Lymphocyte regulation Flashcards
(15 cards)
How can lymphocytes be regulated
tolerance - see it a lot so immune response decrease
removal of infectious agent - no signal for lymphocytes - apoptosis
Th release cytokines that stop it
T cell exhaustion
What is tolerance
Tolerance limits response to persisting antigens (immunosuppressants/allergy immunotherapy) specific unresponsiveness to an antigen that is induced by exposure of lymphocytes to that antigen. Active
• Central tolerance – destroy T/B cells before enter circulation – b receptors edited and T cells may become regulatory
o If B cell recognise self – activate apoptosis of b cell in bone marrow
o T – bind MHC…
• Peripheral tolerance – in circulation
What is the function of the autoimmune regulator (AIRE)
- Transcription factor – thymic expression of genes from peripheral tissues – self tolerance
- Mutations in AIRE – autoimmune polyendocrinopathy syndrome type 1
- Specific window of types of autoimmunity
- Good Ab against flu – immune response against virus, normally these T cells are destroyed because they’re similar to self antigens
How does anergy affect regulation
less likely to be stimulated with co-stimulation if been exposed to antigen without costimulatory proteins previously. Need both MCH peptide combination and co-stimulatory factor
What is ignorance
antigen level too low to be detected – immunologically privileged site. Risk of response is greater than that of infection/ compartmentalised from DC
Antigen induced cell death
influenced by initial T cell activation events – induction of Fas ligand – CD8
What is regulation
- T regulatory cells (Treg)
- Mutation in FoxP3 – IPEX (Immune dysregulation, Polyendocrinopathy, enteropathy, X-linked syndrome)
- Treg – CD4, FoxP3, high IL2 low IL7 receptors
- Secrete immune suppressive cytokines IL 10
- Natural – thymus (self recognition)
- Inducible – from mature CD4 – limit collateral damage
When is regulation important
pregnancy - parasite
Importance of regulation
avoid collateral damage
allergy - things not infections
autoimmune disease - attack own cells
What is autoimmunity
- Immune response against self antigen
- Organ specific/systemic
- Susceptibility genes/env trigger
- Chronic and self-perpetuating
- Failure to get rid of self- reactive cells
- Inflammation
- Immune response against self/microbial antigens
- T cells and Ab
- RA IBD MS PSORIASIS
What is allergy
- Response to non-infectious antigens
- IgE and mast cells – acute anaphylactic shock
- T cells – delayed type hypersensitivity
what are hypercytokinema and sepsis
- Too much immune response
- Bacteria in blood stream/failure to regulate response
- Cytokine storm
- +ve feedback
What is the cross regulation of cytokines
All have many effects on different cells
influence outcome
Focus immune response on 1 Th subset – one is dominant and shuts down the rest
The way T cells provide instructions for the rest of the immune system
what is the function of IL-10
- Pleiotropic
- Downreg macrophages
- Antiinf
- Viral mimics – turn off immune system
what is TB cell communication `
- T cell make CD40 ligand and B cell have receptor
- B licences T,. T licences B
- Cytokine from T changes the B cell output ie there is a different constant region - Ig class switch