Immunopathology I Flashcards
What does B cell antigen recognition lead to?
Neutralization of microbe, phagocytosis, complement activation
What do helper T cells do?
Activation of macrophages
Inflammation
Activation (proliferation and differentiation) of T and B cells
What is the function of cytotoxic T cells?
Killing of infected cell
What is the function of the regulatory T cells?
Suppression of immune response
What is type I hypersensitivity reactions?
Injury caused by TH2 cells, IgE antibodies, and mast cells and other leukocytes
What is type II hypersensitivity reaction?
Antibody mediated disorders
Secreted IgG and IgM antibodies injure cells by promoting their phagocytosis or lysis and injure tissues by inducing inflammation
What is type III hypersensitivity reaction?
Immune complex-mediated disorders
IgG and IgM antibodies bind antigens usually in the circulation and anitgen-antibody complexes deposit in tissue and induce inflammation
What is type IV hypersensitivity reaction?
Cell mediated immune disorders
Sensitized T lymphocytes (TH1 and TH17 cells and CTLs) are the cause of tissue injury
What is the process of type I hypersensitivity reaction?
Exposure to allergen
Activation of TH2 cells and IgE class switching in B cells
Production of IgE
Binding of IgE to Fc receptor on mast cells
Repeat exposure to allergen
Activation of mast cells causes degranulation
Mediators lead to immediate hypersensitivity reaction
or release cytokine for late phase reaction
What is the antigen and manifestation of systemic lupus erythematosus?
Nuclear antigens - circulating or planted in kidney
Nephritis, skin lesions, arthritis
What is the specificity of T cells, mechanisms of injury, and manifestations of rheumatoid arthritis (type IV)?
Collagen or citrullinated self proteins
Inflammation mediated by Th17 (and Th1) cytokines, role of antibodies and immune complexes
Chronic arthritis with inflammation and destruction of articular cartilage
What are the types of grafts?
Autograft - own tissue
Isograft - identical twin, same genetic background
Allograft - same species, different genetic background
Xenograft - different species
What is transplant rejection?
Immune damage resulting from recipient response to allograft HLA antigens
What is hyperacute rejection?
Recipient sensitized by prior transplant, multiple transfusions or pregnancies
Preformed Ab react against Ag in allograft endothelium - local IgG antibodies react (Type II hypersensitivity), complement activation, vasculitis with fibrinoid necrosis, thrombosis, ischemia
Immediate or within minutes to hours
Avoided by cross matching recipient serum with donor lymphocytes to determine presence of cytotoxic Ab to donor MHC class I and II antigens
What is acute rejection?
Progresses rapidly once initiated
Mediated by cellular, humoral or combined/overlapping mechanisms
Occurs days-moths post transplant or after withdrawal of immunosuppressive therapy
What occurs morphologically and with the cells with acute rejection?
Cytotoxic (CD8+) lymphocytes infiltrate tubular and vascular basement membranes - tubular damage, endothelitis
Helper T cells (CD4+) produce cytokines - extensive interstitial inflammation
Typical morphology - lymphocytic infiltrates and tubular necrosis
What are the mechanisms of Type IV hypersensitivity mechanisms?
Cell-mediated cytotoxicity
Delayed type hypersensitivity
What is cell mediated cytotoxicity?
Host cytotoxic lymphocytes destroy graft parenchymal and endothelial cells by releasing perforins and granzymes - apoptosis
What is delayed type hypersensitivity?
Helped lymphocytes secrete cytokines which leads to recruitment of mononuclear cells, release of inflammatory mediators (TNF, INF-gamma, IL-2), and tissue damage
What are humoral mechanisms?
Ab bind to HLA molecules in graft endothelium , activate complement - acute inflammation or vasculitis resembling Type II hypersensitivity reaction
Ag-Ab complexes form in circulation or in situ (Type III), fix complement - necrotizing, immune complex vasculitis
What is acute humoral rejection?
Anti-graft antibody deposit in graft vasculature
Patterns:
necrotizing vasculitis
intimal thickening due to accumulation of fibroblasts, foamy macrophages, myocytes
What is chronic rejection?
Occurs months to years after transplantation from repeated humoral or cellular insult
Humoral injury - proliferative vascular lesions
Cellular injury - cytokine induced proliferation of vascular smooth muscle and production of collagen in ECM
Morphology - vascular changes, interstitial fibrosis, tubular atrophy, chronic inflammation
When does a heart transplant occur and what occurs?
Treatment for advanced, irreversible myocardial disease with intractable congestive heart failure
Classic cellular rejection with interstitial and perivascular T cell infiltrates - myocytes necrosis that histologically resembled myocarditis
Complication - diffuse intimal proliferation - coronary artery disease
What are the complications of cardiac transplant?
Graft arteriopathy - silent MI leading to coronary heart failure or sudden death
Infections
Malignancies - Epstein-Barr virus associated B cell lymphomas that arise in the setting of T cell immunosuppression
