Immunodeficiency disease Part 1、Introduction Part 2、Primary immunodeficiency diseases Part 3、Secondary immunodeficiency diseases

Part 1、Introduction 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.

Pathogenesis: abnormalities of immunocyte、molecules in development、 differentiation、metabolism、regulation, etc. Clinical features: increased susceptibility to infection、 recurrent、hard to be cured、deferment、the infection of low virulence pathogens. increased incidence of malignant tumor、autoimmune disease 、 hypersensitivity Classification: Primary immunodeficiency diseases (PIDD)、Secondary immunodeficiency diseases (SIDD) specific、nonspecific

Part 2、Primary immunodeficiency diseases Inducement: heredity、developmental defect Age: infancy and childhood Pathogenesis: the differentiation and development of hemopoietic stem cells 1、IDD characterized by humoral immunity deficiency 2、IDD characterized by cellular immunity deficiency 3、 Combined immunodeficiency diseases 4、 Nonspecific immunodeficiency diseases

1、IDD 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

1）Bruton’s syndrome（x-linked agammaglobulinaemia） Immunological features: the absence of B cells in blood and IgG Pathogenesis: block in the differentiation and development of the pre-B cells Genetic features: x-linked recessive inheritance, males Clinical features: recurrent bacterial infections，no Ab responds to vaccination Treatment: inject pooled gamma globulin preparations

2）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

3） 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

2、IDD 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 1）DiGeorge syndrome (genetical thymus hypoplasia，third and fourth pharyngeal arch syndrome） 2）Structure and function defect of T cell surface molecules

1）DiGeorge syndrome (genetical thymus hypoplasia，third and fourth pharyngeal arch syndrome） Immunological features：absent or hypogenesis of the thymus Pathogenesis：non heredity Genetic features：decreased function of the cellular immunity，defect function of the parathyroid gland Clinical features： recurrent infections of intracellular bacteria，no reaction to HVGR Treatment：fetal thymic transplantation

2）Structure and function defect of T cell surface molecules 1.   absent of the TCR：TCRab 2.   mutant of the CD3 molecular： 3.    defect of the NF-AT gene：reduced ability of the immune response，reduced level of IL-2 4.    others：

3、 Combined immunodeficiency diseases 1）SCID: severe combined immunodeficiency disease 2） immunodeficiency diseases with enzymes defect 3） immunodeficiency diseases with other severe defects

SCID: severe combined immunodeficiency disease lose of the humoral immunity and cellular immunity at the same time 1. Autosomal recessive SCID Immunological features：defect of the common precursors of T and B cells 2. Defects in HLA II molecular SCID Immunological features： increased susceptibility to virus infection， no CD4+T cells in peripheral blood 、 decreased Function of the B cells 3. x-linked SCID Pathogenesis：gene mutation of IL-2 receptor g chain reduced numbers of peripheral blood T cells and NK cells

4、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

Part 3、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 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 antineoplastic for a long time  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 But HIV was difficult to grow from the infected patients blood. It killed the cells on which it grows and it could not be grown on ordinary cultured T4 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. The establishment that the disease is caused by a virus and therefore the ability to produce antibodies against viral antigens led to the first tests for HIV, the ELIZA and Western blot tests. However, there is a 1 to 2 month time lag before antibodies are produced. This can be overcome by using a test that identifies viral RNA rather than antibodies produced against viral protein e.g PCR. The very fact that we can use an antibody test shows us that there is a good immune response and it is neutralizing antibody which gives hope for a vaccine. But the virus is not completely neutralized which argues that a vaccine may be difficult to develop. The virus goes underground within the cells and because it is a retrovirus, is prone to genetic drift. As it changes it overcomes the immune system. As we shall see retroviral vaccines pose special problems and HIV is more complicated than other retroviruses

HIV - life cycle without infection infection enter into cell CD4+T cell is the major target cell human HeLa cells transfected with CD4 antigen human HeLa cells Human HeLa cells are not infected by HIV because they do not have CD4 antigen. When CD4 gene was transfected into the HeLa cells, they became able to bind HIV and were infected. without infection 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-to- child transmission 5）detection and Treatment Ab detection： treatment：vaccine

to mast the concept and the features of the immunodeficiency diseases to mast the immunological features of the DiGeorge syndrome、Bruton’s syndrome、Selectively IgA deficiency to be familiar with the immunological features of PIDD to be familiar with the pathogenesis、 immunological features and clinical features of AIDS to know the classification of the immunodeficiency diseases and the features of all types of immunodeficiency diseases to know the types of Combined immunodeficiency diseases to know the pathogenesis and immunological features of SIDD