Natural immune deficiency

(No defect)

(A) children's immune characteristics (in a state of low physiological immune function)

1. Nonspecific immune characteristics

(1) Children are in the process of growth and development, and the development of non-specific immune function is not yet mature, but it gradually matures with age.

⑵ Neonatal skin is thin and tender, and the barrier effect is poor.

⑶ Newborns and infants have high intestinal permeability, low gastric acid and weak bactericidal power.

(4) The function of infant lymph nodes is not yet mature.

5. The serum complement content is low.

2. Cellular immune characteristics

⑴ The cellular immune function of the fetus is not mature enough to produce enough immunity against intrauterine virus infection (CMV), which may cause the fetus to carry the virus for a long time.

⑵ The cellular immune function of newborns has been fully developed, and skin delayed hypersensitivity has been formed soon after birth. A few weeks after inoculation with BCG, the tuberculin test was positive.

3. Humoral immune characteristics

⑴IgM: The fetal period is low, and the normal umbilical cord blood content is only 65,438+00% for adults and 75% for adults aged 65,438+0.

Fetal infections such as rubella, CMV and IgM↑ in umbilical cord blood.

IgM does not pass through the placenta, so the mother IgM will not be transmitted to the fetus.

IgM is the main antibody against G- bacilli, so newborns are easily infected with G- bacilli.

⑵IgG: It is the only Ig that passes through the placenta, and it is the main antibody to resist infection within a few months after birth.

It is divided into four categories: IgG 1, IgG2, IgG3 and IgG4.

After birth, IgG from the mother gradually decreased due to metabolic decomposition, and all of them disappeared within half a year, and IgG production gradually increased in the third month after birth, reaching the human level at the age of 6-7.

⑶ IgA: IgA only appears at 30 weeks of pregnancy, and the serum at birth does not exceed 5mg/dl, but secretory IgA can be obtained from breast milk.

Serotype IgA is the third in Zhou Hecheng after birth, with 65,438+03% in adults aged 65,438+0, and reaching human level at 65,438+02.

The S IgA of newborns and infants is low, which is 3% for adults aged 1 2, reaching the human level.

Therefore, newborns and infants are vulnerable to respiratory and gastrointestinal infections.

⑷IgE: The content of IgE in cord blood is only 15% of that in adults, and it reaches the human level at the age of 7.

(2) Classification of primary immune diseases

1. Definition: Primary immunodeficiency disease is a group of diseases with immune function caused by abnormal occurrence, differentiation or interaction of immune cells. The etiology is not completely clear, which may be related to congenital immune organ hypoplasia, intrauterine infection and heredity. Clinically, the anti-infection function is low, and serious infectious diseases are prone to recur.

2. Classification:

(1) Humoral immune deficiency.

Congenital hypogammaglobulinemia

Transient hypogammaglobulinemia in infants

Selective immunoglobulin deficiency

Selective Igm deficiency

(2) cellular immune deficiency.

Congenital thymic hypoplasia

(3) Combined immunodeficiency.

Severe combined immunodeficiency disease

* * * Ataxia telangiectasia syndrome

(4) Phagocytosis

5] Complement deficiency

(3) Clinical manifestations of primary immunodeficiency disease.

1. infection: its characteristics are: ① the number of infections increases; 2 rare serious infections, such as septicemia and meningitis; ③ The infection persists and the treatment effect is not good; ④ Low pathogenic bacterial infection.

Humoral immunodeficiency -G+ infection

Cellular immune deficiency -G- bacterial infection, fungi, protozoa, viruses and mycobacteria

2. Weight loss, short stature and stunted growth.

3. Gastrointestinal dysfunction, such as diarrhea, malabsorption and vomiting.

About 20% of humoral immune deficiency has chronic diarrhea.

People with cellular immune deficiency have more diarrhea, which can cause exfoliation of epidermis around anus.

