13: Diff and Fxn of Cd8+ cells Flashcards
percent of CD8+ in blood
33%
B cells make up what % of blood
30%
what are CD marker for
number of T cells by fluorescent microscopy and flow cytometry
where does rearrangement of genes for T cells occur
thymus
what is functional polarization
T cells take on a particular set of task that promote adaptive immune response as effector fxn
what can CD8+ become
CTL or memor cells
what are granules
lysosomes that have perforin and granzymes to kill other cells
secreted from CTLS
cytokines, mostly IFN-y that activate macrophages
what is the role of T bet in CTL
regulates TC of perforin
how does cross presentation work
DC ingest cell with intracellular microbes and produce both MHC II and MHCI due to phagosome in DC cytoplasm
what is it called when CD4+ enhance ability of APCs to stimulate CTLs
APC licensing
how does APC licensing work
CD4+ produces IFNy to DC then once CTL binds DC, IL12 is released to CTL
what is needed in APC licensing
CD40 to CD40L to up-regulate CD 80/86 expression for more efficient binding of CTLs
what signal do CD4+ provide for CTL
signal 3 via IL12 and IFNy
when are CD4+ required for CTL activation
weak innate immunity to latent viral infection and tumors
IL2 for CD8 means
proliferation and differentiation into CTL and memory
what does IL2 share
IL2R with IL15 and IL 21 at y
role of IL12 and IFNy to Naive CD8
effector CTLs
why are IL12 and IFN y required for effector CTLs
induce survival and development
what is role of IL15
produced by DC and tissue Macrophages for survival of memory CD8 T cells
IL21 role
produced by activated CD4+ T cells for induction of T cell memory and prevent CD8 + memory
how does IL2 work
autocrine loop for activation of T cells and up-reg of IL2, IL2R
CD4+ derived IL2 for activation of CD8+ via
paracrine
structure of IFNy from CD4+
homodime
what releases IFNy
TH1, CTLs, NK cells
role of IFNy
activator of macrophages to increase metabolic, phagocytic and killing
what does IFNy increase the expression of
MHC I and MHC II
what might be an important component for antiviral protection
IFNy making more MHC
key cytokine made by activated DC and macrophages
IL12
profound effect of IL12
CD4 to TH1 effector cells
what determines whether CD4 becomes TH1 or 2
balance of IL12 and 4
which pro-inflammatory cytokines are promoted by IL12
IFNy and TNF B
why are CD8+ stimulated by IL12 needed
effective in controlling tumors and maintain higher numbers
what does IL12 prevent
CD8+ T cell exhaustion
what other cells are activated by IL12
NK cells
source of IL 15
macro and DCs
what is IL15 similar to
IL2 for shared receptor
what can IL 15 cause
proliferation of CTLS but favors TH1 cell in vitro
what is a chemoattractant for T cells from blood
IL 15
causes proliferation of memory CD4+ and CD8+ cells
IL 15
IL21 is derived from
CD4+
what does IL21 cause
DC, CD4+, NKT, NK, CTL, macrophage, macrophage activation. CD4 becomes TH17, B cell switching
role of CD8 in acute viral infection
eliminate infection by becoming CTLs
activated CD8+ cells produce what
chemokines and cytokines for eliminate infection
role of CD4+ for CD8+ cells
stimulate DC and CD8 for CD8+ T memory cells
which Ags are presented to CD8 T cells
viral Ags
what happens after viral clearance
contraction for apoptosis
same virus means
CD8+ memory cells that last for years
what is exhaustion of CD8+ T cells
chronic viral infection leads to gradually extinguished CD 8+ T cells
exhaustion leads to
active suppression of immune due to more PD1 and less IFNy
what diseases are more PD1 on T cells related to
HIV and Hep C virus infection
effective immuno-therapy for tumors
Anti-Pd-1 Abs
PD1 blocks production of
CTLS
why does an immunological synapse have to be formed
protect bystander cells
release of perforin and granzymes by
granule exocytosis
point of no return for CTL
capase 3
How is apoptosis induced
FasL on activated CTLs binds Fas on surface of target cells
what activates capase 3
perforin for apoptosis
two types of killing by CTLS
perforin/granzyme and Fas/FasL
what ion is involved in Granzyme mediated apoptosis
Ca2+
what types of proteases are Granzyme A,B,C
serine
which granzyme is required for CTL cytotoxicity
B
what is perforin homologous to
C9 complement protein
what does perforin cause
internalization of it and granzymes
what does Granzyme B activate
capase 3 for apoptosis
what doe FAS/FasL cause in type 1 cells
recruitment of procapase 8 by FADD for active capase 8 to cleave capase 3
Fas-FasL in type II cells
capase 8 cleaves Bid for cyt c release from mitochondria. cyt c and Apaf1 and ATP activate Capase 9 to activate Caspase 3 that activates CAD for DNA degradation
caspase 3=
degrades ICAD for CAD activation to degrade DNA
how are intracellular microbes defended against
CD8 and 4 together. Macrophage ingest then CD4= IFNy and IL2 to kill bacteria ad produce MHC I for CD8+ to kill cell
virus enters cell and infects directly leads to
viral proteins degraded for MHCI presentation so APCs Take up viral product then present with MHC I and II for CD4+ by CD40 and CD8 to CD 80/86 for activation of CD8+. release of perforin and granzyems as well as TNFa and IFNy produced