Cell Immunity 2 Flashcards
What T cells play an important role in orchestrating the adaptive immune response via secretion of a wide range of cytokines?
CD4
What provides B cell help for antibody production that is critical to prevent secondary infection with most viruses?
Tfh
what cells direct the differentiation of naive CD4 T cells?
DCs
What activates transcriptional regulator NFAT?
TCR stimulation and Ca influx
What is T-bet induced by?
NFAT
What works cooperatively to fully open up the IFN-gamma gene locus for transcription?
Hlx and Tbet
What sequesters GATA-3
T bet which prevents Th2 cell development
What does IFN-gamma do?
increase expression of IRF-1 and IRF-2 which repress IL-4
The effector activities of Th1 cells is mediated by what?
IFN-gamma
What do Th1 cells do?
help to activate macrophages to kill intracellular microorganism
Does GATA 3 bind its own promoter?
yes as well as for the IL-4 genes
What activates expression of c-MAF?
ICOS and ICOSL
What lead to the Th2 differentiation?
GATA 3
What does IL-4 do for B cells?
growth and differentiation, and secretion of immunoglobulins [IgE]
True or false– IL-4 is an important regulator of mast cell and eosinophil function?
True
What does IL-5 do?
IgA differentiation and synthesis
also helps regulate eosinophils
What does IL-10 up regulate?
MHC class II expression on macrophages
What does IL-10 inhibit?
Th1 response
What does IL-4 and IL-13 do to mucosal epithelial cells?
increase proliferation and turnover as well as up regulate mucin
What does IL-4 and IL-13 do to smooth muscle?
Increases contractility
What does Th2 cells do to macrophages?
alternative activation–exert anti-inflammatory functions and promote tissue remodeling and repair
What does IgE bind to? What does it do?
Fcepsilon receptors on mast and basophils—->degranulation when cross linked with antigen
What happens at T:B cell border of the follicle?
CD4 T cells interact with B cells presenting Ag.
What do Tfh cells provide?
B cell help for antibody production that is critical to prevent secondary infection
What cells amplify immune responses mediated by neutrophils?
Th17 cells
What causes down regulation of Th17 response?
Uptake of dead neutrophils by macrophages inhibits IL-23 secretion
How are Th17 cells maintained?
IL-23 secreted by activated macrophages
Why is tight regulation of immune activation necessary?
prevent self response
permit immune response to foreign antigens
limit collateral damage
What is a Treg?
regulatory T cell formed naturally by thymic differentiation [nTreg] or are induced in periphery [iTreg]
Can Tregs inhibit early activation events- 6-10 hours?
No
How do Tregs inhibit proliferation of multiple cell types?
prevent IL-2 production
What can Tregs do to inhibit on effector functions of lymphocytes ?
inhibit cytokine production
inhibit release of granules
inhibit antibody production
What are Tregs suppressive cytokines?
IL-10, TGF-beta
Protective immunity versus Immunopathology Depends on balance between what>?
Tregs and Effector T cells
What syndrome? x-linked, mutations affecting FoxP3, Treg dysfunction, autoimmunity, early onset males, psoriasiform, eczematous dermatitis, alopecia,
Immunodysregulation polyendocrinopathy X-linked syndrome (Ipex)
Limited success in bone marrow transplants
What cytokines to effector cytotoxic CD8 T cells release when encountering infected cells?
IFN-gamma or TNF-alpha
2 types of cell death?
necrosis or apoptosis—-both cleared by phagocytosis
Hallmarks of apoptosis?
blebbing, chromatin condensation, dna frags.
What type of cell death does CD8 T cells induce?
apoptosis
what molecule is secreted by CD8 that creates pores in cell membranes?
perforin
What are serene proteases which activate apoptosis once in the cytoplasm?
granzymes–cleaves Caspase 3 [released on TCR ligation without recruitment of more production]
Do granzymes A,B,H,K have different enzymatic activity?
Yes each one is different
What protects the CD8 T cell from perforin?
Cathepsin B
What alternative killing pathway is shared by Th1 and CD8 T cells?
Fas/FasL —>caspace cascade and cell death.
What inhibits viral replication, increases MHCI expression, activates macrophages?
IFN-gamma
what cytokine is directly involved in target cell killing and activating macrophages?
TNF-alpha
What does the dectin receptor recognize?
Fungi