For example, a number of microorganisms spontaneously acti-
close to blood vessels in most tissues and some of their media- vate the complement system, via the so-called ‘alternative path-
tors act on cells in the vessel walls. Basophils are functionally way’, which is an innate immune defence. This results in the
similar to mast cells, but are mobile, circulating cells. microorganism being opsonized (i.e. coated by complement
Platelets are small cellular fragments that are essential in molecules, leading to its uptake by phagocytes). The comple-
blood clotting, but they can also be activated during immune ment system can also be activated by antibodies bound to the
responses to release mediators of inflammation. pathogen via the ‘classical pathway’ or by mannose binding
lectin bound to the pathogen surface via the ‘lectin pathway’.
Soluble Mediators of Immunity Complement activation is a cascade reaction, where one
A wide variety of molecules are involved in the development of component acts enzymatically on the next component in the
immune responses, including antibodies, opsonins and comple- cascade to generate an enzyme, which mediates the following
ment system molecules. The serum concentration of a number step in the reaction sequence, and so on. (The blood clotting sys-
of these proteins increases rapidly during acute infection and tem also works as an enzyme cascade.)
they are therefore called acute phase proteins. Activation of the complement system generates protein mol-
One example of an acute phase protein is C-reactive protein ecules or peptide fragments, which have the following effects:
(CRP), so-called because of its ability to bind to the C protein • opsonization of microorganisms for uptake by phagocytes
of pneumococci; it promotes the uptake of pneumococci by pha- and eventual intracellular killing;
gocytes. Molecules such as CRP that promote phagocytosis are • attraction of phagocytes to sites of infection (chemotaxis);
said to act as opsonins. There are a number of these evolution- • increased blood flow to the site of activation and increased
arily ancient molecules in mammals and they recognize conserved permeability of capillaries to plasma molecules;
structures on the surface of pathogens called pathogen-associated • damage to plasma membranes on cells, Gram-negative bac-
molecular patterns (PAMPs) (see Chapter 3). Another important teria, enveloped viruses, or other organisms that have caused
group of molecules that can act as opsonins are components of complement activation;
the complement system (see Chapter 4). • release of inflammatory mediators from mast cells.
complement
IFN␣
IFN␤
virus
infected cell
virus-resistant
bacteria phagocyte bacteria T IFN␥ cell
antigen
1. lysis 2. chemotaxis 3. opsonization
Fig. 1.7 Interferons Host cells that have been infected by virus secrete
interferon-α (IFNα) and/or interferon-β (IFNβ). TH1 cells secrete interferon-
γ (IFNγ) after activation by antigens. IFNs act on other host cells to induce
resistance to viral infection. IFNγ has many other effects.
Chemokines are a large group of chemotactic cytokines that

direct the movement of leukocytes around the body, from the
Fig. 1.6 Functions of complement Components of the complement blood stream into the tissues and to the appropriate location
system can lyse many bacterial species (1). Complement fragments within each tissue. Some chemokines also activate cells to carry
released in this reaction attract phagocytes to the site of the reaction out particular functions.
(2). Complement components opsonize the bacteria for phagocytosis
(3). In addition to the responses shown here, activation of the comple-
Tumour necrosis factors, TNFα and TNFβ, have a variety of
ment system increases blood flow and vascular permeability at the site functions but are particularly important in promoting inflam-
of activation. Activated components can also induce the release of inflammation and cytotoxic reactions.
matory mediators from mast cells. Transforming growth factors (e.g. TGFβ) are important in
controlling cell division and tissue repair.
Each set of cells releases a particular blend of cytokines,
depending on the type of cell and whether, and how, it has been
Cytokines signal between lymphocytes, phagocytes and activated. For example:
other cells of the body. Cytokine is the general term for a large • TH1 cells release one set of cytokines, which promote activa-
group of secreted molecules involved in signalling between cells tion of mononuclear phagocytes to deal with pathogens they
during immune responses. All cytokines are proteins or glyco- have phagocytosed;
proteins. The different cytokines fall into a number of categories • TH2 cells release a different set of cytokines, which activate
and the principal subgroups of cytokines are outlined below. B cells;
Interferons (IFNs) are cytokines that are particularly impor- • TH17 cells release cytokines that control inflammatory
tant in limiting the spread of certain viral infections: one group responses.
of interferons (IFNα and IFNβ or type-1 interferons) is pro- Some cytokines may be produced by all T cells and some just
duced by cells that have become infected by a virus; another by a specific subset.
type, IFNγ, is released by activated TH1 cells. Equally important is the expression of cytokine receptors.
IFNs induce a state of antiviral resistance in uninfected cells Only a cell that has the appropriate receptors can respond to
(Fig. 1.7). They are produced very early in infection and are a particular cytokine. For example, the receptors for interferons
important in delaying the spread of a virus until the adaptive are present on all nucleated cells in the body, whereas other
immune response has developed. receptors are much more restricted in their distribution. In gen-
The interleukins (ILs) are a large group of cytokines pro- eral, cytokine receptors are specific for their own individual
duced mainly by T cells, although some are also produced by cytokine, but this is not always so. In particular, many chemo-
mononuclear phagocytes or by tissue cells. They have a variety kine receptors respond to several different chemokines.
of functions. Many interleukins cause other cells to divide and to
differentiate.
Colony stimulating factors (CSFs) are primarily involved in
INFLAMMATION
directing the division and differentiation of bone marrow Tissue damage caused by physical agents (e.g. trauma or
stem cells and the precursors of blood leukocytes. The CSFs radiation) or by pathogens results in the tissue response of
partially control how many leukocytes of each type are released inflammation, which has three principal components:
from the bone marrow. Some CSFs also promote subsequent • increased blood supply to the infected area;
differentiation of cells. For example, macrophage CSF • increased capillary permeability as a result of retraction of the
(M-CSF, also known as CSF1) promotes the development of endothelial cells lining the vessels, permitting larger mole-
monocytes in bone marrow and macrophages in tissues. cules than usual to escape from the capillaries;
• migration of leukocytes from the venules into the surround- venule

ing tissues: in the earliest stages of inflammation, neutrophils endothelium
site of
are particularly prevalent, but in later stages monocytes and inflammation
lymphocytes also migrate towards the site of infection or
basement
damage. Inflammation allows the body’s immune defences membrane
to concentrate at a site of infection or cell damage. phagocyte
Leukocytes enter inflamed tissue by crossing venular endothelial mediators of

endothelium. The process of leukocyte migration is controlled activation inflammation
by chemokines (a particular class of cytokines) on the surface of
venular endothelium in inflamed tissues. Chemokines activate
the circulating leukocytes, causing them to bind to the endothe-
lium and initiate migration across the endothelium (Fig. 1.8).
Once in the tissues, the leukocytes migrate towards the site of chemotactic
infection by a process of chemical attraction known as chemo- mediators
taxis. For example, phagocytes will actively migrate up concen-
tration gradients of certain (chemotactic) molecules.
A particularly active chemotactic molecule is C5a, which is a
fragment of one of the complement components (Fig. 1.9) that chemotaxis
attracts both neutrophils and monocytes. When purified C5a is
applied to the base of a blister in vivo, neutrophils can be seen
sticking to the endothelium of nearby venules shortly after-
wards. The cells then squeeze between the endothelial cells
and move through the basement membrane of the microvessels
to reach the tissues. This process is described more fully in Fig. 1.9 Chemotaxis At a site of inflammation, tissue damage and com-
plement activation cause the release of chemotactic peptides (e.g. che-
Chapter 3. mokines and C5a), which diffuse to the adjoining venules and signal to
circulating phagocytes. Activated cells migrate across the vessel wall
and move up a concentration gradient of chemotactic molecules towards
IMMUNE RESPONSES TO PATHOGENS the site of inflammation.
Effective immune responses vary depending on the
pathogen. The primary function of the immune system is to
prevent entry of and/or to eliminate infectious agents and min- The exterior defences of the body (Fig. 1.10) present an effec-
imize the damage they cause, ensuring that most infections in tive barrier to most organisms. Very few infectious agents can
normal individuals are short-lived and leave little permanent penetrate intact skin. In contrast, many infectious agents gain
damage. Pathogens, however, come in many different forms, access to the body across the epithelia of the gastrointestinal
with various modes of transmission and reproductive cycles, or urogenital tracts; others, such as the virus responsible for
and the immune system has therefore evolved different ways the common cold, infect the respiratory epithelium of nasophar-
of responding to each of them. ynx and lung; a small number of infectious agents infect the
1 2 3
Fig. 1.8 Three phases in neutrophil migration across endothelium A neutrophil adheres to the endothelium
in a venule (1). It extends its pseudopodium between the endothelial cells and migrates towards the basement
membrane (2). After the neutrophil has crossed into the tissue, the endothelium reseals behind (3). The entire
process is referred to as diapedesis. (Courtesy Dr I Jovis.)
destroy infected cells. This is largely the function of cell-

