Transcript IDD

Immunodeficiency Disease
1. Introduction
2. Primary immunodeficiency disease
3. Secondary immunodeficiency disease
1. Introduction
Immunodeficiency Disease，IDD：
Integrity of the immune system is essential for defense against
infectious agents. Defects in one or more components of the
immune system can lead to serious and often fatal disorders.
Mechanism: Abnormalities in different aspects of immune cells,
molecules in the development, differentiation, metabolism,
regulation.
Characteristics: Susceptible, recurrent, refractory, delayed healing,
infection of low pathogenicity pathogens. Increased incidence of
cancer, autoimmune diseases, allergy.
Classification: Primary IDD, Secondary SIDD
specific, non-specific
2. Primary immunodeficiency disease
Induction factors: genetic, congenital hypoplastic
Age: infant
Pathogenesis: Hematopoietic stem cell
differentiation and development
Classification:
 IDD mainly to humoral immune
 IDD mainly to cellular immune
 Combined immunodeficiency
 Non-specific immune deficiency
1) IDD mainly to humoral immune
Feature: Increase the susceptibility of bacteria, intestinal viruses,
intestinal parasites, Growth retardation
High incidence of autoimmune disease, malignant tumors
Reduction in the number of peripheral blood B cells
Decrease or absence of the Ig
Mechanism: Disorders of B cell differentiation, developmental
Th dysfunction
Bruton Disease
Selective IgA deficiency
X-linked hyperimmunoglobulin M syndrome
Bruton Disease (X-linked agammaglobulinemia)
Feature: Lack of B cells and IgG in blood
Mechanism: Pre B cell differentiation, developmental
disorders
Pathogenesis: x-linked recessive , most male
Clinical: Repeatedly sustained bacterial infection, no
antibody response to vaccination
Treatment: Intramuscular injection of gamma globulin
Albumin
Globulin
a1
a2
（a）
（b）
（c）
X-linked agammaglobulinemia ,
b
g
Selective IgA deficiency: common variable
Feature: Lack of IgA in serum <50mg/L, sIgA 
Mechanism: Final stages of B cell development
stagnate
Clinical: Recurrent respiratory tract, gastrointestinal
tract, urinary tract infection
Treatment: Breastfeeding
Endoscopic imaging of the duodenum shows multiple prominent nodules
3–5 mm in size, consistent with nodular lymphoid hyperplasia
X-linked hyperimmunoglobulin M syndrome
Feature: With IgM , others 
Mechanism: T cell lack of CD40L
B cells remain in the IgM stage
Antibody type conversion defect
Pathogenesis: x-linked recessive , most male
Clinlcal: Recurrent pyogenic infections,
IgM , IgA, IgG 
2) IDD mainly to cellular immune
Feature:
Increased susceptibility to intracellular bacteria
Significantly delayed growth and development, who
died in infancy
High incidence of malignant tumors
Decreased peripheral blood T cells, DTH response to
negative, Graft rejection negative.
T cell differentiation, developmental disorders
2) IDD mainly to cellular immune
DiGeorge Syndrome
T cell surface molecular structure and function of defect
DiGeorge Syndrome （Congenital thymic aplasia ,
III, IV pharyngeal pouch syndrome ）
Feature: Absence or hypoplasia of thymus
Mechanism: Non-hereditary
Pathogenesis: Low cellular immune function,
Parathyroid dysfunction
Clinical: Repeated intracellular bacteria infection,
Graft rejection-free
Treatment: Thymus transplantation
Patient with DiGeorge syndrome
Depleted thymus-sependent area (TDA)
small primary folicles (PF)
Normal subject:
The populated T-cell area
the well-developed secondary folicle
with its mantle of small lymphocytes (M)
Germinal center (GC)
Nude mice who had no T cells in the thymus is a
natural animal model of selective defects
T cell surface molecular structure and function of defect
TCR loss: TCR ab
CD3 Mutations
NF-AT gene defect: reduced immune response
IL-2 
others
3) Combined immunodeficiency
Severe combined immunodeficiency disease
IDD with enzyme deficiency
IDD with other deficiency
Severe Combined Immunodeficiency Disease, SCID
Humoral, cellular immune dysfunction at the same time
Autosomal recessive SCID
Feature: defects in the common stem cells of T, B cell
HLA class II molecules defects SCID
Clinical: Increased susceptibility to infection, no
peripheral blood CD4 + T, B cell function decreased
x-sex-linked genetic SCID
Mechanism：IL-2 receptor g chain gene mutation
Peripheral blood T, NK cells decreased
A child with severe combined
immunodeficiency showing skin
lesions due to infection with
vaccinia gangrenosum resulting
from smallpox immunization.
