Transcript Document

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：