4. Skin abnormalities: pyoderma, eczema, petechiae, alopecia and macula.

5. Other manifestations: hepatosplenomegaly, swelling of small joints and limited joint activity.

6. Special manifestations: gangrenous vaccinia reaction, tetany, short limb dwarfism, ataxia, telangiectasia, granuloma, and blood abnormality (thrombocytopenia).

(four) the experimental examination of primary immunodeficiency disease

1. General test:

(1) hemogram

⑵ Lymphocyte count: < 1.2× 109/L, suggesting that T cells are immune deficiency.

⑶ Bone marrow examination: Decreased plasma cells indicate humoral immune deficiency.

2. Examination of humoral immune function:

⑴ Quantitative determination of serum immunoglobulin: IgG < 2.5g/L means deficiency.

IgA < 0.05-0. 1g/L is deficient.

IgM < 0.05-0. 1g/L is deficient.

⑵ Homologous blood group lectin: It is a natural antibody, and the content of IgM in serum can be estimated. The titer of anti-A or anti-B is over 65,438+0 ∶ 4, which indicates humoral immune deficiency.

⑶ Determination of specific antibody: The positive Schick test (diphtheria toxin test) indicates humoral immunodeficiency and combined immunodeficiency.

⑷EAC rose formation test: the normal value is 15-20%. Below this value indicates humoral immune deficiency.

3. Examination of cellular immune function

⑴ skin delayed hypersensitivity: ① tuberculin test for 48-72h；; ; (2) Streptokinase-Streptokinase (SK-SD) test; ③ Plant hemagglutinin test.

⑵ Lymphocyte transformation test: the normal value is 60-70%.

⑶ E rose formation test: the normal value is 50-80%.

4. Pathological examination

⑴ Lymph node biopsy: Deep LC around subcortical layer rarely indicates cellular immune deficiency.

Skin? B style='color: black; Background color: # A0FFFF'> This is a careless nest, isn't it? ⒅ Peptone C rarely indicates humoral immune deficiency.

Both of them rarely put forward joint immunodeficiency.

5.x-ray examination: those with thymus deficiency in infancy suggest cellular immunodeficiency or combined immunodeficiency.

(5) Diagnosis and differentiation of primary immunodeficiency

Immunodeficiency syndrome lacks specific symptoms and signs, and the diagnosis should be based on comprehensive medical history, physical examination and laboratory examination, especially laboratory examination. Repeated or severe infection is often a clue to suspect the disease and should be further understood.

1. Birth history: including maternal pregnancy history.

2. Vaccination history:

3. History of infectious diseases: measles and chickenpox are common.

4. Other medical history: including tumor, autoimmune diseases, tonsillectomy and splenectomy, radiotherapy and immunosuppressive therapy.

5. Family history:

Several common primary immunodeficiency diseases

Several common primary immunodeficiency diseases

disease

Genetic model

gender

Age of onset

clinical features

survey fee

1, humoral immunity 50%-70% is the most common.

(1) Congenital hypogammaglobulinemia

Sex linked recessive autosomal recessive

male

Both sexes

6- 12 months

① Recurrent bacterial infection

② SLE and rheumatoid arthritis are often complicated.

③ dysplasia

④ Absence or abundance of lymph nodes and tonsils.

⑤ Thymus develops normally.

⑥ Half of them died before 10 years old.

① serum immunoglobulin < 2g/l

② There are few or no antibodies after immunization.

③ The titer of hemagglutinin is very low or not.

④ There were no plasma cells in bone marrow and lymph nodes.

⑤ The peripheral blood LC is normal.

⑥ The cellular immune function is normal.

⑵ Temporary hypogammaglobulinemia in infants.

Both sexes

6 months to 3 years old

① Time delay of IG generation.

9- 18 months after birth; 2-4 years old to reach the normal level.

② susceptible to G+ infection.

① immunoglobulin < 4.0g/L, immunoglobulin < 2.5g/L.

② Insufficient immune antibody formation.

③ The peripheral blood LC is normal.

④ The cellular immune function is normal.

