Autoimmune disorders

Saurabh PalJunior Research Fellow

Environmental Carcinogenesis LabCSIR-IITR, Lucknow.

srvpal888@gmail.com

Our immune system

Outline: What is autoimmunity…? History of auto immune disorders. Why autoimmune disorders occur….? How autoimmunity develops…? Classification of autoimmune disorders. Examples of autoimmune disorders Toxicology and auto immune disorders. Drugs and Current therapies. Recent advances and future perspective. Summary.

Historical aspect 1965 - Sjogren's sydrome were first

described . 1970.s - autoimmune heart disease was first

linked to hemolytic streptococcus.

Historical aspect

What ? Auto or self antigens.

Are antigens that presents in ones own cells.

Auto antibodies.

Altered cell (Auto Ag) - elicits the productions of Antibody.

 Grammatikos A, Tsokos G (2012). "Immunodeficiency and autoimmunity: lessons from systemic. Trends Mol Med. 

What causes immune system to attack own healthy cells ?

Environ Health Perspect. 2003 Apr; Chemical agents and the immune response. M I Luster and G J Rosentha

Possible mechanism ?

Mechanism

Genetic factors

Super-Antigens

Formation of neo-antigenCross

reactivity –

molecular mimicry

Release of sequestered

AntigenEnvironmental chemicals and autoimmune disease: Evelyn V. Hess,, Toxicology 181–182 (2002)

Putting it all together..the big picture

Autoimmunity can be caused by immunological, genetic, viral, drug-induced, and hormonal factors.

There are 5 immunological mechanisms of autoimmunity.

All mechanisms cause abnormal B or T cell activation.

Most instances of autoimmune diseases occur with multiple mechanisms, which makes treatment difficult.

Classification

Auto -immune

Disorders

Hemolytic autoimmune

disorders

Localised autoimmune

disorders

Systemic autoimmune

disorders

A Proposed Classification of the Immunological Diseases,Dennis McGonagle , August 29, PLOS Medicine.

Hemolytic Anemia Definition:

Those anemias which result from an increase in RBC destruction

Classification:Congenital / HereditaryAcquired

RBC Membrane

Classification of Hemolytic Anemias

Hereditary 1. Abnormalities of RBC interior a.Enzyme defects: G-6-PD def, b.Hemoglobinopathies 2. RBC membrane abnormalities a. Hereditary spherocytosis etc. b. PNH

 

Acquired c. Spur cell anemia3. Extrinsic factors a. Hypersplenism b. Antibody: immune hemolysis c. Mechanical trauma. d. Infections, toxins, etc

 Ref : Harrison’s

Grave disease

Current concepts in Graves’ disease ,Girgis et al 2011

Meng et al 2015, NATURE GENETICS | LETTER

Addison’s disease

autoimmune society.org

Rheumatoid Arthritis

eternessehyd.com/rheumatoid-arthritis

Polymorphism of interleukin 18 gene promoter in south India .

Gurram et al, 2014, Genetic Polymorphism of Interleukin-18 Gene Promoter Region in Rheumatoid Arthritis Patients from Southern India

Insulin dependant diabetes mellitus

Females are more prone….

Toxicology and Autoimmune disorders

Pollard et al, 2014, Chem Res Toxicol. PMC 2011 Apr 13.Chem Res Toxicol. Toxicology of Autoimmune Diseases

Mechanism underline toxicant mediated Autoimmunity

Pollard et al 2014, Chem Res Toxicol. PMC 2011 Apr 13.Chem Res Toxicol. Toxicology of Autoimmune Diseases

DiagnosisTests that may be done to diagnose an autoimmune disorder may include:

Antinuclear antibody test. Complete blood count test. C-reactive protein. Erythrocyte sedimentation rate .

Current Therapies Immunosuppressive drugs.

- corticosteroids, azathioprine- slows the proliferation of lymphocytes.

Cyclosporin A.

- blocks signal transduction mediated by the TCR (inhibits only antigen-activated T cells).

Thymectomy

- removal of thymus from patients with myasthenia gravis Plasmapheresis

- removes antigen-antibody complexes for a short- term reduction in symptoms.

N A Gillett and C Chan (2000). "Applications and evaluation of immunosuppressive agents". Human & Experimental Toxicology .

Recent advances and future perspective

January 12, 2016. First fully human

Monoclonal antibody drug.

It is a TNF – inhibiting anti inflammatory drug.

R.A. , Psoriasis, Ankosylating spondylitis.

The Hindu.com

Recent advances and future perspective

Nanoparticle based insulin delivery

Sharma et al. J Nanobiotechnol (2015)

Summary

Autoimmune diseases and conditions exists when the body produces abnormal cells, which attack the body ,itself.

Many biological, chemical , and environmental irritants may play central role.

There are five possible mechanism and collectively most of the auto immune disorders can be classified into three class.

Most autoimmune diseases strike women more often than men.

Strike any part of the body, symptoms vary widely and diagnosis and treatment are often difficult.

Medical science is striving to design therapies that prevent autoimmune diseases.

Acknowledgement

Dr. Kausar M Ansari. Lab mates. AcSIR 2015 Batch mates. UGC, New Delhi.

Thank you…