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IMMUNOLOGY > Lecture 10+11: T cells > Flashcards

Lecture 10+11: T cells Flashcards

1
Q

where do B, T and NK cells derive from

A

hematopoietic stem cell –> multipotent progenitor cell —> common lymphoid progenitor cell

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2
Q

where does T cell development occur

A

in the thymus

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3
Q

T cell progenitor cells originate in _______ and migrate to the thymus

A

originate in bone marrow

*movement dictated by chemokines

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4
Q

what directs the movement of T cell progenitors from bone marrow to thymus

A

chemokines
- receive signal from thymic stromal cells to differentiate into thymocyte

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5
Q

what interleukin is incredibly important to T cells so much so that mutations of this IL leads to no T cells

A

IL7

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6
Q

lymphocyte development (B,T and NK cells) is orchestrated by what cells and messengers

A

stromal cells and cytokines

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7
Q

mature T cells leave the thymus and travel to…

A

secondary lymphoid tissue

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8
Q

if a patient is unable to make IL7, what happens

A

they cannot make T cells = no adaptive immune response

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9
Q

what cells make IL7

A

thymic stromal cells

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10
Q

what is notch1, what does it do

A

Notch1 is a receptor on thymocytes that binds to thymic epithelium

it induces cleavage by protease & activates T cell-associated genes

*induces the expression of genes associated w/ activation of T cells

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11
Q

what are the 2 classes of T cell receptors?

A

gamma delta (γδ) - CD4/CD8
alpha-beta (αβ) (binds things other than CD4/CD8)

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12
Q

______ interact w/ folded proteins, _____ interact w/ linear peptides

A

Antibodies - folded proteins
TCR - linear

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13
Q

γδ T cells only express ____

A

CD3

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14
Q

what occurs at T cell checkpoint 1

A
  • A pre-T cell receptor pairs a β chain w/ pTα
  • pTα checks the functionality of the β chain
  • if functional, forms a superdimer

-superdimer checks for interaction w/ CD3

-if there is appropriate interaction w/ CD3, that β chain starts to proliferate, initiates rearrangement of the α chain, and synthesis of CD4/CD8 begins

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15
Q

The rearrangement of α chains in pre T cells is mediated by what

A

RAG 1 and RAG 2
- recombination activating genes

*rearrangement is very inefficient, only about 2% make it, rest undergo apoptosis

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16
Q

what structural characteristic (of gene organization) allows for the α chain in pre-T cells to undergo successive arrangements

A

no diversity segment in the middle

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17
Q

what happens next once a functional α chain is made from rearrangements

A

the α chain gets sent to the ER and is checked for its interaction w/ β

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18
Q

What occurs at T cell checkpoint 2

A

interaction b/w new alpha chain and β

  • if interaction is successful, the line proliferates
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19
Q

what dictates antigen binding of T cells

A

the way the alpha and β chains come together

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20
Q

what is Omenn syndrome

A

RAG deficiency
- patients lack T and B cells
- treated w/ bone marrow transplant otherwise fatal

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21
Q

the T cell development path is marked by _____

A

gene expression

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22
Q

what does the double positive T cell make

A

(positive) CD4+, CD8+

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23
Q

what does the double negative T cell make

A

(negative) CD4-, CD8-

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24
Q

at what stages of T cell development is RAG expression turned on

A

between the Pro-T and Pre-T stage and as the Pre-T cells becomes the double positive (and so it can make the alpha chain)

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25
Q

what is positive selection of T cells, where does it occur

A

checks for TCR binding to MHC complexes
determines CD4 vs CD8 expression
*ends w/ single positive T cells
- occurs in cortex of thymus

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26
Q

at what steps of T cell development does Negative selection occur

A

double positive and single positive step
- “goldilocks”
- can’t bind too weakly to MHC but also can’t bind too strongly (means it recognizes self peptides as antigen and would cause autoimmune response)

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27
Q

After negative selection occurs, the single positive T cell migrates where

A

to peripheral lymphoid organs (regional lymph nodes, Peyer’s patches, etc)

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28
Q

What occurs during the progenitor T cell phase

A
  • RAG-mediated V-D-J recombination of the β chain is occurring
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29
Q

what occurs during the precursor T cell phase

A
  • The β chain has successfully recombined and is expressed on the cell surface
  • RAG-mediated V-J recombination of the α chain is occurring
  • Surrogate α chain (pTα) is expressed
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30
Q

What occurs during the double-positive T cell phase

A

both alpha and beta chains have successfully rearranged and are expressed w/ CD3 + zeta chains as the membrane bound TCR complex

  • expression of both CD4 + CD8
  • positive and negative selection occurs
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31
Q

what occurs during single positive T cell phase

A

downregulation of either CD4 or CD8 and final maturation

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32
Q

what occurs during the stage of mature, naive T cell

A

Cell gets released into circulation as a single positive T cell

33
Q

what are Naive T cell

A

mature T cells that have not yet encountered their specific antigen

34
Q

when do naive T cells encounter their specific antigen? And what happens once they do?

