Ch. 10.

1
Ch. 10. T cell development Maturation - in
thymus Activation Differentiation
2
p. 245
3
T cells migrate to thymus Positive selection of
T cells that recognize self-MHC Negative
selection of T cells that react too strongly
with self-MHC (self-tolerance) Cell-surface
protein expression changes
4
p. 247
5
p. 248
6
p. 249
7
p. 250
8
TH cell activation Central to CMI and humoral
response (CMIcell-mediated immunity) TCR-CD3
Ag-MHC on target cell and many accessory
molecules Resting T cell begins to go through
cell cycle immediate genes- transcription
factors intermediate genes- cytokines
and receptors late genes- adhesion factors
9
p. 256
10
(No Transcript)
11
p. 257
12
Naïve T cells TCR-Ag-MHC is not
enough Co-stimulatory signal B7 on APC CD28
and CTLA-4 (on activated T cells) this can be
circumvented in vitro Block B7 or CD28 clonal
anergy
13
p. 259
14
p. 260
15
(No Transcript)
16
(No Transcript)
17
(No Transcript)
18
(No Transcript)
19
p. 262
20
p. 265
21
p. 266
22
Superantigens - bacterial, viral,
endogenous Bind to TCR-MHC complex in
nonspecific way, on the outside of the V-beta
chain Certain V? sequences are targets
23
p. 261
24
Since any T cell with that V? can be
activated, reaction is polyclonal Cytokine
overproduction Systemic toxicity Staphylococcus
toxins- food poisoning, toxic shock syndrome
25
p. 261
26
T cell differentiation CD4 cells outnumber CD8
cells 21 in the periphery More than 95 of
peripheral T cells express the ?? receptor CD4
cells recognize antigen complexed with MHC Class
II antigen CD8 cells recognize antigen
complexed with MHC Class I antigen
27
Circulating naïve T cells circulate
between blood and lymphoid tissues
circulation increases chance for antigen
exposure Cells may circulate for many weeks or
longer
28
What happens when a T cell is activated? Ag-MHC
engaged with TCR-CD3 Co-stimulation with CD28-B7
interaction After 48 hours, cell begins to
divide rapidly IL-2 gene transcription IL-2
receptor transcription IL-2 mRNA is
stabilized By 4-5 days cells are ready to
differentiate Effector cells Memory cells (more
easily activated)
29
TH1 and TH2 subsets TH1- secretes IL-2, INF-?,
TNF-? cell-mediated immunity TH2 secretes
IL-4, IL-5, IL-6, IL-10 B cell
activation Memory T cells can persist for years
30
p. 263
31
1980s- a new population of T cells was
discovered ??-TCR Rare in periphery Prominent
in skin, gut and pulmonary epithelium Most of
these cells express neither CD4 nor CD8 but one
subset in intestinal epithelium of mice is CD8
32
?? T cells, continued Cells seem to be
tissue-fixed TCR diversity seems to be
restricted maybe they tend to respond to
certain antigens How do they work? Many isolated
reports not too conclusive Respond to
bacterial antigens viruses heat shock
proteins tumor cells
33
Summary T cells mature in the thymus.
Self-reactive cells are eliminated through
positive and negative selection. T cell
activation requires the CD3-TCR complex as well
as co-stimulatory signals. Most T cells express
the ?? receptor.