⑤ Plasma cells were found in rectal mucosa lamina propria biopsy and lymph node biopsy.

(3) selective IgA deficiency

Recessive or dominant inheritance of normally bright chromosomes

Both sexes

initial stage

① Some patients may be asymptomatic ② Recurrent respiratory or gastrointestinal infections in infancy.

③ Often accompanied by allergic diseases or autoimmune diseases.

④ Its symptoms get worse with age.

① Serum IgA < 0.05g/L.

②SIgA deficiency

③ Other immunoglobulins were normal.

(4) selective IgM deficiency

Both sexes

initial stage

(1) A few people are asymptomatic.

② Recurrent bacterial infection

③ Autoimmune hemolytic anemia often occurs.

④ The prognosis is serious.

① serum IgM < 100 mg/L

② The peripheral blood LC is normal.

③ Plasma cells can be seen in bone marrow.

④ The cellular immune function is normal.

2. Cellular immune deficiency (5%- 10%)

(1) Congenital thymic hypoplasia George syndrome

Both sexes

65438+ 0-2 hours after birth

① Hypocalcemic convulsion occurred 1-2 hours after birth.

② Special face shape (short and wide eyes, short nasolabial groove, low ear position, fish mouth and small jaw)

③ It is often accompanied by congenital heart disease, esophageal atresia and hypothyroidism.

④X-ray examination showed that there was no thymus.

⑤ Poor prognosis.

① peripheral blood LC <1.2×109/l.

② skin delayed hypersensitivity (-)

③ The cellular immune function is low.

④ Blood calcium ↓ p =

Urine Ca is 0.

Parathyroid hormone ↓

3. Combined immunodeficiency (10%-25%)

Severe combined immunodeficiency disease

Swiss type is autosomal recessive, while gitlin type is sex-linked recessive.

Both sexes

1- February after birth

① Recurrent infection, among which candida infection is the earliest and most common.

(2) often suffer from serious infection.

③ Chickenpox and measles are symptoms of fulminant severe poisoning.

④ Immunization can cause serious infection.

5 stunting and malnutrition.

⑥ Lymph nodes, tonsils, dysplasia and hepatosplenomegaly were not found.

①Ig↓

② peripheral blood LC

③ No antibody reaction.

④ The blood group homologous lectin is extremely low or missing.

⑤ Cellular immune function ↓

⑥ Bone marrow plasma cells and LC↓

All landowners rectal mucosa biopsy showed stickiness.

(six) the treatment of primary immunodeficiency disease

1. General therapy

⑴ Choose appropriate antibiotics for complex infections.

⑵ Transfusion with cellular immunodeficiency and combined immunodeficiency (graft versus host reaction) should be used with caution.

⑶ Calcium supplement, vitamin D and parathyroid hormone should be added to patients with congenital thymic hypoplasia with hypocalcemia.

(4) Patients with cellular immunodeficiency and combined immunodeficiency are prohibited from being vaccinated with epidemic live bacteria or vaccines.

2. Alternative therapy

⑴ Routine intramuscular injection of gamma globulin is used for most humoral immunodeficiency, but not for selective IgA deficiency.

⑵ Infusion of fresh plasma or frozen plasma.

Fresh plasma must agglutinate, and there can be no cross agglutination reaction.

Plasma infusion of SCID and patients with cellular immunodeficiency requires X-ray therapy.

Patients with selective IgA deficiency should not receive fresh plasma.

3. Immune reconstruction: methods and means to restore patients' immune function by transplanting immune organs or tissues.

(1) bone marrow transplantation

⑵ Fetal thymus transplantation

⑶ Embryonic liver transplantation

⑷ Umbilical cord blood stem cell transplantation

5. Peripheral blood stem cell transplantation

(7) prevention of primary immunodeficiency disease

1. Screening the patient's family members.

2. Genetic counseling, detection of disease-causing gene carriers, and guidance on fertility.

3. Prenatal diagnosis