T cell development and effector cell function (Michels) Flashcards

1
Q

What type of recombination do TCR receptors undergo

A

VDJ

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2
Q

How many CDR regions are there on TCR

A

3 per V region, 2 V regions

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3
Q

Which CDR of TCR is the most hypervariabl

A

CDR3

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4
Q

What are the differences between TCR and BCR

A

TCR have no class switching or affinity maturation. also small population of lambda and gamma T cells instead of alpha and beta

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5
Q

What is the minimun number of residues that TCR recognize on MHC complex

A

1-3

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6
Q

Which interation is weaker:

Ab-Ag

or

TCR binding to peptide presented on MHC

A

TCR-MHC molecule is weaker

additional surface molecules are necessary

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7
Q

Describe the MHC Restriction

A

TCR must recognize MHC molecule and the presented antigen

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8
Q

Where is the TCR beta chain locus and components

A

chromosome 7

leader sequences infront of variable regions then has diveristy junctional and constant regions

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9
Q

describe location and components of TCR alpha chain locus

A

chromosome 14

leader, variable, juntional and constant region

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10
Q

Which enzymes mediate TCR recombination

A

Rag 1 and Rag2

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11
Q

What are the light chains of TCR

A

Kappa alpha and beta

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12
Q

Which chains of TCR have diversity regions

A

Heavy chain and the beta chain

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13
Q

During what phase of thymocyte maturation does it undergoe positive selction- describe process as well

A

Thymocytes are double positive at this stage still.

They need to bind MHC to recognize self- this is positive selection. Those that don’t bind are killed

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14
Q

During what phase in thymocyte maturation do they udnergo negative selection and describe this process

A

Thymocytes are single positive at this time

Negative selection is if they bind too strongly to MHC they are killed. so those that have low affinity survive

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15
Q

If you have a deficiency of MHC I or HLA I R what is the outcome on T cell populations

A

Have alot of CD4+

no CD8 CTL

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16
Q

predict outcome of MHCII deficiency on T cell population

A

have lots of CD8 or CTL

no CD4+

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17
Q

Cell mediated Immunity is used it what cases

A

Ingested microbes (phagosomes)

Viruses (non-phagocytotic cell)

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18
Q

All nucleated cells have what type of molecule

A

MHC class I or HLA class I

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19
Q

T cell expansion takes out long after antigen exposure

A

about 2 weeks

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20
Q

What cytokine is responsible for clonal expansion of CD4+

A

IL2

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21
Q

What is the role of effector CD4+ T cells

A

Activation of macrophages, B cells, other cells

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22
Q

What is the role of effector CD8+

A

Killing infected target cells; macrophage activation

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23
Q

All TCR must also have what complex

A

CD3 and epsilom

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24
Q

What molecule interaction assists in slowing down lymphocytes so they can interact with MHC

A

LFA-1 on lymphocyte. ICAM-1 on T cell

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25
Q

What are the T cell accessory molecules

A

CD3, epsilom, CD28, CTLA4

LFA1

VLA-4(endothelium)

CD4 or 8 depending on type of T cell

26
Q

What T cell accessory molecules assist in signal transduction

A

CD28 on T cell binds to B7 on APC

CD4 or 8 depending on T cell

27
Q

What is the co stimulatory molecule of T cells

and its actions?

A

CD28 which binds B7of APC to produce IL2

when produced it will activate CTLA-4 which will send inhibitory signals.

28
Q

Activation of T cells triggers the expression of what proteins on T cels

A

CD40L and IL2 Receptor

29
Q

CD4+ T cells produce which cytokines

A

IL2

IL4

IL5

IFN-gamma

TGF beta

30
Q

What cytokines do CD8+ T cells produce

A

IL2

IFN-gmma

31
Q

What is the role of IL2

A

proliferation and differentiation of effector and CD4+ cells

32
Q

What is the role of IL4

A

B cell switching to IgE

33
Q

What is the role of IL5

A

Activation of eosinpohils

34
Q

What is the role of IFN-gamma

A

activation of macrophages— will produce IL12 to activate NK to release more IFN-gamma

35
Q

Role of TGF-beta

A

Inhibition of T cell activation

differentiation of Tregulatory

36
Q

When and what changes in ILR to make it high affinity

A

secretion of IL2- activation of T cells induces expression of IL2R-alpha chain which makes IL2Rabgamma complex= high affinity

37
Q

Blocking CTLA-4 cases what?

