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cell mediated immunity Flashcards

1
Q

mature naive T cells have

A

CD4 or CD8, CD28, MHC Class I, TCR complex including CD3, LFA-1 and VFA-4, chemokine receptor CCR7

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2
Q

how naive T cells are activated

how are memory T cells activated

A

circulate and activated in lymph nodes with help of innate immune response DC’s

B cells and macrophages activate memory T cells

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3
Q

activation and migration of T cells by DC’s steps (8 steps)

A
  1. lose adhesive markers,
  2. upregualte CCR7,
  3. increase exp of MHC and CD80,
  4. travel to secondary lymphoid- mature as they migrate
  5. present ag to T cells
  6. naive T cells cross HEV,
  7. T cells sample antigen
  8. cells that do differentiate into effector T cells with increase in CD4 and CD8

T cells that dont encounter antigen travel down to next lymph node become unresponsive- anergic and tolerant

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4
Q

what are the acessory molecules of T cells, what do they bind to, and what do they do

A

CD4 T cells helper cells- recognize class II

CD8 cytotoxic T cells-recognize HLA class I

CD 28 on T cell binds to CD 80 on MHC- signal transduction

CTLA-4 on T cells binds to PD-1- adhesion and inhibition

LFA-1- adhesion binds to ICAM-1- adhesion and signal transduction

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5
Q

how does integrin avidity increase?

A
  1. TCR/HLA ag changes integrin conformation
  2. chemokines act on integrin to change it from low affintiy to high affinity
  3. adhesion molecules cluster for immune synpase
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6
Q

co stimulatory molecules in T cell activation have these 2 signals

A

1) binding MHC to TCR— increase in CD40 on APC’s and CD40 on T cells, exp of B7 (CD80) on APC’s and CD28 on T cells
2) specific to epitope

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7
Q

activation of mature T cells steps and what does it produce?

A

1) formation of synapse
2) activation of ITAMs- major player ZAP 70
3) phosphorylated and acitvated by LCK (SRC family)
4) produces INF-ab and AP-1 and protein synthesis (transcription factors)

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8
Q

what are proteins produced by t cell activation? what do they do and what are they produced by?

transciption factors

membrane effector molecules

cytokines

cytokine receptors

A

transcription factors: c-fos, c-myc

membrane effector molecules:

  • CD40- strengthens adhesion and prolongs contact
  • Fas ligand

cytokines:

  • IL-2— T cell proliferation- helper T cells— comes from actived T cells
  • IFN-y- activation of macrophages— comes from CD4 and CD8 T cells, NK cells
  • IL-4- b cell switching to IgE— comes from CD4 T cells, mast cells
  • IL-5- activation of eosinophils— comes from CD4 T cells, mast cells, innate lymphoid cells
  • IL-17- stimulation of acute inflammation— comes from CD4 T cells, etc
  • IL-22- maintence of epithelial barrier— comes from CD4 T cells, NK cells, innate lymphoid cells
  • TGF-b- inhibition of T cell activation, differentiation of reg T cells— comes from CD4 T cells, etc

cytokine receptors: IL-2r (CD25)

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9
Q

proliferation of T cells by IL-2 steps

A

autocrine signal

  1. binds IL-2Ra (CD25) – low affinity receptor
  2. becomes a high affinity receptor (IL-2RaByc)
  3. promotes T cell proliferation and differention
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10
Q

trapping and activating of naive T cells steps

A
  1. ag binds to specific T cell through IFNa
  2. increasses exp of CD69 which binds to S1PR
  3. signal internalized five days afterwards
  4. effector cells go from lymph to peripheray
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11
Q

What are the four different types of T helper cells, what cytokines are they differentiated by, and what do they induce?

