T cell Flashcards
What do mature naïve t cells express?
- Cd4/ CD8
- cd28
- mhc/ HLA class 1
- tcr complex with cd3 and gama
- LFA1 and VLA4 adhesion molecules
- chemokine receptor ccr7
Where are T cells activated? What is the only cell that activates naieve t cells?
In the lymph nodes by dendritic cells DC cells
What do B cells and macrophages activate?
memory t cells
what do CD4 cells activate
b cells and macropahges
Decribe dendritic presentation to T cells?
- antigen is captured and DC cell is activated when it puts the antigen on its MHC
- looses adhesive markers that keeps it in the tissues and upregulates CCR7 (found in the lympatic endothelium)
- increases expression of MHC and CD80 (B7)
- TRAVELS TO secondary tissue and matures as it migrates
- presents ag to t cells
Native t cells enter lymphnodes across what?
High endothelium venules in the cortex of lympoid tissues
if t cells dont encounter a specific ag in a lymphnode what happens?
they leave the node through the lymphatics and travel down the chain to the next lymphode.
TCR antigen regocnition changes what?
integrin conformation on T cells from low to high affinity. This allows for a strong immune synapse.
Decribe the T cell activation steps
1) T cell regongizes antigen (frist signals)
second signals:
2) this causes CD40 L expression to be upregulated on T cells to bind to cd40 on APC cells (consititivley expressed)
3) expression of B7 (cd80) is upregulated on APC now to bind to CD28 on T cells which is consitivley expressed
4) dendrdic cell will release IL12 which will enhance T cell proliferation and differentiation
immuno synapse
T cell activation
- initation of formation of the immunologic synape
- then activation of ITAM motives will cause LCK (src kinase associated receptor associated with cd4 and 8) phosprorlyate and activates tyrosine kinase zap 70 (that is assocaited with gama chain) which will have a bunch of down stream effects sitmulating nfkb
ANERGY
-a t cell recgonizes antigen without binding of costimulatory ligands or cytokine support will not be activated. They will become unresponsive or anergeic or tolerant….
How does a t cell promote proliferation?
- resting T cell have an IL2 on their receptor that is low affnity
- once you are fully activated the DENDRITIC cell will release IL-12
- this will cause the t cell to produce IL2 and the expression of high affnity chain for IL2 is put on the sruface with the intial complex
- the binding of IL2 to high affinity IL-2R promotes cell prolif and differentiation
What is the IL-2a chain?
put on with the other il2 receptors, and it is also known as cd25
How do you trap t cells
- t cells recognize antigen in a space thus it needs to chill there to be functionally active and activate b cells
- we have transient activation of CD69 which binds to s1pr TO IMPAIR migration (pulls in S1PR into the cell)
- s1pr binds to s1p normally which is in the blood and lymph thus when cd69 is bound to it it is taken up via endocytic vessicles and cant respond to s1p
- 5 days after the arrival of the antigen, the activated effector cell emigrates from the lymph node into the periphery
cytokine influence of Th development
Differntaion into Th subsets are dictated by the cytokines present.
Th1
- IFN gamma or IL-12 stimulate it
- targets macrophages for intracellular pathogens defense
TH2
- IL 4,5,13 make it
- targets eosinophils: will activate esnophils, mast cells, alt macrophages
- host defense against helminths
T helper 17
TGF-B, IL-17 and IL22 makes it
-targets neutrophils used for extracellular bacteria and fungi defence
TfH
IL21, IFN Gamma and IL-4 will make it
-used for b cells for ab production/ class switching
Activated CD8+ effector T cells are
not sequetered in lymph
during cross presentation what does CD4 to for CD8
shits out IL-2 which stimulates colonal expansion and differentiation.
Describe the migration of activated T helper cells.
-will change chemokine receptors ccr7 is down regulated and cxcr5 is upregulated -will migrate to folicular area to link up with b cells
lastly ctla-4 is stimulated (inhibitory response)
Cytokines that t cells make which link up with B cells do what?
regulate class switching of Ab production
Describe T reg cells
- they are cd4+ cells
- infulenced by IL2 and TGFB
- constitiulviey express ctla 4 and cd25 (can respond to IL-2 by t helper cells that have been activated hear it)
- novel TF is fox p3 -secrete IL-10 and tgf beta
Gamma detla t cells
- found in epithelial boundries of the gut mucosa
- ag restricted: have limited diveristy of peptides recognized and can reognize non protien ag
- not restricted to MHC/HLA presentation
An effector T CELL is able to do what?
