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The Adaptive Immune Response
Chapter 16
Strategy of Adaptive Immune Response
First response to particular antigen called primary response May take a week or more to develop
Immune systems remembers pathogen on subsequent exposure Termed secondary response
Adaptive immunity divided into Humoral immunity
Eliminates extracellular pathogens Cellular immunity
Eliminates intracellular pathogens
Strategy of Adaptive Immune Response
Overview of humoral immunity Mediated by B lymphocytes
A.k.a B cells Develops in bone marrow B cells may be triggered to
proliferate into plasma cells Plasma cells produce
antibodies Antibodies produces when
antigen bonds B cell receptor
Some B cells produce memory cells
Strategy of Adaptive Immune Response Overview of cellular
immunity Mediated by T
lymphocytes A.k.a T cells
Matures in thymus Divided into 2 subsets
Cytotoxic T cells Helper T cells
T cell receptors help with antigen recognition
Anatomy of the Lymphoid System
Lymphoid system collection of tissues and organs designed to bring B and T cells in contact with antigens In order for body to mount
appropriate response immune cells must encounter antigen
Lymphoid system includes Lymphatic vessels Secondary lymphoid organs Primary lymphoid organs
Lymphatic vessels Carry lymph to body tissues
Lymph formed as result of body’s circulatory system
Lymph travels through vessels to lymph nodes Material such as protein is removes
Fluid portion empties back into blood stream
Anatomy of the Lymphoid System
Secondary lymphoid organs Sites where lymphocytes gather to encounter
antigens, organs include Lymph nodes Spleen Tonsils Adenoids Appendix
Organs situated strategically Allows for initiation of immune response from nearly
any place in body
Anatomy of the Lymphoid System
Primary lymphoid organs Bone marrow and thymus are primary
lymphoid organs Location where stem cells destined to become B
and T cell mature B cells mature in bone marrow T cells mature in thymus
Once mature, cells leave primary lymphoid organs and migrate to secondary lymphoid organs
Anatomy of the Lymphoid System
Nature of Antigens
Coined from compounds that elicit antibody production Antibody generator
Includes an enormous variety of materials Today term used to describe any compound that elicits
and immune response Antigen that causes immune response termed
immunogen Proteins and polysaccharides induce swong response
Lipids and nucleic acids often do not Recognition of antigen directed at antigenic determinant
or epitope
Nature of Antibody Structure of the Ab
Basic unit is the monomer Made of four chains of amino acids held together by disulfides
bonds Two chains are heavy Two chains are light
Each heavy and light chain has a constant region The constant region is known as Fc regions
Each heavy and light chain has a variable region Variable region is unique to each Ab This region binds to a specific Ag and is know as Fab region
Nature of Antibody
Protective outcomes of antibody-antigen binding Neutralization
Prevents virus or toxin from interacting with cell
Immobilization and prevention of adherence
Antibody bonding to cellular structures to interfere with function
Agglutination and precipitation Clumping of bacterial cells by
specific antibody Bacteria more easily phagocytized
Protective outcomes of antibody-antigen binding Opsonization
Coating of bacteria with antibody to enhance phagocytosis
Complement activation Antibody bonding triggers
classical pathway Antibody-dependent cellular
cytotoxicity Multiple antibodies bind a cell
which becomes target for certain cells
Nature of Antibody
Nature of Antibody
Ab divided into five classes Class is based on
constant region of the Ab
Classes include: IgG IgA IgM IgD IgE
Five classes of antibody IgM
First Ab to respond to infection 5 – 13% of Ab in circulation Structure: pentamer
Five monomer units joined together at the constant region Found on the surface of b lymphocytes as a monomer Only Ab that can be formed by the fetus
Nature of Antibody
Five classes of antibody IgG
Dominant Ab in circulation 80 – 85% Ab in circulation
Structure = monomer Only Ab that can cross the placenta The antibody of memory!!!!!