lysozyme in tears removal of particles
and other secretions by rapid passage of mediated immunity.
air over turbinate Intracellular pathogens cannot, however, wholly evade the
commensals bones extracellular defences because they must reach their host cells
bronchi by moving through the blood and tissue fluids. As a result, they
skin mucus, cilia are susceptible to humoral immunity during this portion of their
physical barrier gut
fatty acids life cycle.
acid
commensals rapid pH change Any immune response involves recognition of the pathogen
commensals or other foreign material and then a reaction to eliminate it.
low pH and flushing of
commensals urinary tract
Innate immune responses are the same on each encounter
of vagina
with an antigen. Broadly speaking, immune responses fall into
Fig. 1.10 Exterior defences Most infectious agents are prevented from two categories: those that become more powerful following
entering the body by physical and biochemical barriers. The body toler- repeated encounters with the same antigen (adaptive immune
ates a number of commensal organisms, which compete effectively with responses) and those that do not become more powerful follow-
many potential pathogens.
ing repeated encounters with the same antigen (innate immune
responses).
body only if they enter the blood directly (e.g. malaria and Innate immune responses (see Chapters 3–5) can be thought
sleeping sickness). of as simple, though remarkably effective, systems present in all
Once inside the body, the site of the infection and the nature animals that are the first line of defence against pathogens and
of the pathogen largely determine which type of immune allow a rapid response to invasion.
response will be induced, most importantly (Fig. 1.11) whether Innate immune response systems range from external bar-
the pathogen is: riers (skin, mucous membranes, cilia, secretions and tissue
• an intracellular pathogen (i.e. invades the host cells to divide
fluids containing anti-microbial agents; see Fig. 1.10) to sophis-
and reproduce); or ticated receptors capable of recognizing broad classes of patho-
• an extracellular pathogen (i.e. does not invade the
genic organisms, for example:
host cells). • innate immune receptors on leukocytes recognize PAMPs;
Many bacteria and larger parasites live in tissues, body fluids • intracellular receptors in many cells recognize nucleic acids
or other extracellular spaces, and are susceptible to the multi- characteristic of viral replication;
tude of immune defences, such as antibodies and complement • some plasma proteins bind to bacterial and fungal cell walls
that are present in these areas. Because these components are and opsonize them;
present in the tissue fluids of the body (the “humours” of ancient • the complement system includes components that can be
medicine), they have been classically referred to as humoral specifically activated by bacterial surface molecules.
immunity. Receptors and proteins that recognize PAMPs are broadly
Many organisms (e.g. viruses, some bacteria, some parasites) referred to as pattern recognition receptors (PRRs). It takes
evade these formidable defences by being intracellular patho- several days for adaptive immune responses to develop and
gens and replicating within host cells. To clear these infections, the innate immune responses limit pathogen spread during this
the immune system has developed ways to recognize and to critical period. The innate defences are also closely interlinked
with adaptive responses.
influenza malaria tuberculosis streptococcus
erythrocyte Adaptive immune responses display specificity and
macrophage memory. In contrast to the innate immune response, which rec-
ognizes common molecular patterns (such as PAMPs), the
adaptive immune system takes a highly discriminatory
approach, with a very large repertoire of specific antigen recep-
tors that can recognize virtually any component of a foreign
invader (see Chapters 6, 9 and 10). This use of highly specific
antigen receptor molecules provides the following advantages:
• pathogens that lack stereotypical patterns (which might
Fig. 1.11 Intracellular and extracellular pathogens All infectious
agents spread to infect new cells by passing through the body fluids or avoid recognition by the innate immune system) can be
tissues. Many are intracellular pathogens and must infect cells of the recognized;
body to divide and reproduce (e.g. viruses such as influenza viruses • responses can be highly specific for a given pathogen;
and malaria, which has two separate phases of division, either in cells • the specificity of the response allows the generation of
of the liver or in erythrocytes). The mycobacteria that cause tuberculosis
can divide outside cells or within macrophages. Some bacteria (e.g. strep- immunological memory: related to its use of highly individ-
tococci, which produce sore throats and wound infections) generally ual antigen receptors, the adaptive immune system has the
divide outside cells and are therefore extracellular pathogens. capacity to remember a pathogen.
These features underlie the phenomenon of specific immu- antigen antibody

nity (e.g. diseases such as measles and diphtheria induce adap-
tive immune responses that generate life-long immunity).
Specific immunity can, very often, be induced by artificial
Ag1 recognition
means, allowing the development of vaccines (see Chapter 17).
ANTIGEN RECOGNITION Ag2 recognition

Originally the term antigen was used for any molecule that
induced B cells to produce a specific antibody (antibody gener-
Ag3 recognition
ator). This term is now more widely used to indicate molecules
that are specifically recognized by antigen receptors of either B
cells or T cells. Fig. 1.12 Antigens and epitopes Antibodies recognize molecular
shapes (epitopes) on the surface of antigens. Each antigen (Ag1, Ag2,
Antigens, defined broadly, are molecules that initiate adap- Ag3) may have several epitopes recognized by different antibodies. Some
tive immune responses (e.g. components of pathogenic organ- antigens have repeated epitopes (e.g. Ag3).
isms), although purists may prefer the term immunogen in this
context.
Antigens are not just components of foreign substances such
as pathogens. A large variety of ‘self’ molecules can also act as a restricted part of the antigen. A particular antigen can have
antigens, provoking autoimmune responses that can be highly several different epitopes or repeated epitopes (Fig. 1.12). Anti-
damaging and even lethal (see Chapter 20). bodies are specific for the epitopes rather than the whole antigen
molecule. In some cases, the same epitope may be present on
Antigens initiate and direct adaptive immune responses. different antigens and an antibody that binds to that epitope will
The immune system has evolved to recognize antigens, destroy recognize both antigens. This is referred to as cross-reactivity.
them and eliminate the source of their production – when an
antigen is eliminated, immune responses switch off. Fc regions of antibodies act as adapters to link phagocytes
Both T-cell receptors and immunoglobulin molecules (anti- to pathogens. The constant region of the antibody (the Fc
bodies) bind to their cognate antigens with a high degree of region) can bind to Fc receptors on phagocytes, so acting as
specificity. These two types of receptor molecules have striking an adapter between the phagocyte and the pathogen
structural relationships and are closely related evolutionarily, (Fig. 1.13). Consequently, if an antibody binds to a pathogen,
but they bind to very different types of antigens and carry out it can link to a phagocyte and promote phagocytosis, i.e. opso-
quite different biological functions. nization. This process is an important example of collaboration
between the innate and adaptive immune responses.
Functions of Antibodies Other molecules (such as activated complement proteins)
Antibody specifically binds to antigen. Soluble antibodies are can also enhance phagocytosis when bound to microbial sur-
a group of serum molecules closely related to and derived from faces. Binding and phagocytosis are most effective when more
the antigen receptors on B cells. All antibodies have the same than one type of adapter molecule (opsonin) is present
basic Y-shaped structure, with two regions (variable regions) (Fig. 1.14). Note that antibody can act as an adapter in many
at the tips of the Y that bind to antigen. The stem of the Y is
referred to as the constant region and is not involved in antigen
binding (see Chapter 10).
microbe
The two variable regions contain identical antigen-binding
sites that, in general, are specific for only one type of antigen.
antigen
The amino acid sequences of the variable regions of different antigen-binding site
antibodies vary greatly between antibodies produced by differ- epitope
ent clones of B cells. As a B cell develops, a process of somatic Fab region
gene-recombination affects the antibody gene loci so that each
clone of B cells produces antibody with a different specificity antibody
Fc region
(binding site). The antibody molecules in the body, derived
from millions of B cells, therefore provide an extremely large Fc receptor
repertoire of antigen-binding sites. The way in which this great
diversity of antibody variable regions is generated is explained in phagocyte
Chapter 9.
Fig. 1.13 An antibody acts as an adapter linking a microbe to a
phagocyte The antibody binds to a region of an antigen (an epitope) on
Each antibody binds to a restricted part of the antigen called the microbe surface, using one of its antigen-binding sites. These sites
an epitope. Pathogens typically have many different antigens are in the Fab regions of the antibody. The stem of the antibody, the
on their surface. Each antibody binds to an epitope, which is Fc region, can attach to receptors on the surface of the phagocytes.
phagocyte opsonin binding
infected cell
MHC molecule presents
peptide
2
complement antigen peptide bound
C3b to MHC molecule
T-cell receptor recognizes

