Immunology 3 Flashcards
What B cell markers and when?
CD 34 from Pro-B cell to large pre-B cell
CD10 from pro-b cell to small Pre-B cell
CD19 from pro-B cell to mature B cell
CD 20 only later, from large pre-B ell to mature B cell
Rag1,2, and TdT are downregulated on successful rearrangement
Role of BAFF (ie target of belimumab in lupus)
Promotes survival of naive B cells
During Ag activation upregulates TLR expression, promotes Ig Class switching, induces memory B cell differentiation to plasma cells.
Do memory B cells need T cell help to become activated?
minimal if any
What are T cells?
Lymphocytes generated in the thymus
What is the role of AIRE?
These are genes that control expression of tissue specific antigens in the medullary epithelial cells of the thymus
- so that there can be deletion of high affinity T cells
- induction of thymic regulatory T cells
What is APECED? AKA autoimmune polyendocrinopathy type 1
Autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy.
- failure to express specific T cell Ag in thymus due to AIRE mutation
- no deletion of self reactive T cells
- autoimmunity
Get Autoimmune hypoparathyroidism, Addisons, chronic mucocutaneous candidiasis
Candida supression relies on Th17 response
What is foxp3?
master regulator of T reg cells
IPEX is a disorder when foxP3 is defective
Name a B7 blocker and an anti-CTLA4 molecule>
B7 blocker is Abatacept- used in RA to downreg immune response
Anti CTLA4 is ipilimumab in melanoma, prostate ca- stimulates immune response
Which is the major CK for generation and maintenance of Tregs?
IL-2
How do superantigens trigger things off?
Link the Vbeta chain of TCR with the MHC II outside the peptide groove (ie bridge the first signal receptors)
eg TSS, staph enterotoxins
Describe how perforin granzmes work?
CD8 T cells recognise virus infected cell Perforins punch holes Granzymes get in through holes Induse caspase enzymes in cell targeted apoptosis
Fas pathway to kill cells- how does it work?
FasL on T cell
binds
Fas on target cell
Caspases activated
Apoptosis and cleavage of viral genes
Non cytotoxic innaate lymphoid cells do what?
Promote tolerance to intestinal microbiota
HLA-DM role?
Describe MHC1 and 2 methods of Ag presentation
In MHC2 antigen presentation, catalyses ripping out of CLIP so that the Ag can bind and be presented on cell surface
MHC1: Proteasomes break down whatever is in the cytoplasm. In the ER, bits of peptide are stuck on to MHC and then vesicles are shuttled to the surface
MHC2: after endocytosis, lysosomes break down contents. Then garbage trucks fuse with vesicles from golgi containing MHC2 (inhibited by clip)- clip displaced and Ag gets in before whole thing sjuttled to surface of cell.
What does dendritic cell stain with?
CD1
What do plasmacytoid dendritic cells do?
release loads of IFN in response to viral infection
Not so important for antigent presentation and activation of T cells
DIfference between humanised and chimeric monoclonals
On Chimeric the V domain is mouse the C domain is human eg ritux inflix “xi”
On Humanised both human with just the cap of variable (AB site) mouse “zu”
Fully human is just “u”
Why would you make a monoclonal IgG1 or IgG4
IgG1 will maximise phago or complement related properties eg ritux
IgG4 will minimise this eg inflix
TNF alpha is a major cause of inflammation in what autoimmune disease?
RA
Discovered by Australian
What is adalimumab?
What is abatacept?
Adalimumab is TNF alpha blocker
Abatacept is CTLA4 mimic that binds B7
In RA very similar outcomes except infusion site reaction more on adalimumab
When is IL-6 blocker used?
RA
JIA
not Ank spond
Tocilizumab
What is the problem in familial mediterranean fever?
IL-1 beta overproduction
Block with anakinra
What are two fancy new drugs in psoriasis?
Secukinumab- blocks IL-17A
Ustekinumab0 IL12/23 monoclonal binds to the p40 subunit
Ipi vs nivol?
Fewer autoimmune side effects with nivol than ipi
What is the Ag in pemphigus (autoimmune)
desmoglein-3 and desmoglein-1
goodpastures target
alpha 3 chain of type 4 collagen
HLA DR2 effect on DM1
protective
Drug induced lupus (4)
Minocycline
TNF blcokers
procainamide
hydralazine
Which TNFs are worse for TB?
Inflix
Adalim
worse than etanercept
Why is TNF important in TB?
IFN needed to maintain an ordered granuloma that sequesters the TB organisms
What happens in NO dependent killing?
bacteria binds macrophages
produces TNF alpha
this upregulates iNOs
Release of NO which is toxic to infected cells in the vicinity of the macrophage
TLR2 recognises
Gram pos eg lipoteichoic acid
TLR4 recognises
Gram neg eg lipopolysacharide
Mutations in this also predispose to severe RSV
NK cells look like…
large granular lymphocytes
