Rheumatic Fever Flashcards
Central tolerance
developing lymphocytes are negatively selected for in lymphoid organs
Peripheral tolerance
mature lymphocyte in the periphery
T reg function, anergy, cell death
Molecular mimicry
activation of cross reactive Th1 cells that recognize both microbial and self epitopes
release of cytokes—>M0
activates B cells…..
Epitope spreading
damage to self tissue which releases self Ags
further activates lymphocytes
Leading to more self Ags being release, processed and presented
Bystander activation
Non-specific activation of self reactive lymphocytes
inflammation, C’, T cells infiltrate
Cryptic antigens
differential processing of self Ags by DCs
IFNg activates DCs—>inc uptake and processing of self AGs
activates even more self-reactive lymphocytes
Activate lymphocytes against self
○ Taken up in such a way that they are not processed in the thymus or Bone marrow and are presented to lymphocytes in a novel way
Causes them to be recognized as a foreign antigen
Type IV HS
Fertile field hypothesis
Infection with the right virus at the right time creates a transient, localized fertile field. The autoreactive cells generated can either crossreact with viral antigens (molecular mimicry) or can react only with autoantigens (bystander activation)
**for a given age, gender, and immune hx if a person is exposed to a certain pathogen, they could have an aberrant response that leads to a.i.
M protein
Strain specific fragments that act as superantigens—>non-specific expansion of immune cells
ARF
Acute Rheumatic fever
inflammatory disease of the CT (heart joints, subcut tissues)
high prevalence in 5-15 y.o.
present with polyarthritis, symmetrical large joints, mumr (from valve incompetence), fever
Pathogenesis of ARF
1) Molecular mimicry due to cross reactive T cells
2) Bystander and epitope spreading (IFNg and TH1 response)
3) Bystander, cryptic Ags, and epitope spreading
