Autoimmunity Lecture 2 Flashcards Preview

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1

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.

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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.

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Common autoimmune diseases

rheumatoid arthritis

type I diabetes mellitus

multiple sclerosis

myasthenia gravis

systemic lupus erythematosus

autoimmune thyroid diseases (graves, Hashimoto)

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Etiology

Genetic

environmental

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Proposed model of autoimmmunity

CARTOON****

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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

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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

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Environmental factors

infections, medications, stress, diet, chemicals, hormones

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Mechanisms by which microbes may promote autoimmunity ****

Photo

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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

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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

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Rheumatoid arthritis presentation

Inflammatory arthritis, rheumatoid nodules eye disease serologic abnormalities

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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

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Multiple sclerosis Symptoms

Sensory symptoms in limbs, visual symptoms, motor symptoms, diplopia, gait problems, pain

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Myasthenia gravis Symptoms

Ocular symptoms, Dysarthria, dysphagia, respiratory involvement

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MuSK-LRP4-ColQ complex ****

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Systemic Lupus erythematosus

Inflammatory multi-system disease primarily seen in females highly variable course of prognosis often has significant constitutional symptoms associated with characterisitc autoantibodies

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SLE symptoms

Skin and mucous membranes, synovium, serosal membranes, kidneys, CNS, lungs, heart, and Hematopoietic system Malar rash: lupus

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Graves disease

Anxiety, wt loss, diarrhea, eye disease

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Graves opthalmopathy

Hypertrophy of the circular eye muscles which leads to the bulge of the eyes.

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Hashimoto's thyroiditis

fatigue, constipation, skin involvement, muscle weakness

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Therapies

Steroids: prednisone, methypredinisolone immunosuppressant antimetabolites targeted (biological) therapies