A

all T helper cells defined by CD4

Th1— IFN-y and IL-12— macrophages

Th2— IL-4, IL-5, IL-13— eosinophil and mast cells

Th17— TGF-b, IL-17, IL-22— neutrophil

Tfh—IL-21, IFN-y, IL-4— anitbody production

**CD4 cells help to activate CD8 cells, cross presentation occurs

cytokine that differentiates one type of Th cell will inhibit differentiation of another

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12
Q

migration of activated Th cells steps

A
  1. activated in medullary,
  2. change CD4 exp,
  3. downregulate expression of CCR7 and upregulates CxCR5
  4. migrate to follicular zone,
  5. secrete cytokines and co stimulatory molecules, which help B cells present ag to activated T helper cell
  6. start expressing CTLA-4
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13
Q

T regulatory cells are what kind of cells?

influenced by?

express what?

A

they are CD4 cells

influenced by IL-2 and TGF-b,

express: CTLA-4, cd25, Foxp3, secrete IL-10 and TGF-b

they are the cells that shut everything down

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14
Q

what are gamma delta T cells? where can you find them? what are their responses?

A

less than 5%

found in epithelial boundaries, especially gut muscusa

ag restricted- limited diversity, can recognize non protein ag, recognize self and non self ligands, not restricted to mhc

responses are chemokines, cytokines, cytolysis, ag presentation, epithelial gf’s

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15
Q

purpose of T cell CMI

A

transfers immune cells to non-immune individuals

intracellular microbes killed by CTL’s or macrophages (phagocytes or nonphagocytes)

**serum cannot protect against intracellular microbes

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16
Q

major difference between effector T cells and naive T cells

A

An effector T cell is able to respond to specific antigen WITHOUT need for co-stimulation via B7 (CD80)-CD28 interaction!

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17
Q

T helper 1 mediated by __ and secrete, novel trans factor

A

proliferate in response to IL-12 and IFN-y

secrete IL-12 and ifn-y (postive feedback) which activate DC’s, macrophages and NK’s, TNF

novel trans factor T-bet

18
Q

Th1 cells are activates (3 things __) and secretes __

A

characterized by IFN-y:

  • activates macrphages against intracellular microbes- classical activation
  • activates b cells to stimulate class switching and complement binding
  • stimulates class II HLA and B7 expression

secretes TNFa to activate two different pathways: classical macrophage and complement inding/opsonizing/IgG antibodies

helps to combat microbes

19
Q

Th1 phagocyte activation steps

A
  1. effector T cells migrate to infection
  2. sample antigen and present it macrophages
  3. immune synapse forms between T cell and macrophage
  4. macrophage is activated— activated with CD 40, produces ROS, NO, and cytokines/chemokines (TNFa, IL-1, IL-12)
20
Q

T helper 2 respond to _ and secrete, novel transcription factor

A

responds to IL-4, helminths, and allergens

secrete IL-4, IL-5, IL-13

novel trans factor GATA-3

21
Q

Th2 cells mediate phagocyte involves __ (3 things)

what does it do overall

A

stimulate IgE, mast cells, eosinophils rxns that attack helminths through IL-5

isotype class switching to IgE

support alternative macrophage development through IL-4 and IL-13 (tissue repair)

inhibits microbe killing

22
Q

Th2 immunity involves __ by producing

A
  1. protection against helminths
  • mast cell production
  • mucus production
  • peristalisis
  • IgA production
  • eosinophil production

atopic disease

23
Q

diseases caused by predominance of Th2 over Th1

A

leishmania major

mycobacterium leprae— leprosy

24
Q

Th 17 repsond to _, secrete _, does _, novel transcription

diseases associated with it

A

respond to IL-1 and IL-6 (acute phase cytokines), bacteria and fungus

secrete IL-17 and IL-22

induce inflammation and leukocyte (neutrophil) recruitment, destruct extracellular bacteria, important barrier function

novel transcription factor RORYT

known to be involved in multiple sclerosis, IBD, RA

25
Q

migration of cd4 helper T cells to infection steps

A
  1. leave lymphatics and re enter circulation- sequester S1P
  2. circulate until find inflammatory molecules, chemokines, adhesion molecules (different than ones for naive t cells) in peripheal tissues that bring them to infection
26
Q

what are the molecules that are responsible for antigen-specific T cells being retained in the peripheal tissue with the infection? what do they bind to? what do these effector cells want to activate with??