3
MHC and peptide
antibody
T
4
antibody and
complement
C3b
Fig. 1.15 T-cell recognition of antigen Major histocompatibility com-
plex (MHC) molecules transport peptides to the surface of an infected cell
Fig. 1.14 Opsonization Phagocytes have some intrinsic ability to bind to where they are presented to T cells, which may recognize the MHC–
bacteria and other microorganisms via their pattern recognition receptors peptide combination. If a cell is infected, MHC molecules present
(1). Binding is much enhanced if the bacteria have been opsonized by peptides derived from the pathogen and the cell’s own proteins.
complement C3b (2) or antibody (3), each of which cross-links the bacteria
to receptors on the phagocyte. Antibody can also activate complement,
and if antibody and C3b both opsonize the bacteria, binding is further
enhanced (4). ANTIGEN PRESENTATION
Virtually all cells of the body can present antigen to CTLs, but
there is a more limited group of specialized antigen-presenting
other circumstances, not just phagocytosis. For example, anti- cells (APCs) which process and present antigens to helper T
bodies bound to parasitic worms allow them to be recognized cells. Several different types of leukocyte can act as APCs,
by eosinophils. Another type of antibody binds to receptors including dendritic cells, macrophages and B cells. All of these
on mast cells and allows them to recognize soluble antigens cells internalize antigens from the extracellular space by
(see Chapter 10). phagocytosis or endocytosis. These APCs then display antigenic
peptide–MHC complexes on the cell surface and they express
co-stimulatory molecules that are essential for initiating
Peptides from intracellular pathogens are displayed on the immune responses. Activation of a TH cell requires both the
surface of infected cells. Antibodies are present only in extra- signal from antigenic peptide–MHC and co-stimulation.
cellular spaces, including blood, lymph and tissue fluids, and Co-stimulatory signals are upregulated by the presence of
they can usually only target extracellular pathogens. Intracellu- pathogens, which can be detected by the engagement of innate
lar pathogens (such as viruses) can escape antibody-mediated immune receptors that recognize PAMPs.
responses once they are safely located within a host cell. The Most immune responses to infectious organisms are made up
adaptive immune system has therefore evolved a specific of a variety of innate and adaptive components. In the earliest
method of displaying portions of virtually all cell proteins on stages of infection, innate responses predominate; later the lym-
the surface of each nucleated cell in the body so that they can phocytes start to generate adaptive immune responses. After
be recognized by T cells. recovery from infection, immunological memory remains
For example, a cell infected with a virus will present fragments within the population of lymphocytes, which can then mount
of viral proteins (peptides) on its surface that are recognizable by a more effective and rapid response if there is re-infection with
T cells. The antigenic peptides are transported to the cell surface the same pathogen at a later date.
and presented to the T cells by MHC molecules (a group of mol- The two major phases of any immune response are antigen
ecules encoded within the major histocompatibility complex, see recognition and a reaction to eliminate the antigen.
Chapter 6). T cells use their antigen-specific receptors (TCRs) to
recognize the antigenic peptide–MHC molecule complex Antigen activates specific clones of lymphocytes. In adap-
(Fig. 1.15). If an infected cell (target) is recognized by a cytotoxic tive immune responses, lymphocytes are responsible for
T cell (CTL), the T cell can signal to the target cell to induce immune recognition, which is achieved by clonal selection. Each
apoptosis (programmed cell death). The process by which lymphocyte is genetically programmed to produce one specific
MHC molecules facilitate recognition of antigenic peptides is antigen receptor (BCR or TCR) capable of recognizing just one
one component of a wider process called antigen presentation particular antigen. However, the immune system as a whole can
(see Chapter 7). specifically recognize many thousands of antigens and the
lymphocytes that recognize any particular antigen are only a Lymphocytes that have been stimulated, by binding to their
tiny proportion of the total. specific antigen, take the first steps towards cell division. They
How then is an adequate immune response to an infectious express new receptors that allow them to respond to cytokines
agent generated? The answer is that, when an antigen binds to from other cells and will usually go through a number of cycles
the few lymphocytes that can recognize it, they are induced to of division before differentiating into mature cells, again under
proliferate rapidly. Within a few days there is a sufficient num- the influence of cytokines. They may also start to produce sets of
ber to mount an adequate immune response. In other words, the cytokines themselves.
antigen selects and activates the specific clones to which it binds Even when the infection has been overcome, some of
(Fig. 1.16), a process called clonal selection. This operates for the newly produced lymphocytes remain, available for re-
both B cells and T cells. stimulation if the antigen is ever encountered again. These cells
How can the immune system know which specific antibodies are called memory cells, because they are generated by past
will be needed during an individual’s lifetime? It does not know. encounters with particular antigens. Memory is partly the result
The immune system generates antibodies (and T-cell receptors) of the expansion of the responding population of lymphocytes
that can recognize an enormous range of antigens even before it in the first immune response and partly because these cells are
encounters them. Many of these specificities, which are gener- more easily activated on subsequent encounters with the anti-
ated more or less at random, will never be called upon to protect gen. Memory cells confer lasting immunity to a particular
the individual against infection. pathogen.
What is the advantage of generating billions of lymphocytes
that do not recognize any known infectious agent? Many path-
ogens mutate their surface antigens. Indeed the immune system ANTIGEN ELIMINATION
provides selective pressure for the evolution of new strains of
pathogen with altered antigens. If the immune system could There are numerous ways in which the immune system can
destroy pathogens, each being suited to a given type of infection
not recognize new variants of pathogens, it would not be able
at a particular stage of its life cycle. These defence mechanisms
to make an effective immune response. By having a wide range
are often referred to as effector systems.
of antigen receptors, at least some of the lymphocytes will be
able to recognize any pathogen that enters the body.
Antibodies can directly neutralize some pathogens. In one of
the simplest effector systems, antibodies can combat certain
antigen selection
pathogens just by binding to them. For example, antibody to
the outer coat proteins of some rhinoviruses (which cause colds)
can prevent the viral particles from binding to and infecting
host cells.
BCR
1 2 n Phagocytes kill pathogens in endosomes. More often, anti-

