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Transcript
Autoimmune Diseases
2008 C.K.Shieh
Spectrum of Autoimmune Diseases
HLA Association of Autoimmune Diseases
Depletion of Autoreactive T Cells in the Thymus
How does autoantibody cause diseases
• Direct binding to target cells
thyrotoxicosis
Myasthenia gravis
Goodpasture’s syndrome
• Immune complex deposition
SLE (systemic lupus erythematosus)
Rheumatoid arthritis
* SLE is a disease best known for dysregulation of B cells and hence the production of
autoantibodies. Different from organ specific autoimmune diseases, various
autoantibodies found in other antibody-mediated autoimmune diseases may be found in
SLE patients. Self-damage caused by type II and type III hypersensitivity mechanisms
thus may be found in SLE patients.

Cell Mediated cytotoxicity
Diabetes mellitus (DM): CMI targets beta cells in the pancreas
Hashimoto’s thyroiditis: CMI targets thyroid gland
Experimental allergic encephalitis (EAE): CMI targets myelin in CNS, an animal
model of the human disease multiple sclerosis.
A spectrum of autoimmunity to thyroid gland is apparent clinically
On the one end of the spectrum is the antibody mediated stimulation (non-goitrous
hyperthyroidism), on the other end is the cell mediated thyroid gland destruction
(Hashimoto’s (橋本) thyroiditis)
Autoimmunity Is Antigen driven
Anti-thyroid autoantibody disappears after thyroidectoy in OS chicken
Rheumatoid factor: anti-antibody antibody found in patients with seropositive
rheumatoid arthritis
Breaking Self Tolerance
•
•
Direct stimulation of autoimmune cells e.g. EBV
Molecular mimickry e.g. rheumatic fever
Cross-reactive microbial antigens (T Cell Antigen)
Cross-reactive B cell antigen (not protected by T Cell tolerance)
•Cytokine dysregulation
Breaking of ignorance by changed cytokine in the tissue milieu (Immune Deviation)
•Breaking of tolerance by disturbed central tolerance machinery:
e.g. myasthenia gravis in patients with thymoma
•Cytokine dysregulation
Breaking of ignorance by changed cytokine in the tissue milieu (Immune Deviation)
*CD25+FoxP3+ CD4+T cells block the effect of autoimmune responses mediated by
autoreactive T cells. This blocking may or may not require the secretion of suppressive
cytokines such as TGF and IL-10. Some autoimmune diseases appear to correlate with
the compromised function of regulatory T cells. Successful treatment of the
autoimmune disease can restore the compromised regulatory function.
*Abnormal maturation of Th-17 cells, which secrete IL-17 and respond to IL-23, may
play an important role in many autoimmune diseases including EAE (an animal model of
multiple sclerosis).
How to Treat Autoimmune Reactions
By trying to restore homeostasis in the immune system, various approaches have been
employed to treat autoimmunity. Cytokines, anti-cytokines, and immunosuppressive
agents are in use for treating patients with autoimmune diseases.
自體免疫疾病是免疫控制基轉失調的最終表現,所以經常表現出複
雜的免疫反應。在已經發生的自體免疫疾病中,找出引起疾病的元凶經
常是很困難的。學習自體免疫疾病的致病機轉,重點在於了解引發這些
自體免疫疾病的免疫控制機轉失調的原因和起始點。近十多年來基因轉
殖動物的研究對這個問題提供了全新的觀點。
本節課的另外一個重點是熟悉這些自體免疫疾病的名稱和表現。請
各位將 20.3 圖多看幾遍。