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PMCOL 344 > Immune-2 > Flashcards

Immune-2 Flashcards

1
Q

what are cells that express CD4

A

helper T cells

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2
Q

what happens when naive helper T cells interact with DCs

A

they differentiate into TH1, TH2, TH17, THreg

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3
Q

what does the type of TH cell depend on

A

the specific type of cytokine released from the DCs

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4
Q

what determines the the specific type of cytokine released from the DCs

A

the specific type of pathogen

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5
Q

what 2 things characterize each TH cell

A

the cytokines that they produce, the innate immune effector mechanism that is activated

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6
Q

what are the three phases in CD4 T cell activation

A

recognition, activation, effector

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7
Q

what happens in recognition phase

A

macrophages display foreign antigens on their surface in a form that can be recognized by antigen-specific TH lymphocytes.

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8
Q

what happens in activation phase

A

TH cells produce cytokines that promote the proliferation and differentiation of the T cells as well as other cells, including macrophages

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9
Q

what happens in effector phase

A

activated macrophages carry out phagocytosis and cytolysis

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10
Q

what is a super important thing that is released during T cell activation (CD4+)

A

the release of IL-2

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11
Q

what is the role of IL-2 + how do they work

A

These are essential to allow maturation of t cells

It works in autocrine mechanism, they start proliferating, dividing - clonal expansion

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12
Q

what is the 3 signals in CD8+ T Cell activation

A

TCR-MHC class interaction
co-stimulation
pro-inflammatory cytokines

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13
Q

what is the early outcome of CD8+ T Cell activation

A

no cytokine secretion

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14
Q

what is the late outcome of CD8+ T Cell activation

A

clonal expansion and cytotoxicity

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15
Q

what are the 3 mechanisms of CD8 killing

A
  • granzymes
  • Fas ligand on their surface (death receptor)
  • make cytokines, like TNF-alpha
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16
Q

what happens to T cells with T cell activation + how

A

increased T-cell survival and differentiation through production of cytokines like IL-2

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17
Q

what happens to metabolism with T cell activation

A

increased

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18
Q

what happens to cell survival genes with T cell activation

A

upregulated

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19
Q

what happens to cell division with T cell activation

A

upregulated

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20
Q

what happens to cytotoxic cells with T cell activation

A

they are activated (killer functions)

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21
Q

what happens to memory cells with T cell activation

A

they become activated

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22
Q

why do you have death of t cells as a consequence with t cell activation

A

because you need to down regulate the immune response

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23
Q

what are the 2 transcription factors that are activated once the t cell receptor is activated

A

NFAT and mTOR

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24
Q

what is the role of NFAT

A

the activation of T cells, increases IL 2 production and also more proliferation and differentiation

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25
Q

what is the role of mTOR

A

activation, differentiation and migration

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26
Q

what activates mTOR

A

IL2 and TCR

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27
Q

is t cell activation regulated

A

yes highly

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28
Q

what are the 2 checkpoints for the immune pathway

A

CTLA-4 and PD1

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29
Q

what is the point of checkpoints for t cell activation

A

to balance protective immunity and immunopathology

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30
Q

what is a bad thing about the immune checkpoints

A

during responses to chronic pathogens, they can limit protective immunity

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31
Q

which is the leader of the immune checkpoint inhibitors

A

CTLA-4

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32
Q

what causes CTLA-4 to be upregulated

A

stimulatory signals from both TCR and CD28(B7) binding induces upregulation of CLTA-4 on cell surface

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33
Q

what is CTLA-4 similar to (explain)

A

CD28 homolog with much higher affinity for CD80/86 (B7)

34
Q

what is b7

A

another name for CD80/86

35
Q

what competes for binding of CD80/86 (immune checkpoint)

A

CLTA-4 and CD28

36
Q

where does CTLA-4 work

A

at the lymph node (starting location of immune response/ naive T cell activation)

37
Q

what happens once CTLA-4 binds to CD80/86 (2 things)

A
  • can prevent the costimulatory signal by CD28

- produces inhibitory signals

38
Q

what happens to t cell activation when CTLA-4 and B7 bind

A

full activation is prevented

39
Q

how is full activation of t cells by CTLA-4 inhibited

A

by inhibiting IL-2 production and inhibits cell cycle progression

40
Q

what can CTLA-4 do for autoreactive t cells

A

stops then at the initial stage of activation

41
Q

what is PD-1

A

a member of the B7/CD28 family of costimulatory receptors

42
Q

which cells does PD-1 regulate/ effect + where

A

previously activated T cells in peripheral tissues

43
Q

how does PD-1 regulate t cell activation

A

PD-L1 and PD-L2 (programmed death ligand 1 and 2)

