IMMUNE SYSTEM

Dr Abas Hassan Ahmed

Dr Almis

MBBS
 Immunology

INTRODUCTION
Lecture contents
 Components of the innate and adaptive immune
responses
 Attributes of innate and adaptive immune
responses
 Interactions between innate and adaptive
immune responses
 The cells of the immune system , their origin,
tissue distribution, and function
 The primary lymphoid organs: structure and
function
 The structure and function of the secondary
lymphoid organs
The immune system
The immune system is designed to produce
a coordinated response to the introduction of
foreign substances or antigens into the body.
It is organizationally divided into two
complementary arms: the innate (or native
or natural) immune system and the adaptive
(or acquired or specific) immune system.
Innate immunity
Innate immunity provides the body's early
line of defense against microbial invaders.
It comprises 4 types of defensive barriers:
1. Anatomic barriers
Skin Mechanical barrier retards entry of
microbes.
Mucous membranes
-Mucus entraps foreign microorganisms.
-Cilia propel microorganisms out of body.
 2. Physiologic barriers
 Temperature
Normal body temperature
inhibits growth of some
pathogens.
Fever response inhibits growth of
some pathogens.
Low pH Acidity of stomach contents
kills most ingested
microorganisms.
Chemical mediators Lysozyme cleaves
bacterial cell wall.
Interferon induces antiviral state in
uninfected cells.
Complement lyses microorganisms or
facilitates phagocytosis.
Toll-like receptors recognize microbial
molecules, signal cell to secrete
immunostimulatory cytokines.
Collectins disrupt cell wall of pathogen.
3. Phagocytic/endocytic barriers
Various cells internalize (endocytose) and
break down foreign macromolecules.
Specialized cells (blood monocytes,
neutrophils, tissue macrophages) internalize
(phagocytose), kill, and digest whole
microorganisms.
4. Inflammatory barriers Tissue damage and
infection induce leakage of vascular fluid,
containing serum proteins with antibacterial
activity, and influx of phagocytic cells into
the affected area.
Attributes of innate
Innate immune defenses have in common
that they:
Are present intrinsically with or without
previous stimulation
 Have limited specificity for shared
structures of microbes
Are not enhanced in activity by repeated
exposure
 Have limited diversity of expression
Adaptive immunity
Once the barriers of the innate immune
response have been breached, the adaptive
immune response is activated in an antigen-
specific fashion to provide for the elimination
of antigen and lasting protection from future
challenge.
The components of the adaptive immune
system are:
Lymphocytes (T cells and B cells) and
plasma cells (end cells of B-lymphocyte
differentiation)
Antigen-presenting cells (macrophages, B
cells, and dendritic cells
Attributes of Adaptive
Adaptive immune defenses have in common
that they are:
Specific for particular antigens and are
specialized to provide the best protection
Diverse in their specificity
Enhanced with each repeated exposure
(express immunologic memory)
Capable of self/non-self recognition
Self-limiting
Interactions between innate and
adaptive immune responses
The innate and adaptive arms of the immune
response do not operate independently of one
another.
Phagocytic cells process and display antigen
to facilitate stimulation of specific T
lymphocytes.
Macrophages secrete immunoregulatory
molecules (cytokines), which help trigger the
initiation of specific immune responses.
 T lymphocytes produce cytokines, which
enhance the microbicidal activities of
phagocytes.
Antibodies produced by plasma cells bind to
pathogens and activate the complement
system to result in the destruction of the
invaders.
Antibodies produced by B lymphocytes bind
to pathogens and assist with phagocytosis
(opsonization).
Cells and Organs of the Immune
System
a. Lymphocytes – specialized for adaptive
immunity
b. Granulocytes/Agranulocytes – func in
accessory roles in adaptive immunity
Immune Organs – 2 major
groups
a. 1° lymphoid organs – where lymphocytes dev.
and mature
b. 2° lymphoid organs – where lympho’s interact
w/ Ag
Hematopoiesis
Begins with hematopoietic stem cells (HSC)
 Few in in bone marrow; difficult to culture
 Pluripotent; able to produce RBC’s, WBC’s,
megakaryocytes
HSC differentiates to become:
either a) Myeloid progenitor cell
or b) Lymphoid progenitor cell

Myeloid RBC’s and WBC’s and dendritic cells

Lymphoid B and T cells and dendritic cells
Fig 2-1 Kuby, 5e
Cells= Leukocytes= white blood cells
Granulocytes
1. neutrophils
2. eosinophils
3. basophils

Non-granulocytes

4. monocytes
5. lymphocytes
Plasma (56%)
RBCs
After centrifugation in Ficoll, leukocytes are found
in the “buffy coat” 1%
Plasma- with anticoagulant
Serum- after coagulation
 Where do all these cells come
from?

