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

2. 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.

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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：

12. 3、 Combined immunodeficiency diseases
1）SCID: severe combined immunodeficiency disease
2） immunodeficiency diseases with enzymes defect
3） immunodeficiency diseases with other severe defects

13. 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

14. 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

15. Part 3、Secondary immunodeficiency diseases
1、succeed some diseases SIDD
2、iatrogenic SIDD
3、acquired immunodeficiency syndrome AIDS

16. 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

17. 2、 iatrogenic SIDD antineoplastic for a long time
 1)  using immunosuppressive drugs、some antibiotics，
antineoplastic for a long time
2) damage by irradiation

18. 3、 acquired immnodeficiency syndrome，AIDS
     1)   etiology：RNA retrovirus HIV HIV-1
HIV-2
infect CD4+T、Mf、glial cell

19. HIV and AIDS an infectious agent
only 2 cases of Pneumocystis carinii pneumonia in Los Angeles in
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

20. 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.

21. 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.

23. HIV - virus membrane:derived from the host cell membrane
two kinds of glycoproteins: gp 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

24. 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

25. 2） Pathogenesis and Immunological features
HIV gp 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

26. 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

27. 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

28. 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