T Cell Receptors and MHC Complex Flashcards
1
Q
What determines what kind of T cell a Th0 becomes?
A
the conditions in the periphery when it was stimulated, what TLR was engaged, what cytokines and chemokines predominated
2
Q
Th1 CD4+ polarized by
A
IL-12, IL-18 and IFN-gamma
3
Q
Th1 CD4+ effector cytokines
A
IFN-gamma and TNF
4
Q
Th1 CD4+ role
A
Secrete IFN gamma = proinflammatory and chemotactic for blood monocytes and tissue macrophages –> angry macrophages
5
Q
angry macrophages release
A
TNFa and IL-1 (intensify inflammation)
6
Q
T cells behind poison ivy
A
Th1
7
Q
Th17 CD4+ polarized by
A
TGF-b, IL-1, IL-6, IL-23
8
Q
Th17 CD4+ effector cytokines
A
IL-17 and IL-22
9
Q
Main role Th17
A
cause inflammation (similar to Th1) - maintain integrity of mucosal surfaces angry macrophages
10
Q
Th2 CD4+ T Cells polarized by
A
IL-4
11
Q
Effector cytokines Th2
A
IL-4, IL-5, IL-13
12
Q
Th2 CD4+ T cells function
A
IL-4 and IL-13 attract macrophages - alternatively activated M2
IL-4 chemotactic for eosinophils
IL-4 Give rise to Tfh –> B cells to make IgE
Parasites
13
Q
Th2 and parasitse
A
IL-4 – chemotactic for eosinophils
M2 macrophages (heal/wall off)
IgE production
14
Q
Tfh polarized by
A
IL-6 and IL-21
15
Q
Tfh effector cytokines
A
IL-4 and IL-21
16
Q
Tfh role
A
Migrate to follicles of the cortex where B cells are abundant - role is to help B cells that have recognized antigen become activated and differentiate into ab-secreting plasma cells
Help with class switching - depend on where infection was (ie Tfh in gut make B cells secrete IgA)
17
Q
Treg polarized by
A
IL-2, TGF-b
18
Q
Treg effector cytokines
A
IL-10 and TGF-b
19
Q
Treg role
A
suppress activation and function of all other Th cells (anti-helpers)
20
Q
Th1 master transcriptional factor
A
T-bet
21
Q
Th2 master transcriptional factor
A
GATA3
22
Q
Th17 master transcriptional factor
A
ROR -gamma-t
23
Q
Tfh master transcriptional factor
A
Bcl-6
24
Q
Treg master transcriptional factor
A
FOXP3
25
Role CD8+ T Cell
Induce apoptosis in cells expressing PAMPS/DAMPs on MHC class I
26
2 ways CTL can signal a cell to undergo apoptosis
Death receptor = Fas
| Secrete contents of lytic granules (granzymes and perforins)
27
How are CTLs activated
In lymph nodes after contact w/ antigen-bearing DC
| Require help from Th1 in form of IL-2 for activation
28
Memory cells
T cell clones left weeks after infection/immunization - have some attributes of stem cells (replace themselves) and can rapidly differentiate into effector cells
29
2 kinds of memory cells
central (in lymph node) and peripheral (looking for infection - at original infection site)
30
B cell markers
CD19 and CD20
31
T cell markers
CD3, CD4, CD8
32
2 chains of TCR
alpha and beta OR
gamma and delta
each has a constant and a variable portion
33
T cell makes its receptor out of what genes
V (D) J regions of T cell genes in the thymus
34
alpha/beta TCRS highly specific for
antigen (like antibody)
35
gamma/delta TCRs specific for
classes of antigens that are present on groups of pathogens (like TLRs)
36
What is intimately associated with TCR
complex of molecules called CD3
| transduce signals for the T cell
37
2 ways T cell gets signal about antigen/activation
Correct antigen + MHC --> CD3
| Cytokines from DC
38
CD3 structure
3 dimers
Gamma/epsilon, delta/epsilon and zeta/zeta
Cytoplasmic transduction domain called ITAM (immunoreceptor tyrosine-based activation motif)
39
CD4 and CD8 structures
co-receptors
CD4 - monomer, 4 Ig domains
Cd8 - 1 Ig domain (hetero or homodimer)
40
Affinity of TCR for MHC/peptide
Affinity of the TCR for the MHC/peptide complex is relatively modest.
CD4 or CD8 adds to binding affinity.
Other co-receptors add to binding affinity.
CD28 binds to B7 (CD80/CD86) (co-stimulatory molecule).
