cell mediated immunity Flashcards by Natalie Powell

mature naive T cells have

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

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how naive T cells are activated

how are memory T cells activated

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

lose adhesive markers,
upregualte CCR7,
increase exp of MHC and CD80,
travel to secondary lymphoid- mature as they migrate
present ag to T cells
naive T cells cross HEV,
T cells sample antigen
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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what are the acessory molecules of T cells, what do they bind to, and what do they do

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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how does integrin avidity increase?

TCR/HLA ag changes integrin conformation
chemokines act on integrin to change it from low affintiy to high affinity
adhesion molecules cluster for immune synpase

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co stimulatory molecules in T cell activation have these 2 signals

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

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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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

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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proliferation of T cells by IL-2 steps

autocrine signal

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

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trapping and activating of naive T cells steps

ag binds to specific T cell through IFNa
increasses exp of CD69 which binds to S1PR
signal internalized five days afterwards
effector cells go from lymph to peripheray

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

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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migration of activated Th cells steps

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

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T regulatory cells are what kind of cells?

influenced by?

express what?

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

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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purpose of T cell CMI

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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major difference between effector T cells and naive T cells

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

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

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

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

Th1 phagocyte activation steps

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

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

responds to IL-4, helminths, and allergens

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

novel trans factor GATA-3

Th2 cells mediate phagocyte involves __ (3 things)

what does it do overall

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

Th2 immunity involves __ by producing

protection against helminths

mast cell production
mucus production
peristalisis
IgA production
eosinophil production

atopic disease

diseases caused by predominance of Th2 over Th1

leishmania major

mycobacterium leprae— leprosy

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

diseases associated with it

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

migration of cd4 helper T cells to infection steps

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

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??

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**

naive T cells homing receptors and their binding

L selection--- binds to L selectin ligand LFA-1---- binds to ICAM-1 CCR7---- binds to CCL19 or CCL21

migration of cd8 effector cell (CTL killing) steps

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

CTL killing purpose, produces, mechanisms and enhancers are

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

NK killer cells mechanisms, enhanced by\_\_, inhibited by\_\_, surface markers

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

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

NK cells macrophages monocytes neutrophils eosinophils target pathogen using: IgG or IgE kiling by: lytic enzymes, TNF, perforin, granzymes

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

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

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

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

mycobacteria evasion mechanisms

inhibition of phagolysosome infusion

HSV evasion

inhibition of antigen presentation, interferes with TAP

CMV evasion

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

EBV evasion

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

pox virus evasion

blocks cytokine activation of effector cells

how do CD4 cells help CTL development

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

what happens in T cell exhaustion?

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