Immunodeficiency

Immunodeficiency
Immunodeficiency can occur in any of the four major components of the immune system: (1) B cells (antibody), (2) T cells, (3) complement, and (4) phagocytes. The deficiencies can be either congenital or acquired. Clinically, recurrent or opportunistic infections are commonly seen. Recurrent infections with pyogenic bacteria, e.g., staphylococci, indicate a B-cell deficiency, whereas recurrent infections with certain fungi, viruses, or protozoa indicate a T-cell deficiency.
I- Congenital Immunodeficiency
1- B-Cell Deficiencies
A- X-Linked Hypogammaglobulinemia (Bruton s Agammaglobulinemia)
Very low levels of all immunoglobulins (IgG, IgA, IgM, IgD, and IgE) and a virtual absence of B cells are found in young boys; female carriers are immunologically normal. Pre-B cells are present, but they fail to differentiate into B cells. Cell-mediated immunity is relatively normal. Clinically, recurrent pyogenic bacterial infections, e.g., otitis media, sinusitis, and pneumonia caused by Streptococcus pneumoniae and Haemophilus influenzae, occur in infants at about 6 months of age, when maternal antibody is no longer present in sufficient amount to be protective. Treatment with pooled gamma globulin reduces the number of infections.
B- Selective Immunoglobulin Deficiencies
IgA deficiency is the most common of these; IgG and IgM deficiencies are rarer. Patients with a deficiency of IgA typically have recurrent sinus and lung infections. (However, some individuals with IgA deficiency do not have frequent infections, possibly because their IgG and IgM levels confer protection). Patients with a deficiency of IgA should not be treated with gamma globulin preparations, because these patients may form antibodies against the foreign IgA.

2- T-Cell Deficiencies
A- Thymic Aplasia (DiGeorge s Syndrome)
Both the thymus and the parathyroids fail to develop properly. The most common presenting symptom is tetany due to hypocalcemia caused by hypoparathyroidism.
Severe viral, fungal, or protozoal infections occur in affected infants early in life as a result of a profound deficit of T cells. Pneumonia caused by Pneumocystis Jiroveci and thrush caused by Candida albicans are two common infections in these patients.

B- X-linked Hyper-IgM Syndrome
Severe, recurrent pyogenic bacterial infections resembling those seen in X-linked hypogammaglobulinemia begin early in life. Patients have a high concentration of IgM but very little IgG, IgA, and IgE. They have normal numbers of T cells and B cells. The main manifestations is inability of the B cell to switch from the production of IgM to the other classes of antibodies. This is due to a mutation in the gene encoding the CD40 ligand in the CD4-positive helper T cells that interacts with CD40 on the B-cell surface .Treatment with pooled gamma globulin results in fewer infections.

3- Combined B-Cell & T-Cell Deficiencies
Severe Combined Immunodeficiency Disease (SCID)
This is a group of inherited diseases, all of which are due to a defect in the differentiation of an early stem cell. There are two types: X-linked and autosomal; the X-linked form constitutes about 75% of cases. Recurrent infections caused by bacteria, viruses, fungi, and protozoa occur in early infancy (3 months of age), because both B cells and T cells are defective. In some children, the B and T cells are absent; in others, the number of cells is normal but they do not function properly. Immunoglobulin levels are very low and tonsils and lymph nodes are absent. Pneumocystis pneumonia is the m