• Terms:
  • Autologous
  • Tissue or organ transferred into a new position in the body of the same individual. Syn: autotransplant, autogeneic graft, autologous graft, autoplastic graft.
  • Syngenic
  • A tissue or organ transplanted between genetically identical individuals. Syn: isogeneic graft, isologous graft, isoplastic graft, syngeneic graft, isograft.
  • Allogenic
  • A graft transplanted between genetically nonidentical individuals of the same species. Syn: allogeneic graft, homologous graft, homoplastic graft, homograft.
  • Xenogenic
    • A graft transferred from an animal of one species to one of another species. Syn: heterologous graft, heteroplastic graft, xenogeneic graft, heterograft.

• Rejection of graft
• Infection
• Graft-versus-host disease
• Cancer
• Recurrence of origional disease (e.g., renal disease)

• The immunologic response to incompatibility in a transplanted organ.

• Invasion of the body with organisms that have the potential to cause disease.

• An incompatibility reaction (that may be fatal) in a subject (host) of low immunologic competence who has been the recipient of immunologically competent lymphoid tissue from a donor who is immunologically different from the recipient; the reaction, or disease, is the result of action of the transplanted cells (CD4+ and CD8+ - mediated)against those host tissues that possess an antigen not found in the donor. Seen most commonly following nonautologous bone marrow transplantation, acute disease is seen after 7–30 days and chronic disease weeks to months after transplantation, affecting, principally, the gastrointestinal tract, liver, spleen, and skin. Syn: GVH disease.

• Lymphoma
• Kaposi sarcoma
• Squamous cell CA of the skin
• Cancer is a general term frequently used to indicate any of various types of malignant neoplasms, most of which invade surrounding tissues, may metastasize to several sites, and are likely to recur after attempted removal and to cause death of the patient unless adequately treated; especially, any such carcinoma or sarcoma, but, in ordinary usage, especially the former.

• Any neoplasm of lymphoid tissue; in general use, synonymous with malignant lymphoma.

• A multifocal malignant neoplasm of primitive vasoformative tissue, occurring in the skin and sometimes in lymph nodes or viscera, consisting of spindle cells and irregular small vascular spaces frequently infiltrated by hemosiderin-pigmented macrophages and extravasated red cells; clinically manifested by cutaneous lesions consisting of reddish-purple to dark-blue macules, plaques, or nodules; seen most commonly in men over 60 years of age and, in AIDS patients, as an opportunistic disease associated with human herpes virus 8 infection. Syn: multiple idiopathic hemorrhagic sarcoma.

• A malignant neoplasm derived from stratified squamous epithelium, but which may also occur in sites such as bronchial mucosa where glandular or columnar epithelium is normally present; variable amounts of keratin are formed, in relation to the degree of differentiation, and, if the keratin is not on the surface, it may accumulate in the neoplasm as a keratin pearl; in instances in which the cells are well differentiated, intercellular bridges may be observed between adjacent cells.

• An antigen on the surface of nucleated cells, particularly leucocytes and thrombocytes. See Also: H-2 antigens. Syn: transplantation antigen.

• Cell-membrane–bound glycoproteins found on most nucleated cells and platelets that are coded by genes of the major histocompatibility complex on chromosome 6.
• There are three groups coded on three loci:
  • HLA-A
  • HLA-B
  • HLA-C
  • These glycoproteins will elicit antibodies in nonidentical individuals
  • Function to bind endogenously synthesized antigen (e.g., viral products in infected cells) and then present processed antigens to CD8+ cytotoxic T-cells

• A cell membrane glycoprotein encoded by genes of the major histocompatibility complex. These antigens are confined to and distributed on antigen- presenting cells such as:
• dendritic cells
• macrophages
• B-cells
• Activated T-cells
• Inflammed endothelial cells
• Epithelial cells

• Sensitization phase
  • Host cells are recognized by transplant cells as foreign.
• Effector phase
  • T-cells react to processed MHC antigens in graft.
  • Cells involved:
    • CD4+ T-cells
      • These cells recruit macrophages
    • CD8+ T-cells
    • Natural Killer (NK) Cells

large granular lymphocytes which do not express markers of either T or B cell lineage. These cells do possess Fc receptors for IgG and can kill target cells using antibody- dependent cell-mediated cytotoxicity. NK cells can also use perforin to kill cells in the absence of antibody. Killing occurs without previous sensitization. Syn: NK cells.