When would this help?

A

Keeps T cells on

anti-cancer therapy but run the risk of autoimmunity

38
Q

What are the subsets of CD4+ cells and what cytokines are they assoc with

A

Th1: IFNgamma- macrophage activation

Th2: IL4 IL5 IL13- humoral immunity

Th17: IL17- host defense and pathogenesis of autoimmune disease

T reg- suppress T cell function

39
Q

What directs the development of T cell subsets?

A

cytokines

40
Q

Describe CD4+ role in cell mediated immunity vs humoral immunity

A

cell-mediated: activates macrophages for killing phagocytosed material

humoral immunity: causes secretion of Ab with enhanced abilities to neutralize and eliminate Ag

41
Q

What type of infections usually cause activation of Th1 subset

A

Intracell microbes- usually chronic because IFNgamma and TNFalpha are pretty hardcore.

42
Q

What type of infection causes activation of Th2 subset

A

helminthic parasites and allergic diseases. usually upregulate IgE and mast cell activation

43
Q

What types of infections activate the Th17 subset

A

Extracell bacteria and fungi causing neutrophilic, monocytic inflammation.

Usually assoc with autoimmune and inflammatory diseases

44
Q

What activates the Th2 subset

A

TSLP thymic stromal lymphoprotein

45
Q

IFNgamma secretion activates what

A

MAcrophages

B cells to stimulate C’ binding

Class II HLA and B7 expression on APCs

46
Q

What is the main overal role of Th17 cells

A

maintaining gut tolerance. Increased barrier function of epithelium

47
Q

What CD4 subset will be present during an asthma attack

A

Th2

48
Q

What CD4 subset will be present in multiple sclerosis patients

A

Th1

49
Q

Why is L selctin down regulated ater T cell activation

A

Don’t what the T cells stuck in lymph nodes, need to return to circulation

50
Q

What T cell molecules are involved in homing native T cells and what are their complementary molecules on endothelial cells

A

L selectin- L selectin Ligand

LFA-1 - ICAM-1

CCR7 - CCL19 or CCL21

51
Q

What T cell molecules are involved in himoning activated T cells and what are their complementary molecules on endothelial cells

A

E and P selctin ligands - E or P selectin

LFA-1 or VLA-4 - ICAM-1 or VCAM-1

CXCR3- CXCL10

52
Q

What is the basis for delayed-type hypersensitivity reaction

A

DTH reaction: Macrophage activation by Th1 subset is depended on antigen-recognition on presenting cells (CD4)

The macrophage increase MHC molecules and B7 costimulators

also macrophages secrete TNF, IL1 and IL12

53
Q

What is an example of delayed-type hypersensitivity reaction

A

PPD test for TB

54
Q

What determines the outcome of intracellular infections?

A

Balance between Th1 and Th2 cell activation

55
Q

What do Th2 cells inhibit when activated

A

Microbicidal activity of macrophages

56
Q

Mycobacterium elicits what responses in patients

A

Usually Th1 and you have Tuberculoid leprosy however some patients are defective in Th1 so predominately Th2 response leading to Lepromatous leprosy

57
Q

How do CTLs induce apoptosis

A

activation of perforin and granzymes to enter cell and iduce apoptosis

or Fas-FasL interactions

58
Q

How are TCRs overall different from BCRs

A

they are not secreted and do not undergo somatic hypermutation

59
Q

Which T Cells can do cell-mediated immunity

A

CD4 activate macrophages

CD8 directed kill of infected cell

60
Q

Which Th subset has a response characterisitic of DTH

A

Th1 after secreting IFN-gamma

classical activation of macrophages