B cells
bodies activate complement or act as opsonins to promote
clonal ingestion by phagocytes (see Fig. 1.14). Phagocytes that have
selection bound to an opsonized microbe engulf it by extending pseudo-
2 2
proliferation/ podia around it. These fuse and the microorganism is internal-
maturation ized (endocytosed) in a phagosome. Phagocytes have several
ways of dealing with internalized microbes in phagosomes.
2 2 2 2 For example:
• Macrophages reduce molecular oxygen to form microbicidal
reactive oxygen and nitrogen intermediates (ROIs and
2 2 2 2 2 2 2 2 RNIs), which are secreted into the phagosome.
• Macrophages pump H+ ions into the phagosome to lower
plasma cells memory the pH.
cells • Neutrophil granules contain anti-microbial peptides called
defensins, which fuse with the phagosome.
• Neutrophils contain lactoferrin, which chelates iron and pre-
vents some bacteria from obtaining this vital nutrient.
production of antibody 2
Once a pathogen has been killed, lysosomes fuse with the
Fig. 1.16 B-cell clonal selection Each B cell expresses just one variant phagosome, pouring enzymes into the resulting phagolysosome,
cell surface antibody (i.e. with specificity for a single particular antigen), to digest the contents.
which it uses as its antigen receptor (BCR). Antigens bind only to B cells
with the specific BCR (number 2 in this example), driving these cells to
divide and to differentiate into plasma cells and memory cells, all with Cytotoxic cells kill infected target cells. Cytotoxic reactions
the same specificity as the original B cell. Thus an antigen selects just are usually directed against whole cells, i.e. targets that are too
the clones of B cells that can react against it. large for phagocytosis.
The target cell may be recognized by:

