Week 7 - Immune Regulation (Ben) Flashcards
How dose viral antigen dose affect Th cell response mechanisms?
- Small dose - mostly stimulates Th1 response and IFNy release, leading to incr. antiviral cytotoxicitiy
- Large dose - mostly stimulates Th2 response and IL-4 release, stimulating antiviral antibody response via B cells
How can previous exposure to an inhaled aerosol form of an antigen alter later responses to injected antigen?
- normally, response to antigen injection is fast and intense
- after previous exposure via inhaled aerosol, response intensity decreases
How does MHC expression level affect immune response?
Give an exampe of a situation in which MHC expression is altered.
- surface density of MHC molecules expressed can up/downregulate immune response (direct correlation)
- in pregnancy, trophoblasts express low levels of MHC to decrease maternal immune responses against fetus
What are “professional” vs. “non-professional” APCs?
- Professional - DCs, macrophages, etc.; process antigens + present via MHC-II
- Non-professional - any nucleated cell can process self/tumor antigens + present via MHC-I
How does CD40 play a role in APC activity?
- CD40L on T cells acts as a co-stimulatory molecule when it binds CD40 on APCs
- binding leads to further increase of CD40 and TNF-R expression -> further activation + ROS/NO production
How does PD-L play a role in cancer?
- some tumor cells express PD-L which binds to PD-1 on T cells leading to their apoptosis
- Ab therapy against PD-L to increase T cell activity against tumors is being developed
Describe a “competitive inhibition” mechanism of Ab-mediated immune suppression.
- soluble antibodies may bind soluble antigens, essentially “competing” with B cells’ BCRs for antigen binding
- this leads to B cell suppression + a decreased immune response
Describe “antibody feedback” as a mechanism for Ab-mediated immune suppression.
- On B cell surfaces, Ag-Ab complexes can bind to Fc receptors and cross-link them with nearby BCRs
- Cross-linking leads to negative co-stimulation and a B cell suppression
- (Apparently erythroblastosis fetalis in Rh incompatibility is an example of this, though not sure how)
How can B cells be positively costimulated by an antibody/antigen/complement interaction?
- Soluble antibody may bind another epitope on an antigen that is already bound to a BCR
- C3d then binds Ag-Ab complex
- CR2 on B cell binds this C3d -> very strong positive co-stimulation
What % of T cells are Treg?
What are their surface markers?
- 5-10% of T cells
- Surface Markers: Foxp3 (most important); CD25; CD103 and GITR (Glucocorticoid-inducible TNF-R)
What cytokines do Tregs secrete?
What other effector molecule(s) do they use?
- TGF-beta
- IL-10
- IFN-y
- Other effector: CTLA-4 (constitutive expression on Tregs)
What are 4 suppression mechanisms that Treg cells use?
- Direct contact inhibition of CD4+/CD8+ cells via upregulated negative co-stimulation
- Cytokine secretion (IL-10, TGF-B, IFNy)
- Non-specific Inhibition - “bystander effect” (no clue what this is, sorry)
- Decrease MHC expression on APCs
At what time in the course of an immune reaction do Tregs act to suppress inflammation?
What kind of T cell responses do they inhibit?
- Act on ongoing immune responses after activation; do not inhibit activation, but rather prevent chronic/damaging responses
- Suppress both Th1 and Th2 responses
What surface molecules do NKT cells express?
And how do they develop, with regards to thymic selection processes?
- Express both NK-type receptors and TCRs
- Leave thymus without any selection process (like gamma-delta Ts)
What kind of molecules do iNK cells recognize?
How are these molecules presented?
- recognize lipid/glycolipid antigens via their invariant TCRs
- CD1d on APCs present these antigens
