Download 1. The Cell-Mediated Immune Response

Chapter 17B:
Adaptive Immunity – Part II
1. Cell-Mediated Immune Response
2. Humoral Immune Response
3. Antibodies
1. The Cell-Mediated
Immune Response
Basic Steps of Cell-Mediated IR
1) APC processes
intracellular
pathogen
1
2a
CD4+
2) peptides are
presented on
MHC class I &
MHC class II
3
4
MHC
cl. I
2b
CD8+
3) APC activates
specific TH cell
to become TH1
4) TH1 releases cytokines to activate specific CD8+ CTL
to divide, differentiate into active CTLs, memory cells
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Primary Cell-Mediated IR
The initial activation of cytotoxic T cells due to
an intracellular pathogen occurs as follows:
1) a dendritic cell or macrophage ingests or is
infected by an intracellular pathogen
2) peptides fr. pathogen presented on MHC class II
and MHC class I molecules
3) specific TH cells activated to become TH1 cells
4) TH1 cells activate specific CTLs to:
• undergo mitosis to produce more of that T cell clone
• differentiate into active CTLs OR memory T cells
CTL-mediated Killing of Infected Cells
Activated CTLs will cause the death of any cells that
present the foreign peptide on MHC class I by:
• inducing programmed cell death (apoptosis) OR
• inducing cell lysis by releasing the protein perforin
**Dendritic cell APCs are spared this fate!**
Programmed Cell Death (Apoptosis)
Programmed cell death (aka apoptosis) is a
built in program present in every cell which
which results in “cell suicide”:
• activated CTLs express a protein called Fas-ligand
when they encounter a cell presenting an MHC class
I-peptide complex that binds their T cell receptor
• Fas-ligand sets off a series of events that result in
the destruction of the infected cell’s DNA and its
proteins (i.e., cell death!)
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Summary of Cell-Mediated Immunity
• this takes several days to complete
T Cell Memory
Like B cells, T cells (whether TH or CTL) also
produce extremely long-lived memory cells:
• activated directly upon subsequent exposure
• no need for activation signals from other T cells
or APCs
• secondary responses are much more rapid
and much more intense than primary responses
• this is the basis for immunizations
• the enhanced secondary response is so much more
effective that the individual is largely protected
from re-infection with the same pathogen
2. The Humoral
Immune Response
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Basic Steps of Primary Humoral IR
For the sake of simplicity,
we will consider humoral
immunity in which a B cell
serves as the APC:
1) specific B cell binds native
antigen with its membranebound antibody (BCR)
• antigen is internalized and
broken down into peptides
• peptides (processed antigen)
are “loaded” onto MHC class II
molecules
2) MHC class II
molecules bearing
peptides from the
internalized
pathogen are
presented on the
B cell surface
• various TH cells will now be able to “sample” peptides
from the ingested pathogen
• any TH cells expressing a T cell receptor (TCR) that
binds to peptides (processed antigen) from the ingested
pathogen can now be activated
3) TH cells that
“recognize”
peptides from
the pathogen
are activated
by the B cell,
and in turn
activate the
B cell
A
B
A) special proteins on the B cell surface will activate any
TH cells that bind to the presented peptide antigens
to become TH2 cells
B) activated TH2 cells then release cytokines that in turn
activate the B cell
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4) the activated B cell
clone divides multiple
times and then these
cells differentiate into
plasma cells or
memory B cells
• plasma cells are B cells that have become specialized to
continually produce and secrete soluble antibody for a few
days and then die
• initially plasma cells produce IgM class antibodies, however
they can be induced to “switch classes”
• other B cell progeny instead become memory B cells
**TH2 cells also divide and produce memory T cells**
Summary of Primary Humoral IR…
The initial exposure of a B cell to its specific
antigen results in its activation as follows:
1) dendritic cell, macrophage or B cell ingests
extracellular antigen by phagocytosis
2) peptides fr. antigen presented on MHC class II
3) specific TH cells activated to become TH2 cells
4) TH2 cells in turn activate specific B cells to:
• undergo mitosis to produce more of that B cell clone
• differentiate into antibody secreting plasma cells OR
memory B cells
…Summary of Humoral IR
Primary
immune
response
1
antigen
2
BCR
(TH2 cell help)
3
proliferation (mitosis)
4
5
5
plasma cells
memory B cells
• the entire
process
takes
several days
to complete
antigen
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Secondary
immune
response
plasma cells
memory B cells
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T-independent B Cell Activation
Some antigens such as certain bacterial
polysaccharides can activate B cells to
secrete antibody without the help of T cells:
• results in a much more rapid antibody response
• however memory
B cells are NOT
produced
• thus there will NOT
be any kind of
enhanced response
upon subsequent
exposure
Antibody Class Switching
Following the first exposure to its specific
antigen, an activated B cell will generate
IgM producing plasma cells.