• specific antibody bound to the cell surface; complement antibody
• cytotoxic T cells using their specific TCRs;
• NK cells using immunoglobulin-like and lectin-like
CTL
receptors.
virus
In cytotoxic reactions, the attacking cells direct their granules
killing
towards the target cell (in contrast to phagocytosis where the infected
contents are directed into the phagosome). As a result, granules viral cell
infection replication
are discharged into the extracellular space close to the target cell.
antiviral
The granules of CTLs and NK cells contain molecules called
perforins, which can punch holes in the outer membrane of resistance
the target. (In a similar way, antibody bound to the surface of
a target cell can direct complement to make holes in the cell’s
plasma membrane.) Some cytotoxic cells can signal to the target interferons
cell to initiate programmed cell death (apoptosis). These pro-
cesses must be closely regulated as the release of toxic molecules
into the extracellular space could cause collateral damage to Fig. 1.17 Reaction to extracellular and intracellular pathogens Differ-
nearby cells. ent immunological systems are effective against different types of infec-
tion, here illustrated as a virus infection. Antibodies and complement can
Termination of immune responses limits damage to host block the extracellular phase of the life cycle and promote phagocytosis of
the virus. Interferons produced by infected cells signal to uninfected cells
tissues. Although it is important to initiate immune responses to induce a state of antiviral resistance. Viruses can multiply only within
quickly, it is also critical to terminate them appropriately once living cells; cytotoxic T lymphocytes (CTLs) recognize and destroy the
the threat has ended. To clear the offending pathogen, immune infected cells.
responses often involve millions of activated lymphocytes and
activation of huge numbers of phagocytes. These responses, if
left unchecked, can also damage host tissues. A number of (Fig. 1.17). These factors play an important part in the develop-
mechanisms are employed to dampen or to terminate immune ment of effective vaccines.
responses. One is a passive process, i.e. simple clearance of anti-
gen should lead to a diminution of immune responses; in the VACCINATION
absence of antigen, lymphocytes that recognize the antigen will
not be stimulated to divide and to differentiate. The study of immunology has had its most successful applica-
Antigen elimination can be a slow process, however, there- tion in vaccination (see Chapter 17), which is based on the key
fore the immune system also employs a variety of active mech- elements of adaptive immunity, namely specificity and memory.
anisms to downregulate responses (see Chapter 12). Memory cells allow the immune system to mount a much stron-
ger response on a second encounter with antigen. Compared
Immune responses to extracellular and intracellular with the primary response, the secondary response is:
pathogens. In dealing with extracellular pathogens, the • faster to appear;
immune system aims to destroy the pathogen itself and to neu- • more effective.
tralize its products. The aim in vaccine development is to alter a pathogen or its
In dealing with intracellular pathogens, the immune system toxins in such a way that they become innocuous without losing
has two options: antigenicity. This is possible because antibodies and T cells rec-
• T cells can destroy the infected cell (i.e. cytotoxicity); or ognize particular parts of antigens (the epitopes) and not the
• T cells can activate the infected cell to deal with the whole organism or toxin.
pathogen itself (e.g. helper T cells release cytokines, which Take, for example, vaccination against tetanus. The tetanus
activate macrophages to destroy the organisms they have bacterium produces a toxin that acts on receptors to cause
internalized). tetanic contractions of muscle. The toxin can be modified by
Because many pathogens have both intracellular and extra- formalin treatment so that it retains its epitopes but loses its tox-
cellular phases of infection, different mechanisms are usually icity. The resulting molecule (known as a toxoid) is used as a
effective at different times. For example, the polio virus travels vaccine (Fig. 1.18).
from the gut through the blood stream to infect nerve cells in the Whole infectious agents, such as the poliovirus, can be
spinal cord. Antibodies are particularly effective at blocking the attenuated so they retain their antigenicity but lose their
early phase of infection while the virus is in the blood stream, pathogenicity.
but to clear an established infection CTLs must kill any cell that
has become infected.
Consequently, antibodies are important in limiting the
IMMUNOPATHOLOGY
spread of infection and preventing reinfection with the same Strong evolutionary pressure from infectious microbes has led
virus, while CTLs are essential to deal with infected cells to the development of the immune system in its present form.
Another random document with
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have slain.” Here Mr Godwin assured us that he had visited the
Gannet Rock ten seasons in succession, for the purpose just
mentioned, and added, that on one of these occasions, “six men had
destroyed five hundred and forty Gannets in about an hour, after
which the party rested a while, and until most of the living birds had
left their immediate neighbourhood, for all around them, beyond the
distance of about a hundred yards, thousands of Gannets were yet
sitting on their nests, and the air was filled with multitudes of others.
The dead birds are now roughly skinned, and the flesh of the breast
cut up in pieces of different sizes, which will keep good for bait about
a fortnight or three weeks. So great is the destruction of these birds
for the purpose mentioned, that the quantity of their flesh so
procured supplies with bait upwards of forty boats, which lie fishing
close to the Island of Brion each season. By the 20th of May the rock
is covered with birds on their nests and eggs, and about a month
afterwards the young are hatched. The earth is scratched by the
birds for a few inches deep, and the edges surrounded by sea-
weeds and other rubbish, to the height of eight or ten inches,
tolerably well matted together. Each female Gannet lays a single
egg, which is pure white, but not larger than a good-sized hen’s egg.
When the young are hatched, they are bluish-black, and for a
fortnight or more their skin is not unlike that of the common dog-fish.
They gradually become downy and white, and when five or six
weeks old look like great lumps of carded wool.”
I was well pleased with this plain statement of our pilot, as I had with
my glass observed the regularity of the lines of nests, and seen
many of the birds digging the earth with their strong bills, while
hundreds of them were carrying quantities of that long sea-weed
called Eel-grass, which they seem to bring from towards the
Magdalene Islands. While the Ripley lay to near the rock, thousands
of the Gannets constantly flew over our heads; and although I shot at
and brought several to the water, neither the reports nor the sight of
their dead companions seemed to make any impression on them.
On weighing several of the Gannets brought on board, I found them
to average rather more than seven pounds; but Mr Godwin assured
me that when the young birds are almost ready to fly, they weigh
eight and sometimes nine pounds. This I afterwards ascertained to
be true, and I account for the difference exhibited at this period by
the young birds, by the great profusion of food with which their
parents supply them, regardless in a great measure of their own
wants. The Pilot further told me that the stench on the summit of the
rock was insupportable, covered as it is during the breeding season,
and after the first visits of the fishermen, with the remains of
carcasses of old and young birds, broken and rotten eggs,
excrements, and multitudes of fishes. He added that the Gannets,
although cowardly birds, at times stand and await the approach of a
man, with open bill, and strike furious and dangerous blows. Let me
now, Reader, assure you that unless you had seen the sight
witnessed by my party and myself that day, you could not form a
correct idea of the impression it has to this moment left on my mind.
The extent of the southward migration of the Gannet, after it has
reared its young, is far greater perhaps than has hitherto been
supposed. I have frequently seen it on the Gulf of Mexico, in the
latter part of autumn and in winter; and a few were met with, in the
course of my last expedition, as far as the entrance of the Sabine
River into the Bay of Mexico. Being entirely a maritime species, it
never proceeds inland, unless forced by violent gales, which have
produced a few such instances in Nova Scotia and the State of
Maine, as well as the Floridas, where I saw one that had been found
dead in the woods two days after a furious hurricane. The greater
number of the birds of this species seen in these warm latitudes
during winter are young of that or the preceding year. My friend John
Bachman has informed me that during one of his visits to the Sea
Islands off the shores of South Carolina, on the 2d of July 1836, he
observed a flock of Gannets of from fifty to an hundred, all of the
colouring of the one in my plate, and which was a bird in its first
winter plumage. They were seen during several days on and about
Cole’s Island, at times on the sands, at others among the rolling
breakers. He also mentions having heard Mr Giles, an acquaintance
of his, who knows much about birds, say, that in the course of the
preceding summer he had seen a pair of Gannets going to, and
returning from, a nest in a tree! This is in accordance with the report
of Captain Napoleon Coste, who commanded the United States
Revenue Cutter, the Campbell, placed at my disposal during my visit
to the Texas, and who was Lieutenant as well as Pilot of the Marion.
He stated that he had found a breeding place on the coast of
Georgia, occupied by a flock of old, and therefore White Gannets,
the nests of all of which were placed upon trees. No one can be
greatly surprised at these reports, who knows, as I do, that the
Brown Gannet, Sula fusca, breeds both on trees and on dry elevated
sand bars. During winter months I have generally observed single
birds at some considerable distance from the shore out at sea,
sometimes indeed beyond what mariners call soundings, but rarely
young ones, they generally keeping much nearer to the shores, and
procuring their food in shallower water.
The flight of the Gannet is powerful, well sustained, and at times
extremely elegant. While travelling, whether in fine or foul weather,
they fly low over the surface of the water, flapping their wings thirty
or forty times in succession, in the manner of the Ibis and the Brown
Pelican, and then sailing about an equal distance, with the wings at
right angles to the body, and the neck extended forwards. But,
Reader, to judge of the elegance of this bird while on wing, I would
advise you to gaze on it from the deck of any of our packet ships,
when her commander has first communicated the joyful news that
you are less than three hundred miles from the nearest shore,
whether it be that of merry England or of my own beloved country.
You would then see the powerful fisher, on well-spread pinions, and
high over the water, glide silently along, surveying each swelling
wave below, and coursing with so much ease and buoyancy as to
tempt you to think that had you been furnished with equal powers of
flight, you might perform a journey of eighty or ninety miles without
the slightest fatigue in a single hour. But perhaps at the very moment
when these thoughts have crossed your mind, as they many times
have crossed mine on such occasions, they are suddenly checked
by the action of the bird, which, intent on filling its empty stomach,
and heedless of your fancies, plunges headlong through the air, with
the speed of a meteor, and instantaneously snatches the fish which
its keen sight had discovered from on high. Now perchance you may
see the snow-white bird sit buoyantly for a while on the bosom of its
beloved element, either munching its prey, or swallowing it at once.
Or perhaps, if disappointed in its attempt, you will see it rise by
continued flappings, shaking its tail sideways the while, and snugly
covering its broad webbed feet among the under coverts of that
useful rudder, after which it proceeds in a straight course, until its
wings being well supplied by the flowing air, it gradually ascends to
its former height, and commences its search anew.
In severe windy weather, I have seen the Gannet propelling itself
against the gale by sweeps of considerable extent, placing its body
almost sideways or obliquely, and thus alternately, in the manner of
Petrels and Guillemots; and I have thought that the bird then moved
with more velocity than at any other time, except when plunging after
its prey. Persons who have seen it while engaged in procuring food,
must, like myself, have been surprised when they have read in
books that Gannets “are never known to dive,” and yet are assured
that they “have been taken by a fish fastened to a board sunk to the
depth of two fathoms, in which case the neck has either been found
dislocated, or the bill firmly fixed in the wood.” With such statements
before him, one might think that his own vision had been defective,
had he not been careful to note down at once the result of his
observations. And as this is a matter of habit with me, I will offer you
mine, good Reader, not caring one jot for what has been said to you
before on the subject.
I have seen the Gannet plunge, and afterwards remain under the
surface of the water for at least one minute at a time. On one
occasion of this kind, I shot one just as it emerged, and which held a
fish firmly in its bill, and had two others half-way down its throat. This
has induced me to believe that it sometimes follows its prey in the
water, and seizes several fishes in succession. At other times I have
observed the Gannet plunge amidst a shoal of launces so as
scarcely to enter the water, and afterwards follow them, swimming,
or as it were running, on the water, with its wings extended upwards,
and striking to the right and left until it was satiated. While on the
Gulf of Mexico, I wounded a Gannet, which, on falling to the water,
swam so fast before the boat, that we rowed about a quarter of a
mile before we reached it, when it suddenly turned towards us,
opened its bill, as if intent on defending itself, but was killed with the
stroke of an oar by one of the sailors. When shot at without even
being touched, these birds often disgorge their food in the manner of
Vultures; and this they always do when wounded, if their stomach
and gullet happen to be full. Sometimes, after being wounded in the
wings, they will float and allow you to take them, without making any
attempt to escape. Nay, my young friend, George C. Shattuck, M.
D., of Boston, while with me at Labrador, caught one which he found
walking amongst a great number of Guillemots, on a low and rocky
island.
When they are on their favourite breeding rocks, and about to fly,
they elevate their head, throw it backward, open the bill, and emit a
loud prolonged cry, before launching themselves into the air, in doing
which they waddle a few paces with their wings partially extended.
After starting, their first motion is greatly inclined downwards, but
they, presently recover, and seem to support themselves with ease.
When they are twenty or thirty yards off, you observe them shaking
the tail sideways, and then hiding their feet among the under coverts
of the tail. At other times they suddenly open their feet, moving them
as if for the purpose of grasping some object below, in the same
manner as some hawks, but only for a few moments, when again the
tail is shaken, and the feet hidden as before. They beat their wings
and sail alternately, even when flying around their breeding places.
On the ground the movements of the Gannet are exceedingly
awkward, and it marches with hampered steps, assisting itself with
the wings, or keeping them partially open, to prevent its falling. Their
walk, indeed, is merely a hobble. When the sun shines, they are fond
of opening their wings and beating them in the manner of
Cormorants, shaking the head meanwhile rather violently, and
emitting their usual uncouth guttural notes of cara, karew, karow.
You may well imagine the effect of a concert performed by all the
Gannets congregated for the purpose of breeding on such a rock as
that in the Gulf of St Lawrence, where, amidst the uproar produced
by the repetition of these notes, you now and then distinguish the
loud and continued wolfish howling-like sounds of those about to fly
off.
The newly-finished nest of this bird is fully two feet high, and quite as
broad externally. It is composed of seaweeds and maritime grasses,
the former being at times brought from considerable distances. Thus,
the Gannets breeding on the rocks in the Gulf of St Lawrence, carry
weeds from the Magdalene Islands, which are about thirty miles
