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PHRD5015 Lecture 16 (Ju) - Regulation of the Immune System
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humoral immunity
Ab specificity and diversity
Ab/Ig site for attachment to phagocytic cells
constant region (Fc)
Ab/Ig site for attachment to Ag
variable region (Fab)
types of bonds holding Ig's together
disulfide bonds
CDR
complementary-determining region
location of Ag binding
determines specificity
Ab structure
2 heavy chains, 2 light chains
variable (V) domain located at N-terminus
goodness of fit
affinity between antigenic determinant/epitope & Ab
Instruction Theory
Ag tells the immune system to make Ab of appropriate conformation
("tailor made dress")
Clonal Selection Theory
each cell of immune system is programmed to make only 1 Ab - entire population preexists before Ag contact
choice of which Ab to make is RANDOM
("store bought dress")
5 ways to maximize Ab diversity
1) multiple germ line V genes
2) V-J & V-D-J recombination
3) combinatorial diversity (recombinational inaccuracies)
4) somatic point mutation
5) pairing of heavy & light chains
segments in light-chain DNA
V-J-C
how many genes encode each constant region?
ONE
segments in heavy-chain DNA
V-D-J-C
enzyme responsible for VDJ splicing
RAG recombination enzyme
recombinational inaccuracies
VDJ joins are sloppy, with some nucleotides lost/added (by TdT) at random without a template -> increased diversity
TdT
terminal deoxynucleotide transferase
replaces lost nucleotides during VDJ recombination
types of cells expressing class I MHC
all nucleated cells
types of cells expressing class II MHC
B cells
APCs (DCs)
macrophages
what do cells expressing class I MHC present Ag to?
CD8
+
cells (CTLs)
what do cells expressing class II MHC present Ag to?
CD4
+
cells (Th1 & Th2)
describe the MHC region presented to T cells
and
chains are folded to form a groove
groove base is a beta sheet, and sides are 2 alpha helices
Ag peptide is in groove & presented to T cells
3 requirements for a successful T cell
1) not recognize or bind too tightly to self
2) recognize Ag-selfMHC complex
3) not recognize free Ag
negative selection
cells are eliminated through apoptosis if they recognize self peptides with too high affinity or don't recognize self MHC at all
where does T cell development/maturation occur
thymus
positive selection
selection of T cells with low (but real) affinity for self MHC
low affinity for self may = high affinity for self+Ag
3 stages of central tolerance
1) negative selection
2) rescue from programmed cell death
3) lineage determination (based on low affinity to specific MHC class)
3 mechanisms of peripheral tolerance
1) anergy
2) activation-induced cell death
3) suppression by regulatory T cells
example of costimulatory molecule binding during T cell activation
B7 on APC binds to CD28 on T cell
anergy
incomplete activation
absence of sensitivity to substances that would normally elicit an antigenic response
2 causes of T cell anergy
1) lack of costimulatory molecule
2) inhibition of/competition with costimulatory molecule for B7 binding
CTLA-4
cytotoxic T lymphocyte associated molecule
competes with CD38 for binding to B7 -> T cell anergy/suppression of activation
how are costimulatory molecules expressed?
TLR binding activates NF-
B pathway -> costimulatory molecules expressed
type of cell death important in preventing autoimmunity
activation-induced T cell death
T cells express what 2 molecules that lead to cell death?
Fas & FasL
immunosuppressive cytokines secreted by Tregs (2)
1) IL-10
2) TGF-
2 ways Tregs can inhibit activation/effector fcn of other T cells
1) acts as an IL-2 "sink"
2) secrete IL-10 & TGF
Author
daynuhmay
ID
243867
Card Set
PHRD5015 Lecture 16 (Ju) - Regulation of the Immune System
Description
Regulation of the Immune System
Updated
2013-10-30T09:55:30Z
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