A

E or P selectin ligand– binds to E or P selectin

LFA-1, VLA-1— binds to VCAM-1 or ICAM-1

CxCR3— binds to CxCL-10

cd44— binds to hyaluronan (tethering)

**these actions are less dependent on co stimulation

T cells that bind to ligand are retained at site, otherwise return to circulation

wanting to interact with macrophages class II

27
Q

naive T cells homing receptors and their binding

A

L selection— binds to L selectin ligand

LFA-1—- binds to ICAM-1

CCR7—- binds to CCL19 or CCL21

28
Q

migration of cd8 effector cell (CTL killing) steps

A
  1. antigen recognition in lymphoid organ
  2. T cell expansion and differention
  3. differentiated CD8 cells enter circulation
  4. migration to site of infection
  5. activated by antigens in peripheal tissue
  6. CTL killing
29
Q

CTL killing purpose, produces, mechanisms and enhancers are

A

TCR recognizes MHC class 1 (self peptides), kills intracellular pathogens, kills host cell, serial killer

produces IFN alpha/beta (antiviral)

contain preformed granules that contain cytotoxins (granzymes, which require perforins for endocytosis) that are delivered to surface of antigen after binding through ICAM-1/LFA-1 complex– direct apoptosis after exocytosis of granular contents

FasL (ligand on CTL’s) and Fas (cd95) (death receptor) activate caspase and induce apoptosis of Fas expressing targets

**Th1 effector cells enhance proliferation, differentiation and cloning of CD8 T cells through IL-2

**IFN’s increase MHC expression

30
Q

NK killer cells mechanisms, enhanced by__, inhibited by__, surface markers

A

kills tumor cells and virus-infected cells through granzymes and perforin

enhanced by IFN-a, IFN-b, IL-12

inhibited by mhc class 1

CD16 and CD56

31
Q

cells mediated by antibody-dependent cytoxicity (ADCC), target __, killing using

A

NK cells

macrophages

monocytes

neutrophils

eosinophils

target pathogen using: IgG or IgE

kiling by: lytic enzymes, TNF, perforin, granzymes

32
Q

memory cells are made by and express, require what for survival

A

the small percentage of T cells that dont undergo apoptosis after antigen is removed

increases expression of anti-apoptotic protein, BCL-2

require IL-7 and IL-15 for survival

**memory T cells can respond in peripheal, more rapidly than naive T cells, require reactivation to regain their function

33
Q

Treg expression, trans factor, mechanism, what are they helpful for

A

CD4 cells

express CTLA-4, CD25, PD-1 (regulatory factor that’s inducible on T cells, B cells, myeloid cells)

trans factor Foxp3

CTLA-4 binds B7 (CD80) and shuts off co-stimulatory ligand signaling

**binds more avidly that CD28- competitve inhibition

34
Q

mycobacteria evasion mechanisms

A

inhibition of phagolysosome infusion

35
Q

HSV evasion

A

inhibition of antigen presentation, interferes with TAP

36
Q

CMV evasion

A

inhibition of antigen presentation, inhibition of proteosome activity, removal of MHC class I molecules from ER

37
Q

EBV evasion

A

inhibition of antigen presentation and proteosome, production of IL-10, macrophage and DC inhibition

38
Q

pox virus evasion

A

blocks cytokine activation of effector cells

39
Q

how do CD4 cells help CTL development

A

produce IFN-y and IL-2 that stimulate costimulator between APC and CD8 t cell

40
Q

what happens in T cell exhaustion?

A

happens to both CD4 and CD8 cells

ctla and pd 1 are produced in normal T cell cycle, and they cause the cells to not respond to chronic infection

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