Chapter 3 - Adaptive Immunity
Adaptive Immunity- the body’s third line of defense behind: physical barriers and innate immunity.
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Adaptive immunity is initiated in:
1. lymph nodes
2. White pulp of the spleen
Peyer’s patch of the gut
** Multiple V and J segments lie upstream of the constant region. After gene rearrangement
has juxtaposed one V and one J segment the gene can be transcribed. Additional diversity is
generated by random insertion of nucleotides at the joint between the V and J segment (the
dark orange line). Expression of the rearranged gene produces a cell- surface antigen receptor.
Individual lymphocytes express different antigen receptors as a result of different combinations
of V and J segments being brought together by rearrangement process. The same principle
applies to the genes for the proteins that make up B cell receptors, Ab’s and T-cell receptors.
Gene rearrangement in B and T cells- this makes the variable region sequence that can be transcribed
and translated. This allows for multiple combinations of receptors.
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Variable regions of the immunoglobulin’s and T cell receptors are encoded by gene segments
V,D, and J
Immunoglobulin heavy chain and T-cell beta chain are encoded by = V,D, and J segments
Immunoglobulin light chain and T- cell alpha chain are encoded by- V and J segments.
1. Dendritic cells carry the pathogen from the infected site to the nearest secondary lymphoid tissue.
Dendritic cells (are a type of phagocytic leukocyte related to machrophages, and like macrophages, they
are resident in tissues and are specialized in the uptake and breakdown of infectious agents. Unlike
macrophages however the presence of the infection causes dendritic cells to differentiate into mobile
cells that transport bacteria and their antigens through the lymph to the secondary lymphoid tissue that
drains the infected site.
2. Dendritic cells meet and activate T cells. Upon entering the lymphoid tissue, dendritic cells settle in
the T- cell areas where they can test the receptors. These T cells have yet to encounter their antigens so
they are named naïve T cells. The T cells that are receptor specific (on the dendritic cell) for the antigen
will bind. The T cells will bind to the antigen but will still be attached to the dendritic cell until it is
activated, allowing the dividing and differentiating into effector T cells to occur.
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Dendritic Cell Processing- ( takes place in dendritic cells) The production of antigenic peptides
from pathogen proteins by using proteases that are normally used to remove dendritic cell
proteins that are misfolded or no longer needed, or the proteases that break down proteins
made by other cells of the body.
Once the pathogens are spliced into peptide antigens the antigenic peptide must be carried to
the cell surface where it is accessible to the T cell receptors.
Pathogen bound peptides are bound by glycoproteins called MHC molecules, which are encoded
by genes in the MHC region of the genome. Each MHC molecule binds a SINGLE peptide. The
peptide- MHC complex is then taken to the cell surface where it can bind to T cell receptors.
Antigen- presenting cells- cells carrying peptide- MHC complexes on the surfaces
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There are two types of MHC molecules that present peptide antigens to two types of T cells:
1. MHC class I molecules- They present antigens from intracellular pathogens. They bind
pathogens and take them to the cell surface where they meet with - Cytotoxic T cells.
2. MHC class II molecules- They present antigens from extracellular pathogens. They bind
pathogens and take them to endosomal vesicles, where they bind peptides produced by
lysosomal degradation of extracellular pathogens before moving to the cell surface where they
meet with – Helper T cells.
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MHC class I molecules- they are specific for cytotoxic T- cells. The cytotoxic T cells carry a cell
surface molecule CD8 which is specific for MHC1. CD8 acts as a co receptor in that MHC
molecules must bind to both the T-cell receptor and the CD8 molecule.
MHC class II molecules- to ensure that helper T cells recognize only antigens presented by MHC2
molecules they express a co- receptor called CD4. CD4 binds to a conserved site on MHC2
molecules and functions analogously to the CD8 co- receptor of cytotoxic cells.
** Cytotoxic CD8 T cells respond ONLY to antigens from intracellular infections presented by
MHC1 molecules.
** Helper CD4 T cells respond only to antigens from extracellular infections presented by MHC
class II molecules.
In a cell infected by a virus, new viral proteins are made on the ribosomes of cytoplasm. Some of
these proteins are degraded in the cytoplasm and the resultant peptides are transported into
the ER. MHC1 molecules bind peptides in the ER and then transport them to the surface of the
infected cell, where they can be recognized by a virus- specific effector cytotoxic T cell.
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When T cell receptors and CD8 co- receptors bind to these complexes, the interaction triggers
the cytotoxic T cell to deliver a battery of toxic substances onto the surface of the infected cell,
which induces its death by apoptosis. Destruction of the infected cell interrupts viral replication
and prevents the further infection of healthy cells.
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When a tissue is infected by bacteria, a macrophage phagocytoses extracellular bacteria and
degrades their proteins in endocytic vesicicles. MHC2 molecules bind peptides in these
endocytic vesicles and transport the peptides to the cell surface. CD4 helper T cells recognize
these peptides on the MHC2 molecules and bind. Upon contact the helper T cell releases
cytokines and activates the macrophage making it more effective in killing bacteria.
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Intact pathogens or proteins within the lymph node can interact with the antigen receptors of B
cells that ender the node from the blood. When the pathogen binds to the B-cell receptor,
receptor- mediated endocytosis occurs, which causes the bacterium to be engulfed and
delivered to endocytic vesicles in the B- cell cytoplasm. Peptides are then bound by the MHC2
molecules in the endocytic vesicles and delivered to the B-cell surface. The B- cells will then act
as an antigen- presenting cell to CD4 helper T cells and become activated.
This mutual interaction causes the helper CD4 T cell to secrete cytokines that, together with
signals from the antigen-bound B cell receptor itself, help drive the B cell to proliferate and
differentiate into plasma cells.
Extracellular pathogens are eliminated via:
1. neutralization- Ab’s bind to a site on the pathogen to inhibit growth, reproduction, or
interaction with other human cells. The pathogen is then ingested and phagocytosed.
2. opsonization- the bacterium is coated with igG (responsible for engulfment and destruction of
extracellular microbes and toxins by phagocytosis. Neutrophils and macrophages can bind to
IgG) and is more efficiently phagocytosed.
- It can also be achieved by coating of complement- IgM binds to C1 and initiates complement
activation. The pathogen is then coated with c3b and phagocytosed via macrophages.
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2 mutational mechanisms to improve effectiveness of the Ab’s that B cells will make:
1. Somatic hypermutation- introduces nucleotide substitutions throughout the variable regions
of the rearranged immunoglobulin heavy and light chaings to increase affinity for antigen.
2. Isotype switching- changes the isotype but not its antigen binding site. This changes the
isotype to a more effective form.
These two mutational mechanisms select for:
1. The Ab will be more tightly bound to a pathogen
2. The Ab will be more efficiently delivered to site of infection
3. The Ab will be better able to involve phagocytes and other inflammatory cells in
pathogen elimination.
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Drawback of an infinite number of binding site specificities? Potential binding to normal healthy
cells and damaging them.
Immunological tolerance towards self- mechanism to prevent B and T cells from binding to
healthy cells and damaging them.
1. Positive selection- immature T cells (thymocytes) from the thymus that bear antigen
receptors that work effectively with MHC1 and 2 molecules are identified and selected to go
through rounds of clonal selection.
2. Negative selection- identity’s cells bearing receptors that bind too strongly to self MHC and
are capable of attacking healthy cells expressing these proteins. This produces self tolerant Tcells.
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