Manipulation of Immune Response Flashcards
How can MHCs be polymporphic?
- MHC
- type of response based on class 1 or class 2 presentation
- if doesnt display Ag, No response
- if the antigen is presented, the polymorphic MHC generates multiple unique antigen binding grooves that guarantee almost infinite variety on how the peptide is displayed by the DC
- MHC in some ways determines suscesibitlity to diabetes
How can TLRs be polymorphic?
- TLR
- activation determines type and intensity of response
- DNA sensing TLR-if this is hyperstimulated this can be associated to systemic lupus
How can cytokine and cytokine receptors be polymorphic?
- Cytokines and cytokine receptor
- less or more production - patients who produce IL 10-they should do better after transplant-becuase they suppress graft vs host
- mutations of IL 10 are associated with inflammatory bowel disease (Low0
- specific tlrs have increased risk of fungal infection
Through what cells do bacterial populations in the gut dictate how we respond to various antigens by manipulating our T regs?
DC
What do you need to know to make a vaccine?
- need to know the pathogen
- what type of response it needs:
- TMMI for intracellular infections
- IL 17 for fungal infections
- B cell for toxins and organisms that resist phagocytosis
- T and B for viruses - need to generate memory cells in all cases
What does the adjuvant do?
- *Stimulates TLRs
- depots for prolonged antigen exposure by slow release
- induce innate immunity and prime APC by activating PRR like TLRs
- Alum is the most common adjuvant for TH2 stimulation
- others are available for Th1
Do all tumor cells look different than regular cells?
no
How can the immune system react to tumor cells when they can be detected?
- presenting it in class 1-NK cells see it
- CD 8 cells - Tumor cell is producing proteins that are expressed on the surface of the cell
- tumor antigens in peripheral blood
- B cell reacts
- Th2
- antibodies bind
- kill with complement
- kill with NK cells with Fc receptors - APC–>Th1–>Mac–>kill
How do tumors fight off immune responses?
- Tumor cells elaborate immunosupressive cytokines
- TGF B
- IL 10 - Turn cells trying to convert a tumor into Tregs–>these cells are protecting the tumor now
What is CCL21?
tumors secrete it creating a suppressive envvironmet
- converts cells to tregs
- and fibroblast to secrete that too
What response is not blocked by tumor?
NK cells only if tumor is presenting in MHC 1
- B cells blocked
- CD 4 blocked
- CD 8 blocked
What does PD1 ligand-program death (paralyzed) do?
when it is upregulated, it binds PD-1 receptor on T-cells paralyzes T cells
What is immune checkpoint therapy?
- anti CTLA4
CD 8 cells migrate into the tumor - anti PD-1
CD 8 can now attack
Anti-TNF targeted manipulation strategies based on pathogenesis
rheumatoid arthritis