LFA-1 (leukocyte functional antigen (integrin on T cell)) binds to ICAM-1 (intercellular adhesion molecule).
CD2 (T cell) binds to LFA-3 (APC)
41
alpha chain
V, J, and C gene segments -->
VJ +C
transmembrane tail making TCR a receptor a membrane-bound chain
42
beta chain
V, D, J and C gene segments
| transmembrane cytoplasmic tail - membrane-bound chain
43
LFA-1 is on the
T-cell
44
How to get diversity in TCR
```
VDJ combinations (also VJ, VDJ or VDDJ)
Somatic mutation (0-6 nt between VD and DJ)
NO SOMATIC HYPERMUTATION (may lead to self)
```
45
positive selection
pick T cells that have affinity for antigen
46
negative selection
don't allow T cells to have affinity for self (too much affinity for antigen - cannot be regulated)
47
T cell must (in thymus)
Not recognize “self”. Cannot bind so firmly to a self structure (MHC alone, or MHC loaded with a ‘self’ peptide) that the T cell becomes activated; this would be autoimmunity.
Not recognize free antigen (which is antibody’s job).
Recognize antigenic peptide plus self MHC.
48
MHC restriction
T cells are antigen-specific and MHC-restricted (must show antigen on MHC of same allele - self)
49
2 kinds of MHC genes
Class I products are on all nucleated cells.
Class II products are expressed on the surfaces of dendritic and macrophage-type cells, B cells, and just a few other cell types, all of which are involved in some way in presenting antigenic peptides to Th cells.
50
Class II MHC (what kind of antigen, what recognizes)
antigen endocytosed and presented by a dendritic cell (DC) it associates primarily with Class II MHC molecules in the endocytic vesicle, and these complexes are what the DC presents to a CD4+ Th cell.
Th1, Th17, Tfh, Treg, and Th2 are programmed to recognize peptides on Class II molecules.
51
Class I MHC (what kind of antigen, what recognizes)
peptides sampled from proteins synthesized within cell itself (usually self, maybe mutated or virus-encoded)
CTL see MHC Class I
52
cross presentation
The dendritic cell is special in that it allows some peptides from antigens it’s eaten to leak over into its ‘intrinsic’ pathway, so that it can present them on Class I as well as Class II MHC at the same time. This is called cross presentation.
53
APCs
Dendritic cells, macrophages, B cells
54
DCs express what
Constitutively express high levels of Class II MHC molecules
Constitutively express CD80/CD86 and other costimulatory molecules
55
Macrophages express what
Must be activated by phagocytosis to express Class II molecules
Must be activated to express costimulatory molecules
56
B cells express what
Constitutively express class II MHC molecules
Must be activated by antigen binding to antibody before they express costimulatory molecules
57
MHC I - general structure
alpha 1, 2, 3 and associated b2 microglobulin
1 transmembrane segment
peptide binding groove between a2 and a1
58
MHC Class II general structure
a1, a2, b1, b2 all combined (not a2 and b2 on bottom)
2 transmembrane segments
groove between a1 and b1
59
subclasses MHC Class I
```
HLA-A
HLA-B
HLA-C
1 letter = class 1
Associate w/ B2 peptide
```
60
subclasses MHC Class II
DP
DQ
DR
2 class = 2 letters
a and b subunits expressed together on cell surface
can have mother/father alpha/beta binding - need to stay same class
61
comparison of MHC binding clefts
```
class 1 closed both ends - 8-10 AA
class 2 both open - 13-18 AA
```
62
activation of CD8 T cells
Class I MHC presents antigen to CD8+ CTLs.
If there are appropriate co-stimulatory signals and cytokines produced, CTLs can get activated.
Activation of CTLs results in the death of cells expressing the recognized antigen.
63
activation of CD4 T Cells
Class II MHC presents antigen to CD4+ helper T cells.
If there are appropriate co-stimulatory signals and cytokines produced, activation of the helper T cells may occur.
Activation of helper T cells may result in the activation of CD8+ CTLs to proliferate and attack antigen bearing cells or in the ability of B cells to become antibody-producing plasma cells.
64
MHC polymorphism
Many known alleles for class I and class II locus
unique ID, permits recognition of self vs non self
affects ability to immune response, susceptibility, AI and allergies
PMs in cleft region (ag binding)
65
How many Class I MHC can cell express
6
3 subclasses
from 2 parents
alpha chains w/ common beta chain
66
How many Class II MHC can cell express
12
3 subclasses
alpha and beta chains can be from mom or dad --> 4 possibilities of combos
