Severe forms of immunodeficiency states are so incompatible with life that they are rarely seen in clinical practice. What are these specific disorders?

They can be classified as:
1. Combined immunodeficiency states,
2. Humoral immunity deficiency
3. cellular immunity deficiency
4. Phagocyte deficiency
5. Complement system deficiency, and
6. States of secondary immunodeficiency.

combined immunodeficiency: There is deficiency of both cellular and humoral immunity. This occurs as a consequence of the blockage of the maturation of stem cells that give rise to immunocytes. Severely affected children are unable to limit bacterial, viral, and fungal infections and die in infancy. Severe subtypes have been described, for example, sex-linked recessive types (thymic type) and autosomal recessive (Swiss) types. Relatively benign types are Wiskott-Aldrich syndrome (sex-linked) and telenglectasia ataxia (autosomal recessive). more common.

humoral immunodeficiency: This may be a selective primary deficiency affecting only one of the immunoglobulin classes G, M, or A. In IgG deficiency, affected individuals suffer from repeated pyogenic infections, especially from encapsulated organisms such as H. Influenza and Streptococcus pyogenes. In IgA deficiency, respiratory and atopic allergies are also common. IgA deficiency also reduces resistance to intestinal commensals leading to malabsorption syndrome. Congenital hypogammaglobulinemia may be sex-linked (Bruton type) or autosomal dominant. In these cases, severe depletion of B cells and circulating immunoglobulins is observed with consequent serious bacterial infections. The incidence of autoimmune diseases such as hemolytic anemia is high in primary agammaglobulinemia. Immunodeficiency with normal amount of functionally deficient immunoglobulins (Job’s syndrome) has been described.

Cellular immunodeficiency: Primary T cell deficiency leads to severe viral and monilial infections and affected children usually die within the first years of life. Lymphocytes from patients are unable to respond to mitogens in vitro. The thymus may be almost absent (Nezelof syndrome) or aplastic (Di George syndrome) or in some cases it may be normal, eg, chronic mucocutaneous candidiasis.

phagocytosis defect: Chronic granulomatous disease is a sex-linked hereditary condition in which hydrogen peroxidase is deficient within phagocytes, leading to decreased microbial activity. Recurrent suppurative granulomas due to catalase-positive and peroxidase-negative organisms (Staphylococcus aureus and proteus) are common in this condition. In myeloperoxidase deficiency, infections with peroxidase-positive bacteria such as hemophilus are common. In Chediak-Higashi syndrome, neutrophils show defective degranulation and slow motility with subsequent pyogenic infections.

Deficiencies in the complement system: Hereditary angioneurotic edema is inherited as an autosomal dominant disease and is characterized by the absence of the enzyme that normally inhibits CI esterase activity that activates complement cascade reactions leading to the release of kinins and vasoactive peptides. Recurrent attacks of edema of the skin and mucosa are very common, and edema of the glottis can sometimes be life-threatening. C3 deficiency is inherited as an autosomal recessive trait. Deficiencies of other complement components, although reported, are very rare. Generally, the clinical conditions mimic immunoglobulin deficiency states.

Secondary immunodeficiency: Transplacental transfer of immunoglobulins takes place mainly in the last weeks of pregnancy. Therefore, premature babies may suffer from mild hypoglobunemia. Secondary defects in lymphocyte function are seen in many conditions, including burns, malnutrition, leukemias, lymphomas, and uremia. In multiple myeloma, although total immunoglobulins are increased, the biologically active ones are depressed, leading to functional deficiency. Treatment of immunodeficiency states as a whole is unsatisfactory. Immunoglobulin injection (0.25 g/kg/week) can abort recurrent pyogenic infections in hypogammaglobulinemia. Treatment of cell-mediated immunodeficiency states is even more difficult. Thymus and bone marrow transplants are gaining acceptance.