IgA Found in secretions 10 - 13 % of Ab in circulation Structure
Monomer in serum Dimer in secreations
Breast milk, mucous, tears and saliva
Nature of Antibody
Five classes of Ab IgD
<1% of total Ab in circulation Structure = monomer Maturation of antibody response
IgE Barely detectable in circulation Structure = monomer Active in allergic reaction
Nature of Antibody
Clonal Selection of Lymphocytes
When antigen introduced into body only appropriate antibody bind Initiates multiplication of
specific antibody Process called clonal
selection Repeated cycles of cell
division generates population of copied cells
Termed clonal expansion
Without sustained stimulation cells undergo apoptosis
Lymphocyte characteristics include Naïve
Have antigen receptor but have not encountered antigen Activated
Able to proliferate Have bound antigen
Effectors Descendents of activated lymphocytes Able to produce specific cytokines Plasma cells, T helper and cytotoxic T cells effector cells
Memory lymphocytes Long-lived descendents of activated lymphocytes Memory cells responsible for speed and effectiveness of
secondary response Remembers antigen on subsequent exposure
Clonal Selection of Lymphocytes
B Lymphocyte and Antibody Response
Antigen binds to B cell receptor Poises B cell to respond
In many cases B cell needs conformation from helper T cells
Ag enters the body and is phagocytized and processed by macrophages These macrophages destroy Ag
and present a portion on the surface of the macrophage next to self Ag
Macrophages are call antigen presenting cells (APC)
Processed Ag combines with specific TH with the appropriate receptor
APC releases substances to activate TH cell
TH cell activates B cells to divide and differentiate Produce plasma cells and memory B cells
B Lymphocyte and Antibody Response
Characteristic of primary response Lag period of 10 to 12 days occurs before antibody
detection in blood Activated B cell proliferate and differentiate into increasing
numbers of plasma cells as long as antigen in present Net result is slow steady increase in antibody titer Overtime some B cells undergo changes enhancing
immune response including Affinity maturation Class switching Formation of memory cells
B Lymphocyte and Antibody Response
Affinity maturation Form of natural selection
Occurs among proliferating B cells Fine tunes quality of response with respect to
specificity B cell receptors more and more specific to
antigen Antibody binds antigen more tightly
B Lymphocyte and Antibody Response
B Lymphocyte and Antibody Response
Class switching B cells initially programmed to
differentiate into plasma cells Plasma cells secrete IgM
antibodies Helper T cell produce
cytokines Some B cells switch
programming Differentiate to plasma cells
that secrete other classes of antibody
Commonly IgG
Formation of memory B cells that have undergone class switching
Produce IgG antibody IgG is antibody of memory
IgG antibody can circulate in body for years allowing protection against specific antigens
B Lymphocyte and Antibody Response
Characteristics of secondary response Memory cells responsible for swift effective
reaction of secondary response Often eliminating invaders before noticeable
harm is done Vaccine exploits phenomenon of immunologic
memory Some memory B cells will differentiate into
plasma cells Results in rapid production of antibodies
B Lymphocyte and Antibody Response
B Lymphocyte and Antibody Response
T-independent antigens Can stimulate antibody
response Activate B cells without
helper T cells Few antigens are T-
independent B cell receptors bind antigen
simultaneously Leads to B cell activation
Some polysaccharides and lipopolysaccharides act as T-independent antigens
T LymphocytesAntigen Recognition and Response
General characteristics of T cells Have multiple copies of T cell
receptors Receptors have variable site of
antigen bonding Role of T cells different from B
cells T cells never produce antibody T cells armed with effectors that
interact directly with antigen T cell receptor does not react
with free antigen Antigen must be presented
by APC
T LymphocytesAntigen Recognition and Response
General Characteristics During antigen presentation
antigen cradled in grove of major histocompatability complex molecule (MHC molecule)
Two types MHC MHC class I
Bind endogenous antigen
MHC class II Bind exogenous
antigen
General characteristics Two major function T cell populations
Cytotoxic T cells Proliferate and differentiate to destroy infected or
cancerous “self” cells Have CD8 marker Recognize MHC class I
Helper T cells Multiply and develop into cells that activate B cells and
macrophages Stimulate other T cells orchestrate immune response Have CD4 marker Recognize antigen display by MHC class II
T LymphocytesAntigen Recognition and Response
Functions of Tc (CD8) cells Induce apoptosis in “self” cells
Cells infected with virus or intracellular microbe Destroys cancerous “self” cells
Nucleated cells degrade portion of proteins Load peptides into groove of MHC class I molecule MHC class I molecule recognized by circulating Tc
cell Cell destroyed by lethal effector function of Tc cell
Tc cells releases pre-formed cytokines to destroy cell
T LymphocytesAntigen Recognition and Response
Functions of TH (CD4) cells Orchestrate immune response
Recognize antigen presented by MHC class II molecules
MHC class II molecules found only on APC
If TH cell recognizes antigen cytokines are delivered
Cytokines activate APC to destroy antigen
T LymphocytesAntigen Recognition and Response
Role of TH cells in B cell activation If TH cell encounters B cell bearing peptide:
MHC class II complex TH cell responds by producing cytokines
B cell is activated in response to cytokine stimulation
B cell proliferates and undergoes class switching Also drive formation of B memory cells
T LymphocytesAntigen Recognition and Response
Role of TH cells in macrophage activation Macrophages routinely engulf invading
microbes resistant to lysosomal killing TH cells recognize macrophage with engulfed
microbes resistant to killing TH cells activate macrophages by delivering
cytokines that induce more potent destructive mechanisms
T LymphocytesAntigen Recognition and Response
Natural Killer Cells
Natural killer cell descend from lymphoid stem cells They lack antigen specificity
No antigen receptors Recognize antigens by means of Fc portion of IgG
antibodies Allows NK cells to attach to antibody coated cells
Actions augment adaptive immune response Important in process of antibody dependent cellular toxicity
Enable killing of host cells with foreign protein in membrane
Natural killer cells recognize destroyed host cells with no MHC class I surface molecules Important in viral infection
Lymphocyte Development
During lymphocyte development B and T cells acquire ability to recognize distinct epitopes Once committed to specific antigen cell
“checked out” to ensure proper function B cells undergo developmental stages in bone
marrow T cell go through process in thymus
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