distant. The grasses are pulled or dug up from the surface of the
breeding place itself, often in great clods consisting of roots and
earth, and leaving holes not unlike the entrances to the burrows of
the Puffin. The nests, like those of Cormorants, are enlarged or
repaired annually. The single egg, of a rather elongated oval form,
averages three inches and one-twelfth in length, by two inches in its
greatest breadth, and is covered with an irregular roughish coating of
white calcareous matter, which on being scraped off, leaves exposed
the pale greenish-blue tint of the under layer.
The birds usually reach the rock when already paired, in files often of
hundreds, and are soon seen billing in the manner of Cormorants,
and copulating on the rocks, but never, like the birds just mentioned,
on the water, as some have supposed. The period of their arrival at
their breeding grounds appears to depend much on the latitude of
the place; for, on the Bass Rock, in the Firth of Forth, which I had the
pleasure of visiting in the agreeable company of my learned friend
William Macgillivray and his son, on the 19th of August 1835, the
Gannets are first seen in February, whereas in the Gulf of St
Lawrence they rarely reach the Great Rock until the middle of April
or beginning of May; and at Chateau Beau in the Straits of Belle Isle,
not until a fortnight or three weeks later. Like the members of most
large communities, the Gannets, though so truly gregarious at this
season, shew a considerable degree of animosity towards their more
immediate neighbours as soon as incubation commences. A lazy
bird perhaps, finding it easier to rob the nest of its friend of weeds
and sods, than to convey them from some distant place, seizes
some, on which the other resents the injury, and some well-directed
thrusts of their strong bills are made, in open day and in full view of
the assembled sitters, who rarely fail to look on with interest, and
pass the news from one to another, until all are apprized of the
quarrel. The time however passes on. The patient mother, to lend
more warmth to her only egg, plucks a few of the feathers from some
distance beneath her breast. In sunny weather, she expands those
of her upper parts, and passing her bill along their roots, destroys the
vile insects that lurk there. Should a boisterous gale or a thick cold
fog mar the beauty of the day, she gathers her apparel around her,
and shrinks deeper into her bed; and should it rain, she places her
body so as to prevent the inundation of her household. How happy,
Reader, must she be when now and then her keen eyes distinguish
in the crowd her affectionate mate, as he returns from the chase,
with loaded bill, and has already marked her among the thousand
beauties all equally anxious for the arrival of their lords! Now by her
side he alights as gently as is in his nature, presents her with a
welcome repast, talks perhaps cheeringly to her, and again opening
his broad wings departs in search of a shoal of herrings. At length,
the oval chest opens, and out crawls the tender young; but lo! the
little thing is black. What a strange contrast to the almost pure white
of the parent! Yet the mother loves it, with all the tenderness of other
mothers. She has anxiously expected its appearance, and at once
she nurses it with care; but so tender is it that she prefers waiting a
while before she feeds it. The time however soon comes, and with
exceeding care she provides some well macerated morsels which
she drops into its open mouth; so well prepared are they that there is
no instance on record of a Gannet, even of that tender age, having
suffered from dyspepsia or indigestion.
The male Gannet assists in incubating, though he sits less
assiduously than the female; and, on such occasions, the free bird
supplies the other with food. The sight of the young Gannet just after
birth might not please the eye of many, for it is then quite naked, and
of a deep bluish-black, much resembling a young Cormorant. Its
abdomen is extremely large, its neck thin, its head large, its eyes as
yet sightless, its wings but slightly developed. When you look at it
three weeks afterwards, it has grown much, and almost entirely
changed its colour, for, now, with the exception of certain parts of the
neck, the short thighs, and the belly, it is covered with yellowish soft
and thick down. In this state it looks perhaps as uncouth as at first,
but it grows so rapidly that at the end of three weeks more, you find
its downy coat patched with feathers in the most picturesque manner
imaginable. Looking around you, you observe that all the young are
not of the same growth; for all the Gannets do not lay on the same
day, and probably all the young are not equally supplied with food. At
this period, the great eyrie looks as if all its parts had become
common property; the nests, which were once well fashioned are
trampled down; the young birds stand everywhere or anywhere;
lazy-looking creatures they are, and with an appearance of non-
chalance which I have never observed in any other species of bird,
and which would lead you to think that they care as little about the
present as the future. Now the old birds are freed of part of their
cares, they drop such fish as they have obtained by the side of their
young, and, like Cormorants, Pelicans, or Herons, seldom bring a
supply oftener than once a-day. Strange to say, the young birds at
this period do not appear to pay the least attention to the old ones,
which occasionally alight near them, and drop fish for them to feed
upon.
Gannets do not feed, as some have supposed, and as many have
believed, on herring only; for I have found in their stomachs codlings
eight inches in length, as well as very large American mackerels,
which, by the way, are quite different from those so abundantly met
with on the coasts of Europe.
The young never leave the spot on which they have been reared
until they are well able to fly, when they separate from the old birds,
and do not rejoin them until at least a year after. Although I have in a
few instances found individuals yet patched with dark-grey spots,
and with most of their primary quills still black, I am confident that it
is not until the end of two years that they acquire their full plumage. I
have seen some with one wing almost pure black, and the tail of that
colour also; others with the tail only black; and several with pure
black feathers interspersed among the general white plumage.
I know of no other bird that has so few formidable enemies as the
Gannet. Not one of the species of Lestris with which I am
acquainted, ever attempts to molest it; and, although I have seen the
Frigate Pelican in quest of food within a short distance of it, I never
saw it offer injury. The insular rocks on which it breeds are of course
inaccessible to quadrupeds. The only animals, so far as I know, that
feed on the eggs or young, are the Larus marinus and Larus
glaucus. It is said that the Skua, Lestris Cataractes, sometimes
pursues the Gannets, but that species does not exist in North
America; and I am inclined to doubt the truth of this statement, for I
have never seen a Lestris of any kind attack a bird equal to itself in
size and strength.
Soon after the young Gannets are able to fly, all the birds of the
species leave the breeding place, and absent themselves until the
following season. While at Newfoundland, I was told that the English
and French fishermen who inhabit that country salt young Gannets
for winter provision, as is done in Scotland; but I saw none there. In
my estimation, the flesh of this bird is so bad that, as long as any
other can be procured, it ought to be rejected.
It is a curious fact, that the Gannets often procure mackerels or
herrings four or five weeks before the fishermen fall in with them on
our coast; but this is easily explained by their extensive wanderings.
Although this bird is easily kept in captivity, it is far from being a
pleasant pet. Its ordure is abundant, disagreeable to the eye as well
as the nose; its gait is awkward; and even its pale owl-like eyes glare
on you with an unpleasant expression. Add to this, the expense of its
food, and I can easily conceive that you will not give it a place in your
aviary, unless for the mere amusement of seeing it catch the food
thrown to it, which it does like a dog.
The feathers of the lower parts of the Gannet differ from those of
most other birds, in being extremely convex externally, which gives
the bird the appearance of being covered beneath with light shell-
work, exceedingly difficult to be represented in a drawing.
My highly esteemed and talented friend William Macgillivray
having given a full account of the habits of the Gannet, as observed
on the Bass Rock in Scotland, I here present it to you.
“The Bass is an abrupt rock, having a basis of about a mile in
circumference, and of an oblong form. The cliffs are perpendicular in
some places, overhanging in others, and everywhere precipitous,
excepting at the narrow extremity next the land, where, sloping less
abruptly, they form at the base a low projection, on which is the only
landing-place. Above this are the ruins of the fortifications and
houses, the Bass having formerly been used as a State-prison. The
rocks are in some places apparently two hundred feet in height, and
the summit, towards which the surface rises in an irregular manner,
is probably a hundred and fifty feet higher. In as far as I observed,
the whole mass is of a uniform structure, consisting of trap,
intermediate between greenstone and clinkstone, of a dull brownish-
red colour, and small granular structure. Although a great portion of
the upper surface of the island is composed of rock, there is an
abundant vegetation, consisting chiefly of Festuca ovina, F.
duriuscula, and a few other grasses, mixed with the plants usually
found in maritime situations.
“The circumstance connected with the Bass most interesting to the
Zoologist, is its being one of the few places in Britain to which the
Gannet resorts during the breeding season. The number which I saw
on the 13th May 1831, when I for the first time visited it along with
some friends, might be estimated at twenty thousand. Every part of
the mural faces of the rock, especially towards their summits, was
more or less covered by them. In one spot near the landing place,
about forty yards in circumference, and on a gentle slope of gravelly
ground, about three hundred individuals were sitting in peaceful
security on their nests.
“The Gannets arrive about the middle of February or the beginning of
March, and depart in October; some years a few individuals remain
during the winter. The nests are composed of grass and sea-weeds,
generally placed on the bare rock or earth, elevated in the form of a
truncated cone, of which the base is about twenty inches in diameter,
with a shallow terminal cavity. On the summit of the island are
numerous holes in the turf, from eight to fifteen inches deep, and
from six to nine broad, formed by the Gannets in pulling away grass
and turf for their nests. They are placed on all parts of the rocks
where a convenient spot occurs, but are much more numerous
towards the summit. Some of them on the face of the rock, or in a
shallow fissure, and which have been occupied for years, are piled
up to the height of from three to five feet, but in this case they always
lean against the rock. The egg, which is solitary, and presents
nothing remarkable in its position, is of an elongated oval form,
bluish-white, dull, with a chalky surface, usually patched with
yellowish-brown dirt. It is subjected to what might appear rough
usage, for the bird in alighting, flying off, or when disturbed by the
intrusion of human visitors, tosses it about, and often stands upon it.
“When sitting, the Gannets usually allow a person to approach within
three feet, sometimes much nearer, so that one may even touch
them. When one approaches them, they merely open their bill, and
utter their usual cry, or they rise and express some degree of
resentment, but seem to have very little apprehension of danger.
They take advantage of the absence of their neighbours to pilfer the
materials of their nests, frequently two join in this act, and
occasionally two may be seen tugging at the same bunch,
endeavouring to wrest it from each other. They are constantly
repairing their nests, which being composed in a great measure of
sea-weeds, shrink up in dry weather, and decompose in wet; and
when seated close together they have frequent quarrels. I saw one
seize its neighbour by the back of the neck, until the latter, I may say,
roared out; but in general, they are satisfied with menacing each
other with open bills and loud clamour. In leaving the nest, they
generally scatter about a quantity of the materials of which it is
composed, for they are extremely awkward in their motions when on
the ground, hobbling and limping along, aiding themselves with their
wings, and draggling the abdominal feathers and tail.
“In launching from the cliffs, they frequently utter a single plaintive
cry, perform a curve, having its concavity upwards, then shake the
tail, frequently the whole plumage, draw the feet backwards, placing
them close under the tail, on each side, and cover them with the
feathers. In some the feet were entirely covered, while in others
parts of the toes were apparent. In flying, the body, tail, neck, and
bill, are nearly in a straight line, the wings extended and never
brought close to the body, and they move by regular flappings,
alternating with short sailings. In alighting, they generally ascend in a
long curve, keeping their feet spread, and come down rather heavily,
often finding it difficult to balance themselves, and sometimes, when
the place is very steep, or when another bird attacks them, flying off,
to try it a second time. On the rocks they stand with the body nearly
horizontal, or they lie on their belly, although some may be seen in
an oblique or even nearly erect posture. They usually repose with
the head resting between the shoulders, the bill concealed among
the feathers of the back. I caught one in that state, by walking up to
it, and seizing it by the tail and the tips of the wings, which cross
each other over it.
“Owing to their interference with each other, a constant noise is kept
up amongst them. Their cry is hoarse and harsh, and may be
expressed by the syllables carra, carra, carra, or kirra, kirra, kirra, or
crac, crac, crac. The cry varies considerably in different individuals,
some having a sharper voice than others, and when unusually
irritated they repeat it with great rapidity. An ornithological writer
thinks they cry grog, grog; but neither Mr Audubon nor myself
interpreted their notes so, otherwise we could have satisfied a few at
least, as we had a bottle of whisky and a keg of water.
“The young are at first covered with very beautiful close snow-white
down; at the age of about six weeks the feathers make their
appearance among the down; when two months old the birds are
pretty well fledged, and at the end of three months they are able to
fly. The old bird at first feeds the young with a kind of fish-soup
prepared in its gullet and stomach, and which it introduces drop by
drop as it were into its throat. But when its nursling is pretty well
grown, it places its bill within its mouth, and disgorges the fish either
entire or in fragments. They never carry fish to the rock in their bills.
The smallest number of young killed in a year is a thousand, the
greatest two thousand; but in general the number is fifteen or sixteen
hundred. After being plucked, they are sold at from sixpence to a
shilling each. The price of a young bird for stuffing is two shillings; of
an old bird five, of an egg one. For the information contained in this
paragraph I am indebted to the keeper.
“At the period of my second visit with Mr Audubon (the 19th August
1835), the nests in most places had almost entirely disappeared, for
it is only during incubation that the birds keep them in constant
repair. The young were in various stages, a few quite small and
covered all over with white down, the greater number partially
fledged, with the down remaining on the head and neck, and some
nearly ready to fly, and having merely a few tufts of down on the hind
neck. The young lay flat, either on the remnants of their nest, or on
the bare rock or ground. They are very patient and uncomplaining; in
fact, none uttered a single cry while we were inspecting them. I
observed an old bird, with its own young beside it, squeeze the neck
of another youngling with considerable force The poor bird bore the
persecution with perfect resignation, and merely cowered under the
bill of the tyrant. The young of the latter also attacked its neighbour,
but was instantly checked, on which it meekly desisted. One of the
men informed me that last year there were fourteen nests, each with
two eggs. In such cases, one of the young is said to be much smaller
than the other.”
Pelecanus bassanus, Linn. Nat. vol. i. p. 217.—Lath. Ind. Ornith. vol. ii. p.
891.
Sula bassana, Ch. Bonaparte, Synopsis of Birds of United States, p. 408.
Gannet, Nuttall, Manual, vol. ii. p. 495.
Adult Male. Plate CCCXXVI. Fig. 1.

