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Autoimmune Disease PowerPoint Presentation

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Description : Check out this medical PowerPoint presentation titled "AUTOIMMUNe disease" by Ass.Prof. Dr.ESRA HASSAN. This medical PowerPoint presentation talks about autoimmune disease.

Tags : Autoimmune Diseases, immune system, inflammation

Published on : Mar 16, 2023 | Views : 1922 | Downloads : 3

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AUTOIMMUNe disease Ass.Prof. Dr.ESRA HASSAN PH.D Clinical Immunolog
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Autoimmune diseases Normally, the immune system does not attack the self. This is ensured by elimination of auto-reactive lymphocytes during their development (negative selection).. The attack can be either humoral (by auto-antibodies) or cellular (by auto-reactive T cells). The attack can be directed either against a very specific tissue )organ specific ) , or to a large number of tissues (systemic autoimmune disease), depending on the self-antigen which is attacked.
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AUTOIMMUNITY Ability of immune system to differentiate between self and non-self antigens lost Immune system response against self antigens
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IMMUNOLOGICAL TOLERANCE A state in which the individual is incapable of developing an immune response against specific antigen. SELF TOLERANCE Lack of immune response to individual .s own tissue antigen (which is a good thing) TYPES OF TOLERANCE 1- CENTRAL TOLERANCE Occur during lymphocyte development. Iateans the deletion of self-reactive react against self-antigen) . T and B lymphocytes during their development in the bone marrow or thymus
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2- PERIPHERAL TOLERANCE Occur after lymphocyte leave their primary organ (B.M or thymus). After maturation of the immune system, there should be some mechanism to prevent auto-reactively of lymphocyte after their formation from the B.M. or thymus, some of these mechanisms are: 1-IGNORANCE The antigen is in low concentration which will not be sensed by the T-cell. Or some self-antigens are sequestrated (hidden) from the immune system during it is development such as eye, CNS, testis. 2- SUPPRESSION There is suppression of the reactive T cells by the help of other types of T cells.
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3- ENERGY Energy of T cells means prolonged irreversible inactivation of T cells. DEVELOVEMENT OF AUTOIMMUNE DISEASE 1- Failure of self-tolerance. 2-Genetic factors. 3- Infection FAILURE OF SELF TOLERANCE BY: A- Failure of T -Cell Anergy. B- Failureof Autoreactive T Cell Apoptois C- Failure of T Cell Supprtion. D- Modification of the molecule (By Drug). E-Molecular Mimicry , some microorganism have Ag similar to some tissue Ags so there will be cross reaction of the Ab that are formed against the microorganism and react with tissue creating autoantibody F- Release of Sequestered Ag
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Failure of central tolerence Inside primary lymphoid organ; positive selection negative selection (Deletion of self reacting T cells in thymus apoptosis). .
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Autoimmune Diseases Some examples of autoimmune diseases include: Type I diabetes attacks insulin-producing cells. Rheumatoid arthritis attacks connective tissues around joints. Myasthenia gravis attacks neuromuscular junctions. Multiple sclerosis (MS) destroys functions of brain and spinal cord neurons
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Autoimmune diseases Specific: Juvenile diabetes (attacks insulin-producing cells) Multiple sclerosis (attacks myelin coating of nerve axons) Myasthenia gravis (attacks nerve-muscle junction) Thyroiditis (attacks the thyroid) … Systemic: Immune complexes accumulate in many tissues and cause inflammation and damage. Systemic Lupus Erythematosus (anti-nuclear antibodies): harms kidneys, heart, brain, lungs, skin… Rheumatoid Arthritis (anti-IgG antibodies): joints, hearts, lungs, nervous system… Rheumatic fever: cross-reaction between antibodies to streptococcus and auto-antibodies.
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Development of Autoimmune Disease Autoimmune disease occurs as a result of breakdown in tolerance to self Mediated by B-lymphocytes that produce antibodies to self antigens And / or T-lymphocytes with T-cell receptors that recognize selfantigens – Autoreactive CD4 Th and autoreactive CD8 cytotoxic T cells
