Adaptive Immune Response
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Transcript of Adaptive Immune Response
First response to particular antigen called primary response› May take a week or more to develop
Immune system remembers pathogen on subsequent exposure› Termed secondary response
Adaptive immunity divided into› Humoral immunity
Eliminates extracellular pathogens
› Cellular immunity Eliminates intracellular pathogens
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 produce when antigen bonds B cell receptor
› Some B cells produce memory cells
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
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 removed
Fluid portion empties back into blood stream
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
Primary lymphoid organs› Bone marrow and thymus are primary
lymphoid organs Location where stem cells destined to
become B and T cells 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
Coined from compounds that elicit antibody production› Antibody generator
Includes an enormous variety of materials Today, term used to describe any
compound that elicits an immune response› Antigen that causes immune response termed
immunogen Proteins and polysaccharides induce
string response› Lipids and nucleic acids often do not
Recognition of antigen directed at antigenic determinant or epitope
Structure of the Antibody (Ab)› Basic Y-shaped structure› Made of four chains of amino acids held together by disulfide
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 region
› Each heavy and light chain has a variable region Variable region is unique to each Ab This region binds to a specific Antigen and is known as “Fab”
region
Protective outcomes of antibody-antigen binding› Neutralization
Prevents 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› Opsinization
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
Five classes of Ab› 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
Five classes of Ab› 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 secretions
Breast milk, mucus, tears and saliva
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
When antigen introduces into body, only appropriate antibody bonds› Initiates multiplication of
specific antigen Process called clonal
selection Repeated cycles of cell
division generates population of copied antibodies Termed clonal expansion
Without sustained stimulation, cells undergo apoptosis
Lymphocyte characteristics include› Immature
Antigen specific receptors not fully developed› Naive
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 seed and effectiveness
of secondary response Remembers antigen on subsequent exposure
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 called 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
Characteristic of primary response› Lag period of 10 to 12 days occurs before
antibody detection in blood Activated B cells proliferate and differentiate into increasing
numbers of plasma cells as long as antigen is present
› Net result is slow steady increase in antibody titer
Over time, some B cells undergo changes enhancing immune response including
Affinity maturation Class switching Formation of memory cell
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 bonds antigen more tightly
Class switching› B cells initially programmed to differentiate into plasma
cells Plasma cells secrete IgM antibodies
› Helper T cells produce cytokines Some B cells switch programming
Differentiate to plasma cells that secrete other classes of antibodies 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
Characteristics of secondary response› Memory cells responsible for swift effective
reaction of secondary response Often eliminate 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
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
General characteristics of T cells› Have multiple copies of T cell
receptors Receptors have variable sites of
antigen bonding› Role of T cells different from B cells
T cells never produce antibodies T cells armed with effectors that
interact directly with antigen T cell receptor does not react with
free antigen Antigen must be present by APC
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
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
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
Role of TH cells in B cell activation
› If TH cell encounters B cell bearing peptide: MHC calls 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 drives formation of B memory cells
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
Natural killer cells descend from lymphoid stem cells› They lack antigen specificity
No antigen receptors Recognize antigens by means of Fc portion of IgG
antibodies Allow 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
During lymphocyte development, B and T cells acquire ability to recognize distinct epitopes› Once committed to specific antigen, cells
“checked out” to ensure proper function› B cells undergo developmental stages in bone
marrow› T cells go through process in thymus