T Cell Development and Effector Function Flashcards

1
Q

T Cell Receptor

A
V (D) J recombination
uses RAG proteins
V region has 3 hypervariable regions
TCR remains membrane bound
non class switching or affinity maturation**
majority alpha beta
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2
Q

smaller subset of T Cell Receptors?

A

gamma-delta

**only 5-10%

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3
Q

why is it important to have no affinity maturation in T Cell receptor?

A

increases the likelihood they will recognize a self peptide

this could lead to autoimmunity

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4
Q

what does the TCR recognize?

A

1-3 residues on the MHC-peptide complex

much weaker interaction than with antibodies

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5
Q

what is necessary for TCR binding?

A

binding to both the antigen and the MHC molecule

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6
Q

beta chain locus for TCR?

A

on chromosome 7
includes D regions

**undergo combinatorial and junctional diversity

RAG1 and RAG 2 proteins mediate recombination

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7
Q

double negative cell

A

naive mature T cell that does not express the CD4 or the CD8

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8
Q

double positive cell

A

express both CD4 and CD8 on the cell

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9
Q

what will express CD4?

A

something that interacted with MHC II

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10
Q

wha will express CD8?

A

something that interacted with MHC I

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11
Q

what T cells make it to the periphery

A

those that had weak affinity for MHC and self antigens

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12
Q

positive selection

A

weak interacting TCRs with antigen/MHC are selected to survive

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13
Q

negative selection

A

strong interacting TCRs with antigen/MHC are selected against and undergo apoptosis

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14
Q

where does positive and negative selection occur

A

cortex

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15
Q

as maturing T cell moves to the medulla what happens?

A

becomes single positive

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16
Q

MHC restriction

A

TCR only recognizes an antigen bound to MHC

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17
Q

what happens if you can’t express MHC class I

A

will only have CD4 (no CD8 expression)

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18
Q

cell-mediated immunity involves what to processes?

A

combats intracellular microbes (ingested microbes and viruses

T cells recognize peptides presented in the context of MHC (APC’s and infected host cells)

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19
Q

APCs express what MHC?

A

MHC class II (also Class I)

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20
Q

what cells express MHC class I?

A

all nucleated cells

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21
Q

what happens when naive CD4 cells are activated?

A

change their IL-2 receptor to higher affinity

can undergo clonal expansion and mature to effector or memory CD4 T cells

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22
Q

what do you need to make sure if you remove a patient’s spleen?

A

that they are up to date on their immunizations

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23
Q

what makes up the TCR complex?

A

CD3, zeta chain, and TCR

on all the T cells

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24
Q

CD28

A

interacts with B7 molecules on APC
this increases IL-2 production
activate the T cell
after T cells have been activated, the CTLA-4 is increased - inhibitory structure

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25
Q

CTLA-4

A

outcompetes the CD28 and decreases IL-2 production

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26
Q

cross-presentation

A

dendritic cell can place antigens on MHC class I and II

CD4 secretes cytokines that help to activate the CD8 cells

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27
Q

activation of CD8 T cells

A

can be activated directly but also by cross-presentation CD-4 cytokines

28
Q

CD40L

A

helps to prolong the interaction of the T cell with the APC

29
Q

what happens to IL-2 receptor during activation?

A

increases its affinity for IL-2

30
Q

IL-2

A

survival, differentiation of the CD4 and CD8 T cells

31
Q

TGF-beta

A

inhibition of T cell activation

32
Q

IL-4

A

switches B cell to IgE

**Th2

33
Q

IL-5

A

activation of eosinophils

**Th2

34
Q

Interferon-gamma

A

activation of macrophages

35
Q

what would happen after you block CTLA-4 action?

A

would not be able to inhibit the T cell proliferation and they would always stay on

**may be beneficial in anti-cancer therapy

side-effects: autoimmunity

36
Q

types of CD4 T cells?

A

Th2, Th1, Th17, T regulatory cells

37
Q

Th1 cells

A

produce IFN-gamma

activate macrophages

38
Q

Th2 cells

A

produce IL-4, IL-5, and IL-13

promote humoral immunity

39
Q

Th17 cells

A

produce IL-17

involved in host defense AND pathogenesis of autoimmune disease

40
Q

T regulatory cells

A

suppress the T cell function

41
Q

CD40L

A

on the CD4 T cells that interacts with CD40 on macrophage

leads to macrophage activation

42
Q

what happens with asthma (which T cells)?

A

Th2 which activates eosinophils and mast cells

43
Q

what activates Th1 formation?

A

IL-12 and IFN-gamma

44
Q

what activation Th17 formation?

A
IL-6**
TGF-beta
IL-1
IL-23
GM-CSF
45
Q

what activates Th2 formation?

A

TSLP

46
Q

what do Th1 cells do?

A

secrete IFN-gamma

also produce TNF-alpha

47
Q

what does IFN-gamme release from Th1 cells cause?

A

activation of macrophages
stimulation of complement binding
Class II MHC and B7 expression

48
Q

what may lead to multiple sclerosis?

A

Th1 response

49
Q

what does the classical macrophage activation lead to?

A

enhance microbial killing

50
Q

what do Th2 cells release?

A

IL-4, IL-5, and IL-13

51
Q

IL-4

A
  • activate B cells to produce IgE

- also activate the macrophage to increase fibrosis/tissue repair (alternative)

52
Q

IL-5

A

activate eosinophils

53
Q

alternative macrophage activation?

A

leads to fibrosis and tissue repair

**stimulated by IL-4 and IL-13

54
Q

Th17

A

secretes IL-17

55
Q

IL-17

A

recruits the leukocytes to sites of infection

functions to maintain epithelial barrier and important in gut tolerance

56
Q

phagocyte with ingested microbes causes what?

A
MHC class II presented antigens
activates Th1 and Th17 CD4 T cells
57
Q

infected cell with cytoplasm microbes causes what?

A
MHC class presented antigens
activates the CD8 T cells
58
Q

what adhesion molecules move T cells to the lymph node?

A

expression of L selectin and LFA-1 and CCR7 on naive T cells

59
Q

what adhesion molecules move T cells to sites of infection?

A

E and P selectin, LFA-1 and VLA-4 and CXCR3 (chemokines)

** T cells get to where they need by homing signals

60
Q

what activates a naive CD4 cell to become Th1?

A

IL-12
dependent on antigen-recognition

basis for delayed-type hypersensitivity reaction

61
Q

macrophage activation by Th1 cells?

A

increases ROS and NO, secretes cytokines TNF, IL-1, IL-12, increased MHC and B7

62
Q

PPD test?

A

example of a Delayed-type hypersensitivity reaction of the Th1 activation

63
Q

balance between the Th1 and Th2 cells?

A

Th2 cell cytokines shuts down the classical activation of macrophages (microbicidal)

defects in either can cause problems
ex/ leprosy

64
Q

what happens with CD8 T cell activation?

A

secretion of granzymes and perforins

perforins poke holes and granzymes enter and activate the caspases > apoptosis

65
Q

cooperation between the CD4 and CD8?

A

yeah.