IMMUNOLOGY TEXTBOOK - Mercury Podillya 2013

CONGENITAL IMMUNE DEFICIENCY

Resistance to infections is ensured by the body's defense mechanisms. The first line of defense is represented by the mechanical barriers of the Skin and mucous membranes. The barrier function of mucous membranes is complemented by the action of ciliated epithelium, the protective properties of mucus, Lysozyme, lactoferrin, and interferons. Complement, neutrophils, and macrophages participate in clearing microbes that have penetrated through the skin and mucous membranes, constituting the second line of the body's defense against foreign agents. However, Antibodies, T AND B lymphocytes play the primary role in resistance to infection. Therefore, congenital defects in the Structure and function of lymphocytes most frequently lead to The Development of Primary immunodeficiencies.

Although primary immunodeficiencies are rare, their detection must be pursued intensively, because such children can become reservoirs for the spread of A wide variety of pathogens against the Background of suppressed immune system function.

Primary immunodeficiencies are disorders of The Immune System present at birth. They are most commonly manifested During the first months of life; in some cases, the first symptoms appear during adolescence or, even more rarely, in adulthood. Patients with severe primary immunodeficiencies typically die in childhood. With moderate and mild clinical manifestations of primary immunodeficiencies, patients may reach adulthood. Nevertheless, in virtually all cases of primary immunodeficiency, the prognosis is unfavorable.

Thus, primary immunodeficiencies are disorders associated with Genetic Defects in the Development of the immune system that sooner or later lead to specific clinical manifestations. Primary immunodeficiency can be caused by impairments in the adaptive immune system (T and B Cells) as well as the innate Immunity (neutrophils, phagocytes, complement, and natural killer (NK) cells). Furthermore, the damaged genes may be expressed either exclusively in Cells of the immune system (e.g., the recombination-activating Gene RAG or CD3) or across various Tissues. In the latter case, abnormalities are observed not only in the immune system but also in other Organs and tissues. Today, the International Classification of Diseases clearly identifies 120 nosological entities of primary immunodeficiencies, with the underlying molecular-genetic defect defined for many of them. This is a crucial point for verifying the Diagnosis and predicting the course of the disease at the embryonic development stage.

Below is a classification of primary immunodeficiencies based on the structural localization of the defect within a specific arm of the immune system.

Classification of Primary Immunodeficiencies

I. Deficiencies of the HUMORAL Immune Response (B-lymphocyte system):

1. X-linked agamma- (hypogamma-) globulinemia (Bruton syndrome).

2. Common variable immunodeficiency (common variable hypogammaglobulinemia).

3. Transient hypogammaglobulinemia of infancy (delayed immunological onset).

4. Selective immunoglobulin deficiency (dysgammaglobulinemia):

a) selective IgA deficiency;

b) immunoglobulin deficiency with elevated IgM levels (hyper-IgM syndrome);

c) IgG subclass deficiency with or without IgA deficiency.

II. Deficiencies of Cell-mediated immunity (T-cell system):

1. Hypoplasia and Aplasia of the Thymus and Parathyroid glands (DiGeorge syndrome).

2. Lymphocytic dysgenesis (Nezelof syndrome, French-type immunodeficiency).

3. Chronic mucocutaneous candidiasis.

III. Combined T- and B-cell immunodeficiencies:

1. Severe combined immunodeficiency (SCID):

a) X-linked;

b) autosomal recessive;

2. Ataxia-telangiectasia (Louis-Bar syndrome);

3. Wiskott-Aldrich syndrome;

4. Nijmegen breakage syndrome;

5. Immunodeficiency with hyper-IgM (X-linked);

5. Immunodeficiency with dwarfism;

6. Good syndrome;

7. McKusick metaphyseal chondrodysplasia (short-limbed dwarfism syndrome, Cartilage-Hair hypoplasia syndrome).

8. MHC Class II deficiency ("bare lymphocyte" syndrome).

IV. Phagocytic system deficiency:

1. Impaired chemotaxis, migration, and degranulation:

a) Chediak-Higashi syndrome;

b) hyper-IgE syndrome (Job's syndrome);

2. Defect of endocytosis and intracellular degradation:

a) chronic granulomatous disease;

b) enzymopathies of neutrophil granulocytes (myeloperoxidase deficiency, NADH oxidase deficiency, Glutathione peroxidase deficiency, glucose-6-phosphate dehydrogenase deficiency);

3. Defects of opsonization and engulfment:

a) opsonization defects;

b) tuftsin deficiency;

c) absence of membrane Glycoproteins LFA-1, CD18, gp150, Mac-1, etc.

4. Deficient expression of adhesion molecules.

V. Congenital defects of The Complement System:

1. C1 inhibitor deficiency (hereditary angioneurotic edema).

2. Deficiency of classical complement pathway activation components, etc.