Hematopoeisis
• Pleuripotent Hematopoeitic Stem Cells give rise to
second generation stem cells with restricted lineage
potential= progenitors
Granulocytes
•Front line of attack during immune response part of innate immune
response
•Identified by characteristic staining patterns of “granules”
–Released in contact with pathogens
–Proteins with distinct functions: killing, regulation of other cells,
tissue remodeling
•All have multilobed nuclei
Neutrophils
•One of the main effector cells in the innate immune
system
•50-70% of white blood cells

•Named based on staining qualities of granules

•Multilobed nucleus= polymorphonuclear leukocyte=
PMN
•Neutrophilic granules stain lightly blue to pink
•7-10 hrs in blood, then migrates into tissues
•First responders- Motile & phagocytic
•“Leukocytosis” indicates infection
•Extracellular “traps”
Basophil
•<1% all leukocytes
•Non-phagocytic
•Nucleus obscured by coarse blue (H&E) granules
•Important in some allergic responses
•Critical to response to parasites
•Bind circulating Abs and release histamine-
increasing permeability of blood vessels
•Leave bone marrow as undifferentiated cells and
mature in tissues
Eosinophil
•Bilobed nuclei
•Motile, phagocytic
•Killing of antibody coated parasites
•Degranulation of substances that kill parasites,
worms
Myeloid antigen presenting cells:
Monocytes, macrophages, dendritic cells
•Phagocytic
•Ingest, digest into peptides, present on cell surface
•Bridge between innate and adaptive immune responses
•Make contact with antigens in periphery and then interact with
lymphocytes in lymph node
•Secrete proteins that attract and activate other immune cells
Monocytes
•Mononuclear
•Circulate in blood~ 8 hrs
•Bean-shaped nucleus
Are largest ofleukocytes with diameter 14
To 18
Monocytes play important role in the defense
Against germs and inflamation
Macrophage
•Monocytes enter tissues and become fully mature
macrophages or dendritic cells
–Enlarge
–Become phagocytic
–Special names in different organs- Kupffer cells-
liver
•Digest and/or present Ag
•Surface receptors for Abs (opsinized Ags)
Dendritic cell
Dendritic cells(DCs) are antigen
presenting cells (also known as accesory
cells) of mammalian immunue system
their main function is to process antigen
material and present it on the cell surface
to the Tcells of the immune system they
act as massengers between thr innate and
addaptive immune system
Lymphocytes: 3 types
•20-40% of WBC
•Cannot be distinguished morphologically
•T-cells
–helper CD4+ recognize Ag in context of MHCII
–cytotoxic CD8+ recognize Ab in MHCI
•B-cells
–become antibody producing plasma cells
•NK cells
–part of the innate immune response
T and B Lymphocytes
•Large nucleus with dense heterochromatin
•Thin rim of cytoplasm
•Recognizes specific antigenic determinants
•Therefore are responsible for specificity and
memory of the adaptive immune response
Examples of lymphocytes:
Tonsils Organs of the 2. Distribution to
Immune System Secondary lymphoid
Lymph organs for engagement
nodes with antigens

Spleen B-LYMPHOCYTES

Peyer’s T-LYMPHOCYTES
Patches
Bone
Appendix
Marrow
Thymus

B-LYMPHOCYTES
1. Development & maturation Stem cell
in primary lymphoid organs (in bone marrow)
Maturation of T cells-

1.Hematopoesis/
development of
myeloid and lymphoid
cells
2.Maturation of
myeloid and B-cells
The Thymus is the Site of T-cell
Maturation:
•Epithelial cells (thymic stroma)
– forming a sponge-like meshwork of epithelial cells=
reticular epithelial cells
•T-cells- Lymphopoiesis (proliferate and mature)
•mature T-lymphocytes leave via venules in the
medulla and travel through the blood to populate
peripheral organs
•If the thymus fails to form, and T-cells do not
develop
BONE MARROW
In humans and mice, bone marrow is the site of B-cell
origin
and development. Arising from lymphoid progenitors,
immature
B cells proliferate and differentiate within the bone
marrow, and stromal cells within the bone marrow
interact
directly with the B cells and secrete various cytokines
that are
required for development. Like thymic selection
during Tcell
maturation, a selection process within the bone
marrow
eliminates B cells with self-reactive antibody receptors
Lymphatic System
As blood circulates under pressure, its fluid component
(plasma) seeps through the thin wall of the capillaries into
the surrounding tissue.Much of this fluid, called interstitial
fluid, returns to the blood through the capillary membranes.
The remainder of the interstitial fluid, now called lymph,
flows from the spaces in connective tissue into a network of
tiny open lymphatic capillaries and then into a series of
progressively
The largest lymphatic vessel, the thoracic duct, empties
into the left subclavian vein near the heart (see Figure 2-13).
In this way, the lymphatic system captures fluid lost from the
blood and returns it to the blood, thus ensuring steady-state
levels of fluid within the circulatory system. The heart does
not pump the lymph through the lymphatic system; instead
the flow of lymph is achieved as the lymph vessels are
squeezed by movements of the body’s muscles. lymph flows only in
one direction.
Cont..
A series of
one-way valves along the lymphatic vessels ensures that
lymph flows only in one direction.

When a foreign antigen gains entrance to the tissues, it

is picked up by the lymphatic system (which drains all the
tissues of the body) and is carried to various organized
lymphoid tissues such as lymph nodes, which trap the
foreign antigen as lymph passes from the tissues to lymphatic
vessels,
Secondary Lymphoid Organs

Lymph nodes and the spleen are the most highly organized
of the secondary lymphoid organs; they comprise not
only lymphoid follicles, but additional distinct regions of Tcell
and B-cell activity, and they are surrounded by a fibrous
capsule. Less-organized lymphoid tissue, collectively called
mucosal-associated lymphoid tissue (MALT), is found in
various body sites. MALT includes Peyer’s patches (in the
small intestine), the tonsils, and the appendix, as well as numerous
lymphoid follicles within the lamina propria of the
intestines and in the mucous membranes lining the upper
airways, bronchi, and genital tract.
Next lecture
Antigen, antigen processing
and presentaion and first
response to an antigen
CD DIFFERENTIATION
AND CYTOKINES.
COMPLEMENT SYSTEM