by Dr. Saul Greenberg

What is it?

Immunodeficiency is a disorder or condition where the immune response is reduced or absent. The immune system protects the body from potentially harmful substances (antigens) such as microorganisms, toxins, cancer cells, and blood or tissues from another person. The immune response consists of responses by white blood cells composed of neutrophils and lymphocytes. Neutrophils engulf and destroy foreign material (phagocytosis). Lymphocytes are divided into two groups: T lymphocytes and B lymphocytes. T lymphocytes directly attack antigens (cellular immunity). B lymphocytes produce antibodies (humoral immunity) that attach to the antigen and make phagocytes and body chemicals, such as complement proteins, much more efficient in the destruction of the antigen.

Immunodeficiency can be traced to the failure of one or more parts of the immune system. The causes include primary immunodeficiency caused by congenital/inherited defects and acquired immunodeficiency caused by a disease that affects the immune system.

One of the more convenient ways to group the primary immunodeficiencies is according to the part of the immune system that is faulty:

B cell (antibody) deficiencies

Examples of congenital immunodeficiency disorders of antibody production (B lymphocyte abnormalities) include hypogammaglobulinemia (decrease of one or more specific antibodies) which usually causes repeated mild respiratory infections, and x-linked agammaglobulinemia (lack of all or most antibody production) which results in frequent severe infections and is often fatal. Other B cell deficiencies include selective IgA deficiency and less commonly Hyper IgM syndrome and IgG subclass deficiency.

T cell deficiencies

Congenital disorders affecting the T lymphocytes may cause increased susceptibility to viruses and fungi, resulting in repeated Candida (yeast) infections. An example of this is DiGeorge Syndrome.

Combined T cell and B cell (antibody) deficiencies

Inherited severe combined immunodeficiency (SCID) affects both T lymphocytes and B lymphocytes. It is often fatal within the first year of life because there is no resistance to disease or infection. Other less severe combined deficiencies include Wiskot-Aldrich and Ataxia Telangiectasia.

Defective phagocytes

In this inherited disorder defective phagocytes result in infections that are unusually frequent or severe, often causing deep abscesses. The infections often respond poorly to standard antibiotics. Examples of this disorder are chronic granulomatous disease, Chediak-Higashi syndrome and leukocyte adhesion defect.

Complement deficiencies

Disorders of the complement system account for about 2% of people with primary immunodeficiency. Some complement deficiencies result in the same kinds of bacterial infections seen with antibody deficiencies, as well as causing immune system disorders such as systemic lupus erythematosus (SLE). Other complement deficiencies lead to an increase of blood-borne infections such as meningitis.

Acquired immunodeficiency

This may be a complication of diseases such as HIV infection and AIDS (acquired immunodeficiency syndrome). Malnutrition, particularly with lack of protein, and many cancers, can cause immunodeficiency. It may also be caused by chemotherapy to treat many types of cancer, because the chemotherapy often reduces the number of white blood cells available to fight infection. Drugs such as corticosteroids or other immunosuppressant medications to treat autoimmune disorders or used to prevent rejection of organ transplants can also cause immunodeficiency.

What does it look like?

Patients with immune deficiency diseases generally present with frequent or unusual infections which may or may not respond well to antibiotic therapy. The type and pattern of infection depends on which part(s) of the host defenses are missing or defective since some defenses are more important against some pathogens than others. Defects in phagocyte function or humoral immunity (B cell deficiency) result in infections with common and unusual bacteria. Defects in T cell immunity usually present with recurrent viral, fungal, or protozoal (Pneumocystis carinii) infections. Very serious inherited immunodeficiencies become apparent shortly after birth or in the first year of life. Others (usually the milder forms) may not show up until people reach their twenties and thirties. Persistent, recurrent infections, or severe infection by germs that do not usually cause severe infection, may be clues that an immunodeficiency disorder is present.

The 10 warning signs of primary immunodeficiency:

Other clues include:

How is it diagnosed?

Some tests that indicate an immunodeficiency disorder include:

How is it treated?

The treatment for immunodeficiency disorders includes specific medical therapies as well as protection against and treatment of diseases and infections. Intravenous gammaglobulin may be given to individuals who are unable to produce adequate amounts of antibodies or immunoglobulins, such as patients with hypo or agammaglobulinemia. Certain immunodeficiency conditions may be treated by bone marrow transplant specifically those diseases that are characterized by deficient T-lymphocytes or combined deficiencies of T-lymphocytes and B-lymphocytes. Bone marrow transplantation is most often used to treat Severe Combined Immunodeficiency (SCID). Gamma interferon, given as a subcutaneous injection to children with chronic granulomatous disease, has been shown to decrease the numbers of serious infections. Recently, several children with X-linked Severe Combined Immunodeficiency have undergone gene therapy (inserting normal genes into cells that contain the defective gene) with near complete restoration of both T- and B-lymphocyte function. This very exciting breakthrough proves that gene therapy can be successful and perhaps one day gene therapy will be the procedure of choice for the majority of immunodeficiency disease. Acquired immunosuppression that results from medications is often reversible once the medication is stopped.

Children with primary immunodeficiency diseases, especially those with defective T cells, X-linked agammaglobulinemia, and ataxia telangiectasia should not receive live virus vaccines, such as the oral polio, measles, and chicken pox (varicella) vaccines. They should avoid contact with persons who have any infection or contagious disorder. One needs to treat any febrile illness or infection aggressively. This may involve use of powerful antimicrobials to treat any infection and occasionally prolonged use of antimicrobials (antibiotics, antifungal medications, etc.) and preventive (prophylactic) treatments.

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