Part 1Introduction

Part 2Primary immunodeficiency diseases

Part 3Secondary immunodeficiency diseases
Immunodeficiency disease
Part 1Introduction

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 immunocytemolecules in development
differentiationmetabolismregulation, etc.
Clinical features: increased susceptibility to infection recurrenthard to
be cureddefermentthe infection of low virulence
pathogens.
increased incidence of malignant tumorautoimmune disease
hypersensitivity
Classification: Primary immunodeficiency diseases (PIDD)Secondary
immunodeficiency diseases (SIDD)
specificnonspecific
Part 2Primary immunodeficiency diseases
Inducement: hereditydevelopmental defect
Age: infancy and childhood
Pathogenesis: the differentiation and development of
hemopoietic stem cells
1IDD characterized by humoral immunity deficiency
2IDD characterized by cellular immunity deficiency
3 Combined immunodeficiency diseases
4 Nonspecific immunodeficiency diseases
1IDD characterized by humoral immunity deficiency
Features increased susceptibility to bacteriaenterovirus
intestine parasitesdelayed in growth and development
increased incidence of autoimmune disease malignant tumor
reduced numbers of peripheral blood B cellsabsent or reduced
levels of Ig
Pathogenesis: the block of the differentiation and development of B cells
reduced function of Th cells
1Brutons syndromex-linked agammaglobulinaemia
2Selectively IgA deficiency
3Ig immunodeficiency with increased IgM
1Brutons syndromex-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 infectionsno Ab
responds to vaccination
Treatment: inject pooled gamma globulin preparations
2Selectively IgA deficiencythe 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 canalurogenital tract
Treatment: breast feedingfew 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 CD40LCD40L
can not bind to CD40 of B cellsand therefore
do not stimulate B cells to undergo Ab class
switching
Genetic featuresx-linked recessive inheritanceboy
Clinical featuresrecurrent pyogenic infections increased
level of IgM decreased levels of IgAIgG
2IDD characterized by cellular immunity deficiency
Features increased susceptibility to intracellular microbes
notable delay in growth and developmentdeath in the early age
increased incidence of malignant tumor
reduced numbers of peripheral blood B cellsno reaction to
DTH no reaction to HVGR
block in the differentiation and development of the T cells
1DiGeorge syndrome (genetical thymus hypoplasiathird and
fourth pharyngeal arch syndrome
2Structure and function defect of T cell surface molecules
1DiGeorge syndrome (genetical thymus hypoplasiathird
and fourth pharyngeal arch syndrome
Immunological featuresabsent or hypogenesis of the thymus
Pathogenesisnon heredity
Genetic featuresdecreased function of the cellular immunity
defect function of the parathyroid gland
Clinical features recurrent infections of intracellular
bacteriano reaction to HVGR
Treatmentfetal thymic transplantation
2Structure and function defect of T cell surface
molecules
1. absent of the TCRTCRab
2. mutant of the CD3 molecular
3. defect of the NF-AT genereduced ability of the immune
responsereduced level of IL-2
4. others
3 Combined immunodeficiency diseases
1SCID: 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 featuresdefect 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
Pathogenesisgene mutation of IL-2 receptor g chain
reduced numbers of peripheral blood T cells and NK
cells
4Nonspecific immunodeficiency diseases
1deficiency of phagocytes
Immunological featuresdecreased number and defected function of
macrophages
Clinical featureschronic granulomatous disease
Pathogenesisdeficient in NADH/NADPH oxidase in neutrophils
decreased the ability in bacterial killing dependent on
oxygen radical
2deficiency of complement components
genetic deficiencies of complement components or complement
regulatory proteins
hereditary angioneurotic oedema, deficiency of C1INH
vasodilatationincreased permeability of the blood capillary
skinmucous membrane edema
Part 3Secondary immunodeficiency diseases
1succeed some diseases SIDD
2iatrogenic SIDD
3acquired immunodeficiency syndrome AIDS
1succeed some diseases SIDD
infectionvirus infection decreased function of cellular immunity,
decreased function of the T cells

malignant tumorsdecreased 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 drugssome antibiotics
antineoplastic for a long time
2) damage by irradiation
3 acquired immnodeficiency syndromeAIDS

1) etiologyRNA retrovirus HIV HIV-1
HIV-2

infect CD4
+
TMfglial cell
HIV and AIDS
an infectious agent
1979 5 cases of Pneumocystis carinii
pneumonia
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

only 2 cases of Pneumocystis carinii pneumonia
in Los Angeles in 1967-1978
All of them were homosexual
HIV and AIDS
cellular basement
Decreased number of another type of cells in the later stage of the disease
CD8+ T cells
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
AIDS is an infectious disease induced by a type of virus.
AIDS is the results of the persistive infection of HIV.
Defination of AIDS
The blood CD4+ T cell count drops below
200 cells/mm
3
in the HIV-infected patients.
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
human HeLa cells
transfected with
CD4 antigen
without infection infection
2 Pathogenesis and Immunological features
HIV gp120 infect CD4 host cells lead to
1 virus replicationcell death
2 fusion of the cells multinucleated giant cells cell death
3decrease or invert the ratio of CD4/CD8
the decline of Th cellsthe 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 cellsincreased incidence of malignant
tumorvirus infection
3Clinical features
Latent period6 month4 year
Infection phaseinfluenza-like symptominfectious
Abs production3-20 weeks
symptomAIDS related complex ARC
1 opportunistic infections
2 malignant tumorsKaposis sarcomamalignant
lymphoma
3 abnormal of the central nervous system
4epidemiologyprevention and cure
major group at riskhomosexualdrug abusers
infected blood or blood products
spread mannersexual contactbloodmother-to-
child transmission
5detection and Treatment
Ab detection
treatmentvaccine
to mast the concept and the features of the immunodeficiency
diseases
to mast the immunological features of the DiGeorge syndrome
Brutons syndromeSelectively 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