-repond to a specific antigen w/o need for costimulation via B7 (cd80) or cd28 interaction
3 roles of IFN gamma
- activates macrophages against intracellular microbes when Th1 expresses it
- activates B cells to stimulate class swithing and complement binding when Tfh makes it
- stimulates class 2 HLA and cd80 expression
TH1 pahgocyte activation
- migrates to the area of infection
- sample antigen presented by macrophage
- immune synapse occurs between them
- macrophage expresses cd40 and cd40 ligand is on th1 cell (for the immune synapes) -th1 will shit out ifn gamma which will enhance the macrophage to make it a better killer
What does Th2 do
- novel tf is GATA 3
- secretes IL-4, IL5, IL13
What does IL-4 do?
What does IL-4, IL-13 do?
What does IL -5 do?
- Stimulates class switching to IgE
- alternative macrophage activation and tissue repair, also intestinal mucous secretion and parastlsis
- IL-5 activates eosinophils
How does Th2 protect against helminths?
- activates mast cells
- mucous production
- perastlisis
- iGa PRODUCTION
- eosinophil activation
T helper 17
- they secrete IL17 and IL22
- important in barrier function and neutrophil activation
regulation of macrophages 1 and 2
- IFN gamma will stimulate M1 being produced m1 makes: inflamation via IL- 1, IL-12, IL-23,chemokines, ros, NO and lysozomal enzymes
- IL23 AND 14 will stimulate m2 being produced: used for wound repair and fibrosis, antifinalmatory effects
argo: one set will inhibit the other - a predominant Th2 response to an intracellular microbe can lead to poor disease outcomes.
th1 and 2 influcence on dz
Th2 cells will inhibit microbicidal activtity of macrophages which can cause a problem…
Migration of CD4 + T helper cells
- have to leave lymphatics and reenter circulation
- put the S1pr receptor back
- circulate until they are expressed to acute inflamatory molecules which are made by innate imunology by the acute inflamatory response
What is the homing receptor for Naieve t cells
- L selectin and L selectin ligand (on endothelial cell)
- LFA-1 (b1 integrin) and I cam 1 (on endothelial cells)
What is the homing receptor for activated T cells
E and P selectin ligand and E and P selectin (on endothelial cell)
-LFA-1/VLA-4 (beta one and two integrin) and Icam/vcam 1 (on endothelial cells)
Why are every effector t cell that enters the area will not be specific for an antigen
selectins and inegrins are not specific they just say “I have something here come check it out”.
How are antigen specific t cells retained in peripherial tissues
- enter by vla binding to ICAM and fibronectin on the endothelial cell and then P and E slectins ligands will bind and it will come in.
- CD44 will then bind to a hydrauronan that can allow T cells to be theadered and interact with the infected area.
Cytotoxic T lympocytes
- TCR recognizes MHC class one and altered self peptides
- they kill cells infected with intracellular pathogens or tumor transformed cells
- TH1 effector cells enhance proliefration and diffenation and cloaning of activated cd8+ cells by providing IL2
What are the two killing mechanisms of Cytotoxic T lymphocytes?
1) cytotoxins are delivered directly nto the surface of the infected target cell and granular proteins are dropped off
- granzymes: activated caspases (activate apoptosis)
- perforins: necessary for delviery of the granzymes
2) FAS and FAS L (EXPRESSED ON CTL)
- will bind to Fas receptor and kill it
IFN alpha and beta
produced on nk cells and dendritic cells
-ihibit rep of virus and increase expression of MHC calss one on other infected cells
NK cells
- kills tumor cells and virus infected cells by granzymes and perforins
- enhanced by IFN alpha, beta and IL-12
- INHIBITED BY MHC class 1
- cd16 and 56 are cell surface markers
What is Antibody dependent cell mediated cytotoxcity
- ADCC
- NK cells, macrophages, monocytes, neutrophils, eosinophils, all target recognition thoguh IgG or IgE
- killing by lytic enzymes, TNF and perforins
The majority of effector T lymphocytes will undergo ______. A small percentage of the clones will become _______. These clones will express ______.
- apoptosis
- memory cells
- anti apoptotic protein Bcl-2
Memory T cells will require what to regain their effector function?
They can respond more _____ than naïve and respond where?
what do they require for sruvivial?
reactivation
rapidly, can respond in peripheral tissue
IL-7 and IL15
Describe CD4+ Th cell exhaustion:
when activated you have CTLA 4 and PD1 expressed on T cells. Thus they will be inhibited at some point. Your bacterial and viral load will not be handled because the supply of T cells will be diminished.
-This occurs in CD4 and CD8 cells.
