Autoimmunity Lecture 2 Flashcards
Autoimmunity
defined as the breakdown of mechanisms responsible for self tolerance and the induction of an immune respnose against components of the self
May not always be harmful (anti-idiotype antibodies) numerous autoimmune diseases it is well recognized that products of the immune system cause damage to the self.
Tolerance
specific immunological non reactivty to an antigen resulting from previous exposure to the same antigen.
most important form is nonreactivity to self do not mount a strong immune response against our own self autoimmune disease develops when the immune system recognize as self antigen and mounts a strong response against it.
Common autoimmune diseases
rheumatoid arthritis
type I diabetes mellitus
multiple sclerosis
myasthenia gravis
systemic lupus erythematosus
autoimmune thyroid diseases (graves, Hashimoto)
Etiology
Genetic
environmental
Proposed model of autoimmmunity
CARTOON****
Genetic factors
inherited risk for most autoimmune diseases can be attributed to multiple loci several autoimmune diseases are linked to particular MHC alleles polymorphisms in non HLA geens are associated with various autoimmune diseases. These may contribute to failure of self tolerance and or abnormal activation of lymphocytes
Major Histocompatibility Complex
Located on Human chromosome 6 Have human leukocyte antigen genes
HLA genes are polymorphic- many different allelles MHC I: A, B, C
MHC II: DP, DQ, DR
MHC presents antigens to the developing thymus- role in tolerance
The difference between disease promoting MHC and their disease protective counterparts shows is only a few amino acids at positions in the antigen binding groove these changes can result in faulty negative selection which leads to the failure to delete or modfiy self reactive lymphocytes
Environmental factors
infections, medications, stress, diet, chemicals, hormones
Mechanisms by which microbes may promote autoimmunity ****
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Rheumatoid arthritis
RA is a prototypic auto immune disease
Can occur in response to an antigenic trigger such as an infection
smoking increases the risk of Developing RA
genetic factor play a role- The presence of HLA DRB1*0401 or HLA DRB1*0404 is highly associated with disease development
Rheumatoid arthritis pathophysiology
Pathologic changes start in the synovial lining with neovascularization and thickening of the synovial membrane
synovial proliferation leads to pannus formation which acts like a local tumor several cytokines have been implicated in the pathogenesis including TNF alpha, IL1, IL6, and IL17
Rheumatoid arthritis presentation
Inflammatory arthritis, rheumatoid nodules eye disease serologic abnormalities
Type 1 diabetes mellitus Symptoms
By the time it is noticed, the damage has been done Elevated blood sugar levels, eye disease, neuropathy, vasculopathy, insulin dependent
Multiple sclerosis Symptoms
Sensory symptoms in limbs, visual symptoms, motor symptoms, diplopia, gait problems, pain
Myasthenia gravis Symptoms
Ocular symptoms, Dysarthria, dysphagia, respiratory involvement
MuSK-LRP4-ColQ complex ****
