lecture 14 Flashcards
(27 cards)
how can activated T cells become quiescent?
inhbitory receptor (CTLA4 and PD1)
immune inhibitory cytokines– IL10 and TGF Beta
activation induced cell death
active suppression by reg T cells
what is granuloma formation?
how can it be developed?
activated macrophages fail to clear the infection—causing continuous production of cytokines
local tissues will be modified
when intracellular bacterial infections are partially cleared, leads to granuloma formation
what are mechanisms of down regulating immune responses?
via attrition ( removal of antibody, apoptosis of T and B cells in absences of antigen stimulation)
inhibitory co stimulation
anergy— state of immune unresponsiveness
regulatory T cells & cytokines
what are inhibitory receptors and how do they work??
expressed when T cells are activated
bind to ligand ( CTLA4 w B7, PD1 w/ PDL1) and deliver negative signaling —leading to inactivation or T cell death
what is central vs peripheral tolerance?
central—bone marrow or thymus
peripheral— secondary lymphoid organs
what are antigens tolerized?
self antigens are tolerized centrally
self antigens not expressed in
bond marrow or thymus, are tolerized peripherally
what are mechanisms of tolerization?
central of T cells includes negative selection in the thymus
peripheral: induced when naive T cells are activated in the absence of co stimulation
positive selection of reg T cells in thymus also contributes to tolerance
what are reg T cells?
antigen specific T cells that suppress immune system rather than activate other immune cells
how to reg T cells suppress the immune system?
how are they identified?
secretion of regulatory cytokines
OR expression of regulatory co stimulatory molecules to directly suppress immune cells , inhibit immune cells interactions or induce anergy
express FoxP3 Tf
what happens with a Foxp3 deficiecy?
no Treg
autoimmune features
early mortality
IPEX
what happens with AIRE deficiency?
failure of negative selection of T cells in the thymus
autoimmune
APECED
why are all self reactive lymphocytes not elimated in the thymus of bone marrow?
central tolerance eliminates those with receptors displaying affinity for self antigens
self reactive may escape eliminate in the primary lymphoid organs if the self antigen is not encountered
OR if the affinity for the self antigen is less than what is needed to trigger apoptosis
how are self reactive lymphocytes prevents from harming the host??
eliminated by peripheral tolerance
-involves: apoptosis induction, induction of anergy (non responsiveness state), indications of antigen- specific population of regulatory T cells
why is tolerance critical to the normal functioning of the immune system?
necessary tot remove or regulate self reactive B and T lymphocytes that escape negative selection during development
-w/o tolerance ( unresponsive to self antigen), reactions can arise against self antigens, resulting in autoimmune diseases
examples of human disorders where there has been a breakdown in self tolerance?
SLE, lupus, RA, diabetes
what is anergy?
how does it occur?
antigen specific T or B cells that it becomes unable to respond tot its antigen
clone remains present but is unable to induce effector response
mechanisms: absence of co stimulation or absence of T cell help
what do T reg express in thymus and in the periphery?
what does Treg produce to suppress immune responses?
thymus: Foxp3, naturally occurring– prevent autoimmune
periphery: inducible treg, express FOxp3–suppress antigent specific
TGFB
what are the stage of CD8 T cell response?
priming phase:
active by DC, antiviral effector T cells repspone, to promote humoral immune response
–goes from naive to effector
resolution:
Treg mediations of environment, T cell goes quiet thru CTLA4
memory:
continued prevention, those that don’t die become memory
how does CTLA4 and PD1 work on T cells?
CTLA binds B7 at a higher affinity that it does to CD28– inhibit signals
PD1 interact w/ PDL1– delivery inhibitory signals
-CTLA4 and PD1 has immunotrecptor tyrosine based inhibit motif
what are key characteristics of B memory immune cells?
differentiated into plasma cells faster than from naive B cells –better secondary immune response
** independent of antigen or stimulation***
can survive for decades
have already undergone class switching, so express a lot of Ig classes
*foundation for booster shots
what is important for T memory cells??
IL7 and IL15
indepentdent of antigen
why do B memory cells have higher production of antibodies??
due to somatic hypermutions
how does mRNA vaccine work?
gives you intrusions to make the Spike protein
immune recognizes, then produces anti spike antibodies
mRNA does not enter the nucleus of the cell
what are the fates of activated CD8 T cells ?
functional memory– appropriate and inflammation
tolerance— tolerogenic context
exhaustion— during chronic infection
