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Musculo skeletal system
 

Musculo skeletal system

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    Musculo skeletal system Musculo skeletal system Presentation Transcript

    • Autoimmune disease and the musculoskeletal system
      • Learning Objectives
      • describe two autoimmune diseases of the musculoskeletal system
      • describe how different pathogenic mechanisms lead to myasthenia gravis and rheumatoid arthritis
      • list the possible mechanisms leading to breakdown in self tolerance and subsequent autoimmune diseases
        • Two types of Immunity
      Innate/natural Adaptive
    • Cells Function Phagocytes (neutrophils and macrophages) Eating cells Mobile Neutrophils (Blood borne) Inflammation Resident Macrophages (present in tissues) Mast cells and Basophils Resident Mast cells (mucosal surfaces and in connective tissues) Mobile Basophils (blood borne) Natural Killer cells killing viruses Mobile Blood borne Cells of the Innate System
    • Molecules of the Innate System
      • Complement proteins (alternative pathway) - around 20 proteins - cascade system
      • - role in phagocytosis, lysis and inflammation
      • Acute Phase proteins - eg. C reactive protein, fibrinogen etc
      • Cytokines eg. interferons  ,  and  - blocks virus replication
    •  
    • T lymphocytes: T helper cells Tcytotoxic cells B lymphocytes Adaptive Immunity: Two kinds of lymphocytes: T and B
    • B lymphocytes make antibodies Plasma cells in tissues With T helper cells
    • T and B lymphocytes compared T cells B cells Origin thymus bone marrow Memory + + Ag Receptors TCR BCR Products cytokines antibodies Subsets Th/Tc - (+) Target microbes intracellular extracellular
    • Innate Adaptive Cells Phagocytes Lymphocytes Neutrophil B lymphocyte Macrophages T lymphocyte Mast cell, basophil helper Natural killer cell cytotoxic Molecules Complement Antibody (‘humoral factors’) Cytokines Cytokines Acute phase proteins Speed and duration Rapid, short-lived Slow, prolonged, can increase Development of memory NO YES
    • Range of organisms that invade man
    •  
    • Spectrum of autoimmune diseases
    • Rheumatoid arthritis
      • peak incidence: young adults and premenstrual women
      • common (1-2%) of population) severe inflammatory disorder which can affect men and women of all ages
      • marked by variable course, with exacerbations and remissions
      • many patients have chronic progressive course resulting in severe morbidity and mortality
      • main target organ is synovium: inflammation vasculitis, oedema,infiltration by lymphocytes and macrophages, synovial proliferation and cartilage erosion
    •  
    • X-RAY - Rheumatoid Arthritis
    • Synovial follicles with germinal centres GC
    •  
      • Pathogenesis of RA
      • Immune complexes
      • T cells and cytokines
    • Classification of hypersensitivities Type Immune mechanisms I IgE antibodies (enhancement of acute inflammatory response II Antibody and complement III Antigen/antibody complexes IV T cell mediated (can be granulomatous)
      • Polymyositis/dermatomyositis
      • associated skin involvement occures in 50-60% of cases (dermatomyositis)
      • muscle disease associated with inflammation and autoantibodies (to histidyl-tRNA synthetase)
    • Myasthenia gravis
      • A disorder of neuromuscular transmission characterised by weakness and fatiguability of voluntary muscles
      • aetiology unknown
      • can occur at any age
      • affects mainly young women and middle-aged men
      • usually presents with weakness in the external ocular muscles
    •  
    •  
    •  
    • Localisation of IgG and complement at the motor end plate in myasthenia gravis IgG Complement
    • Myasthenia gravis:motor end plate
    • Classification of hypersensitivities Type Immune mechanisms I IgE antibodies (enhancement of acute inflammatory response II Antibody and complement III Antigen/antibody complexes IV T cell mediated (can be granulomatous)
    • Myasthenia Gravis
      • disorder of neuromuscular transmission characterised by abnormal fatigability of skeletal muscle ranging from transient double vision to life-threatening respiratory paralysis
      • prevalence is 5-9 per 100,000 and the incidence 2-4 per million
      • all ages and and races can be affected
      • 12% of babies born to myasthenic mothers due to transfer of maternal antibodies
      • Lambert-Eaton syndrome
      • (another autoimmune diseases affecting availability of acetylcholine at motor endplates)
      • defective release of acetyl choline
      • autoantibodies directed against components of voltage-gated calcium channels or against the synaptical vescicle protein synaptotagmin
      • Why do we develop autoimmune diseases?
      • Normally we are tolerant of our own molecules
      • Tolerance maintained at 2 levels :
      • Central
      • Peripheral
    • c Central Tolerance - T cells
    • Central tolerance - B cells
    • Breakdown in peripheral tolerance
    • Possible mechanisms leading to autoimmune diseases Polyclonal activation microbes and their products activate majority of B cells - low affinity antibodies eg. EBV Cross-reactive antigens microbial antigens have similar a.a sequences to self eg. rheumatic fever with Strep A
    • Polyclonal activation of B cells
    • Possible mechanisms leading to autoimmune diseases (2) Aberrant presentation most cells cannot present self of self antigens peptides to CD4+ T cells - viruses may induce MHC class II Release of sequestered eg. from the eye Regulatory regulatory T cells could be abnormalities defective
    • Autoimmune disease and the musculoskeletal system
      • Learning Objectives
      • describe two autoimmune diseases of the musculoskeletal system
      • describe how different pathogenic mechanisms lead to myasthenia gravis and rheumatoid arthritis
      • list the possible mechanisms leading to breakdown in self tolerance and subsequent autoimmune diseases
    • IMMUNOLOGY & CELL PATHOLOGY IMMUNOLOGY & CELL PATHOLOGY Student B-cell
    • Immunology and Cell Pathology Intercalated BSc Don’t forget about this exciting BSc programme. Details will shortly be on this website.
    • Windeyer Web Site http://windeyer.ucl.ac.uk/Students/medical students/Phase 1 Year 2 index.htm