Bio 328 Immunology Autoimmunity

Negative selection bone marrow

Peripheral tolerance B cells: Clonal Deletion

Peripheral tolerance B-cells: Clonal Anergy. HEL expressed under liver- specific promotor

Negative selection thymus

Transfection of re-arranged TCR  and  chain genes. Negative selection Thymus.

Negative selection in the thymus

Freemartin.

Reproductive tract of Freemartin

Prevalance of chimeric cells in 15 pairs of freemartin twins. Pessa-Morikawa, et. al, 2003

Peripheral tolerance T cells: Clonal Anergy

Non-Obese Diabetic mice BioBreeding rats

IPEX = Foxp3 deficiency = Immunodysregulation Poly- Endocrinopathy Enteropathy X-linked

Non-Obese Diabetic mice and BB rats prone to develop spontaneous, autoimmune (type I) diabetes: T reg deficiency. ALPS, Autoimmune Lymphoproliferative Syndrome Fas deficiency (gld/gld) APECED, Autoimmune polyendocrinopathy- candiadiasis-ectodermal dystrophy AIRE deficiency IPEX, Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (Scurfy) Foxp3 deficiency

Healthy control Hashimoto’s thyroiditis

Fluorescent anti-IgG staining of kidney in Goodpasture syndrome.

Healthy control Insulin-dependent diabetes mellitus

Skin depigmentation in Vitiligo (Auto-antibodies against melanocytes)

Myasthenia gravis

Autoimmune adreocortical insufficiency

Addison disease: Autoimmune adrenocortical insufficiency Abdominal pain Weakness Low blood pressure

Maggie Smith as Professor Minerva McGonagall.

Clearance Hypothesis Tolerance Hypothesis

Methods to detect RF: Rose-Waaler test and Latex- agglutination test.

Scleroderma Systemic Sclerosis

Parotid enlargement Sjogren's syndrome

Sjögren's syndrome. (A)Tongue with atrophic papillae and dry and deeply fissured epithelium that replaces functional glandular epithelium; cheilitis is evident bilaterally. A possible cause of these manifestations might be xerostomia, either alone or in combination with fungal infection. (B) Missing teeth and multiple caries. (C) Persistent enlargement of parotid glands.

Ankylosing spondylitis

Experimental and many organ-specific autoimmune diseases are -driven by CD4 + T-cells. -T H 1/T H 2 dichotomy

Mechanisms for Induction of Autoimmunity. 1.Release of sequestered antigen 2.Molecular mimicry 3.Inappropriate expression MHC II INF  4.Polyclonal B cell activation.

Non-Obese Diabetic mice and BB rats prone to develop spontaneous, autoimmune (type I) diabetes: T reg deficiency. ALPS, Autoimmune Lymphoproliferative Syndrome Fas deficiency (gld/gld) APECED, Autoimmune polyendocrinopathy- candiadiasis-ectodermal dystrophy AIRE deficiency IPEX, Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (Scurfy) Foxp3 deficiency

Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination Kerstin Berer1, Marsilius Mues1, Michail Koutrolos1, Zakeya Al Rasbi1, Marina Boziki1, Caroline Johner2, Hartmut Wekerle1 & Gurumoorthy Krishnamoorthy1 Nature 24 November 2011, 479 p

The End