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20/11/08
Dr Ekta, Microbiology
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Click to edit Master title style
Click to edit Master text styles Second level Third level Fourth level Fifth level
20/11/08
Dr Ekta, Microbiology
Click to edit Master text styles Second level Third level Fourth level Fifth level
AUTOIMMUNITY
TEACHING OBJECTIVES
1. Understand the concept and significance of tolerance 2. Understand the concepts of autoimmunity and disease 3. Know the features of major autoimmune diseases 4. Know the theories on etiology of autoimmune diseases
Tolerance The absence of specific immune response to a particular antigen in a fully immunocompetent person. Tolerance is a mechanism which the immune system can learn Unresponsiveness to self antigens is known as autotolerance.
Tolerance to self antigens We normally do not mount a strong immune response against our own (self) antigens, a phenomenon called self-tolerance
Mechanisms of self-tolerance
Central tolerance
Ch. 16
p. 402
Peripheral tolerance
4-Homeostatic control Due to Lack of T-cells help for autoreactive B cells. As a result , autoreactive B cells do not get stimulated. If the immune system recognizes a self antigen and mounts a strong response against it, autoimmune disease develops.
Ch. 16
AUTOIMMUNITY
A condition in which structural or functional damage is produced by the action of immunologically competent cells or Abs against the normal components of the body.
Autoimmunity Origins
Horror autotoxicus Literally, the horror of self-toxicity. A term coined by the German immunologist Paul Ehrlich (1854-1915) to describe the bodys innate aversion to immunological self-destruction.
Features Of Autoimmune Diseases
An elevated level of Igs. Deposition of Igs or their derivatives at particular sites like glomeruli. Accumulation of lymphocytes plasma cells at the site of lesion. Benefit from corticosteroid or other immunosuppressive therapy. Genetic predisposition.
Features Of Autoimmune Diseases
Occurrence of more than one type of autoimmune disorders in an individual. Higher incidence among females. Usually non-reversible (chronic) Predisposing factors Familial history. Certain HLA haplotypes - Rheumatoid Arthritis - HLA DR4
Mechanisms Of Autoimmunisation
Molecular mimicry - Cross reacting foreign Ags Polyclonal B cell activation Breakdown of immunological homeostasis (tolerance) Sequestered Ags
1 .Molecular Mimicry
Rheumatic fever is a classic example of molecular mimicry
2. Polyclonal B-cell Activation
3. Breakdown Of Immunological Homeostasis
Cessation of tolerance to self Ag. Enhanced helper T-cell and decreased suppressor T-cell functions
4. Release of Sequestered Ags
Sequestered Ags - Certain Ags are present in closed systems (compartments) and are not accessible to the immune apparatus. e.g Lens protein of the eye is enclosed in its capsule does not circulate.
Dr Ekta, Microbiology
Localised Autoimmune Diseases
Localised Autoimmune Diseases
Dr Ekta, Microbiology
Localised Autoimmune Diseases
Localised Autoimmune Diseases
Localised Autoimmune Diseases
Diabetes mellitus type-1
- Also called Insulin dependent diabetes or Juvenile diabetes.
-Autoimmune destruction of insulin-producing (beta cells) of the pancreas -Results in total insulin deficiency.
-Affects 1 in 300 children and more adults.
HGAD65 auto antigen Coxsackie hCMV Viral peptides
Pathophysiology Triggers
Localised Autoimmune Diseases
Systemic Autoimmune Diseases
SLE
Rheumatoid Arthritis (RA)
Diagnosis
Diagnosis of autoimmune diseases is based on symptoms and detection of antibodies (and/or very early T cells) reactive against antigens of tissues and cells involved
Antibodies against cell/tissue associated antigens are detected by immunofluorescence Antibodies against soluble antigens are normally detected ELISA or radioimmunoassay
Treatment
The goals of treatment of autoimmune disorders are to reduce symptoms and control the autoimmune response while maintaining the bodys ability to fight infections. Treatments vary widely and depend on the specific disease and symptoms
Anti-inflammatory (corticosteroid) and immunosuppressive drug therapy (such as cyclophosphamide, azathioprine, cyclosporine ) is the present method of treating autoimmune diseases.