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What could cause the immune system to attack the self? Changes in self-antigens, that make them look like non-self to the immune system, due to: Viral or bacterial infection Irradiation Medication Smoking … Changes in the immune system: Normal auto-antibodies exist; mutations in B cells producing them may create pathogenic auto-antibodies. Problems with control of lymphocyte development and differentiation.
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EXAMPLES 0F ORGAN-SPECIFIC AND NON ORGAN-SPECIFIC (SYSTEMIC) AUTOIMMUNE DISEASES Organ-specific Hashimoto thyroiditis Thyrotoxicosis Addison’s disease Atrophic gastritis Juvenile diabetes mellitus Multiple sclerosis Non organ-specific Systemic lupus (SLE) Rheumatoid arthritis (RA) Scleroderma Dermatomyositis Mixed connective tissue disease (MCTD) Sjögren’s syndrome
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1) Tissue destruction Diabetes: CTLs destroy insulin-producing b-cells in pancreas 2) Antibodies block normal function Myasthenia gravis: Ab binds acetylcholine receptors 3) Antibodies stimulate inappropriate function Graves’ disease: Ab binds TSH receptor 4) Antigen-antibody complexes affect function Rheumatoid arthritis: IgM-IgG complexes deposited in joints inflammation Effects of autoimmunity
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Mechanisms of autoimmunity Ag released from hidden location. Antigen generated by molecular changes. Molecular mimicry. Alteration in Ag processing. Infection. Genetic factors.
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Ag related from hidden location Many self Ag are found in hidden location eg. C N S ,TESTES ,EYE (CORNEA) organ damage Hidden Ag released Reaches blood stream Encounter Ag sensitive cells Stimulate autoimmunity
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Damage to immunologically privileged sites can lead to autoimmunity
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Antigen generated by molecular changes Development of completely new epitopes on normal protein. eg RF immuno conglutinine. Mech of formation of RF : Ab + Ag new epitopes exposed on Fc region of Ab Stimulate the formation of Rf Establishment of disease like rheumatiod artheritis and SLE
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Molecular mimicry Sharing of epitopes between an infectious agent and its host. Antibodies directed against the infectious agents starts reacting with normal self Ag. Triggers autoimmunity.
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GENETIC FACTORS The important genes that regulate the development of autoimmunity are located within MHC. MHC have got critical role in maturation of T cell & induction of IR . MHC ll genes are directly responsible for auto antigen processing and presentation.
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Rheumatiod Arthritis Auto-immune disorder which results in inflammation of the synovial lining of the joint and cartilage destruction. This result in loss of function.
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Rheumatoid arthritis (RA) affects peripheral joints and may cause destruction of both cartilage and bone. The disease affects mainly individuals carrying the DR4 variant of MHC genes. This fact can lead to better prognoses and in aiding efforts to change immune reactions that involve the DR4 variant while leaving other reactions intact.
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SYSTEMIC LUPUSERYTHEMATOSUS (SLE) Auto-antibodies formed against variety of self antigens Anti-double stranded DNA,RNA and histones Immune circulating complexes formed against self deposit on tissues
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Systemic lupus erythematosis is the most commonly known autoimmune disorder. This characteristic “butterfly” rash is made worse by exposure to sunlight. Lupus is a potentially fatal autoimmune disease that strikes 1 in 2,000 Americans and 10 times as many women as men.
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Treatment for autoimmunity Immunosuppression (e.g., prednisone, cyclosporin A) Removal of thymus (some MG patients) Plasmapheresis (remove Ab-Ag complexes) T-cell vaccination (activate suppressing T cells) Block MHC with similar peptide anti-CD4 monoclonal Ab anti-IL2R monoclonal Ab
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THANKS