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Immunopathology

Immunopathology. Dr. Amitabha Basu MD. OUR TOPIC. TRANSPLANT REJECTION Graft Vs Host disease AUTOIMMUNE DISEASES. TRANSPLANT REJECTION and MHC matching. Type of graft. Mechanism of rejection. Graft survival. Complication of immunosuppression. Management. Graft Vs Host reaction.

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Immunopathology

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  1. Immunopathology Dr. Amitabha Basu MD

  2. OUR TOPIC • TRANSPLANT REJECTION • Graft Vs Host disease • AUTOIMMUNE DISEASES

  3. TRANSPLANT REJECTION and MHC matching Type of graft. Mechanism of rejection. Graft survival. Complication of immunosuppression. Management. Graft Vs Host reaction.

  4. Type of Grafts • Allograft: An organ or tissue transplanted from one individual to another of the same species, i.e. human to human. • Auto graft: Tissue that is taken from one site and grafted to another site on the same person; "skin from his thigh replaced the burned skin on his arms“ • Xenograft: A xenograft is a transplantation of tissue from a donor of one species to a recipient of another species • Fetal tissue grafts: Less chance of reaction.

  5. Mechanism of allograft rejection • T cell mediated reaction • Involve Cytotoxic T cell ( CD8+) • Type IV hypersensitivity reaction • Antibody mediated reaction (mainly ADCC).

  6. When you give a graft….. • The organ contain • Tissues of the organ • Some lymphocytes of the donor • Some macrophage (APC) of the donor

  7. In the direct pathway, • Donor class I and class II antigens on APC of the graft are recognized by CD8+ cytotoxic T cells and CD4+ helper T cells of host. • CD4+ cells→ cytokines→ tissue damage by a local delayed hypersensitivity reaction. • CD8+ T cells→ kill graft cells

  8. In the indirect pathway • Activate macrophage= tissue damage. • Form antigen antibody complex and produce vasculitis= tissue damage.

  9. Types of rejection reaction • Hyper acute rejection • Acute rejection: • Chronic rejection

  10. Hyperacute rejection • Hyperacute rejection occurs when preformed antidonor antibodies are present in the circulation of the recipient. • Morphology: shrunken liver, necrotic swollen tubular epithelial cell, may show pyknotic nuclei. • Scanty bloody urine.

  11. Transplant reaction

  12. Kidney change

  13. Management • Drug cyclosporine (block nuclear factor of activated T cells- thus inhibit the gene for IL-2). • Monoclonal anti-T-cell antibodies (e.g., monoclonal anti-CD3 and antibodies against the IL-2 receptor α chain).

  14. Methods of Increasing Graft Survival • HLA ( both Class I and class II antigen) matching in transplants. • Immunosuppressive therapy.

  15. Survival of grafts: HLA matching in transplants • HLA matching ( of donor and recipient cells) for both class I and class II antigens improves survival: MHC MHC Good = Donor R MHC MHC = Bad

  16. Immunosuppressive therapy As a method of graft survival What are the risks?

  17. Complications of Global Immunosuppression Opportunistic infections: Pneumocystis Carinii Sliver stain. Cytomegalovirus (CMV) pseudohyphae : Candida

  18. Candida (C. albicans ) infection Location: skin, mouth, gastrointestinal tract, and vagina . Risk : DM and immuno compromised patient. Presentation:(thrush-oral). Gray-white, dirty-looking pseudomembranes composed of matted organisms and inflammatory debris ,

  19. Others • Risk for developing EBV-induced lymphomas, • Human papillomavirus-induced squamous cell carcinomas, and • Kaposi sarcoma

  20. Transplantation of Hematopoietic Cells • Develop Graft vs host reaction. • GVH disease occurs in any situation in which immunologically competent cells are transplanted into immunologically crippled recipients. • Example: bone marrow, whole blood.

  21. Mechanism • Results from the donor lymphocytes attacking the recipient tissues that has offending HLA antigens. Lymphocyte of donor [CD8+ cells] Host tissue

  22. Types • Acute – days to week • Donor cells infiltrate host’s epithelia, liver, bile duct , Gut, lymphnode and dysfunction them. • Infection – CMV • Clinical: Jaundice, skin rash, bloody diarrhea, hepatomegaly heavy infiltration of lymphocytes in the host tissue.

  23. d/d of acute type of GVH • Transfusion reaction (TR) • in contract to GVH, TR occur immediately after transfusing a mismatched blood. • ( if you donate A+ blood to a person with B+ blood group etc)

  24. Types • Chronic – skin atrophy and cholestatic jaundice.

  25. C/F=GVH disease : Jaundice and Rash,

  26. Time for Autoimmunity

  27. Topic • Immune tolerance • Termination of tolerance • Definition: AUTOIMMUNITY • Mechanisms proposed for development of autoimmunity • Mediators • Autoantibody • Diseases

  28. Immune tolerance • A state of unresponsiveness to a specific antigen or group of antigens to which a person is normally responsive. • Self tolerance: Immune tolerance against self- antigen.

  29. Termination of tolerance • X-irradiation • Immunization with cross reactive antigens. • Autoimmune diseases.

  30. AUTOIMMUNITY  • Autoimmunity can be defined as breakdown of mechanisms responsible for self tolerance.

  31. Mechanisms proposed for development of autoimmunity include: 2 • Failure of “activation induced death” of self reactive T cell. Self reactive T cell So these T cells kills the cell of our body in spite they contain self antigen.

  32. Mechanisms proposed for development of autoimmunity include: • Molecular mimicry ; Some cells of our body share similar antigen like that of microbes, when antibodies produced to kill these microbes , they destroy cells of the body also. Host cell bacteria

  33. Termination of tolerance : examples (nice to know)

  34. Mediators • Cytokines. • Compliments.

  35. Cytokines • Interleukins • TNF-alpha • Interferons

  36. Few examples • IL-1, TNF-α, type 1 interferons & IL-6: innate immunity • IL-2 : Growth factor for T-cells • IL-12 and IFN-γ: involved in both innate and adaptive immunity • IL-10 and TGF-β: down-regulate immune responses

  37. Cytokines induce their effects in three ways: • Autocrine effect: IL-2 produced by antigen-stimulated T cells stimulates the growth of the same cells • Paracrine effect: IL-7 produced by bone marrow or thymic stromal cells promotes the maturation of B-cell progenitors in the marrow or T-cell precursors in the thymus, respectively • Endocrine effect: IL-1 and TNF- produce the systemic acute-phase response during inflammation. • Acute Inflammatory effect: IL1 and IL8.

  38. Autoantibody • Definition : Antibody against “self antigen”. • Mainly against various component of Nuclei. • These are celled : Antinuclear Antibodies (ANA).

  39. ANA DETECTION • By estimation of serum titer • By staining pattern the tissue.

  40. Disease ANA Staining pattern

  41. SLE Diffuse and Rim

  42. Systemic Lupus Erythematosus (SLE) • *Skin rash - Malar or discoid • Sensitivity to light (photo dermatitis) • Serositis/synovitis - inflammation of serosal surfaces along with effusions

  43. Typical skin lesion in SLE An immunofluorescence micrograph stained for IgG reveals deposits of immunoglobulin along the dermal-epidermal junction.

  44. SLE • Glomerulonephritis – Lupus nephritis = Nephrotic syndrome . • *Cytopenias - anemia, leucopenia, thrombocytopenia. • Heart: Libman-Sachs Endocarditis • Thrombosis - Antiphospholipid syndrome (APS) can occur in patients with SLE. • Splenomegaly: periarteriolar fibrosis ("onion skinning") .

  45. SLE • *Arthritis, fever, weight loss. • Vasculitis – with fibrinoid necrosis.

  46. Lupus nephritis : Wire loop lesion. Deposit of C1q occur.

  47. Chronic Discoid Lupus Erythematosus • Less severe. • Skin plaques showing varying degrees of edema, erythema, scaliness. • Diagnosis: positive ANA test, but dsDNA are rarely present.

  48. Drug induced lupus • Hydralazine, procainamide, INH, and D-penicillamine. • Diagnoses: • Positive antihistone antibodies. • Negative (mostly( dsDNA).

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