Exam 2: Dr. Pinchuk T-cell Mediated Immunity 2 Flashcards
What does the third signal for Tc cell activation come from?
The APC in the form of IL-12
The cytokine strongly directs immune responses toward CD8-Tc cell response
What are cytotoxins? Examples?
Protein in the granules of cytotoxic T cells
Perforin, granzymes, and granulysin
What is the action of perforin on target cells?
Aids in delivering contents of granules into the cytoplasm of target cell
What is the action of granzymes on target cells?
Serine proteases, which activate apoptosis once in the cytoplasm if the target cells
What is the action of granulysin on target cells?
It has antimicrobial action and it can induce apoptosis
What cytokines can cytotoxins produce?
IFN-γ
LT-α
TNF-α
Because cytotoxins can produce cytokines, what does that men?
Cytotoxins can activate macrophages
What happens upon specific antigen recognition by cytotoxic T cells to cytotoxins?
The delivery of cytotoxins is aimed directly at the target cell
What is the life cycle of a Tc cell?
Naive CD8 T cell has antien recognition and goes through activation. Then, there is clonal expansion. These all occur in lymphoid organs. After that, the cell differentiates into a memory CD8 T cell or effector CD8 T cell in peripheral tissues.
What are the effector functions of the effector CD8 T cell?
Killing of infected target cells
Macrophage activation
What must T cells see in order to perform effector function?
Self-MHC
What are cytotoxic T cells?
Selective and serial killers of target cells
How does a cytotoxic T cell kill a target cell?
CTL recognizes virus-infected
CTL programs target cell to die
CTL moves to another target cell
First target cell dies
What is apoptotic cell death?
Programmed cell death
What T cells become natural regulatory T cells?
T cells specific for self antigen recognized in the thymus
What T cells become induced regulatory T cells?
T cells specific for self or commensal microbiota antigen recognized in presence of TGF-β in the periphery
What do cytokines produced by Treg cells do?
Inhibit other self-reactive T cells
What makes up regulatory T cells?
FOXP3+ CD4+ CD25+ Tregs
What do regulatory T cells do?
Suppress the proliferation and IL-2 production of naive cells
Could suppress CD4 and CD8 cells
What are the effector mechanisms of Tregs
Surface molecules have a constitutive expression of CTLA-4 which suppresses autoreactive T cells
Cytokines, IL-10, TGF-β are potent immunomodulatory cytokine that have anti-inflammatory function
Cytotoxins, perforin, gransyme A, and Fas-FasL
What does CTLA-4 bind?
B7-1 and B7-2
What is IL-10?
Potent immunomodulatory cytokine
What are functions of IL-10?
Anti-inflammatory*
Down-regulates production of Th1-type cytokines
Decreases the expression of MHC class II and co-stimulatory molecules on DCs (tolerogenic state)*
Regulates the activation and function of mast cells
Regulates cytokine production by eosinophils
Directly suppresses T cell proliferation*
What is the triadic function of TGF-β?
Acts as a SWORD to paralyze cell activation and differentiation to suppress immune response
Acts as a WAND to convert naive T cells into iTregs and Th17 to aid in their combat against inflammation and infection
Acts as a SHIELD to protect and maintain Tregs against apoptosis and destabilization when surrounded by inflammation and consistent stimulation
What is the physiologic role of Th17 cells in the immune system?
Protective function against microbial pathogens
What do Th17 cells represent?
A pro-inflammatory subset that contributes to autoimmunity and tissue damage
What is the non-pathogenic subset of Th17 cells incapable of?
Promoting autoimmune inflammation and might even act anti-inflammatory
What are highly pathogenic Th17 cells from?
Naive precursor cells that occur independently of TGF-β signaling in the presence of IL-23, IL-6, and IL-1β
What is the function of Th17 cells?
To attract neutrophils and monocytes
What are the Th17 and Treg developmental pathways like?
Reciprocally interconnected implicating a balance between both cell types which influences the outcome of the immune response
What does the shared requirement of TGF-β and reciprocal regulation of the transcription factor between Th17 and Tregs provide?
Phenotypic and functional plasticity in both populations allowing differentiated cells to re-differentiate
What kind of effect do Tregs have?
An antagonistic effect, which in failure contributes to the same diseases as excess Th17
What does the Th17/Treg balance provide?
A basis for understanding the immunological mechanisms that induce and regulate autoimmunity and chronic inflammation
When does inflammation occur?
FOXP3 is blocked by IL-6 and IL-21 which causes more Tregs (FOXP3)
When does tolerance occur?
FOXP3 inhibits the expression of RORc causing Tregs and Th17 to be balanced
When are T cells anergic?
In the absence of the co-stimulatory signal
What are the immunologically privileged sites?
Brain Eye Testis Uterus (fetus) Hamster cheek pouch
What is the most import form of tolerance?
Non-reactivity to self antigens
What is it called when an antigen induces tolerance?
Tolerogen
Describe cyctotoxic T cells
CD8 T cells
Kill infected cells by inducing apoptosis
What is Th17 involved with?
Inflammation
What do Tregs do?`
Either kill DCs or make them tolerogenic
What are the mechanisms of central tolerance?
Negative selection in the thymus
Autoimmune regulator
What are mechanisms of peripheral tolerance?
Absence of co-stimulatory signal
Immunological privileged sites
Regulatory T cells
