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?
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?
What kind of surface molecules do Breg cells have?
TLRs - toll-like Rs
B7 - CD28 / CTLA-4 ligand
CD40 - stimulated by CD40L from T cells
What important anti-inflammatory cytokine do Bregs secrete?
What does it do?
- 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?
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?