CMB2004/L07 Acquired Immune Response Flashcards
Why is immunological tolerance needed? (3)
Random generation of repertoire of BCR and TCR
Many self-reactive specificities produced
If no tolerance, autoreactivity would lead to serious pathology
Random TCR (a/B) gene rearrangement leads to T cells expressing TCR that… (3)
Fail to recognise self-MHC (apoptosis)
Recognise self-MHC + peptide from Ag present in thymus (expanded by positive selection, eliminated by negative selection)
Recognise self-MHC + any other peptide not present in thymus (survive)
Describe positive then negative selection of T cells. (3)
T cells with low affinity TCR eliminated during positive selection
T cells binding MHC too well eliminated by negative selection
Leaves population with TCRs with medium affinity for self-MHC
Describe autoimmune regulator protein (AIRE).
Transcription factor
Role in tolerance induction
Allows expression of many tissue-specific Ag (TSA) in thymus (+ve/-ve selection of T cells recognising these Ag)
Explain how selection of B cells is different to that of T cells.
B cells get a second chance to re-arrange self-reactive BCR (receptor editing via a new light chain)
Autoreactive B cells still negatively selected (in bone marrow)
Describe B cell tolerance.
Random Ig gene rearrangement leads to autoreactive BCRs
Autoreactive B cells negatively selected in bone marrow OR
Rearrange another light chain (receptor editing)
What is an anergic B cell?
B cells that bind self-antigen
Describe B cell tolerance via anergy.
When immature B cell BCR encounters Ag in bone marrow that isn’t multivalent, downregulate BCR and leave bone marrow as unresponsive (anergic)
Describe how T cells can become anergic.
Unstimulated macrophages do not deliver co-stimulatory signal to T cells recognising nonbacterial antigen
(Naive T cell receives signal 1 but no signal 2)
Naive T cell becomes anergic/unresponsive
Describe immunological ignorance.
Many Ag not presented at sufficient levels to activate T cells
Describe privileged sites.
Ag sequestered from immune system (suppressive cytokines also prevalent)
Describe how B cell responses can be T cell-dependent.
If Ag-specific T cells are absent/tolerant, no help for B cells is available
No antibody response
Describe the role of T(reg) (CD4+).
Suppresses immune response
Describe the difference between n(atural)T(reg)) and iT(reg).
Arise in thymus from T cells with high affinity TCR for self Ag (nT(reg))
Induced in periphery (iT(reg))
Which cytokines released by T(reg) inhibit self-reactive T cells? (2)
IL-10
TGF-B
What other cell can secrete IL-10 to prevent autoimmunity?
B cells (B(reg/10))
Give 3 reasons for regulation of immune response.
Ensure responses continue only for as long as needed
Minimalise collateral (tissue) damage
Ensure responses are qualitatively appropriate
What is the function of CD4+ T(H)1 cells?
Activation of macrophages, NK cells, cytotoxic T cells
Secrete IFN-y, GMCSF, TNF-a
Express CD40L
What is the function of CD4+ T(H)2 cells?
Promote responses mediated by eosinophils and mast cells
Role in antibody responses, especially IgE
What is the function of CD4+ T(H)17 cells?
Promote responses against fungi by recruiting neutrophils early
Secrete IL-17
What is the function of CD4+ T(FH) cells?
Found in GC to help B cells
Specialised T(H)
How can CD4+ T(H)1 kill chronically infected macrophages? (3)
Fas ligand/Fas induced apoptosis
Released bacteria destroyed by healthy macrophage
Other cells can kill the pathogens
Give 2 types of CD4+ T(reg) cells.
CD4+CD25+
Some CD8+ T cells have T(reg) activity
What is the function of IL-10?
Inhibits APC function
