Immunopathology III Flashcards
(34 cards)
What do GWAS suggest as genes implicated in autoimmune disorders?
PTPN22
NOD2
Cytokine receptors
What does PTPN-22 encode?
protein tyrosine phosphatase. This gene is most frequently implicated in AIDz. Failure to downregulate tyrosine kinase activity causes hyperreactive lymphocytes to form.
- RA
- T1D
What disease is NOD-2 associated with?
Crohn’s disease
What does NOD-2 encode?
Encodes a sensor of microbes in the cytoplasm
Which cytokine receptors are implicated with AIDz?
IL-2R alpha (CD25)
IL-7R alpha
Associated with MS, may be associated with Tregs
What is the adjuvant effect?
Upregulation of costimulators on APC from infection, causing a breaktown of tolerance for self antigens
What is polyclonal B cell activation?
increase production of autoantibodies= (EBV, HIV)
What is active tolerance?
Ability to transfer antigen-specific tolerance from one individual to another.
What CD proteins are present on a Treg cell?
CD4+ and CD25+. Depletion of CD4+CD25+ cells results in autoimmune disorders
What is CD25?
A low affinity IL-2 receptor. Expression is low in resting T cells and increases upon T cell activation
What regulates the development of CD4+CD25+ cells?
FoxP3
Where do Treg cells come from?
Normal T cell development. These specialized cells have increased self-MHC avidity, but below the negative selection cut-off for deletion
A defect in FoxP3 is associated with what disease?
IPEX
What is epitope spreading?
Tissue damage causes release of self antigens and exposes epitopes previously hidden. These new epitopes trigger new autoreactive T cells
How do Tregs suppress other cells?
IL-10, TGF-B release
Cell contact
CTLA-4
Fas-L
What AIDz is antibody mediated?
Lupus
What AIDz are T cell regulated?
T1D
RA
What are important autoimmune diseases associated with type II hypersensitivity?
hemolytic anemia
goodpasture
Anti-receptor antibody diseases (graves, myasthenia gravis, T1D)
What are important autoimmune diseases with type III hypersensitivity?
SLE RA scleroderma Sjogren syndrome polymyositis
What are symptoms of SLE?
vegetations of the heart valves with no inflammation (Libman-Sacks)
Malar rash
Deposition of complexes in the skin causing liquefactive necrosis
What causes SLE?
Multifactorial. These factors cause activation of helper T and B cells releasing autoantibodies
What are the symptoms of RA?
weight loss myalgias sweating fevers morning stiffness lymphadenopathy
Describe the pathogenesis of RA
WBC infiltrate into synovium aggregation of fibrin Penetration of bone by synovium Pannus formation (mass of synovium + stroma) causing granulation tissue and fibroblasts Fibrous ankylosis
What genetic factors predispose one to SLE?
Specific HLA types
Deficiencies in complement