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IHO Week 2 > T Cell Receptors and MHC Complex > Flashcards

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

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2
Q

Th1 CD4+ polarized by

A

IL-12, IL-18 and IFN-gamma

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3
Q

Th1 CD4+ effector cytokines

A

IFN-gamma and TNF

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4
Q

Th1 CD4+ role

A

Secrete IFN gamma = proinflammatory and chemotactic for blood monocytes and tissue macrophages –> angry macrophages

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5
Q

angry macrophages release

A

TNFa and IL-1 (intensify inflammation)

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6
Q

T cells behind poison ivy

A

Th1

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7
Q

Th17 CD4+ polarized by

A

TGF-b, IL-1, IL-6, IL-23

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8
Q

Th17 CD4+ effector cytokines

A

IL-17 and IL-22

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9
Q

Main role Th17

A 
cause inflammation (similar to Th1) - maintain integrity of mucosal surfaces
angry macrophages
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10
Q

Th2 CD4+ T Cells polarized by

A

IL-4

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11
Q

Effector cytokines Th2

A

IL-4, IL-5, IL-13

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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

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13
Q

Th2 and parasitse

A

IL-4 – chemotactic for eosinophils
M2 macrophages (heal/wall off)
IgE production

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14
Q

Tfh polarized by

A

IL-6 and IL-21

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15
Q

Tfh effector cytokines

A

IL-4 and IL-21

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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)

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17
Q

Treg polarized by

A

IL-2, TGF-b

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18
Q

Treg effector cytokines

A

IL-10 and TGF-b

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19
Q

Treg role

A

suppress activation and function of all other Th cells (anti-helpers)

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20
Q

Th1 master transcriptional factor

A

T-bet

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21
Q

Th2 master transcriptional factor

A

GATA3

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22
Q

Th17 master transcriptional factor

A

ROR -gamma-t

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23
Q

Tfh master transcriptional factor

A

Bcl-6

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24
Q

Treg master transcriptional factor

A

FOXP3

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25
Q

Role CD8+ T Cell

A

Induce apoptosis in cells expressing PAMPS/DAMPs on MHC class I

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26
Q

2 ways CTL can signal a cell to undergo apoptosis

A

Death receptor = Fas

Secrete contents of lytic granules (granzymes and perforins)

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27
Q

How are CTLs activated

A

In lymph nodes after contact w/ antigen-bearing DC

Require help from Th1 in form of IL-2 for activation

28
Q

Memory cells

A

T cell clones left weeks after infection/immunization - have some attributes of stem cells (replace themselves) and can rapidly differentiate into effector cells

29
Q

2 kinds of memory cells

A

central (in lymph node) and peripheral (looking for infection - at original infection site)

30
Q

B cell markers

A

CD19 and CD20

31
Q

T cell markers

A

CD3, CD4, CD8

32
Q

2 chains of TCR

A

alpha and beta OR
gamma and delta

each has a constant and a variable portion

33
Q

T cell makes its receptor out of what genes

A

V (D) J regions of T cell genes in the thymus

34
Q

alpha/beta TCRS highly specific for

A

antigen (like antibody)

35
Q

gamma/delta TCRs specific for

A

classes of antigens that are present on groups of pathogens (like TLRs)

36
Q

What is intimately associated with TCR

A

complex of molecules called CD3

transduce signals for the T cell

37
Q

2 ways T cell gets signal about antigen/activation

A

Correct antigen + MHC –> CD3

Cytokines from DC

38
Q

CD3 structure

A

3 dimers
Gamma/epsilon, delta/epsilon and zeta/zeta

Cytoplasmic transduction domain called ITAM (immunoreceptor tyrosine-based activation motif)

39
Q

CD4 and CD8 structures

A

co-receptors
CD4 - monomer, 4 Ig domains
Cd8 - 1 Ig domain (hetero or homodimer)

40
Q

Affinity of TCR for MHC/peptide

A

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
Q

alpha chain

A

V, J, and C gene segments –>
VJ +C
transmembrane tail making TCR a receptor a membrane-bound chain

42
Q

beta chain

A

V, D, J and C gene segments

transmembrane cytoplasmic tail - membrane-bound chain

43
Q

LFA-1 is on the

A

T-cell

44
Q

How to get diversity in TCR

A 
VDJ combinations (also VJ, VDJ or VDDJ)
Somatic mutation (0-6 nt between VD and DJ)
NO SOMATIC HYPERMUTATION (may lead to self)
45
Q

positive selection

A

pick T cells that have affinity for antigen

46
Q

negative selection

A

don’t allow T cells to have affinity for self (too much affinity for antigen - cannot be regulated)

47
Q

T cell must (in thymus)

A

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
Q

MHC restriction

A

T cells are antigen-specific and MHC-restricted (must show antigen on MHC of same allele - self)

49
Q

2 kinds of MHC genes

A

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
Q

Class II MHC (what kind of antigen, what recognizes)

A

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
Q

Class I MHC (what kind of antigen, what recognizes)

A

peptides sampled from proteins synthesized within cell itself (usually self, maybe mutated or virus-encoded)

CTL see MHC Class I

52
Q

cross presentation

A

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
Q

APCs

A

Dendritic cells, macrophages, B cells

54
Q

DCs express what

A

Constitutively express high levels of Class II MHC molecules

Constitutively express CD80/CD86 and other costimulatory molecules

55
Q

Macrophages express what

A

Must be activated by phagocytosis to express Class II molecules

Must be activated to express costimulatory molecules

56
Q

B cells express what

A

Constitutively express class II MHC molecules

Must be activated by antigen binding to antibody before they express costimulatory molecules

57
Q

MHC I - general structure

A

alpha 1, 2, 3 and associated b2 microglobulin
1 transmembrane segment
peptide binding groove between a2 and a1

58
Q

MHC Class II general structure

A

a1, a2, b1, b2 all combined (not a2 and b2 on bottom)
2 transmembrane segments
groove between a1 and b1

59
Q

subclasses MHC Class I

A 
HLA-A
HLA-B
HLA-C
1 letter = class 1 
Associate w/ B2 peptide
60
Q

subclasses MHC Class II

A

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
Q

comparison of MHC binding clefts

A 
class 1 closed both ends - 8-10 AA
class 2 both open - 13-18 AA
62
Q

activation of CD8 T cells

A

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
Q

activation of CD4 T Cells

A

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
Q

MHC polymorphism

A

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
Q

How many Class I MHC can cell express

A

6
3 subclasses
from 2 parents
alpha chains w/ common beta chain

66
Q

How many Class II MHC can cell express

A

12
3 subclasses
alpha and beta chains can be from mom or dad –> 4 possibilities of combos

IHO Week 2 (13 decks)

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