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Immunodeficiency disease Immunodeficiency diseases are caused by congenital or acquired defects in lymphocytes, phagocytes, and other mediators of adaptive and innate immunity. These diseases are associated with an increased susceptibility to infection, the nature and severity of which depend largely on which component of the immune system is abnormal and the extent of the abnormality. Immunodeficiency disease, IDD: results from a genetic or developmental defect or acquired factors in the immune system, and is a syndrome mostly characterized by infection in clinic. The principal consequence of immunodeficiency is an increased susceptibility to infection Patients with immunodeficiencies are also susceptible to certain types of cancer. Certain immunodeficiencies are associated with an increased incidence of autoimmunity. Immunodeficiency may result from defects in lymphocyte development or activation or from defects in the effector mechanisms of innate and adaptive immunity. CONGENITAL (PRIMARY) IMMUNODEFICIENCIES In different congenital immunodeficiencies, the causative abnormality may be in components of the innate causative system, at different stages of lymphocyte development, or in the responses of mature lymphocytes to antigenic stimulation. Defects in Innate Immunity Innate immunity constitutes the first line of defense against infectious organisms. Two important mediators of innate immunity are phagocytes and complement, both of which also participate in the effector phases of adaptive immunity. Antibody Deficiencies: Defects in B Cell Development and Activation Whereas defects in T cell development or in both T and B cell development contribute to the SCID phenotype, more circumscribed defects in B cells result in disorders in which the primary abnormality is in antibody synthesis Primary immunodeficiency diseases Inducement: heredity、developmental defect Age: infancy and childhood Pathogenesis: the differentiation and development of hemopoietic stem cells Therapeutic Approaches for Congenital Immunodeficiencies The current treatment of immunodeficiencies has two aims: to minimize and control infections and to replace the defective or absent components of the immune system by adoptive transfer or transplantation. Passive immunization with pooled gamma globulin is very beneficial for agammaglobulinemic patients and has been lifesaving for many boys with X-linked agammaglobulinemia. 1、characterized by humoral immunity deficiency 2、characterized by cellular immunity deficiency 3、 Combined immunodeficiency diseases 4、 Nonspecific immunodeficiency diseases 1、characterized by humoral immunity deficiency Features: increased susceptibility to bacteria、enterovirus、 intestine parasites,delayed in growth and development increased incidence of autoimmune disease、 malignant tumor reduced numbers of peripheral blood B cells,absent or reduced levels of Ig Pathogenesis: the block of the differentiation and development of B cells、 reduced function of Th cells 1)Bruton’s syndrome(x-linked agammaglobulinaemia) 2)Selectively IgA deficiency 3)Ig immunodeficiency with increased IgM Selectively IgA deficiency:the most common immunodeficiency Immunological features: lack serum IgA, <50mg/L, decreased level of sIgA Pathogenesis: failure in terminal differentiation of B cells Clinical features: recurrent infections in respiratory tract、 alimentary canal、urogenital tract Treatment: breast feeding,few of them can automatically resume the ability to produce IgA Ig immunodeficiency with increased IgM Immunological features: increased level of IgM, decreased levels of other Ig Pathogenesis: absent of the T cell effector CD40L,CD40L can not bind to CD40 of B cells,and therefore do not stimulate B cells to undergo Ab class switching Genetic features:x-linked recessive inheritance,boy Clinical features:recurrent pyogenic infections, increased level of IgM, decreased levels of IgA、IgG characterized by cellular immunity deficiency Features: increased susceptibility to intracellular microbes notable delay in growth and development、death in the early age increased incidence of malignant tumor reduced numbers of peripheral blood B cells,no reaction to DTH ,no reaction to HVGR block in the differentiation and development of the T cells Combined immunodeficiency diseases 1)SCID: severe combined immunodeficiency disease 2) immunodeficiency diseases with enzymes defect 3) immunodeficiency diseases with other severe defects Nonspecific immunodeficiency diseases 1)deficiency of phagocytes Immunological features:decreased number and defected function of macrophages Clinical features:chronic granulomatous disease Pathogenesis:deficient in NADH/NADPH oxidase in neutrophils, decreased the ability in bacterial killing dependent on oxygen radical 2)deficiency of complement components genetic deficiencies of complement components or complement regulatory proteins hereditary angioneurotic oedema, deficiency of C1INH, vasodilatation,increased permeability of the blood capillary skin、mucous membrane edema Secondary immunodeficiency diseases 1、succeed some diseases SIDD 2、iatrogenic SIDD 3、acquired immunodeficiency syndrome AIDS 1、succeed some diseases SIDD infection:virus infection decreased function of cellular immunity, decreased function of the T cells malignant tumors:decreased function of cellular immunity decreased function of the T cells notablely decreased function of the T and B cells Loss of proteins: excessive consume or insufficient synthesis : decreased level of Ig, decreased function of humoral immunity severe malnutrition: decreased function of the T cells 2、 iatrogenic SIDD 1) using immunosuppressive drugs、some antibiotics, antineoplastic for a long time 2) damage by irradiation 3、 acquired immnodeficiency syndrome,AIDS 1) etiology:RNA retrovirus HIV HIV-1 HIV-2 infect CD4+T、Mf、glial cell HIV and AIDS an infectious agent only 2 cases of Pneumocystis carinii pneumonia in Los Angeles in 1967-1978 1979 – 5 cases of Pneumocystis carinii pneumonia All of them were homosexual With giemsa stain at high magnification, the faint bluish dot-like intracystic bodies of Pneumocystis carinii in lung are seen in this cytologic preparation from a bronchoalveolar lavage HIV and AIDS cellular basement Decreased number of a type of cells in the course of the disease CD4+ Th cells Decreased number of CD4+ cells always before the happen of the disease Decreased number of another type of cells in the later stage of the disease CD8+ T cells AIDS is an infectious disease induced by a type of virus. Defination of AIDS The blood CD4+ T cell count drops below 200 cells/mm3 in the HIV-infected patients. AIDS is the results of the persistive infection of HIV. HIV - virus membrane:derived from the host cell membrane two kinds of glycoproteins: gp160 gp120 and gp41 gp41 is a transmembrane protein, and gp120 is an external protein, noncovalently associated with membrane. HIV - life cycle enter into cell CD4+T cell is the major target cell human HeLa cells without infection human HeLa cells transfected with CD4 antigen infection 2) Pathogenesis and Immunological features HIV gp120 infect CD4 host cells lead to (1) virus replication,cell death (2) fusion of the cells multinucleated giant cells, cell death (3)decrease or invert the ratio of CD4/CD8 the decline of Th cells,the depletion and loss of function of Th cells polyclonal activation of the B cells Mf increased levels of the IL-1 and TNF-a Decreased nuber of the NK cells,increased incidence of malignant tumor、virus infection 3)Clinical features Latent period:6 month—4 year Infection phase:influenza-like symptom、infectious Abs production:3-20 weeks symptom:AIDS related complex ARC (1) opportunistic infections (2) malignant tumors:Kaposi’s sarcoma、malignant lymphoma (3) abnormal of the central nervous system 4)epidemiology、prevention and cure major group at risk:homosexual、drug abusers、 infected blood or blood products spread manner:sexual contact、blood、mother-tochild transmission 5)detection and Treatment Ab detection: treatment: