Autoimmune Diseases - Introduction

Introduction

Autoimmune disease is defined as a disease state characterised by a specific antibody or cell mediated response against the body's own tissues ('self' antigens).

The breakdown of tolerance to self antigens and the failure to regulate pathological immune responses are both responsible for autoimmune diseases. It has been shown in mice that thymectomy causes autoimmune disease, and plays a very important role in the recognition of 'self'.

Particular individuals may be more susceptible to autoimmune diseases due to:

Genetic factors

Many autoimmune diseases have a familiar component and the Human Leucocyte Antigen (HLA) haplotype is the predominant genetic factor, however having a particular HLA haplotype does not automatically result in the development of an autoimmune disease.

• HLA-DR3/DR4 (MHC Class II):

1. Diabetes Mellitus

2. Rheumatoid Arthritis

• HLA-B27 (MHC Class I):

1. Ankylosing spondylitis

• TNF alpha

• CTLA-4

Hormonal factors

Testosterone is protective against Systemic Lupus Erythematosus (SLE) and thus it is not seen in males.

Environmental factors

Infection

1. Molecular mimicry

• Some bacteria and viruses have antigens that resemble host-cell components and the body can then also initiate an immune response against itself.

2. Polyclonal activation

• T and B cells activation can occur as a result of an infection resulting in polyclonal activation. This can then cause autoreactive autoantibodies or mediate autoimmunity.

3. Inappropriate MHC expression

• Autoreactive T cells are activated because infection stimulates APC and upregulates MHC class II.

Diet

Stress

	Antibody mediated	Antibody mediated	Cell mediated
Type of hypersensitivity	Type II	Type III	Type IV
Pathogenesis	Antibody to cell surface or matrix antigens	Antibody to soluble self antigens	T cell and macrophage activation to self antigens
Examples of diseases	[[Immune Mediated Haemolytic Anaemia|Immune mediated haemolytic anaemia (IMHA)	Systemic Lupus Erythematosus (SLE)	Rheumatoid Arthritis
	Immune mediated thrombocytopaenia (IMTP)		Diabetes Mellitus type 1
	Myasthenia gravis		Hypothyroidism (lymphocytic throiditis)
	Pemphigus		Hypoadrenocorticism (Addisons disease)
	Bullous Pemphigoid

Originally funded by the RVC Jim Bee Award 2007