Adaptive Immunity

General Overview
Traditionally,
Innate immunity is assumed to be rapid, non-specific and
identical qualitatively and quantitatively each time the same
pathogen was encountered. Many innate immune cells are
thought to be short-lived — for example, the lifespan of a
neutrophil is estimated to be a few hours or days — making
memory an irrelevant concept. Granulocytes, monocytes,
macrophages, dendritic cells and natural killer (NK) cells have
been delegated to the innate immune system, which also
comprises epithelial cell barriers, complement, antimicrobial
peptides and other soluble factors.
The hallmarks of adaptive immunity are thought to include the
generation of long-lived, antigen-specific cells after initial
exposure to an antigen/pathogen that can respond faster and
more robustly on subsequent encounters with the same
antigen/pathogen. It is generally considered to be the exclusive
domain of B and T cells.
Adaptive immunity….
is the protection of a host organism from a
pathogen or toxin. It is mediated by B cells
and T cells, and is characterized by
immunological memory. Adaptive
immunity is highly specific to a given
antigen and is highly adaptable.

Other names: Acquired Immunity,

Specific Immunity
 Types of Acquired Immunity
I. Naturally Acquired Immunity: Obtained in
the course of daily life.
A. Naturally Acquired Active Immunity:
 Antigens or pathogens enter body naturally.
 Body generates an immune response to antigens.
 Immunity may be lifelong (chickenpox or mumps)
or temporary (influenza or intestinal infections).
B. Naturally Acquired Passive Immunity:
 Antibodies pass from mother to fetus via placenta
or breast feeding (colostrum).
 No immune response to antigens.
 Immunity is usually short-lived (weeks to months).
 Protection until child’s immune system develops.
Types of Acquired Immunity (Continued)
II. Artificially Acquired Immunity: Obtained by
receiving a vaccine or immune serum.
1. Artificially Acquired Active Immunity:
 Antigens are introduced in vaccines (immunization).
 Body generates an immune response to antigens.
 Immunity can be lifelong (oral polio vaccine) or temporary
(tetanus toxoid).
2. Artificially Acquired Passive Immunity:
 Preformed antibodies (antiserum) are introduced into body
by injection.
 Snake antivenom injection from horses or rabbits.
 Immunity is short lived (half life three weeks).
 Host immune system does not respond to antigens.
 Duality of Immune System
I. Humoral (Antibody-Mediated) Immunity
 Involves production of antibodies against foreign
antigens.
 Antibodies are produced by a subset of lymphocytes
called B cells.
 B cells that are stimulated will actively secrete
antibodies and are called plasma cells.
 Antibodies are found in extracellular fluids (blood
plasma, lymph, mucus, etc.) and the surface of B cells.
 Defense against bacteria, bacterial toxins, and viruses
that circulate freely in body fluids, before they enter
cells.
 Also cause certain reactions against transplanted
tissue.
Antibodies are Proteins that Recognize Specific Antigens
Duality of Immune System (Continued)
II. Cell Mediated Immunity
 Involves specialized set of lymphocytes called T cells
that recognize foreign antigens on the surface of cells,
organisms, or tissues:
 Helper T cells
 Cytotoxic T cells
 T cells regulate proliferation and activity of other cells
of the immune system: B cells, macrophages,
neutrophils, etc.
 Defense against:
 Bacteria and viruses that are inside host cells and are
inaccessible to antibodies.
 Fungi, protozoa, and helminths
 Cancer cells
 Transplanted tissue
 Antigens
 Most are proteins or large polysaccharides from
a foreign organism.
 Microbes: Capsules, cell walls, toxins, viral capsids,
flagella, etc.
 Nonmicrobes: Pollen, egg white , red blood cell
surface molecules, serum proteins, and surface
molecules from transplanted tissue.
 Lipids and nucleic acids are only antigenic when
combined with proteins or polysaccharides.
 Molecular weight of 10,000 or higher.
 Hapten: Small foreign molecule that is not antigenic. Must be
coupled to a carrier molecule to be antigenic. Once antibodies
are formed they will recognize hapten.
Consequences of Antigen-Antibody Binding
Antigen-Antibody Complex: Formed when an
antibody binds to an antigen it recognizes.
Affinity: A measure of binding strength.
1. Agglutination: Antibodies cause antigens
(microbes) to clump together.
 IgM (decavalent) is more effective than IgG (bivalent).
 Hemagglutination: Agglutination of red blood cells.
Used to determine ABO blood types and to detect
influenza and measles viruses.
2. Opsonization: Antigen (microbe) is covered with
antibodies that enhances its ingestion and lysis by
phagocytic cells.
Consequences of Antibody Binding
Humoral Immunity (Continued)
3. Neutralization: IgG inactivates viruses by
binding to their surface and neutralize toxins by
blocking their active sites.
4. Antibody-dependent cell-mediated cytotoxicity:
Used to destroy large organisms (e.g.: worms).
Target organism is coated with antibodies and
bombarded with chemicals from nonspecific
immune cells.
5. Complement Activation: Both IgG and IgM
trigger the complement system which results in
cell lysis and inflammation.
Consequences of Antibody Binding
 Immunological Memory
Antibody Titer: The amount of antibody in the
serum.
Pattern of Antibody Levels During Infection
Primary Response:
 After initial exposure to antigen, no antibodies are
found in serum for several days.
 A gradual increase in titer, first of IgM and then
of IgG is observed.
 Most B cells become plasma cells, but some B cells
become long living memory cells.
 Gradual decline of antibodies follows.
 Immunological Memory
(Continued)
Secondary Response:
 Subsequent exposure to the same antigen displays
a faster and more intense antibody response.
 Increased antibody response is due to the
existence of memory cells, which rapidly produce
plasma cells upon antigen stimulation.
 T Cells and Cell Mediated Immunity
Antigens that stimulate this response are mainly
intracellular.
Requires constant presence of antigen to remain
effective.
Unlike humoral immunity, cell mediated immunity is
not transferred to the fetus.
Cytokines: Chemical messengers of immune cells.
 Over 100 have been identified.
 Stimulate and/or regulate immune responses.
 Interleukins: Communication between WBCs.
 Interferons: Protect against viral infections.
 Chemokines: Attract WBCs to infected areas.
 T Cells and Cell Mediated
Immunity
Cellular Components of Immunity:
 T cells are key cellular component of immunity.
 T cells have an antigen receptor that recognizes
and reacts to a specific antigen (T cell receptor).
 T cell receptor only recognize antigens combined
with major histocompatability (MHC) proteins on
the surface of cells.
 MHC Class I: Found on all cells.
 MHC Class II: Found on phagocytes.
 Clonal selection increases number of T cells.
T Cells Only Recognize Antigen Associated
with MHC Molecules on Cell Surfaces
 T Cells and Cell Mediated
Immunity
Types of T cells
1. T Helper (TH) Cells: Central role in immune
response.
 Most are CD4+
 Recognize antigen on the surface of antigen presenting
cells (e.g.: macrophage).
 Activate macrophages
 Induce formation of cytotoxic T cells
 Stimulate B cells to produce antibodies.
Central Role of Helper T Cells
 Types of T cells (Continued)
2. Cytotoxic T (Tc) Cells: Destroy target cells.
 Most are CD4 negative (CD4 -).
 Recognize antigens on the surface of all cells:
• Kill host cells that are infected with viruses or bacteria.
• Recognize and kill cancer cells.
• Recognize and destroy transplanted tissue.
 Release protein called perforin which forms a pore in
target cell, causing lysis of infected cells.
 Undergo apoptosis when stimulating antigen is gone.
Cytotoxic T Cells Lyse Infected Cells
 Types of T cells (Continued)
3. Delayed Hypersensitivity T (TD) Cells: Mostly T
helper and a few cytotoxic T cells that are
involved in some allergic reactions (poison) and
rejection of transplanted tissue.
4. T Suppressor (Ts) Cells: May shut down
immune response.
 Nonspecific Cellular
Components
1. Activated Macrophages: Stimulated phagocytes.
 Stimulated by ingestion of antigen
 Larger and more effective phagocytes.
 Enhanced ability to eliminate intracellular bacteria,
virus-infected and cancerous cells.
2. Natural Killer (NK) Cells:
 Lymphocytes that destroy virus infected and tumor
cells.
 Not specific. Don’t require antigen stimulation.
 Not phagocytic, but must contact cell in order to lyse it.
 Relationship Between Cell-Mediated
and Humoral Immunity
1. Antibody Production
T-Dependent Antigens:
 Antibody production requires assistance from T helper cells.
 A macrophage cells ingest antigen and presents it to T H cell.
 TH cell stimulates B cells specific for antigen to become plasma
cells.
 Antigens are mainly proteins on viruses, bacteria, foreign red
blood cells, and hapten-carrier molecules.
T-Independent Antigens:
 Antibody production does not require assistance from T cells.
 Antigens are mainly polysaccharides or lipopolysaccharides with
repeating subunits (bacterial capsules).
 Weaker immune response than for T-dependent antigens.
Humoral Response to T Dependent Antigens
 Relationship Between Cell-Mediated
and Humoral Immunity
2. Antibody Dependent Cell Mediated
Cytotoxicity
 Target cell is covered with antibodies, leaving Fc
portion sticking outwards.
 Natural killer and other nonspecific cells that have
receptors for Fc region are stimulated to kill targeted
cells.
 Target organism is lysed by substances secreted by
attacking cells.
 Used to destroy large organisms that cannot be
phagocytosed.
Destruction of Large Parasites by ADCC
Overview of the Immune Response
 Activated T cells clone
& differentiate into:
Direct physical &  Cytotoxic T cells
stimulate
chemical attack  Helper T cells B cell activation
 Memory T cells
 Suppressor T cells