A
  • when it is presented to them by MHC antigen complex
  • once this happens they can proliferate and differentiate into effector T cells
35
Q

how do antigens get delivered to lymphoid tissue

A

via innate immunity
- inflammation increases blood flow into infected sites, lymph flow increases

Dendritic cells take up antigens and move them into a lymphatic vessel —> lymph node where they settle in T cell areas

36
Q

how do T cells enter a draining lymph node

A
  • blood vessels (HEV)
  • afferent lymphatics from upstream lymph node
37
Q

what happens to T cells that are not activated by antigens presented by dendritic cells

A

they exit the lymph node via cortical sinuses and re-enter the blood - a continuous process of recirculation

38
Q

what cells bring antigens to lymph tissues

A

dendritic cells

39
Q

how do naive T cells find their antigen

A

naive T cells come in from blood stream –> migrate into peripheral lymph tissue where they sample peptides for MHC complexes on dendritic cells

40
Q

what happens once a T cell finds its antigen

A
  • migration ends
  • proliferation and clonal replication occur (‘clonal expansion or priming’)
  • gives rise to effector and memory T cells
  • after effector differentiation, activated T cells can re-enter the bloodstream
41
Q

antigens in the blood are carried to the ____ via APCs

A

spleen

42
Q

pathogens/antigens on** mucosal surfaces** are carried across the mucosa and into ______ or ______

A

tonsils or Peyer’s patches

43
Q

what are the 3 signals for clonal expansion and differentiation?

A

signal 1 - antigen-specific interaction b/w MHC and TCR

signal 2- co-stimulatory signals b/w B7 and CD28 promote survival and expansion of T cell clones

signal 3 -directing T cells differentiate into effector T cells (IL6, IL12, IL14)

44
Q

what does it mean for a developing T cell to be double negative

A

doesn’t express CD4 or CD8

45
Q

what does it mean for a developing T cell to be double positive

A

it expresses both CD4 and CD8

46
Q

Single positive T cell AKA

A

naive Tcell

47
Q

successful TCR:MHC binding results in the generation of survival signals and 3 transcription factors…what are they

A

NFAT
NF-kB
AP-1

48
Q

the release of survival signals and TFs after successful TCR: MHC binding induces a signaling cascade that results in….

A

synthesis and secretion of IL2 and the expression of new cell surface receptors and ligands: CD69, IL2Rα, CD40L

49
Q

what is the role of CD69

A

retains stimulated T cells in the lymph node

50
Q

what is S1P

A

a chemoattractant that is high in the blood and low in tissues (and lymph nodes)

circulating naive T cells have low expression of S1P receptor

51
Q

what is the purpose of circulating naive T cells having S1P receptors

A

allows them to respond to the S1P gradient and exit the lymphatic tissue

– T cells that are NOT stimulated by antigen re-express S1PR1

52
Q

CD69 binds what chemoattractant

A

S1PR1
causes cells to internalize the complex and turn off S1PR expression

53
Q

antigen recognition by TCR induces the expression of what IL receptors

A

IL2 and IL6 via co-stimulatory signals through CD28

54
Q

what is IL-2 critical for

A

differentiation of T cells into effector T cells and memory cells

55
Q

how do drugs that inhibit T cell activation like Cyclosporine work

A

they target the signal transduction pathways in T cells, inhibiting T cell activation

Cyclosporine: binds cyclophilin, the complex inhibits calcineurin, preventing NF-AT generation

–> w/out NF-AT, transcription of IL2 gene cannot occur

—> IL2 needed for T cell proliferation

56
Q

what does the ligand CD40L do

A

binds CD40
- activation of macrophages
- activation of B cells to produce antibodies

57
Q

What is Hyper IgM syndrome

A

unable to undergo antibody class switching

58
Q

what is the role of CTLA-4 inhibitory receptor

A
  • binds B7 on APC to limit T-cell proliferation
  • blocks CD28 signaling (the 2nd signal in T cell activation)
59
Q

the prolonged maintenance of memory T cells is dependent on what

A

Cytokines

60
Q

what cells are especially important in defense against viral pathogens

A

CD8 T cells

61
Q

what are 2 main granules cytotoxic T cells contain

A
  • perforin = pore forming protein
  • granzymes = serine proteases activate caspases in host cells to trigger apoptosis
62
Q

TGF-β stimulates what helper cell

A

T regulatory cells

63
Q

IL-6 stimulates what helper cells

A

TFH

64
Q

TGF-β and IL-6 stimulate what helper cells

A

TH17

65
Q

IL-12 and IFNγ stimulate what helper cells

A

TH1 cells

66
Q

IL-4 stimulates what helper cells

A

TH2

67
Q

TH1 cells do what

A

control bacteria that can grow in macrophages

express IL-2 and IFNγ

68
Q

TH2 cells do what

A

control parasitic infection

express IL4, IL5, IL13 that promote mast cells, eosinophils and B cell class switching to make IgE

69
Q

what do TH17 cells do

A

stimulate neutrophil response to extracellular bacteria and fungi
Make IL 17 & IL 22

70
Q

what do TFH cels do

A

stimulate antibody production from B cells, including class switching and affinity maturation

71
Q

what drives TH2 cell differentiation

A

IL4 in response to helminths and allergens

  • mast cells, when stimulated by helminths, secrete IL4
72
Q

what type of class switching does IL4 stimulate

A

B cells to IgE

73
Q

what does IL5 do

A

activate eosinophils

74
Q

what do IL4 and IL13 do

A

stimulate increased mucus secretion

75
Q

what drives TH17 cell differentation

A

pro-inflammatory cytokines and TGF-β

76
Q

What does IL17 stimulate

A

recruitment of neutrophils and production of anti-microbial peptides

77
Q

what does IL22 do

A

promotes epithelial integrity, antimicrobial peptides and mucins

78
Q

what drives TH17 cell differentiation

A

proinflammatory cytokines + TGF-β

79
Q

what does TH17 secrete

A

IL-17 : stimulates recruitment of neutrophils and production of anti-microbial peptides
IL-22: promotes epithelial integrity, antimicrobial peptides, and mucins

IMMUNOLOGY (26 decks)

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