Immune system regulation & Immunotherapy - 1 Flashcards
1
Q
goals of an immune system
A
- recognise invader
- generate response sufficient to protect
- prompt effective down regulation after resolution of danger
- elminate effector cells so response doesn’t persist
- keep memore for future
2
Q
factors influencing outcome of immune response
A
- antigens
- antibodies
- cytokines
- APC
- T cells
- MHC
3
Q
T-reg cells
A
- negatively regulate ( i.e. prevent exaggerated, chronic responses )
- develop mainly in thymus as CD4+CD25+ cells
- in periphery from classic CD4+CD25+ –> adaptive T reg cells
- their development is induced in response to tigger
- not naturally present
4
Q
what receptors do natural CD25+ T-reg cells express?
A
- CD25 receptor
- CTLA-4 receptor - inhibits T cell responses
5
Q
what is Foxp3?
A
- expressed by CD25+ cells
- transcription factor which promotes T cell differentiation into T-reg cells
6
Q
majority of CD25+ cells are …
A
CD4+ cells that suppress different cell types like :
* CD4+
* CD8+
* B cells
* APC
7
Q
CD+25 T-regs play a key role in …
A
establishing immune homeostasis
8
Q
is suppression mediated by T-reg cells antigen dependent?
A
- to acquire suppressive function, T-reg cells needs to be activated through its TCR
- TCR needs to interact with an Ag to activate T-reg
- so it is Ag-dependent
- once activated - T-reg suppresses T cells with Ag specificities
- effector activity ( suppressive function ) not Ag-specific but Ag-dependent
9
Q
what are immunosuppressive cytokines secreted by T-regs?
A
TGF-beta + IL-10
10
Q
function of TGF-beta?
A
- blocks activation of T cells through inhibition of co-stimulatory pathways
- induces CD4+ cells to differentiate to T-regs
11
Q
function of IL-10
A
- inhibits production of pro-inflammatory cytokines
- inhibits expression of MHC class II on APC & blocks macrophage function —-> preventing Ag presentation
12
Q
what happens when T-reg secretes IL-35?
A
inhibits proliferation of T cells & induces CD4+ cells to differentiate into T-reg cells
13
Q
does suppression need CTLA-4?
A
- CTLA-4 is a receptor expressed by CD4+ cells
- binds CD80/CD86 lignads on APC + inhibits T cell function
- generates inhibitory signals directly inhibit CD28 expression
- enhances Fox3p expression
14
Q
does suppression involve APC?
A
- T-reg cells directly bind APC & down-regulate expression of co stimulatory ligands CD80/CD86
- inhibit dendritic cell maturation & activation by inhibiting effector Th cells —-> Ag presentation inhibited
- induce phenotypic changes in macrophages
- inhibiting matrix metalloproteinase production by macrophages —-> less tissue destruction and less inflammation
