AUTOIMMUNITY

 AUTOIMMUNITY

DEFINITON:-

Autoimmunity is a state in which the body immune system fails to distinguish between “self” and “non-self” and reacts by formation of auto antibodies against one’s own tissue antigens. There is a loss of tolerance to one’s own tissues. Autoimmunity is opposite of immune tolerance.

MECHANISM OF AUTOIMMUNITY:-

Various theories are proposed to explain how normal controlling mechanism fails to maintain self-recognition. Following are the theories:

I. Hidden or sequestered antigen theory:

In this theory tissue antigens which are exposed to lymphoreticular development at the time of embryonic development are recognized as self-antigens and are unable to induce the immune response. As many of the autoantigens are not accessible to cells of immune system as they are hidden inside a cell or tissue. Such antigens are called as sequestered antigens and though they are the self-antigens but are treated as non-self-antigens. These antigens when comes in contact with immunocompetent cells, they lead to immune response and at the same time allows stimulated lymphocytes as well as antibodies to produce trauma or injury by reacting with them.

II. Neoantigens: 

In some circumstances, a native tissue antigen may be altered in some way by physical, chemical or biological means and assume a new antigenic specificity. Altered antigen stimulates the immune reaction which damages native tissue antigen producing tissue injury.

III. Cross reacting agents: 

Various microorganisms carry antigenic determinants which resemble to the host cell component. These are cross reacting agents. Infection by such microorganisms initiate an immune response which dam-age particular organ or tissue in host.

IV. Loss of immunoregulation:

Loss of normal tolerance control due to loss of immunoregulation causes autoimmune disease. Defect or lack of efficiency in lymphoid cell population can cause loss or normal tolerance control.

V. Genetic abnormalities: 

Various genetic abnormalities, i.e. mutation in an immunocompetent cell, defect in immunoglobulin gene can cause antigenic responsiveness to self antigens leading to autoimmune diseases.

PATHOGENESIS:-

The mechanism by which the immune tolerance of body is broken causes autoimmunity.

a. Immunological factors:

• Failure of immunological mechanism of tolerance initiates autoimmunity.

• Polyclonal activation of B cells: Production of self reacting B cell clone because of certain stimuli, i.e. chemicals, bacterial products, enzymes, antibiotics, infection with some bacteria, viruses and parasites.

• Generation of self reacting B cell clone.

• Decreased T suppressor and increased T helper cell activity.

• Defects in idiotype: Anti-idiotype network.

• Defects in thymus, in stem cell development and macrophage function.

• Sequestered antigen released from tissues.

b. Genetic factors:

• There is increased expression of class II HLA antigens on tissues involved in autoimmunity.

• There is increased familial incidence of some of the autoimmune disorders.

c. Microbial factors: 

Infections with microorganisms particularly viruses, e.g. EBV infection, less commonly by bacteria and mycoplasm.

TYPES OF AUTOIMMUNITY:-

Depending upon the type of antibody formation:

1. Organ specific diseases: 

In these the autoantibodies formed react specially against an organ or target tissue component, 

EXAMPLE 

Hashimoto thyroiditis, 

Graves’ disease, 

Myasthenia gravis.

Insulin dependent diabetes mellitus

Idiopathic Addisions’ disease, etc.

2. Non-organ specific (systemic) or Diseases-causes systemic lesions

 EXAMPLE 

 Systemic lupus erythematosus.

 Rheumatoid arthritis

 Scleroderma

 Polyartheritis nodosa

 Sjogren syndrome

 Reiter’s syndrome.