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
What are 3 cytokines which iNK cells secrete upon activation?
- GM-CSF
- IL-4
- IFN-y
What kind of surface molecules do Breg cells have?
- TLRs - toll-like Rs
- BCR
- B7 - CD28 / CTLA-4 ligand
- CD40 - stimulated by CD40L from T cells
What important anti-inflammatory cytokine do Bregs secrete?
What does it do?
- IL-10
- suppresses CD4+ T cells, especially their differentiation into Th1 type CD4+ cells
- stimulates differentiation into adaptive Tregs
- (may also suppress Th17 differentiation)
What is linkage disequilibrium?
- non-random association of alleles at different loci
- 2 loci are at linkage disequilibrium if their alleles occur together either more or less often than would be expected of 2 independent + randomly associated alleles
Name 3 ways that genetic polymorphism can result in varied immune responses between individuals.
- MHC polymorphism - means some people respond better/worse to certain infections (or rather are “susceptible”/”resistant”)
- Cytokine/Chemokine Receptor Polymorphism - slight differences in receptors –> diff. responses
- Non-MHC genes - other genes such as complement regulatory factors + macrophage regulation genes
What is an idiotope?
And idiotype?
- idiotope - variable determinants in an antibody or TCR (can be in the antigen-binding region or not, but are always variable)
- idiotype - the whole set of an antibody molecules individual idiotopes
What are “public” and “private” idiotopes?
- public - found on other cells
- private - unique for given cell or cell clone
What is idiotypic regulation?
(may also be called Jerne’s Idiotypic Network, after the name of the scientist who discovered it)
- a form of immune regulation in which anti-idiotypic antibodies bind to the idiotopes of other antibodies and block their activity
- can have multiple layers of anti-anti-idiotypic + anti-anti-anti-idiotypic etc. antibodies which inhibit each other + thus have inhibiting/dis-inhibiting effects leading to a gradual oscillatory damping of immune responses
In general, what element of immune responses do Th1 cells stimulate? And Th2 cells?
And what are their main mutually inhibiting cytokines?
- Th1 –> cellular immunity; inhibits Th2 response via IFN-y
- Th2 –> humoral immunity; inhibits Th1 response via IL-4
How can anti-idiotypic antibodies be used therapeutically?
- anti-idiotypic Abs against BCRs can treat B cell lymphomas
What two main hormones play a role in neuroendocrine immune modulation?
How? What is their general effect?
- Norepinephrine - immunosuppressive, sympathetic innervation in most lymphoid tissue, many immune cells express beta2 adrenergic receptors
- Cortisol - immunosuppressive; CNS stimulation of adrenal production –> immune regulation
What two cytokines increase adrenal corticosteroid production?
IL-1 and IL-6
What are microvesicles?
What is their main role in immunity?
How do their immunological effects differ based on the cell they come from?
- small vesicles containing proteins, metabolites, and miRNAs sent between cells
- MHC-II-expressing vesicles are sent by DCs, possibly with roles in antigen presentation
- if from immature DCs = immunosuppresive; if from mature = stimulatory
