L6 - Autoimmunity Cause Flashcards
Which two types or cells leaving bone marrow have auto potential
Anergic and clonally ignored b cells
Five some immune tolerance strategies
Privileged sites Central tolerance/negative selection Apoptosis T regs Anergy eg low b7 levels
What are natural autoab seen in both patients and healthy
Naturally auto igm which have low affinitt but are TI
What do anergic auto b cells need
Auto t cell help in order to upregulate and release ab
Graves is an example of high affinity igg. So are auto t cells needed?
Yes to shm and class switch
How do polygenic genetics factor in
Polymorphisms in alleles of grnes to do with immune system eg hla couldn make someone more susceptible
Wht does relative risk mean
How mant time more likely to develop it eg if you have hla b27 allele polymorphism
How do auto ag have effect in genetics
Levels of expresion can make more susceptible
What are the major genes involved
Immune tolerance deficiencies
What 4 genes important in t1d
Hla alleles dq 2 and 8
Ptpn22
Ctla4
Insulin
How does insulin gene have effect
Polymorphisms in the gene promoter can affect levels of mrna for insulin within the thumus ifnkt present more liekly auto reactive
How does ctla4 affect
Usually blcoks b7 so stops t crll activstion. If polymorpgic may not bind as well
What is ptpn22
Phosphatase which stops cd3 signalling in t cells
What are the biggest single gene defects in aids
Aire tf
Fas
Ctla4
Fox p3
How does fas gene defects have impact
Could increase the efficeicy of killing by cd8 eg in type 1 diabetics
How is smokint a risk in ra
Citrullinates peptides which can be recognsied by acpa
Which low viramin level causes me
D
What is cross reactivity
The fsct some self ag look like pathogen proteins pesented on apc. The self ag can be detected by tcr as foreign causing an autoimmune response.
Give rxamples of cross reactivity
Rheumatic fever where instead of strep m protein attach, auto ab attach hesrt tissue proteins
In uc instwad of artacking ecoli proteins attach cllonic proteins
How do self components as prr cause aids
Increased b7 upreg and inflammatort cytokines xauses increase auto t cell activation
Give examples of self ag presenting as pamps or damps
Dna in sle
Ecm frwgments in ra
How can damage to barriers cause aid
Because can affect privileged site ag eg in ms or ra
How can ptms cause aid
No longer detected as self ag in begative selection process eg in ra citrullination
Which disease were commensals found ti pritect males in particular
T1D
Why is cd20 b cell deletion important therapy
They are auto b fells which present to auto t cells. Causes issues like t1d , ra and ms
What is tolerance induction
Adding incerse agonist peptides/ modified peptides which bind and blooc auto t cells
