Presentation on theme: "There are four types of hypersensitivity reaction mediated by immunological mechanisms that cause tissue damage Types I, II and III are antibody-mediated."— Presentation transcript:
1There are four types of hypersensitivity reaction mediated by immunological mechanisms that cause tissue damageTypes I, II and III are antibody-mediated and are distinguished by the different types of antigens recognized and the different classes of antibody involved.Type I responses are mediated by IgE, which induces mast-cell activation, whereas types II and III are mediated by IgG, which can engage Fc-receptor and complement-mediated effector mechanisms to varying degrees, depending on the subclass of IgG and the nature of the antigen involved.Type II responses are directed against cell-surface or matrix antigens, whereas type III responses are directed against soluble antigens, and the tissue damage involved is caused by responses triggered by immune complexes.Type IV hypersensitivity reactions are T cell-mediated and can be subdivided into three groups. In the first group, tissue damage is caused by the activation of macrophages by TH1 cells, which results in an inflammatory response. In the second, damage is caused by the activation by TH2 cells of inflammatory responses in which eosinophils predominate; in the third, damage is caused directly by cytotoxic T cells (CTL).
2IPERSENSIBILITA’ DI TIPO II È MEDIATADA ANTICORPI DIRETTI VERSO ANTIGENI PRESENTI SULLA SUPERFICIE CELLULARE O SULLA MATRICE EXTRACELLULAREAntigene intrinseco della membrana cellulare oppure della matriceAntigene esogeno (metabolita di farmaci adsorbito sulle superfici cellulari o sulla matrice
13IPERSENSIBILTA’ TIPO III I COMPLESSI ANTIGENE-ANTICORPO PRODUCONO DANNI TISSUTALI SOPRATTUTTO PROVOCANDO INFIAMMAZIONE NEI SITI DI DEPOSITOLa presenza di complessi Ag-Ab in circolo non implica la presenza di malattia;Due tipi di Ag provocano lesioni da Immunocomplessi:Ag esogeno (batterio, virus)Ag endogeni (self)Malattie da immunocomplessi possono essereGeneralizzate o localizzate
16MALATTIA DA SIERO ACUTA Prototipo della malattia sistemica da immunocomplessiSerum sickness is a classic example of a transient immune complex-mediated syndrome. An injection of a foreign protein or proteins leads to an antibody response. These antibodies form immune complexes with the circulating foreign proteins. The complexes are deposited in small vessels and activate complement and phagocytes, inducing fever and the symptoms of vasculitis, nephritis, and arthritis. All these effects are transient and resolve when the foreign protein is cleared.
25The stages of a delayed-type hypersensitivity reaction. The first phase involves uptake, processing, and presentation of the antigen by local antigen-presenting cells. In the second phase, TH1 cells that were primed by a previous exposure to the antigen migrate into the site of injection and become activated. Because these specific cells are rare, and because there is little inflammation to attract cells into the site, it can take several hours for a T cell of the correct specificity to arrive. These cells release mediators that activate local endothelial cells, recruiting an inflammatory cell infiltrate dominated by macrophages and causing the accumulation of fluid and protein. At this point, the lesion becomes apparent.
26The delayed-type (type IV) hypersensitivity response is directed by chemokines and cytokines released by TH1 cells stimulated by antigen. Antigen in the local tissues is processed by antigen-presenting cells and presented on MHC class II molecules. Antigen-specific TH1 cells that recognize the antigen locally at the site of injection release chemokines and cytokines that recruit macrophages to the site of antigen deposition. Antigen presentation by the newly recruited macrophages then amplifies the response. T cells can also affect local blood vessels through the release of TNF-a and TNF-b, and stimulate the production of macrophages through the release of IL-3 and GM-CSF. Finally, TH1 cells activate macrophages through the release of IFN-g and TNF-a, and kill macrophages and other sensitive cells through the cell-surface expression of the Fas ligand.
27Type IV hypersensitivity responses Type IV hypersensitivity responses. These reactions are mediated by T cells and all take some time to develop. They can be grouped into three syndromes, according to the route by which antigen passes into the body. In delayed-type hypersensitivity the antigen is injected into the skin; in contact hypersensitivity it is absorbed into the skin; and in gluten-sensitive enteropathy it is absorbed by the gut