Assignment 9 - use pictures too! Flashcards
where does a primary immune response take place?
secondary lymphoid tissue
what is the main function of effector CD4+ T cells?
secretion of cytokines
when are T cells considered naive (Thp)?
when they survive the screening process in the thymus
*note they are unable to perform their biological function without a differentiation stage
where does the antigen-induced differentiation stage occur for naive T cells?
outside of the thymus
Blood –> spleen
Mucosaltissue –>MALT–>laminapropria
Lymph–>lymphnode–>whitepulp
induced by high avidity interaction with foreign peptide/class II MHC in the presence of costimulatory signals
what 2 things can T cells differentiate into?
memory cells
apoptosis
what does the subset of Thp cell activation depend on
the cytokines in the local environment
what does the activation of T cells require?
the antigen to be displayed on the surface of APC in association with class II MHC
what is the most efficient APC
dendritic cell
why is the dendritic cells the most efficient APC
because it expresses both class II MHC and various costimulatory molecules (whose counter products are present on the T cell)
what happens when a T cells interacts with a peptide/class II MHC complex in the absence of costimulatory interactions
the T cell becomes unresponsive = anergic
what are the interactions that take place between a T cell and APC
- class II MHC peptide ——– TCR
- class II MHC ——————-CD4
- ICAM(1,2,3)———————LFA-1 (CD11a/CD18)
- CD40—————————-CD40L (CD154)
- LFA-3—————————-CD2
- CD80—————————–CD28
- CD86—————————–CD28
*all enhance the avidity of peptide/MHC interactions with TCR
what occurs when class II MHC peptide and TCR interact?
Thp express IL-2 receptors and secrete cytokine, IL-2
functions in autocrine + paracrine
what does the interaction of IL-2 with IL-2 receptor induce?
clonal expansion of antigen stimulated T cells = increasing the number of T cells with specificity uniquely recognizing the class II MHC peptide complex that induced the initial differentiation
what is hte role of the CD28 and CD80/86 interaction
to stabilize mRNA for IL-2
if this doesn’t occur = anergic T cell
where are the two forms of B7 (CD80 = CD86/B7-1 and B7-2) expressed and induced
expressed - dendritic cells + peritoneal macrophages
induced - activated B cells, monocytes, Langerhans cells
antigen induced differentiation of Thp proceeds via a _____ intermediate to either a ___ or ___ subset
Th0
Th1
Th2
*defined by the cytokines they secrete
what cytokines do Th0 cells secrete?
IL-4
IL-2
IFNgamma
common to both subsets
if IFNgamma is high, what subset predominates?
Th1
if IL-4 is high, what subset predominates
Th2
what is hte source of IL-4 before differentiation of Thp to Th2
Mast cells
basophils
other non T cells
transiently—Th0
provide in early phase of response
mast cell stimulation –> Th2 development
what produces IFNgamma?
Th0 cells
IL-12 activated NK cells
what cytokines have been shown to enhance the role of IL-12 on NK cell production IFNgamma production
IL-15
IL-18
what cells secrete IL-12
activated dendritic cells
macrophages
influence of IL-12 on development may be indirect
what are type 1 cytokines
IL-2
TNF
IFNg
what are type 2 cytokines
IL-4 IL-5 IL-6 IL-10 TGFbeta IL-13
what is the role of type 1 cytokines
support immune responses in which macrophages, NK cells and CD8+ T cells are effectors
resposnbile for delayed type hypersensitivity responses that are manifestations of activated memory CD4+ Th1 cells
what is the role of type 2 cytokiens
support B cell induced activation
support antigen induced B cell differentiation to plasma cells
support isotype switching to IgG1 and IgE
humoral immunity
what is required for isotype switching to IgE?
IL-4
in general, isotype swithcing requires the contribution of both _____ and ___ cytokines
type 1 and type 2
what is hte role of IL-10
key role in down regulation of Th1 (cells/cytokines) – this occurs via inhibition of IL-12 secretion by APC
what are hte mechanisms that control T cell activation
- loss of T cell stimulation because the infectious agent has been eliminated so class II MHC peptide are no longer being presented to T cells
- reciprocal regulation of cytokine secretion by Th1 and Th2 cells
- CTLA-2/CD152 interaction
- CD200-CD200R interaction
- apoptosis
- regulatory T cells (Tregs)
what are the T cells that leave the thymus?
- CD4+ naïve cell (Thp)
- Precytotoxic CD8+ T cells (pCTL)
what does an active Thp express? What does it secrete and what does the secretion lead to? what does it stimulate the dendritic cell to secrete? what does this do?
IL-2R
secretion IL-2 - induces expansion of Th0 clones form antigen stimulated T-cells
secretion of IL-12 from dendritic cell - activates NK cell to secrete IFN gamma
what cytokines are secreted by Th0 clones?
IFNy –> Th1 cells (type 1 cytokines)
IL-2 –> makes more Th0 clones
IL-4 -> Th2 cells (type 2 cytokines)
what triggers the secretion of IL-4?
mast cell
how does T cell regulation occur in Th1?
CD80/CD86 —CD152(CTLA-4) = T cell downreg
CD80/CD86 —CD28 = T cell activation
what is the role of IFNy?
its a Th1 cytokine that shuts off Th2
what cytokines turn off Th1?
IL-10
IL-4
both are Th2 cytokines
what is the role of IL-10
inhibits secretion of IL-12 by APC
downstream inhibits Th1 and prevents NK cells from producing IFNy
how is pCTL (precytotoxic CD8+ T cell) activated
interaction with:
- CD4+ T cell derived IL-2 cytokine
- Target cell expressing antigen + class I MHC
- CD2—LFA3
- LFA1—ICAM (1,2,3)
- CD8 binds to class I MHC at separate site from where it binds to TCR
what is the difference between the differentiation stage environments between CD4+ and CD8+ T cells
CD4+ need secondary lymphoid tissue
CD8+ it can do it anywhere, site of infection etc.
what occurs in the progression from pCTL to CTL
- IL-2 expression
- preCTL detaches from target cell expressing antigen
- differentiation takes about 1 week
what occurs when there is a delivery of lethal hit
-mature CTL (CD8+) conjugates with target cell
-conjugate formation triggers locatization of lytic granules to membrane where two cells are attached o granules are released outward toward target cell
-polarized release of granules ensures specificity of killing target cell and not self
-death caused by osmotic lysis or apoptosis
-CTL detaches and continues its function of immunological surveillance
-as elimination of virally infected cells occurs the antigenic stimulus for specific CD8+Tcells decrease.
-CTL clones that are generated with TCRs specific for the antigen will die others will become dormant
(memory cells)
-Memory cells will become activated immediately in the event that the antigen reappears
-These cells require less costimulation than for the primary response
how long does it take for pCTL–> CTL
1 week
what does the interaction between CD200 and CD200R lead to?
suppression of T cell mediated immune response - immunosupressent
CD200 is expressed on what cells?
T cells
B cells
Dendritic cells
CD200R is expressed on what
myeloid lineage cells
and some T cells
