T Cells 3 Flashcards
are FasL and CD40L cytokines? how are they different than other cytokines we’ve seen?
yes, they are transmembrane cytokines part of the TNF
they interact with receptors using a cell-to-cell mechanism, rather than autocrine/paracrine/endocrine mechanisms for soluble cytokines
describe the response to a viral infection
- Anti-viral cytokines, Type I IFN (alpha, beta), are first released from innate cells to reduce viral replication
- NK cells recognize infected/tumour cells without MHC I
- virus-specific CTLs directly kill infected cells
- viral titer decreases
- amount of CTLs decrease (contraction) once they’ve done their job
what cytokine do CTLs secrete?
IFN gamma (Type II IFN)
what is the difference and similarity btwn NK and CTL cells?
BOTH kill infected and tumour cells
NK cells kill cells without MHC I, CTLs kill cells via MHC I
what are the 2 roles of IFN gamma?
- increase MHC I expression in neighbouring cells to increase the chance of finding a match
- activate macrophages + stimulate production of CHEMOKINES that recruit additional macrophages and CD8+ T cells to site of infection
if macrophages are already tissue-resident, why does IFN gamma recruit macrophages to site of infection?
IFN gamma just brings them closer within the tissue
what are the 2 differences btwn Type I and Type II IFN?
CELLS
- Type I secreted by innate cells
- Type II secreted by adaptive cells
FUNCTION
- Type I –> antiviral effects due to PRR activation
- Type II –> increase MHC I expression, macrophage activity
describe the general release of cytokines once naive CD4+ T cell is released? (5 steps)
- APC and neighbouring cells release polarizing cytokines (signal 3)
- PROLIFERATION
- different STAT proteins are activated within each cell
- Master transcriptional regulator produced
- DIFFERENTIATION
- effector cytokines released for effector function
what types of pathogens do TH1 respond to?
- viruses
- intracellular pathogens
what types of pathogens do TH2 respond to?
- parasites
- extracellular pathogens
- allergy
what types of pathogens do TH17 respond to?
- extracellular bacteria and fungi
- autoimmunity
what is the role of TFH?
activating B cells in lymph node
where do TFH reside?
lymph node!! dont ever leave LN
what type of immune cell does TH1 affect?
macrophages –> kills intracellular bacteria
what types of immune cells do TH2 affect?
eosinophils, basophils, mast cells –> to release histamines
what type of cells do TH17 affect?
neutrophils
what 2 molecules are involved in TH1 cells?
- IFN gamma
- CD40 ligand
what 4 molecules are involved in TH2 cells?
- IL-4
- IL-5
- IL-13
- CD40 ligand
what 3 molecules are involved in TH17 cells?
- IL-17
- IL-22
- CD40 ligand
what 2 molecules are involved in Treg cells?
- IL-10
- TGF-beta
is only 1 T cell present during an infection?
No, will have combination of many different T cells but one will be more dominant base don the pathogen
describe cross-regulation btwn TH1/TH2/TH17
TH1 secretes IFN gamma which inhibits TH2
TH2 secretes IL-4 which inhibits TH1
IL-4 and IFN gamma both inhibit TH17 differentiation
what is the purpose of cross-regulation?
cytokines are produced by a type of TH cell so it can suppress differentiation of other TH cell types and reinforce the necessary TH cell type
describe TH1/TH2 cross-regulation to promote TH1 (5)
- Signal 3/polarizing cytokine is IL-12
- STAT4 cytokine produced
- Master transcriptional regulator T-bet commits T cells to TH1
- GATA-3 inhibited
- increased IFN gamma, decreased IL-4, IL-5
- TH1 is promoted
describe TH1/TH2 cross-regulation to promote TH2 (5)
- Signal 3/polarizing cytokine is IL-4
- STAT6 cytokine produced
- Master transcriptional regulator GATA-3 commits T cells to TH2
- T-bet inhibited
- decreased IFN gamma, increased IL-4, IL-5
- TH2 is promoted
what is the role of T-bet?
to suppress gene expression of TH2 pathway
what is the role of GATA-3?
to suppress gene expression of TH1 pathway
what is the role of TGF-beta?
polarizing cytokine that allows for differentiation of TH17 and Treg
what cytokine allows TH17 to be differentiated instead of Treg?
IL-6
describe the decision btwn TH17 and Treg differentiation during infection (4)
- TGF-beta is a polarizing cytokine that allows for differentiation of Treg and TH17
- during infection, IL-6 will be secreted from DC
- TH17 will be differentiated
- antibacterial effect
describe the decision btwn TH17 and Treg differentiation in a normal state (4)
- TGF-beta is a polarizing cytokine that allows for Treg and TH17
- in a normal state, IL-6 will NOT be secreted from DC
- Treg will be differentiated
- suppress inflammation
which T cells leave lymph node and migrate to site of infection?
TH1, TH2, TH17
which T cells stay in the lymph node and activate B cells?
TFH
do naive and effector T cells express different cell surface molecules?
YES, there are different cell surface molecules expressed by naive vs effector T cells
what is the role of receptors on effector T cells?
effector T cells bind to specific tissues via receptors depending on site of infection
what are the 2 signal 3/polarizing cytokines of TH1?
- IFN gamma
- IL-12
what is the effector cytokine of TH1?
IFN gamma
what is the master transcriptional regulator of TH1?
T-bet
how do TH1 cells activate adaptive cellular immunity? (2)
- macrophage activation
- activation + differentiation of naive CTL precursors into effector CTL (via licensing)
what are 3 examples of pathogens targeted by TH1?
all intracellular pathogens
- Intracellular bacteria (M. tuberculosis, Salmonella)
- Intracellular parasites (Leishmania, Toxoplasma)
- Viruses
describe the activation and function of TH1 (8)
- Signal 3/polarizing cytokines: IFN gamma and IL-12
- transcription factors: STAT1 and STAT4 activated
- master transcriptional regulator: T-bet gene activated
- DIFFERENTIATION
- T-bet activated IFN gamma gene
- IFN gamma secreted at point of interaction
- IFN gamma targets macrophages
- microbes that persist in macrophage vesicles are killed
how does TH1 target macrophages?
TH1 has TCR which recognizes pMHC II on macrophage surface
why do TH1 target macrophages?
to help kill microbes that PERSIST and cannot be broken down in macrophage vesicles
describe the results from this experiment:
Mice infected with Leishmania major intracellular parasite and receive/don’t receive anti-IL-4 antibody
*TH1 required for INTRACELLULAR parasite
Mice without anti-IL-4-antibody:
- Mice will die –> IL-4 will bind TH1 and prevent its differentiation
Mice with anti-IL-4-antibody:
- Mice will survive –> no IL-4, so TH1 can differentiate and fight against parasite