Autoimmunity and autoimmune disorders

2.  Autoimmunity is a state in which the body’s immune system fails to distinguish
between self and non self and reacts by formation of autoantibodies against one’s
own tissue antigens.
 Autoimmunity is the opposite of immune tolerance.
 Immune tolerance is a normal phenomenon present since foetal life and is defined
as the ability of an individual to recognise self tissues and antigens.

3.  The body is able to distinguish self from non self antigens by the following
mechanisms
 Clonal elimination-during embryonic development T cells maturing in the thymus
acquire the ability to distinguish self from non self.These T cells are eliminated by
apoptosis.
 Clonal anergy-T cells which have acquired the ability to distinguish self from non self
are not eliminated but become inactive and non responsive.
 Suppressor T cells-here tolerance is achieved by a population of specific suppressor T
cells which donot allow the antigen responsive cells to proliferate and differentiate .

4.  Usually autoimmunity is prevented by 3 major processes
 Sequestration of auto antigens and their unavailability for autoimmune response
 Generation and maintenance of tolerance or anergy by T and B lymphocytes
 Regulatory mechanisms limiting response by immune system.
The mechanisms by which immune tolerance is broken-autoimmunity
1.Immunological factors-
 Polyclonal activation of T cells
 Generation of self reacting B cell clones
 Decreased T suppressor and increased T helper cell activity
 Sequestrated antigen released from tissue

5.  2.Genetic factors
 Evidences of genetic factors
 Increased expression of Class II HLA antigen
 Familial incidence of some forms of autoimmune disorders
 Higher incidence of autoimmune disorders in twins
 3.Microbial factors
 Infection with microorganisms like virus (EBV),bacteria(Streptococci, Klebsiella)

6.  Lab evidence
 Presence and documentation of autoantibodies
 Demonstration of T cell reactivity to self antigen
 Lymphocytic infiltrate in lesion
 Production of cytokines by helper T cells
 Evidence to support production of pathological lesion in tissues by transplacental
Transmission
 Transfer of autoimmune disease to experimental animal by administrating
autoantibodies
 Clinical evidence
 Association of other autoimmune disorder
 Improved response to immunosuppressive agent
 Family history.

7.  Organ Specific diseases
 Autoamtibodies formed react specifically against an organ and cause chronic
inflammatory response.
 Egs-thyroid,pancreatic islet of Langerhans,adrenal cortex
 Systemic disease
 Autoantibodies react with antigens in many tissues and cause systemic disease

8.  Endocrine Glands
 Hashimotos thyroiditis
 Graves disease
 Type 1 DM
 Idiopathic Addison’s disease
 Alimentary tract
 Autoimmune atrophic gastritis
 Ulcerative colitis
 Crohns disease
 Blood cells
 Autoimmune hemolytic anaemia
 Autoimmune thrombocytopenia
 Pernicious anemia

9.  Others
 Myasthenia gravis
 Autoimmune orchitis
 Autoimmune encephalomyelitis
 Goodpastures syndrome
 Primary biliary cirrhosis
 Lupoid hepatitis

10.  Systemic lupus erythematosus
 Rheumatoid arthritis
 Scleroderma
 Inflammatory myopathy(polymyositis,dermatomyositis)
 Polyarteritis nodosa
 Sjogrens syndrome
 Wegeners granulomatosis

11.  Thank you