Various cytokines produced by TH and other
cells in the vicinity can induce plasma cells to
switch the antibody class to IgG, IgA or IgE:
• usually switch to IgG and later to IgA or IgE
• involves DNA recombination in the gene
encoding the antibody
B Cell Memory
Memory B cells remaining after the initial
activation of a B cell have the following
characteristics:
• they are extremely long-lived (years!)
• their BCRs are of the IgG, IgA or IgE class
• activated directly upon subsequent exposure
• no need for T cell help
• generate more plasma cells & memory cells
• such secondary responses are much more rapid
and much more intense than primary responses
• generate more plasma cells & memory cells
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• artificial
immunity
results from
the injection
of antigen
(active) or
antibodies
(passive)
• natural
immunity
results from
natural expos.
to antigen or
transfer of
antibodies fr.
mother to child
3. Antibodies
Antibody Structure
Every antibody
have this same
basic structure:
Heavy & Light
chains are all
held together by
disulfide bonds
2 identical
Heavy Chain
polypeptides
2 identical
Light Chain
polypeptides
Each heavy & light chain has a
Variable & a Constant region
• the variable regions together bind Ag & are unique for each
antibody due to heavy & light chain gene recombination
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The Different Classes of Antibody
All antibodies fall into 5 general classes based
on their constant regions (which are the same
for all antibodies in a given class) and other features:
IgM (Immunoglobulin type “M”)
IgM
• a pentameric structure consisting of 5
antibodies connected by disulfide bonds
and a J chain polypeptide
• the first class of antibody produced by a B cell after its
initial exposure to antigen that binds its B cell receptor
• most effective at agglutination, activating complement
IgD
• only used as B cell receptor, never secreted
IgG
• a monomeric class comprising ~80% of serum antibodies
and also found throughout the lymph
• good for opsonization, activating complement
• only class of antibody to cross the placenta to fetus
IgA
• a dimeric structure consisting of 2 Ab’s,
a J chain & a secretory component
• present in saliva, mucus, breast milk & other secretions,
is especially “tough”, and is the most abundant of all Ab’s
IgE
• a monomeric class that binds to IgE receptors on mast
cells & basophils and triggers allergic reactions
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The Roles of Antibodies
Antibodies do no more than bind to antigens,
however there are 5 general consequences of
the binding of antibody to antigen:
1) neutralization
• prevents antigen (e.g., virus, toxin) from functioning
2) agglutination
• the “cross-linking” of antigens into a large complex
3) opsonization
• enhancing the process of phagocytosis
4) antibody-dependent cell-mediated cytotoxicity
• facilitating destruction of eukaryotic pathogens
5) activation of complement
Neutralization of Antigens
Agglutination
Occurs since each antibody has 2 Ag binding sites:
• results in elaborate
antigen-antibody
complexes that
localize pathogens,
make them easier
to dispose of
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Opsonization
Phagocytes such as macrophages have receptors
for the constant region (FC) of antibodies:
• FC receptors
allow phagocytes
to “grab onto”
antigen-antibody
complexes much
more easily
• makes it much
easier to engulf
and destroy
pathogens by
phagocytosis
Facilitating Cytotoxic Responses
Eosinophils and NK cells also have FC receptors:
• in this way
antibodies
can tether
these cells
to parasites
& facilitate
chemical
destruction
of these
pathogens
Complement Activation
Antibody bound to the surface of bacteria and other
cellular pathogens can trigger complement cascade:
• this is the classical
pathway of
complement activation
• results in cell lysis or
opsonization (C3b),
influx of phagocytes
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Key Terms for Chapter 17B
• plasma cell, memory B and T cells
• class switching
• apoptosis, Fas-ligand, perforin
• antibody: heavy & light chains, variable, constant
• agglutination
• natural vs artificial immunity
• active vs passive immunity
Relevant Chapter Questions
rvw: 1, 7, 15-17
MC: 1-4, 8
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