Effector Mechanisms of T Cell Mediated Immunity Flashcards
Th0 cell
Produces several various helper T subsets: Th1, Th2, Th17, Tfh.
Th1 cells
Activate a cell-mediated immune response.
Th2 cells
Activate an Ab-mediated immune response. Helminths and parasites.
Th17 cells
Involved in inflammation and anti-bacterial response.
Tfh cells
Remain in the LN and help B cells.
Inducing cytokines of Treg:
IL-2 and TGF-beta.
Cytokines produced by Treg (3):
Transcription factors of Treg cells (2)
TGF-beta
IL-10
IL-35
STAT6
FXP3
Inducing cytokine of Th1:
IL-12
Cytokines produced by Th1 (1):
Transcription factors of Th1 (2)
IFN-gamma
STAT4
T-bet
Inducing cytokine of Th2:
IL-4
Cytokines produced by Th2 (3):
Transcription factors of Th2 cells (2):
IL-4
IL-5
IL-13
STAT6
GATA3
Inducing cytokines of Th17:
TGF-beta and IL-6
Cytokines produced by Th17 (3):
Trancription factors of Th17 cells (3):
IL-17A
IL-17F
IL-22
CCL20
STAT3
RORyt
Th1 , Th2 and Th17 are all:
CD4+ helper cells.
TGF-beta function
Acts as an inhibitor/dampener of immune responses, but stimulates differentiation of Treg cells.
Development of Th1 cells
STAT4 and T-bet produced via IL-12 and IFN-gamma from NK cells activates STAT1, which together stimulates differentiation of naive CD4+ cells.
How does Th1 cells amplify their reproduction?
They produce IFN-gamma which inhibits the development of Th2 and Th17 cells.
How do macrophages respond to activation?
Produce ROSs, NO, lysosomal enzymes.
Secretion of cytokines.
Increased expression of B7 and MHC molecules.
IL-4 is produced by:
Mast cells and eosinophils.
What stimulates the differentiation of naive CD4+ cells to the Th2 subset?
By activating GATA-3 and STAT6.
IL-4 can also amplify the response by inhibiting the development of Th1 and Th17 cells.
Th1 activate _________, which can cause:
M1. Microbactericidal actions (phagocytosis, killing, etc) and Inflammation.
Th2 activate __________, which can cuase:
M2.
Anti-inflammatory effects.
Development of Th17 cells
Activation o RORyt and STAT3 via IL-1, IL-6 and TGF-beta which cause differentiation of Th17 cells.
IL-21 function in development of T17 cells:
It is induced by RORyt and STAT3 which amplifies generation of Th17 cells in an autocrine manner.
TGF-beta promotes Th17 responses by:
Suppressing Th1 and Th2 cells.
IL-23 can cause:
Activation of Th17 cells.
IL-17 produced by Th17 cells…
Protects from extracellular pathogens and is involved in inflammation and autoimmunity.
Increased IL-17/IL-22 induces:
Inflammation and neutrophil response.
Constitutive levels of IL-17/IL-22 causes:
Homeostasis.
Helper T cells are restricted to:
MHC II.
CTLs are restricted to:
MHC I.
Cross presentation of APCs:
Allows APCs to present extracellular Ags on MHC I.
Which is generated first: CD4+ or CD8+?
CD4+
Licensing of DCs
Occurs when the CD4+ cell delivers activating signal via CD40L/CD40 signaling and cytokines (IFN-gamma) to DC after it recognizes Ag presented by an MHC II APC.
CD40-CD40L and IFN-gamma upregulates:
Expression of CD80/CD86 and stimulates Ag cross-presentation, which makes them more efficient at inducing differentiation of CD8+ cells.
How do CD8+ cells cause CTL differentiation w/o helper T cells?
CD8+ T cells recognize Ag and costimulators on APCs which causes CTL differentiation w/o helper T cells. IL-12.
How do CD4+ helper T cells stimulate CTL differentiation?
CD4+ helper T cells produce cytokines that stimulate CTL differentiation. IL-2.
How do CD4+ helper T cells enhance APCs ability to stimulate CTL differentiation?
They increase IFN-gamma causing increase of IL-12 which produces a potentiated response.
What is the immunologic synapse and what is its fuction?
It is the small space between CTL and target cell. It ensures that normal bystander cells are not injured by CTLs.
Fas/FasL mediated cell killing
FasL on CTL interacts with Fas on target cell, which triggers apoptosis.
Two major mechanisms of killing:
Fas-FasL mediated and granzyme-mediated apoptosis.
Granzymes A,B,C are:
Serine proteases.
Granzyme B is the only one show to be:
Required for CTL toxicity in vivo.
Perforin is homologous to:
C9 complement protein.
Fas/FasL mediated apoptosis mechanism:
Binding of Fas/FasL recruits procaspace-8 via FADD adaptor and converts it to caspace-8.
In type I cells, caspace-8 directly cleaves caspace-3.
In type II cells, caspace-8 cleaves Bid which causes release of cytochrome C. Cytochrome C combines iwth Apaf-1, activates caspace-9 which activates caspace-3. Caspace-3 activates CAD via degredation of ICAD. Activated CAD causes DN degredation.
How does Mycobacteria evade the IS?
Inhibits phagolysosome fusion.
How does HSV evade the IS?
Inhibits Ag presentation by interfering w/ TAP transporter.
How does CMV evade the IS?
Inhibition of Ag presentation via removal of MHC I from the ER.
How does EBV evade the IS?
Inhibition of Ag presentation by inhibiting proteosomal activity.
How does Pox virus evade the IS?
Inhibition of effector cell activation.
