AutoimmunityMBBS Sem I

Based on Robbin’s 9th Edition and Levinson 11th Edition

Objectives

After this lecture, the students should be able to:

• Define Autoimmunity

• Classify Autoimmune Diseases

• Explain the mechanism of Tolerance

• Describe the features of Sjogren syndrome and SLE

Autoimmunity

Immune reactions against self antigens

Conditions to be met for diagnosis of an autoimmune disease

• The presence of an immune reaction specific forsome self antigen or self tissue

• Evidence that such a reaction is not secondary to tissue damage but is of primarypathogenic significance

• The absence of another well-defied cause of the disease.

Classification of Autoimmune Diseases

Important Autoimmune DiseasesAntibodies to Receptors

Autoimmune Disease Target of the Immune Response

Myasthenia Gravis Acetyl Choline Receptor

Grave’s Disease TSH1 Receptor

Insulin Resistance Diabetes Insulin Receptor

Important Autoimmune DiseasesAntibodies to Cell Components other

than ReceptorsAutoimmune Disease Target of the Immune Response

Systemic Lupus Erythematosis dsDNA, Histones,

Rheumatoid Arthritis IgG in joints

Rheumatic Fever Heart and joint Tissue

Hemolytic Anaemia RBC membrane

ITP Platelet membrane

Good Pastture’s Syndrome Basement Membrane Lungs /Kidneys

IDDM Islet cells

Important Autoimmune DiseasesCell Mediated

Autoimmune Disease Target of the Immune Response

Multiple Sclerosis Myelin

Celiac Disease Enterocytes

Immunologic Tolerance

Pathogenesis of Autoimmunity

Mechanisms related to autoimmunity

• Defective tolerance or regulation• Abnormal display of self antigens.• Inflammation or an initial innate immune response.• Antigen Mimicry• Alteration of Normal Proteins• Release of Sequestered antigens• Epitope spreading• Failure of Regulatory T Cells

Genetic Factors Related to Autoimmunity

HLA

Genetic Factors Related to Autoimmunity

Non-HLA Genes

Antigen Mimicry

Autoantibodies and their association with different diseases

General Features of Autoimmune Disease

• Autoimmune diseases tend to be chronic, sometimes with relapses and remissions, and the damage is often progressive.

• The clinical and pathologic manifestations of an autoimmune disease are determined by the nature of the underlying immune response.

Systemic Lupus ErythematosusDisease

SLE is an autoimmune disease involving multiple organs characterized by a vast array

of autoantibodies, particularly antinuclear antibodies (ANAs), in which injury is

caused mainly by deposition of immune complexes and binding of antibodies to

various cells and tissues.

SLEAntinuclear Antibodies

• These are directed against nuclear antigens and can be grouped into four categories:

– Antibodies to DNA

– Antibodies to histones

– Antibodies to nonhistone proteins bound to RNA

– Antibodies to nucleolar antigens.

SLE Features

SLE Prevalence of Clinical Features

SLESummary

1. Systemic autoimmune disease caused by autoantibodies produced against numerous self antigens and the formation of immune complexes.

2. The major autoantibodies, and the ones responsible for the formation of circulating immune complexes, are directed against nuclear antigens. Other autoantibodies react with erythrocytes, platelets, and various complexes of phospholipids with proteins.

3. Disease manifestations include nephritis, skin lesions and arthritis (caused by the deposition of immune complexes), and hematologic and neurologic abnormalities.

4. The underlying cause of the breakdown in self-tolerance in SLE is unknown; it may include excess or persistence of nuclear antigens, multiple inherited susceptibility genes, and environmental triggers (e.g., UV irradiation, whichresults in cellular apoptosis and release of nuclearproteins).

Sjögren Syndrome

Sjögren syndrome is a chronic disease characterizedby dry eyes (keratoconjunctivitis

sicca) and dry mouth(xerostomia) resulting from immunologically

mediated destruction of the lacrimal and salivary glands.

Sjögren SyndromeTypes

• Primary

– Isolated

– Also called sicca syndrome

• Secondary

– Related to other autoimmune disease

Sjögren Syndrome Features

An inflmmatory disease that affects primarily the salivary and lacrimal glands, causing dryness of the mouth and eyes.

The disease is believed to be caused by an autoimmune T-cell reaction against an unknown self antigen expressed in these glands, or immune reactions against the antigens of a virus that infects the tissues.

Sjögren SyndromeFeatures

Thank you