04-26-12 part b autoimmune diseases. 04-12-12 part b autoimmune diseases effector mechanisms of...
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04-26-12 Part B Autoimmune Diseases
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04-12-12 Part B Autoimmune DiseasesEffector mechanisms of autoimmune disease
Endocrine glands as special targets for autoimmunityThyroid gland (Grave’s disease, etc)Islets of Langerhans (Diabetes)Adrenal gland (Addison’s disease)
Systemic autoimmune diseases - autoimmunityagainst common autoantigens (SLE)
Rheumatoid diseases (rheumatoid arthritis)
Autoimmune diseases of the nervous system (MS andmyasthenia gravis)
Genetic and environmental factors that predispose toautoimmune disease – breaking T cell tolerance
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Autoimmune disease
Negative selection eliminates self reactive lymphocytes
Autoimmune diseases caused by body respondingto self antigens; failure of self-tolerance
Relatively common; 5% of population (7-8 people in class)
Caused by self-reactive Abs or inflammatory T cells
MHC genes involved; genetically based
Common sources for autoimmune Ags:Reaction to bacterial and viral Ags similar to self Ags
immune system can’t discriminateTissue injury (eg heart attack) can release self Ags
creating autoantibodies
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The effectormechanisms of autoimmunity
resemble thoseof certain
hypersensitivityreactions
(P13.2)
(Type II)
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Figure 11-2RBC destructionin autoimmune
hemolytic anemia(P13.3)
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Figure 11-3
Autoantibodies specific for type IV collagenreact with the base membrane of kidney
glomeruli, causing Goodpasture's syndrome(P13.4)
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Endocrine glands secrete tissue-specific proteins that makelikely autoimmune targets.
Hormone secretion into the blood makes endocrine cells highly vascularized, facilitating interactions with immunecells and molecules.
Loss of endocrine function has drastic systemic effects, causing disease and death.
Autoimmune diseases target a single type of epithelial cellwithin the endocrine gland, called “organ-specificautoimmune diseases”
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Figure 11-4
(P13.5)
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Figure 11-5Grave's Disease(P13.6)
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Chronic thyroiditis (Hashimoto disease)
Thyroid loses capacity to make thyroid hormones
CD4 TH1 response favors cell-mediated effectors
Lymphocytes infiltrate and destroy thyroid tissues
Patients become hypothyroid, can’t make thyroid hormones
Ectopic lymphoid tissue can form at sites inflamed byautoimmune disease = “tertiary lymphoid” organ
Lymphoid neogenesis resembles formation and function of secondary lymphoid tissue but without lymphatics or capsule
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Hashimoto's thyroiditis (P13.7)
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Figure 11-8
Pancreas from a patient with Type 1insulin-dependent diabetes mellitus
(destruction of islet cells -cells)(P.13.9)
Note infiltration of the isletby lymphocytes
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Figure 11-1 part 2 of 3
The effector mechanisms of autoimmunity resemble thoseof certain hypersensitivity reactions (P13.2)
(Type III)
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Glomerulonephritis(22.7)
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Immune complex deposition in the basement membrane of kidney glomeruli in systemic lupus erythematosus (P13.10)
neutrophils
Fluorescent anti-Ig
antibodies
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Figure 11-10The chacracteristicfacial rash of lupus
erythromatosusis caused by deposition of
immune complexesin the skin
(P13.11)
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Rheumatic diseases are autoimmune in nature (P13.12)
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Figure 11-1 part 3 of 3
The effector mechanisms of autoimmunity resemble thoseof certain hypersensitivity reactions (P13.2)
(Type IV)
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Figure 11-12Rheumatoid arthritis
is caused by inflammation of
the joints exacerbated by rheumatoid factor(anti-immunoglobulin
antibodies)(P13.13)
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Figure 11-13
Treatment of rheumatoid arthritis with
anti-TNR-(P13.14)
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Killing of B cells by anti-CD20 antibody and NK cells (P13.15)
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Figure 11-15
Diseases mediated by antibodies against cell-surface receptors (P13.17)
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Figure 11-14
Myasthenia gravis is caused by autoantibodiesagainst the acetylcholine receptor (P13.16)
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Genetic and Environmental Factors and Autoimmune Disease
All autoimmune diseases involve breaking T-cell tolerance
Incomplete deletion of self-reactive T cells in the thymuscauses autoimmune disease
Regulatory T cells protect cells/tissues from autoimmunity
HLA is the dominant genetic factor affecting susceptibilityto autoimmune disease
Noninfectious environmental factors (eg smoking)influence the course of autoimmune disease
Loss of oral tolerance leads to inflammation, autoimmunity
Infections can trigger autoimmune disease
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Figure 11-16
Arrest and death of autoreactive B cells in secondary lymphoid tissue (P13.19)
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Figure 11-21
CTLA-4 is involved in the action of regulatory T cells (P13.22)
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Figure 11-28
Celiac disease is caused by inflammation of the smallintestines due to CD4 T cells responding to peptides
derived from wheat gluten(P12.40)
Celiac disease = Gluten-sensitive enteropathyan environmentally induced autoimmune diseasewith genetic predisposition for certain HLA types
GlnGlu
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Figure 11-29
Antibodies against streptococcal cell-wall antigenscross-react with antigens on heart tissue (P13.31)
Molecularmimicry
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Treatment of autoimmune diseasesImmunosuppressant (eg cyclosporins)
Anti-inflammatory drugs (eg steroids)
Replacement therapy (eg insulin, thyroid hormone)
eg. including transplantation of pancreatic insulin-producing cells for insulin-dependent diabetes
Feeding or oral tolerance (induce tolerance to antigen)
Feed insulin for diabetes
Collagen for rheumatoid arthritis
Cause local intestinal immune response,
down regulation of antigen receptors
deletion of immune cells
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Figure 11-37(P11.37)