Regulate the immune response

Remain in reserve Prevent autoimmune responses

bacteria
CELL MEDIATED IMMUNITY

ANTIGENS

SPECIFIC APC’s phagocytize Ag & activate T

cells
bacteria DEFENSES
(Immune
response)

viruses
Antibody Mediated (Humoral) Immunity
The body has millions of different B
cell populations, each B cell has its
own particular antibody (Ab) molecule
(transmembrane protein) within its cell
membrane
 When the corresponding Ag invades
the interstitial fluid surrounding the B
cell, the Ag binds to the Ab molecule, &
is taken into the cell, eventually being
displayed on the B cell’s MHC protein.
The B cell is now “sensitized”
Antibody Mediated (Humoral) Immunity

 Helper T cells (that had been

previously activated to the same Ag)
then attach to the sensitized B cells &
activate them by secreting chemicals
(cytokines)
 Cytokine secretion results in B cell
cloning & differentiation into plasma
cells & memory cells
Antibody Mediated (Humoral) Immunity
 Plasma cells produce millions of
copies of antibodies which are
released into the blood & lymph
 Antibodies seek out & bind to the
Ag forming an “Ab-Ag complex”,
eventually leading to the elimination
of the antigen by various means
 Memory cells remain in reserve to
respond to any subsequent
exposure by the same Ag. Upon
secondary exposure, memory B
cells quickly differentiate into Ab
producing plasma cells
Antibody Mediated (Humoral) Immunity
Central Role of Helper T Cells
Summary of
Defense
and
Immune
Responses
 The class I MHC pathway of processing
of endogenous cytosolic protein antigens

Cytoplasmic peptides are actively transported into the ER;

class I MHC molecules are available to bind peptides in the ER
ADAPTIVE IMMUNE RESPONSE
antigen presenting cells

 Cross-presentation of Ag to CD8 T cells. Abbas Fig 5-7

T Cell - Mediated B Cell Activation
The Phases of B cell Responses
Cytokines help B-cell isotype switching & affinity maturation