Flashcards in T Cell Mediated Immunity Deck (27):
What is anergy?
nonresponsiveness to Ag under optimal conditions of stimulation
What is CTLA-4?
high affinity B7 receptor critical for shutting of T cell response
What are granzymes? What cells are they secreted by?
serine proteases in cytotoxic T cells involved in inducing apoptosis in target cells
What is produced by activated naive T cells to further proliferation and differentiation?
Why are integrins important for T cell development?
They strengthen the adhesion with APCS, and T cells must adhere to APC for 6-12 hours to be activated.
What controls routes of T cell migration?
selectins, integrins, chemokines
What does T cell initially bind through? Is it high or low affinity? Does binding induce change?
LFA-1 on T cell binds with low affinity to ICAM-1 on APC. Binding of T cell signals conformational change of LFA-1 to increase affinity and prolong contact
What are the two requirements for activating naive T cells?
Ag recognition and costimulation by substance released during innate immune response to microbe, which indicates that the microbe is immunogenic as well as antigenic
How do adjuvants work?
Bacteria (immunogenic) and nonbacterial (nonimmunogenic) protein presented together. This stimulates the APC to deliver costimulation and T cells recognize the nonbacterial Ag, proliferate and differentitate specific for nonbacterial protein
How do you get peripheral tolerance?
Induce anergy in cells by presenting Ag without costimulatory CD28 signals.
When is B7-2 the major ligand for CD28? B7-1?
B7-2 expression is constitutive and induced faster upon stimulation, so initially is the major ligand. B7-1 expressed later and sustains T-cell activation.
What T cells don't express CD28?
CD8 T cells, gamma-delta T cells, memory and effector T cells
When do you not require costimulation?
If the signal is strong enough, CD28 costimulation isn't needed (i.e. for some high avidity responses to viruses)
Which Thelper cell is involved in CMI? What is its effector action?
Th1 cell, activates infected macrophages
Which Thelper cell is involved in humoral immunity? What is its effector action?
Th2 cell, activates specific B cell to make Ab
Th1 cell, induces B cells to produce opsonizing Ab
What cytokines do activated Th1 cells release?
IFNgamma and CD40L- activates macrophage
FasL or TNFb- kills chronically infected cells so activated macrophages can phagocytose bacteria
IL-2- induces Tcell proliferation
IL3 and GM-CSF- induces macrophage differentiation in BM
TNFa and TNFb- activates epithelium to let new macrophages get to site of infection
CCL2- chemoattractant for macrophages
What does Th2 release that inhibits Th1 response?
What does Th1 release that inhibits Th2 response?
What do CD8 T cells use as effector molecules?
perforin, granzymes, granulysin, Fas ligand, IFN gamma, TNFa, and TNFb
How do CD4 T cells help CD8 T cells?
IL-2 produced by Th1 cells
What are the 3 killing mechanisms of CTLs?
1. granule exocytosis (granzymes, perforin- fast killing)
2. cell surface TNF-family effector molecules expressed (slow killing)
3. Secretion of soluble toxic cytokines (TNF, IFN- slow killing)
How does granzyme B act?
-Cleaves procaspase to activate caspase, which causes DNA fragmentation
-mitochondrial damage causes cytochrome C release and apoptosis
Why don't release lytic granules kill CTL?
-Cathepsin B in the vesicle fuses with the membrane to protect CTL after degranulation/exocytosis
-Proteinase inhibitor 9 (serpin) that inhibits granzyme B is expressed by CTL
What signals production of CTLA-4?
Crosslinking of CD28 delivers costimulatory signal for activation of naive T cells and induces CTLA-4 expression
What does a CTLA-4 deficiency cause?
death, can't shut off immune response and lymphocyte build up drowns mice
Name 4 mechanisms to shut off immune response.
1. eliminate Ag
2. eliminate other signals (APCs)
3. IL-2/IL-2 receptor signals via Tregs
4. kill with immunoregulatory cells (Fas-FasL)