Week 7 - Immune Regulation (Ben) Flashcards Preview

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Flashcards in Week 7 - Immune Regulation (Ben) Deck (28):

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 MarkersFoxp3 (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 effectorCTLA-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.

  1. MHC polymorphism - means some people respond better/worse to certain infections (or rather are "susceptible"/"resistant")
  2. Cytokine/Chemokine Receptor Polymorphism - slight differences in receptors --> diff. responses
  3. 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 proteinsmetabolites, 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