T cell mediated immunity and effector mechanism Flashcards
Cell mediated immunity
defense against intracellular microbes and B class switching
steps of CMI
1- CD4 and CD8 recognize peptides from DC.
2- Ag activtaed T cell express IL2R causing clonal expansion ( autocrine binding to IL2)
3- Some CD4 Cells remain in Lymph nodes and get into follicles for class switching
interaction between CD4 receptors and MHC2 APC
1- CD4 and TCR –> peptide and MHC2
2- CD3 and ITAM coprotiens
3- theta signal transduction
4- CD28 —> B7-1 and B7-2 costimulation
5- PD1 with ITIM –> PDL1 and PDL2 inhibition
6-LFA1 –> ICAM-1 adhesion
Role of costimulation
CD28-B7-1 and B7-2 interaction ensures activation by microbial antigen and not harmless substance of self antigens as B7 is expressed by stimulaion by microbe
ICOS function
homologus to CD28 responsible for development of Tfh cells during germinal center
immune synapse formation
TCR complex, CD4 or CD8 coreceptors, CD28 moves to the center and integrins form a peripheral ring acting as a channel for delivering signals
activation of TCR complex by ZAP70
1- tails of CD4 and CD8 have tyrosine kinase called Lck
2- CD3 made up of gamma, delta and epsilion and theta contain ativatory motifs with 2 ITAMs
3- Lck phosphryates trosine residues contained in ITAMS of theta and CD3 and phoshrylated ITAM become ZAP70 which is phorpylated by lick and then active Zap70 phosphrylates adaptor protiens
Nucelear factor of activated T cell ( NFAT)
1- transcription factor found in cytosole and is. Ca dependent
2- phosprylation and activtion of enzyme phospholipase Cy by itk
3- activated PLCy hydrolyze PIP2 to IP3 causin rlease of Ca from smooth ER and mitochondrial will acitvate calmodulin which will activate calcinum
4- due to loss of Ca from intracellular, Ca channel allow mroe Ca in the cytosol causing acitvation of calcineurin which removes phosphate from NFAT and activtae several genes encoding for IL2 and IL2R
Ras/Rac-map kinase pathway
Zap70 and adaptor protien accumlation a plasma lead to ras and rac recruitment
2- both activate MAP kinase and activate ERK and JNK causing expression of C fos JMK and C-Fos which comebine to form transcription factor AP-1 enhacning T cell transcription
PKCθ–NF-κB pathway
protien kinase C activate transcription factor NF-kB making IL1, IFNy, IL6, IL12 and IL17
IP3 kinase pathway
phopsrylates PIP2 to make PIP3 and PIP3 acivaate Akt protien Kinase B stimualtion antiapoptotic expression and it activates mTOR that is resposnible for protien translation and survival
Th1 cells cytokines
IFNy activating macrophages againt intracellular microbes and it inhibits Th17
IL2 which activates Tc and NK
stimulation ofTH1 increased by IL2 and IFNy and inhibited by il4 and IL10
Th2 cells
secrete IL4
IL5
IL13
IL10
act on eosinophils and mast cells
Increased secretion by IL4 and inhbited by IFNy
Th17 cells
secrete IL17 and IL22
act on neutriphils
secretion increased by TGFbeta, IL6, IL17 and IL21 and inhibited by IFNy and IL4
Tfh cells
secrete IL21
Secrete IFNy or IL4
act on B cell for antibody production
IL2 function
T cell profilration and reg T cell survival from Activated T cellI
IFNy
activate macrophage the classical pathway and secreted from TH1, Tc and NK
IL4
IgE class switching and alternative mccrophage activation
found on TH2 and mast cells
IL5
activation of eosinophils
found on Th2, mast cells and innate lymphoid cells
IL13
Class switching to IgE and alternative amcrophage activation
found on Th2, mast cells and innate lymphoid cells
IL17
stimualte of acute inflammation
from Th17
IL21
B ell ativtaion adn Tfh differnation and from TFh
IL22
maintaince of epithelial barrier
from Th17, Nk cells and innate ymphoid cells
Th1 development
Mycobacterial will present peptides to DC and NK
DC–> IL12 –> activate state4
NK –> IFNy –> activate Stat1
Formation of Th1
Th2 development
parasiteopsnization by Mast cells and eosino phils
secrete IL4 –> activate GATA3 and STAT6 making Th2
Th17 cell development
Extracellular fungi and bacteria bind to DC
–> IL1, IL6, IL23 and TGFbeta —> activate STAT3 and + TCR —> RORyT making Th17
how does mycobacteria evade immune system
inhibition of formation of phagolsysome some
how does HSV evade
inhibtion of antigen presnetion by interruptinf TAP
how does CMV evade
inhibit antigen presention by removing MHC1 from ER
how does EBV evade
inhibition of proteasomal activity and production of iL10 inhbiting macrophage and DC activation
how does POx virus inhbit
Inhibition of effector cell activation adn producetion of soluble cytokine recpetors