Differentiation and Function of CD4+ T cells Test II Flashcards
What are the signature cytokines and host defense in Th1 cells?
IFN-y agaisnt intracellular microbes plays role in autoimmune and chronic infections, ex diabetes
Signature cytokines for Th2 cells, host defense, role in disease?
IL-4 IL-5 IL-13, Helminthic parasites and allergic diseases
Th17 signature cytokines host defense role in disease?
IL-17A IL-17F IL-22
extracell pathogens
autoimmune diseases such as IBD
Development of Th1 cells?
IL-12 and IFN-y produced by Macro/DC’s activates TF STAT4 and STAT1 to express T-bet. The IFN-y produced by NK cells activates STAT1 which stimulates differentiation of naive CD4 cells to TH1 subset.
TH1 amplifies response by producing IFN-y and TNF-B that inhibits development of TH2 and Th17
Development of Th2 cells?
IL-4 produced by activated mast and eosinophils activates the TF GATA-3 and STAT6. GATA3 and STAT6 stimulate differentiation of CD4 to Th2.
IL-4 produced by Th2 cells amplifies this and inhibits the dev of Th1 and Th17. Also produces IL-5 and IL-13
Development of Th17?
IL-1, IL-6, IL-23 and TGF-B activate the TF STAT3 which causes expression of RORyt and . TF induce differentiation into Th17.
RORyt and STAT3 induces IL-21 and amplifies generation of Th17 by autocrine reg manner.
TGF-B can promote Th17 by suppresssing Th1 and Th2. IL-17 produced by TH17 protects from extracell pathogens.
What is death by neglect?
Process that eliminates T cells that would be non-functional due to inability of TCR’s to bind to MHC.
Unsuccessful rearrangement of TCR.
What is the role of FOXp3?
T cells that weakly react with self Ags, rather than be eliminated, they express FOXP3 and are given job of producing IL-10 and TGF-B. They avoid negative selection and only produce these. If FOXP3 is not expressed they undergo negative selection.
Describe CD40 and CD40L and IFN-y in classically activating Macrophages.
CD40 is constitutively expressed on macrophages and CD40L is located on on CD4 effector cell. IFN-y is released by CD4+ which acts on macrophage to activate it. Also need co stimulation of CD28:B7
IL-2 principal action and cellular sources?
T cell proliferation and Treg survival. Source is activated T cellls
IFN-y principal action and cell source?
Activation of macrophages and source is CD4+, CD8+ and NK cells
IL-4 principal action and cell source?
B cell switching to IgE. Source is CD4+ and mast cells
IL-5 principal action and cell source?
Activation of eosinophils. Source is CD4+, mast cells, innate lymphoid cells
IL-17 principal action and cell source?
stimulation of acute inflammation. Source is CD4+ cells
IL-22 principal action and cell source?
Maintenance of epithelial barrier function. Source is CD4+, NK cells, and innate lymphoid cells
TGF-B principal action and cell sources?
Inhibition of T cell activation,(dampens immune response) differentiation of Treg cells. Source is CD4+, and many other types
Upon infection from intracellular microbes such as mycobacterium turbuculosis what is the cascade of events that occurs to differentiate T cells into Th1 cells?
Dendritic cells and NK cells release IL-12 and IFN-y. This acts on the Ag activated T cell to express the TF T-Bet, STAT4 and STAT1. Which differentiates the cell into Th1 which then produces IFN-y TNF.
Upon infection with helminths what cascade of events occurs to differentiate cells into Th2?
Mast cells and eosinophils release IL-4 which acts on Ag activated T-cell and stimulates TF GATA-3 and STAT6 to differentiate the cell into Th2. Th2 cell then releases IL-4, IL-5, and IL-13
Upon infection with extracellular pathogens such as fungi or bacteria, what cascade occurs to differentiate cells into Th17?
Dendritic cells Release IL-1, IL-6, IL-23, and TGF-B to act on the Ag activated T cell. The T cell expresses TF RORyt and STAT3 to differentiate the cell into a Th17 cell. It then produces IL-17, IL-21, IL-22
What are the effector functions of IgG subclasses?