44
Q

what is PD-1 a hallmark of

A

exhausted T cells

45
Q

when does T cell exhaustion occur

A

during chronic infections and cancer

46
Q

what does PD-1 binding do generally

A

reduce activation of T cells

47
Q

what are the 3 signals that PD-1 binding do

A
  • inhibits T cell proliferation
  • inhibits cytokine production
  • reduces T cell survival
48
Q

what are the 2 main differences between CTLA-4 and PD-1

A
  • anatomic locations and timing of immune inhibition

- signalling mechanisms

49
Q

where is CTLA-4 expressed (which cells)

A

only on T cells

50
Q

where is PD-1 expressed (which cells)

A

on activated T cells, B cells and myeloid cells

and in lots of tissue too?

51
Q

what are 2 things that B cells express

A

antigen specific B cell receptors (BCR)

germ-line encoded, pattern recognizing toll like receptors (TLRs)

52
Q

what is responsible for fine tuning functional B cell responses

A

dual BCR and TLR engagement

53
Q

what does dual BCR and TLR engagement link

A

innate and adaptive immune functions

54
Q

what are the 2 types of naive mature B cells

A
  • innate like B cells

- Adaptive follicular B cells

55
Q

what are 2 types of innate like B cells

A

B-1 and marginal zone B cells

56
Q

where do most of the marginal zone b cells stay

A

in the spleen

57
Q

what kind of receptors do B-1 and marginal zone cells have

A

toll like receptors

58
Q

what happens with ligation of TLRs with B-1 and marginal zone cells

A

they redistribute to the blood, lymph and spleen follicles

59
Q

where are b-1 cells (lots of them at least)

A

in the peritoneal cavity

60
Q

what are 4 direct functional responses of b-1 and marginal zone b cell

A
  • proliferation
  • secrete Ig and cytokines
  • upregulate survival pathways
  • increase expression of co-stimulatory molecules to function like APCs
61
Q

what does BAFF do

A

leads to prolonged survival

62
Q

how can you get the 5 direct functional responses of b-1 and marginal zone b cell

A

likely require BCR and TLR engagement

63
Q

why can you call the direct function of b-1 and marginal zone b cell innate

A

because you dont need t cells to activate

64
Q

what can innate like b cells generate independently

A

antibody responses (independently of t cell help)

65
Q

how can b cells recognize pathogens and self ligands

A

using b cells TLRs

66
Q

what plays a crucial role in autoimmune pathogenesis

A

activation of autoreactive b cells by dual BCR and TLR engagement

67
Q

how are b cells activated t-cell-dependently

A

via BCR engagement and interaction with cognate CD4+ T cells

68
Q

what is required for maximum activation (t-cell-dependently)

A

combination of BCR engagement, T cell help via CD40 signalling and TLR stimulation

69
Q

what do TH cells release that help B cells + what does it cause

A

cytokines to promote proliferation and differentiation of B cells into plasma cells and memory cells

70
Q

what do plasma cells do

A

product high affinity antibodies

71
Q

what do memory cells do

A

respond more rapidly and efficiently to subsequent encounters with the antigen

72
Q

do plasma cells divide

A

no

73
Q

what are 5 functions of antibodies

A
  • neutralize pathogens/ toxins
  • complement activation
  • opsonization and phagocytosis
  • degranulation
  • cytotoxicity
74
Q

what kind of cells do antibodies help degranulate

A

mast cells, basophils, eosinophils

75
Q

how do antibodies neutralize pathogens/ toxins

A

prevent interactions with host cell receptors, bring it to barriers (like mucus)

76
Q

what are 3 examples of antibody mediated complement activation

A
  • phagocyte recruitment, make inflammatory mediators
  • opsonization
  • membrane attack complex
77
Q

how do antibodies cause cytotoxicity

A

activation of natural killer cell degranulation to kill infected cells

78
Q

what kind of cells degranulate because of antibodies

A

mast cells, basophils, eosinophils

79
Q

what do mast cells, basophils, eosinophils release with degranulation

A

vasoactive substances, chemoattractants, cytokines

80
Q

which cell expresses PD1

A

T B and myeloid cells

81
Q

which cell expresses PDL1

A

tissue (peripheral)

PMCOL 344 (27 decks)

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