Autoimmune disorders
Download
1 / 21

Autoimmune Disorders - PowerPoint PPT Presentation


  • 271 Views
  • Uploaded on

Autoimmune Disorders. Dr Shoaib Raza. Autoimmune Disorders. Immune reactions against self antigens Affects 1% to 2% of US population Requirements for an autoimmune disorder: Presence of immune reaction specific for some self-antigen or self-tissue

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' Autoimmune Disorders' - heaton


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
Autoimmune disorders

Autoimmune Disorders

Dr Shoaib Raza


Autoimmune disorders1
Autoimmune Disorders

  • Immune reactions against self antigens

  • Affects 1% to 2% of US population

  • Requirements for an autoimmune disorder:

    • Presence of immune reaction specific for some self-antigen or self-tissue

    • Evidence that the reaction is not secondary to tissue damage

    • Absence of another well defined cause of disease

      • DIAGNOSIS OF EXCLUSION


Autoimmune disorders2
Autoimmune Disorders

  • Clinical manifestations are varied

    • Organ specific disease

      • Type 1 diabetes mellitus

      • Multiple sclerosis

    • Systemic or generalized diseases

      • Systemic lupus erythematosus

    • Middle of the spectrum

      • Goodpasture’s syndrome


Immunologic tolerance
Immunologic Tolerance

  • The phenomenon of unresponsiveness to an antigen as a result of exposure to lymphocytes to that antigen.

  • Self tolerance refers to lack of responsiveness to an individual’s own antigen

    • Central tolerance

    • Peripheral tolerance


Central tolerance
Central Tolerance

  • Immature self reactive T or B-Cell clones that recognize self-antigens during their maturation in the central lymphoid organs (Thymus or Bone marrow) are killed or rendered harmless.

  • Central tolerance is however far from PERFECT

  • Self reactive T or B-cells may skip the central tolerance and enter the circulation


Central tolerance of t cells
Central Tolerance of T-Cells

  • In the thymus

    • Negative selection:

      • Self reactive T-Cells die by apoptosis

      • AIRE protein stimulates expression of “peripheral tissue restricted” self-antigens in the thymus

    • Some self reactive CD4+ T-Cells in the thymus do not die, but later on develop into regulatory cells


Central tolerance of b cells
Central Tolerance of B-Cells

  • In the bone marrow:

    • Receptor editing:

      • Some self-reactive B-Cells reactivate the machinery of antigen receptor gene and begin to express new antigens receptors

      • If receptor editing does not occur, self-reactive B-Cells undergo apoptosis


Peripheral tolerance
Peripheral Tolerance

  • Several mechanisms

    • Anergy

      • Prolonged or irreversible inactivation of lymphocytes

      • Absence of co-stimulatory signals induce apoptosis

    • Suppression by regulatory T-Cells

      • Mainly developed in thymus

      • May be developed in peripheral tissues

      • ? immunosuppressive cytokines are released (IL-10)

    • Deletion by activation-induced cell death

      • Self-reactive CD4+ T-Cells undergo apoptosis


Mechanism of autoimmunity
Mechanism of Autoimmunity

  • Autoimmunity arises from a combination of

    • Inheritance of susceptibility genes may lead to breach in self-tolerance

    • Environmental triggers e.g. infections and tissue damage


Role of infection in autoimmune diseases
Role of Infection in Autoimmune Diseases

  • Many autoimmune diseases are:

    • Associated with infections

      • Up-regulation of expression of co-stimulators on APC

      • Molecular mimicry (e.g. rheumatic heart disease)

      • Polyclonal B-Cell activation (e.g. EBV infection)


General features of autoimmune diseases
General Features of Autoimmune Diseases

  • Autoimmune diseases are PROGRESSIVE, with relapses and remissions

  • Clinical and pathological manifestations are determined by nature of underlying immune response

  • Different autoimmune diseases show substantial clinical, serological and pathological overlap.


Systemic lupus erythematosus sle
Systemic Lupus Erythematosus (SLE)

  • Prototype of multisystem disease of autoimmune origin

  • Antinuclear antibodies (ANAs) are usually present

  • Acute or insidious in onset

  • Chronic, remitting and relapsing, often febrile illness characterized principally by injury to the skin, joints, kidney and serosal membranes

  • Complex set of criteria for establishing the diagnosis


Etiology pathogenesis
Etiology & Pathogenesis

  • Exact cause is unknown

  • Failure of the mechanisms that maintain self-tolerance

    • Genetic factors

    • Immunologic factors

    • Environmental factors


Mechanism of tissue injury
Mechanism of Tissue Injury

  • Most of the visceral lesions are caused by Type III Hypersensitivity reaction

  • DNA-AntiDNA complexes are formed

  • Immune complex nature of the disease

    • Autoantibodies specific for RBC, WBC and platelets, opsonize these cells for phagocytosis

      • SLE is a complex disorder of multifactorial origin resulting from genetic, immunologic and environmental factors that act in concert to cause activation of helper T-Cells and B-Cells and result in the production of several species of pathologic autoantibodies.


Morphology
Morphology

  • Kidney:

    • Lupus nephritis

  • Joints:

    • Synovitis, arthritis etc

  • CNS:

    • Due to acute vasculitis

  • Heart:

    • Pericarditis, non-bacterial verrucous endocarditis

  • Lungs, Spleen, etc.

    • Splenomegaly, pleuritis


Clinical features
Clinical Features

  • Variable presentation according to organ involved

  • Unpredictable presentation and course of the disease

    • Chronic discoid lupus erythematosus

    • Subacute cutaneous lupus erythematosus


Rheumatoid arthritis
Rheumatoid Arthritis

  • Chronic systemic inflammatory disease that principally affects joints

  • Non-suppurative proliferative and inflammatory synovitis

  • Often progress to ankylosis

    • Genetic susceptibility

    • Arthritogenic antigen

    • Autoimmunity

      • Anti IgG antibody (Fc portion)


Sj gren syndrome
Sjögren Syndrome

  • Chronic disease, characterized by:

    • Keratoconjunctivitis sicca (Dry Eyes)

    • Xerostomia (Dry mouth)

  • Immunlogically mediated destruction of the lacrimal and salivary glands

    • May be associated with other autoimmune disorders

      • SLE, RA, polymyositis, scelroderma, vasculitis, thyroiditis, MCTD, etc.


Systemic sclerosis scleroderma
Systemic sclerosis (Scleroderma)

  • Chronic disease characterized by:

    • Chronic inflammation as a result of autoimmunity

    • Widespread damage to small blood vessels

    • Progressive interstitial and perivascular fibrosis

  • CREST syndrome

    • Calcinosis

    • Raynaud’s disease

    • Esophageal dysmotility

    • Sclerodactyly

    • Telangiectasia


Mixed connective tissue diseases
Mixed Connective Tissue Diseases

  • Clinical features, mixture of

    • SLE

    • Systemic sclerosis

    • Polymyositis

  • Serologically characterized by:

    • Autoantibodies to ribonucleotide particle containing U1 ribonucleoprotein.


Polyarteritis nodosa
Polyarteritis Nodosa

  • Necrotizing inflammation of small sized blood vessel wall

  • Small size blood vessels of lungs and kidneys are usually affected


ad