Fc receptor dependent phagocyte responses, complement activation, and neonatal immunity
What are the actions of a classically activated macrophage?
Activated by Microbial TLR ligands and IFN-y released by Th1 cells. Release ROS NO and lysosomal enzymes to induce microbicidal actions such as phagocytosis and killing of bacteria and fungi.
Also to Release IL-1, IL-12, and IL-23 for inflammation
What are the actions of an alternatively activated macrohphage?
Activated by IL-13 and IL-4 released by Th2 cells. The Macro then releases IL-10 and TGF-B to have anti-inflammatory effects and help wound repair.
Functions of Th17 cells specifically IL-17 and IL-22?
High ratio of IL-17 to IL-22 results in inflammation and neutrophil response.
Low ratio of IL-17 to IL-22 results in control of homeostasis.
The non redundant role of y/delta T cells in different pathophysiological processes relies on what three properties?
Ag specificity
Tissue distribution
Functional properties
Why are gamma delta T cells considered non conventional?
They are innate like T cell, they have factors from innate immunity as well as factors that make them similar to T cells.
How are gamma delta T cells activated?
After they recognize stress induced ligands resembling PAMP’s or DAMP’s by PRR’s. They are quickly activated as they are Pre-activated and can jump to effector functions.
What cytokines are rapidly produced by gamma delta T cells?
IL-17 IFN-y and TNF to regulate pathogen clearance inflammation and tissue homeostasis in response to stress.
What are the physiological roles fulfilled by gamma delta T cells?
Protective immunity against exta/intra cell pathogens
Constant tumor surveillance
Modulation of innate and adaptive responses
Tissue healing and epithelial cell homeostasis
Regulate physiological organ function
In gamma delta T cells how is detection of stress induced molecules achieved?
Using both TCR’s and TLR’s as well as NKR’s
What three sets of stress induced stimuli can gamma delta T cells recognize?
MCH related and unrelated TCR ligans such as CD1c molecules
MICA, a MHC class I related sequence A which engages NKR’s such as NKG2D
DAMPs or PAMPs recognized by PRR such as TLR’s
Which immune system are gamma delta T cells a part of?
Both adaptive and innate.
Adaptive because they have memmory like characteristics and rearrangement of TCR genes similar to aB T cells.
Innate because a restricted TCR could be considered as a PRR, and yD T cells can recognize unpresented Ags using TLR’s and NKG2D receptors.
Functions of the yD T cell?
Lysis of infected/stressed cell
Cytokine/chemokine production
B cell help and IgE production
Priming of aB T cells via Ag presentation
DC maturation
Regulation of stromal cell function through GF production
What immune system are NKT cells important in?
Innate immunity as their rapid response helps fight some bacterial and viral infections. Their cytokines also have strong impacts on aB T cell differentiation and functions linking NKT to adaptive defense as well.
What makes up NKT cells?
CD3+ the marker for T cells and CD56+ the marker for NK cells
DO NKT cells have memory?
NKT cells express Ag specific TCR generated after VDJ recombination, but don’t have memory
What do NKT cells recognize?
self and foreign lipids and glycolipds. Lipids and glycolipids are presented with non polymorphic CD1d molecule similar to MHC
Upon activation what do NKT cells produce?
IL-10 TGF-B and Th1 (IFN-y) and Th2 (IL-4) cytokines
A dysfunction or deficiency of NKT cells leads to what?
Autoimmune disease such as diabetes or atherosclerosis
Cancers
Asthma progresssion
What occurs when NKT cells recognize glycolipid Ags?
Glycolipid Ags are presented byCD1d and it leads to a release of cytokines and expression of CD40L that results in the activation of APCs and many other cells including NK T and B.
How can Th1 responses be advantageous and deleterious to the host?
It can increase microbial immunity and increase tumor rejection. It can also increase atherosclerosis and autoimmunity.
How can Th2 responses be advantageous and deleterious to the host?
It can decrease autoimmunity and graft rejection.
It can also increase allergies