• B-cells (sometimes)
• Cytokines involved:
  • Interleukin-2
    • A cytokine derived from T helper lymphocytes that causes proliferation of T lymphocytes and activated B lymphocytes.
  • Gamma-interferon (IFN-gamma)
    • interferon elaborated by T lymphocytes in response to either specific antigen or mitogenic stimulation; only one gene codes for +interferon. interferon gamma behaves like a biological response modifies and is highly immunoregulatory. Syn: antigen interferon, immune interferon.
• Cytolysis
  • Cytolysis refers to the dissolution of a cell.
  • In transplant rejection this is manifested by:
    • Microvascular injury
    • Ischemia
    • Macrophage-mediated destruction
• CYTOKINES:  Cytokines are produced by macrophages, B and T lymphocytes, mast cells, endothelial cells, fibroblasts, and stromal cells of the spleen, thymus, and bone marrow. They are involved in mediating immunity and allergy and in regulating the maturation, growth, and responsiveness of particular cell populations, sometimes including the cells that produce them (autocrine activity). A given cytokine may be produced by more than one type of cell. Some cytokines enhance or inhibit the action of other cytokines. The first cytokines to be identified were named according to their functions (e.g., T cell growth factor), but this nomenclature became awkward because several cytokines can have the same function, and the function of a cytokine can vary with the circumstances of its elaboration. Later, as the chemical structure of each cytokine was determined, it was designated an interleukin and assigned a number (e.g., interleukin- 2 [IL- 2], formerly T cell growth factor). Cytokines have been implicated in the generation and recall of long-term memory and the focusing of attention. Some of the degenerative effects of aging may be due to a progressive loss of regulatory capacity by cytokines. Because cytokines derived from the immune system (immunokines) are cytotoxic, they have been used against certain types of cancer.
• Antibody-mediated responces (sometimes)

• Resembles organ infarction
• Observed in individuals previously sensitized to antigens
  • e.g., blood transfusions from previous pregnancy
• Onset in minutes to days
• Preformed circulating antibody fixes to antigens in graft's vascular bed
• Complement-mediated and ADCC- mediated injury
  • ADCC = antibody-dependent cell- mediated cytotoxcicity
• Macroscopic appearance of tissue
• Cyanotic
  • Cyanosis:  A dark bluish or purplish discoloration of the skin and mucous membrane due to deficient oxygenation of the blood, evident when reduced hemoglobin in the blood exceeds 5 g/100 ml.
• Mottled
• Flaccid tissue
• Most often involves the kidney
• Histology
• Fibrionoid necrosis of arterioles
  • necrosis of the arterioles in which the necrotic tissue has some staining reactions resembling fibrin and becomes deeply eosinophilic, homogenous, and refractile.
• NECROSIS:  Pathologic death of one or more cells, or of a portion of tissue or organ, resulting from irreversible damage; earliest irreversible changes are mitochondrial, consisting of swelling and granular calcium deposits seen by electron microscopy; most frequent visible alterations are nuclear: pyknosis, shrunken and abnormally dark basophilic staining; karyolysis, swollen and abnormally pale basophilic staining; or karyorrhexis, rupture and fragmentation of the nucleus. After such changes, the outlines of individual cells are indistinct, and affected cells may become merged, sometimes forming a focus of coarsely granular, amorphous, or hyaline material.
• Fibrin-platelet microthrombi
• Neutrophils
• Infarction
• Sudden insufficiency of arterial or venous blood supply due to emboli, thrombi, mechanical factors, or pressure that produces a macroscopic area of necrosis.

• Any time after transplantation
• Cellular and humoral mechanisms
• Acute cellular rejection
  • Cytolysis
  • Microvascular injury (ischemia)
  • Mononuclear cell infiltrate
    • CD4+ T-cells
    • CD8+ T-cells
    • Macrophages
    • Plasma cells
• Acute rejection vasculitis
  • Mediated by anti-donor antibodies
  • Seen a fewweeks to  months after transplantation
  • Presents with necrosing vasculitis and thrombosis
  • Proliferating fibroblasts & foamy macrophages (resembles accelerated atheroma - infarction)

• Observed months to years
• T-cells play the central role
• Organ dysfunction
• Arteries show intimal fibrosis (ischemia)
• Mononuclear cell infiltrate