Lesions were widespread over
the whole body.
severe combined-immunodeficiency disease, SCID
X-linked SCID, XSCID
Mutations in the g c ( common g chain) chain of the receptors for
interleukins IL-2, -4,-7,-9 and -15
**Signal transduction ,
**lymphocyte differentiation, proliferation and maturation
4) Non-specific immune deficiency
Phagocyte deficiency
Feature: Reduction in the number and function of
phagocytes defects
Clinical: Chronic granulomatous
Mechanism: Neutrophil lack of NADH/NADPH oxidase,
weakening of oxygen dependent disinfection
Chronic granulomatous
xijun
Th1 cell
多核巨大细胞
内皮样细胞
M
纤维母细胞
4) Non-specific immune deficiency
Complement system deficiency
Complement components, regulatory proteins in genetic
defects.
Hereditary angioedema, lack of C1INH, Vasodilator,
capillary permeability, Skin and mucous membrane edema .
3. Secondary immunodeficiency disease
1) SIDD secondary to certain diseases
2) Iatrogenic SIDD
3) Acquired immunodeficiency syndrome
1) SIDD secondary to certain diseases
Infection: Virus infection
Decreased T cell function
Cancer: Significantly decreased of T, B immune function
Protein loss: Excessive consumption or insufficient
synthesis
Ig  , Humoral immune function decline
Severe malnutrition, Decreased T cell function
2) Iatrogenic SIDD
 Long-term use of immunosuppression and
certain antibiotics, antitumor drugs
 Radiation injury
3) Acquired Immnodeficiency Syndrome, AIDS
Etiology: Retroviral RNA
HIV
HIV-1
HIV-2
infect CD4+ T, M, Glial cells
HIV and AIDS
an infectious agent
Los Angeles 1967-1978 only two cases of Pneumocystis
carinii pneumonia
• 1979 – 5 cases of Pneumocystis carinii
pneumonia
All homosexuals
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 Incubation Period (Adults)
Not Infected - Infected - - - Infectious - - - AIDS- - - - Death
- - 3 - 10 years - -
-1 yr-
AIDS Cases by Age and Sex, Reported 1981-1998, United States
Estimated number of AIDS related deaths worldwide 1980-2000 WHO
Mother to child transmission of HIV 1979-1999 by breast-feeding or
other cause WHO
Pathogen:
HIV: dsRNA
Target cells: immune cells
HIV budding from human lymph tissue (TEM x133,335)
The necessity for CD4 antigen expression for entry of HIV into a
human cell. HeLa cells do not have CD4 antigen and are not
infected. HeLa cells transfected with CD4 gene are infected
Chemokine receptors are involved, in association with CD4 antigen, in infection by HIV
(left). The chemokine can block attachment of the virus to its receptors (middle).
Mutations in the chemokine receptor can lead to resistence to HIV infection (right)
Virus titer, CD4 and CD8 cell number during the course of HIV infection
Multinucleated cell (syncytium) in touch preparation from cut surface of enlarged lymph node
from patient with HIV-1 infection. Cell fusion producing a large multinucleated cell is a viral
cytopathic effect characteristic, but not diagnostic, of infection by HIV-1.
Kaposi's sarcoma (skin).
Lesions on the stomach of a patient with Kaposi's sarcoma
Skin showing
AIDS-associated
Kaposi's sarcoma
Figure - Kaposi's Sarcoma
Scanning electron micrograph of HIV-1 budding from cultured lymphocyte. Multiple
round bumps on cell surface represent sites of assembly and budding of virions
Clinical manifestations of AIDS
Clinical manifestations of AIDS
Facial
sarcoidosis in
AIDS
Severe angular cheilitis
Hairy leukoplakia of tongue
Candida and herpes simplex
Oral thrush.
Orofacial granulomatosis with cobble stone mucosa
SUMMARY