Bill longer than the head, opening beyond the eyes, straight,
elongated-conical, moderately compressed. Upper mandible with the
dorsal line straight and declinate, at the end convex and a little
decurved; ridge very broad, convex, with a slight median carina, and
separated on each side, from the sides, which are nearly
perpendicular, slightly convex, and have an additional narrow jointed
piece below the eye; edges sharp, direct, irregularly serrate, with
numerous slender cuts directed backwards; tip compressed, a little
decurved, rather acute. No external nostrils. Lower mandible with the
angle very long and narrow, the dorsal line straight, ascending, the
sides erect, convex, the edges sharp and serrated, the tip
compressed and sharp.
Head large; neck of moderate length and very thick, body of
moderate bulk, rather elongated; wings long. Feet short, strong,
placed rather far behind; tibiæ concealed; tarsus very short, rounded
before, sharp behind, at its upper part anteriorly with rather large
roundish-flat scales, in the rest of its extent with very small oblong
tubercles; anteriorly there are three lines of small transversely
oblong scutella, which rim down the toes. The latter are long and
slender, all united by membranes, which are reticularly granulated,
and have their margins straight; first toe rather small, directed
inwards and forwards, middle toe longest, the outer almost equal.
Claws of moderate size, slightly arched, those of the first and middle
toes depressed, the latter with its inner edge thin and pectinated.
Plumage generally close, rather compact, the feathers small and
rounded; those on the head and neck blended and slightly glossed.
A bare space between the bill and the eye, surrounding the latter,
and extending an inch behind the angle of the mouth. The gular
membrane also bare for a small breadth, extending two inches
beyond the base of the mandible. About a quarter of an inch of the
tibia bare. Wings very long, narrow, acute; primaries strong, narrow,
tapering rapidly to a rounded point; first longest, second about a
quarter of an inch shorter, the rest rapidly graduated; secondaries
short, rather broad, rounded, with a minute acumen. Tail rather long,
cuneate, of twelve narrow tapering feathers.
Bill pale bluish-grey, tinged with green towards the base; the lines on
the upper mandible blackish-blue; the bare space about the eye, and
that on the throat, blackish-blue. Iris white. Tarsi, toes, and webs
brownish-black, the bands of narrow scutella on the tarsus and toes
light greenish-blue; claws greyish-white. The general colour of the
plumage is white; the upper part of the head and the hind neck of a
fine buff colour. Primary quills brownish-black, their shafts white
toward the base.
Length to end of tail 40 1/2 inches, to end of wings 38 1/4, to end of
claws 41; extent of wings 75; wing from flexure 20 3/4; tail 10; bill
along the ridge 4, along the edge of lower mandible 6; tarsus 2 2/12;
first toe and claw 1 1/4; middle toe 3 8/12, its claw 7/12; outer toe
1/
38 /12; its claw 4/12. Weight 7 lb.
2
The Female is similar to the male, but rather smaller.

