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Chapter 6

The Adaptive Immune Response


In adaptive immunity, nonspecific phagocytes present antigen to specific T cells, triggering the production of effector T cells and antibodies. Immune T cells and antibodies react directly or indirectly to neutralize or destroy the antigen.

The adaptive immune response is characterized by specificity for the antigen, the ability to respond more vigorously when reexposed to the same antigen (memory), the ability to discriminate self antigens from nonself antigens (tolerance).

Acquired/Adaptive/Specific Immunity Features


Specificity Memory Specialization Self/Nonself recognition

Innate vs. adaptive immunity


Innate immunity
First line of defense (present in all individuals at all times) Immediate (0 4 hours) Non-specific Does not generate lasting protective immunity

Adaptive (acquired) immune response (late: > 96 hours)


Is initiated if innate immune response is not adequate (> 4 days) Antigen-specific immunity Generates lasting protective immunity (e.g. Antibodies, memory T-cells) Humoral and cell-mediated

Immune system cells


Innate immunity
Granulocytes (i.e.neutrophils) Macrophages Dendritic cells Natural killer (NK) cells

Adaptive immunity
Lymphocyte
B cells T cells
Cytotoxic T cells (CTLs) Helper T cells (Th)

Memory cells
http:// www.gcarlson.com/cellular_active_neutrophils.htm

Cells of the adaptive immune system


Dendritic cells (most important APC cell) B-cells
Humoral immune response Produce antibodies APC cells

T- cells
Cell-mediated immune response Cytotoxic T cells (CD8) Helper T cells (CD4)

Memory cells
http://www.biology.arizona.edu/immunology/tutorials/immunology/graphics/T_helper_act.gif

Induction of the adaptive immune response


Activates

Pathogen ingested by immature dendritic cell Migrate to the lymph nodes Interact with nave T lymphocytes
MHC II

TH1 Macrophage

Dead intracellular bacteria

Lymphocytes (effector cells of the adaptive immune system)


Antigen receptors with single specificity Gene re-arrangement re(T and B cells)

Clonal selection Interaction of antigen and lymphocyte receptor Activation of lymphocyte Differentiation (progeny with identical specificity) T and B cells have 2 distinct recognition systems for detecting pathogens T cells - recognize intracellular pathogens (T cell receptors, TCR) B cells recognize extracellular pathogens (Immunoglobins, BCR

Clonal selection
A single progenitor cell gives rise to a large number of lymphocytes, each with a different specificity Removal of potentially self-reactive immature lymphocytes by clonal deletion

Self antigen Pool of nave lymphocytes Foreign antigen

Self antigen

Effector cells eliminate antigen

Proliferation and differentiation of activated specific lymphocytes to form a clone of effector cells

Membrane-bound form of the antibody V-region (variable) Antigen-binding specificity Fc-region (constant) Determines how the antibody disposes of the bound pathogen

V region; At binding

Fc region

Single antigen recognition site Always a cell surface molecule

Active duty?
Antigen

Effector cells
Active-duty cells Die offclone or just during after battle cells family of
descended from one

Chemical signal

Active Nave
T cell
or

ancestor cell

B cell

Memory cells
Reserve cells Called up to the front for later battles

Reserves?

Humoral immune response


Cell-surface immunoglobulin receptors (BCR) detect extracellular pathogens
 Once activated, secrete immunoglobulins as soluble antibodies

Antibodies
 Variable region (2 identical antigen-binding sites)  Constant region (determines how antibody disposes of the pathogen once it is bound)

Generation of Antibody Diversity: Production of Unique Fab Sites through Gene Translocation

the immune system of the body has no idea as to what


antigens it may eventually encounter.

Therefore, it has evolved a system that possesses the


capability of responding to any conceivable antigen.

The immune system can do this because both Blymphocytes and T-lymphocytes have evolved a unique system of gene-splicing called gene translocation , a type of gene-shuffling process where various different genes along a chromosome are cut out of one location and joined with other genes along the chromosome.

Clonal Selection and Clonal Expansion


During its development, each B-lymphocyte becomes genetically programmed, through a process called gene translocation, to make a unique antibody molecule that will function as a B-cell receptor. Molecules of that antibody are then placed on the cell's surface where it can react with epitopes of an antigen. Cytokines from an activated T4-lymphocyte now enable the activated B-lymphocyte to proliferate into a large clone of identical Blymphocytes. The B-lymphocytes now differentiate into antibody-secreting B-lymphocytes and plasma cells that secrete large quantities of antibodies "fitting" the original epitope. Some B-lymphocytes differentiate into Bmemory cells capable of anamnestic response .

Antibody interactions
Antibodies can participate in host defenses in 3 main ways: Neutralization
Ab bind and neutralize bacterial toxins, bacteria and virus particles preventing interaction with host cells Ingestion by macrophages

Opsonization
Allows recognition by phagocytes or NK cells (antibodydependent cell mediated cytotoxicity, ADCC) Ingestion or killing

Complement activation
Activation of complement system Ingestion by phagocytes

Antigen recognition by T-cells


T cells detect presence of intracellular pathogens
T cells receptors Peptide fragments Major histocompatibility complex (MHC)
MHC I (cytotoxic T cells /CD+8) MHC II (T helper (1 and 2)/ CD+4)

Cell death

Antigen recognition by T-cells


Cytotoxic T cells (CD8) recognize antigen presented by MHC I and kills the cell
Kills Activates

TH1 cells (CD4) recognize antigen presented by MHC II and activates macrophages

TH2 cells (CD4) recognize antigen presented by MHC II and activates B cells
Activates

MHC I

Cytotoxic T cell

Virusinfected cell

TH1

MHC II

TH2 Macrophage Dead intracellular bacteria

MHC II

B cell

Apoptotic cell

Anti-toxin antibodies