Download Adaptive Immune Response

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
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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
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Mediated by B lymphocytes
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A.k.a B cells
Develops in bone marrow
B cells may be triggered to
proliferate into plasma cells
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Plasma cells produce
antibodies
 Antibodies produces when
antigen bonds B cell receptor
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Some B cells produce memory
cells
Strategy of Adaptive
Immune Response
 Overview of cellular
immunity
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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
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In order for body to mount
appropriate response immune
cells must encounter antigen
 Lymphoid system includes
 Lymphatic vessels
 Secondary lymphoid organs
 Primary lymphoid organs
Anatomy of the Lymphoid System
 Lymphatic vessels
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Carry lymph to body tissues
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Lymph formed as result of body’s circulatory
system
Lymph travels through vessels to lymph nodes
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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
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Lymph nodes
Spleen
Tonsils
Adenoids
Appendix
Organs situated strategically
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Allows for initiation of immune response from nearly
any place in body
Anatomy of the Lymphoid System
 Primary lymphoid organs
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Bone marrow and thymus are primary
lymphoid organs
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Location where stem cells destined to become B
and T cell mature
 B cells mature in bone marrow
 T cells mature in thymus
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Once mature, cells leave primary lymphoid
organs and migrate to secondary lymphoid
organs
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
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Basic unit is the monomer
Made of four chains of amino acids held together by disulfides
bonds
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Each heavy and light chain has a constant region
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Two chains are heavy
Two chains are light
The constant region is known as Fc regions
Each heavy and light chain has a variable region
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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
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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
Nature of Antibody
 Protective outcomes of antibody-
antigen binding
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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
 Ab divided into five
classes
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Class is based on
constant region of the
Ab
Classes include:
 IgG
 IgA
 IgM
 IgD
 IgE
Nature of Antibody
 Five classes of antibody
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IgM
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First Ab to respond to infection
5 – 13% of Ab in circulation
Structure: pentamer
 Five monomer units joined together at the constant region
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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
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 Monomer in serum
 Dimer in secreations
 Breast milk, mucous, tears and saliva
Nature of Antibody
 Five classes of Ab
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IgD
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<1% of total Ab in circulation
Structure = monomer
Maturation of antibody response
IgE
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Barely detectable in circulation
Structure = monomer
Active in allergic reaction
Clonal Selection
of Lymphocytes
 When antigen introduced into body
only appropriate antibody bind
 Initiates multiplication of
specific antibody
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Process called clonal
selection
Repeated cycles of cell
division generates population
of copied cells
 Termed clonal expansion
 Without sustained stimulation cells
undergo apoptosis
Clonal Selection
of Lymphocytes
 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
B Lymphocyte and
Antibody Response
 Antigen binds to B cell receptor
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Poises B cell to respond
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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
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Macrophages are call antigen
presenting cells (APC)
B Lymphocyte and
Antibody Response
 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
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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
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Form of natural selection
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Occurs among proliferating B cells
Fine tunes quality of response with respect to
specificity
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B cell receptors more and more specific to
antigen
 Antibody binds antigen more tightly
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
B Lymphocyte and
Antibody Response
 Formation of memory
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B cells that have undergone class switching
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Produce IgG antibody
 IgG is antibody of memory
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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
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Often eliminating invaders before noticeable harm
is done
Vaccine exploits phenomenon of immunologic
memory
Some memory B cells will differentiate into
plasma cells
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Results in rapid production of antibodies
B Lymphocyte and
Antibody Response
 T-independent antigens
 Can stimulate antibody
response
 Activate B cells without
helper T cells
 Few antigens are Tindependent
 B cell receptors bind antigen
simultaneously
 Leads to B cell activation
 Some polysaccharides and
lipopolysaccharides act as
T-independent antigens
T Lymphocytes
Antigen 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 Lymphocytes
Antigen 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
T Lymphocytes
Antigen Recognition and Response
 General characteristics
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Two major function T cell populations
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Cytotoxic T cells
 Proliferate and differentiate to destroy infected or
cancerous “self” cells
 Have CD8 marker
 Recognize MHC class I
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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 Lymphocytes
Antigen Recognition and Response
 Functions of Tc (CD8) cells
 Induce apoptosis in “self” cells
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Cells infected with virus or intracellular microbe
Destroys cancerous “self” cells
Nucleated cells degrade portion of proteins
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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
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Tc cells releases pre-formed cytokines to destroy
cell
T Lymphocytes
Antigen Recognition and Response
 Functions of TH (CD4) cells
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Orchestrate immune response
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Recognize antigen presented by MHC class II
molecules
 MHC class II molecules found only on APC
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If TH cell recognizes antigen cytokines are
delivered
 Cytokines activate APC to destroy antigen
T Lymphocytes
Antigen Recognition and Response
 Role of TH cells in B cell activation
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If TH cell encounters B cell bearing peptide:
MHC class II complex
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TH cell responds by producing cytokines
B cell is activated in response to cytokine
stimulation
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B cell proliferates and undergoes class switching
Also drive formation of B memory cells
T Lymphocytes
Antigen Recognition and Response
 Role of TH cells in macrophage activation
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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
 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
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Important in viral infection
Lymphocyte Development
 During lymphocyte development B and T cells
acquire ability to recognize distinct epitopes
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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