Young fully fledged. Plate CCCXXVI. Fig. 2.
Bill light greyish-brown; the bare space around the eye pale greyish-
blue. Iris green. Feet dusky, the narrow bands of scutella pale
greyish-blue; claws greyish-white. The head, neck, and upper parts
are chocolate brown, each feather with a terminal narrow triangular
white spot; the lower parts greyish-white, spotted with greyish-brown;
each feather having a broad terminal margin of that colour. The quills
and tail-feathers are brownish-black. An individual shot in October
measured as follows:—
Length to end of tail 38 inches, to end of claws 32 1/2; extent of
wings 72. Weight 3 lb. 4 oz. This individual, however, was very poor.
Three individuals shot in the neighbourhood of Boston,
Massachusetts, presented the following dimensions, which are here
given as indicative of the difference of size frequently observed:—
Length to end of tail, 38 3/

4 38 3/
4 37
................................wings, 37 1/
2 37 1/
2 35
................................claws, 34 1/
4 34 1/
2 33
Extent of wings, 73 1/
2 72 68 1/2
Wing from flexure, 19 1/
2 17 1/
2 19 1/2
An adult Male killed near Boston. The cellular tissue of the back
exhibits vacuities of very large size, intervening between the skin
and the muscles: one, at the lower part of the neck behind, being 5
inches in length; another 5 1/2 inches long, extending from the
furcula down the humerus; and behind the wings four others,
extending to the last rib. Branches from these pass between the
muscles, which present the appearance of having been as it were
dissected. A cell of enormous size covers the side of the abdomen,
and another pair run down the middle of it, separated by a partition in
the median line. That part of the cellular tissue which adheres to the
bases of the feathers is also remarkably loose; and, close to each of
them, is a roundish aperture of large size, communicating with the
great cavities mentioned above. Between the pectoralis major and
the subjacent muscles is a large interspace formed by a great cell.
The internal thoracic and abdominal cells are also very large.
On the roof of the mouth are five sharp ridges. The nasal aperture is
1 inch and 5 twelfths long, linear, with a soft longitudinal flap on each
side. The tongue is extremely small, being only 7 twelfths long, 1
twelfth broad, blunt at the extremity, and with two papillae at the
base. The bare skin between the crura of the mandibles is of the
same structure as that of the Pelicans and Cormorants, but of small
extent, its posterior acute extremity not extending farther than that at
the base of the bill. The aperture of the glottis is 7 1/2 twelfths long.
The thyroid bone has an anterior curved prolongation, which projects
forwards, and from the extremity of which comes the elastic ligament
by which it is connected with the hyoid bone. The œsophagus, a, b,
is 15 inches long, measured to the commencement of the
proventriculus, extremely dilated, its diameter 2 1/2 inches at the top,
contracting to 2 inches as it enters the thorax, its narrowest part 1
inch 4 twelfths; its transverse muscular fibres moderately strong. The
proventriculus, c, d, is excessively large, 3 1/2 inches long, its
greatest diameter 2 1/4 inches. The glandules are cylindrical, 3
twelfths long, forming a very broad belt, separated however at its
narrowest part by a longitudinal interval of 5 twelfths of an inch, and
having three partial divisions on its lower edge. The greatest length
of the proventriculus, or breadth of the belt of glandules, is 2 1/2
inches. The mucous coat of the œsophagus is smooth, but thrown
into longitudinal plicæ when contracted; that of the proventriculus is
continuous, and of the same nature, being marked with extremely
minute reticulated lines, of which the more prominent have a
longitudinal direction. The stomach, properly so called, d e, is
extremely small, being only 1 inch 9 twelfths long, and about the
same breadth. Its inner coat is similar to that of the œsophagus and
proventriculus; being destitute of epithelium; several large mucous
crypts are scattered over its surface. The pylorus is small, having a
diameter of nearly 3 twelfths, and a marginal flap or valve on one
side. The intestine, f, g, h, is of moderate length, measuring 53
inches. The duodenum at first passes upwards in the direction of the
liver for 2 inches, f g, is then recurved for 3 inches, g, h, ascends for
4 inches, h, i, and receives the biliary ducts, then passes toward the
spine and forms a curvature. The average diameter of the intestine is
5 twelfths at the upper part, and it gradually contracts to 3 twelfths.
The rectum, k, measured to the anus is 5 1/4 inches. It gradually
enlarges from 4 to 6 1/2 twelfths. The cloaca, m, is globular, 9
twelfths long, 8 twelfths broad. The cœca are 3 twelfths long, 1 1/2
twelfth broad.
The lobes of the liver are extremely unequal, as is always the case
when the stomach or the proventriculus is excessively large, the right
lobe being 2 3/4 inches long, the left 1 inch and 8 twelfths. The gall-
bladder, n, is very large, of an oblong form, rounded at both ends, 1
inch and 8 twelfths long.
The trachea is 12 inches long, moderately ossified, round, its
diameter at the top 7 twelfths, gradually narrowing to 4 twelfths; the
rings 124, the lower 4 united, The bronchi are large, their diameter
greater than that of the lower part of the trachea; of 25 cartilaginous
half-rings. The lateral or contractor muscles of the trachea are of
moderate strength; the sterno-tracheals strong; a pair of inferior
laryngeal muscles attached to the glandular-looking, yellowish-white
bodies inserted upon the membrane between the first and second
rings of the bronchi.
The olfactory nerve comes off from the extreme anterior point of the
cerebrum, enters a canal in the spongy tissue of the bone, and runs
in it close to the septum between the eyes for 10 twelfths of an inch,
with a slight curve. It then enters the nasal cavity, which is of an
irregular triangular form, 1 1/2 inch long at the external or palatal
aperture, 10 twelfths in height. The supramaxillary branch of the fifth
pair runs along the upper edge of the orbit, and by a canal in the
spongy tissue of the bones, enters the great cavity of the upper
mandible, keeping nearer its lower surface, and there branching.
This cavity appears to have no communication with the nasal; nor
has the latter any passage towards the obliterated external nostrils.
The lachrymal duct passes obliquely inwards from the anterior
corner of the eye, and enters the nasal cavity by an aperture 1/2
twelfth in diameter, near its anterior margin.
In the cloaca was found a solid calculus, half an inch in diameter, of
an irregular form, white within, externally pale yellowish-brown, and
marked with grooves impressed by the action of the sphincter ani.
The digestive and respiratory organs of the American Gannet are
thus precisely similar to those of the European. In external form,
proportions, and colours, there are no appreciable differences. The

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Immunology , 9th Edition - eBook PDF

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R. Stokes Peebles, Jr., MD

Victoria Male, BA, MA, PhD

For additional online content visit StudentConsult.com

First edition published by Gower Medical Publishing Ltd., 1985

Content Strategist: Alexandra Mortimer

Last digit is the print number: 9 8 7 6 5 4 3 2 1

Innate mononuclear tissue

soluble antibodies cytokines complement inflammatory interferons

CELLS AND SOLUBLE MEDIATORS OF THE

Phagocytes internalize antigens and pathogens and break

phagosome forming lysosome damage and digestion

B cell is genetically programmed to express a surface receptor

TH1 T H2 TH17 CTL

activation activation cytotoxicity

macrophage inflammatory cells

virally infected cells

plasma cell antibody production

Chemokines are a large group of chemotactic cytokines that

• migration of leukocytes from the venules into the surround- venule

Leukocytes enter inflamed tissue by crossing venular endothelial mediators of

destroy infected cells. This is largely the function of cell-

These features underlie the phenomenon of specific immu- antigen antibody

ANTIGEN RECOGNITION Ag2 recognition

phagocyte opsonin binding

T-cell receptor recognizes

1 2 n Phagocytes kill pathogens in endosomes. More often, anti-

The target cell may be recognized by:

Adult Male. Plate CCCXXVI. Fig. 1.

The Female is similar to the male, but rather smaller.

Length to end of tail, 38 3/

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