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Transcript
6/1/2011
Adaptive Immune Response
Day 2
Chapter 16
The Adaptive Immune Response
1
6/1/2011
The B cell receptor vs. the T cell receptor.
The B cell receptor vs. the T cell receptor.
2
6/1/2011
Which T cells have CD4 and which have
CD8?
Regulatory T cell
3
6/1/2011
Activation of T Cells
The role of dendritic cells
In secondary lymphoid organs: antigenpresenting to naïve T cells; antigen presented by
BOTH MHC Class I AND MHC Class II molecules
In the tissues: antigen-capturing
Migrate to secondary lymphoid
organs
Co-stimulatory molecules expressed
when “danger” is sensed
Activation of T Cells
The role of dendritic cells
In secondary lymphoid organs: antigenpresenting to naïve T cells; antigen presented by
BOTH MHC Class I AND MHC Class II molecules
In the tissues: antigen-capturing
Activates
naïve T cell
Migrate to secondary lymphoid
organs
Co-stimulatory molecules expressed
when “danger” is sensed
4
6/1/2011
Activation of T Cells
The role of dendritic cells
In secondary lymphoid organs: antigenpresenting to naïve T cells; antigen presented by
BOTH MHC Class I AND MHC Class II molecules
In the tissues: antigen-capturing
Naïve T cell
becomes
unresponsive
Migrate to secondary lymphoid
organs
Co-stimulatory molecules expressed
when “danger” is sensed
Activation of T Cells
The role of dendritic cells
In secondary lymphoid organs: antigenpresenting to naïve T cells; antigen presented by
BOTH MHC Class I AND MHC Class II molecules
In the tissues: antigen-capturing
Activates
naïve T cell
Migrate to secondary lymphoid
organs
Co-stimulatory molecules expressed
when “danger” is sensed
5
6/1/2011
Functions of TC (CD8+) Cells
•Induce apoptosis in “corrupt” self cells
(ex. virally-infected)
•Recognize antigen presented by Major
Histocompatibility Complex (MHC) Class I
•Found on all nucleated cells
•Endogenous proteins (i.e. made by the
cell) are presented
•Also secrete cytokines; some increase
surveillance of neighboring cells (↑MHC
Class I expression)
6
6/1/2011
Functions of TC (CD8+) Cells
Functions of TH (CD4+) Cells
“Helps” other cells (operations commander); produces various cytokines that
activate presenting cell and direct other cells
Recognizes antigen presented by Major Histocompatibility Complex (MHC)
Class II
Exogenous proteins (i.e. those that have been taken up by the cell) are presented
Found on antigen-presenting cells (macrophages, B cells….and dendritic cells)
7
6/1/2011
Functions of TH (CD4+) Cells
B cell activation (B cell as the APC)
Multiple types - TH1, TH2 and others
Functions of TH (CD4+) Cells
B cell activation (B cell as the APC)
Antigen represents material that the B cell’s receptor has recognized
8
6/1/2011
Functions of TH (CD4+) Cells
B cell activation (B cell as the APC)
Antigen represents material that the B cell’s receptor has recognized
TH cell directs cytokines to that B cell,
activating it/enabling it to:
•Multiply and differentiate to form
antibody-secreting plasma cells
•Produce memory cells
•Undergo class switching
Note: T-independent
T independent antigens, generally
polysaccharides, can activate B cells without
T cell help.
Children < 2 yo have weak response
Ab are often primarily IgM
T-independent antigens
9
6/1/2011
Functions of TH (CD4+) Cells
Macrophage activation (macrophage as the APC)
Presented peptides are parts of material that the phagocyte has engulfed
TH cell:
•directs
directs cytokines to that macrophage (activating it)
•secretes cytokines that stimulate activated cytotoxic T cells
Review
10
6/1/2011
11
6/1/2011
Figure 16.21
The Big Picture
Presented step-by-step
Lymphocyte Development
Generation of Diversity - B cells as an example (same principles
apply to T cells)
~1/2
1/2 billi
billion naïve
ï B cells,
ll
recognizing ~100 million
different epitopes!
12
6/1/2011
Lymphocyte Development
Generation of Diversity - B cells as an example (same principles
apply to T cells)
~1/2
1/2 billi
billion naïve
ï B cells,
ll
recognizing ~100 million
different epitopes!
gene 1
gene 2
gene 3
antibody (B cell receptor) 1
antibody (B cell receptor) 2
antibody (B cell receptor) 3
Lymphocyte Development
Generation of Diversity - B cells as an example (same principles
apply to T cells)
Concept will be shown shortly
13
6/1/2011
V3
D1
J2
V (variable), D (diversity), J (joining)
V3
D1
J2
V (variable), D (diversity), J (joining)
14
6/1/2011
V3
D1
J2
Rearrangement of DNA (loss of DNA)
V (variable), D (diversity), J (joining)
Imprecise joining
deletions/insertions
Combinatorial associations
heavy chain/light chain
V3
D1
J2
Rearrangement of DNA (loss of DNA)
V (variable), D (diversity), J (joining)
Imprecise joining
deletions/insertions
Combinatorial associations
heavy chain/light chain
15
6/1/2011
V3
D1
J2
Rearrangement of DNA (loss of DNA)
V (variable), D (diversity), J (joining)
Imprecise joining
deletions/insertions
Combinatorial associations
heavy chain/light chain
Rearrangement of DNA (loss of DNA)
V (variable), D (diversity), J (joining)
Imprecise joining
deletions/insertions
Combinatorial associations
heavy chain/light chain
16
6/1/2011
Lymphocyte Development
Positive and negative selection of self-reactive T cells (in thymus)
Positive selection - cells that recognize no material
undergo apoptosis
destroys those that don’t recognize MHC molecules
Negative selection - cells that strongly recognize material
undergo apoptosis (or become regulatory T cells)
17
6/1/2011
Natural Killer (NK) Cells
Kill cells bound by antibody
Natural Killer (NK) Cells
Kill cells bound by antibody
Kill ““self”
Kills
lf” cells
ll th
thatt do
d nott have
h
MHC Cl
Class I on th
their
i surface
f
(b t should)
(but
h ld)
18
6/1/2011
MHC Molecules
Polygenic
MHC Class I molecules, 3 genes
Polymorphic
y
p
Co-dominant
19