T lymphocytes and Natural Killer (NK) cells are chiefly involved in defence against viruses. Besides these cells, B lymphocytes also play a role in defence, when the T lymphocytes attack the virus the B lymphocytes simultaneously produce antibodies. So that on exposure to the same virus for a second time, the antibody prevents infection. The T lymphocytes combat viruses by killing the cell that has been infected with viruses. The T cells (CD8 cytotoxic T cells) contain cytotoxic granules, when the T cell recognizes the infected target cell; it releases the contents from these granules and kills it. Some CD8 cells also act by secreting cytokines (IFN- gamma, TNF- alpha), which contribute to the host defence.TH1 (helper cells) also aid in killing of viruses. NK cells contain cytotoxic granules like T cells and destroy the virus infected cell by similar means. The infections are severe and persistent because the viral load is increasing due continuous viral replication and deficiency in the cell mediated immune components of the system. Thus, infected cells are not being destroyed resulting in spread of infection.
Components that are lacking in an infected infant's immune system
The pathogens that are involved help to indicate which part of the immune system is defective, as in case of this infant the organisms that have invaded are suggestive of defects in the T, B and NK cells. This suggests the presence of Severe Combined Immunodeficiency (SCID) syndrome. In SCID, a defect in T cell production and function is always seen, defects in B cells may be observed, little or no antibody production occurs, and in some cases NK cells may also show defects. Pulmonary symptoms are common in SCID and are characterized by infection with common bacteria or Pneumocystis carinii, cytomegalovirus, which results in low blood oxygen levels in SCID patients. Fungal infection in the mouth (Candida albicans) or infection (yeast) in the bladder is another symptom. Gastrointestinal problems (diarrhea) are also common, which may lead to weight loss and growth retardation. These signs and symptoms further confirm the occurrence of SCID in the infant. There are ten know forms of SCID, depending on the mutations in the genes. Usually patients suffering from SCID are deficient (-) in T cells but their B and NK cells may either be deficient or in some cases may not be deficient. So, in case of this infant his T cells are lacking but further study needs to be conducted in order to positively state whether his B or NK cells are missing.
The diagnosis is usually suspected in children under the age of 1. In some cases there has been a previous child in the family with SCID, this family history may help in diagnosis even before the child develops.
Peripheral blood lymphocyte (PBL) count
Lymhocytes are either taken from the periphery or from cord blood. There are usually two tests; complete blood count and manual differential (% of each different type of white blood cell is counted), from this the absolute lymphocyte count can be determined. There are usually more than 1,500 lymphocytes per cubic millimetre in normal blood in the first year of life, but infants with SCID usually have fewer lymphocytes than this. If a low count is found, the test is repeated to confirm the diagnosis. If the count is low even then, other tests to measure T cell function are conducted to confirm or exclude the diagnosis.
Tests to measure lymphocyte function
Lymphoctes are treated with stimulants like mitogens, they are incubated for several days. Normal lymphocytes react to these stimuli, lymphocytes from SCID individuals do not react.
Ig (A, M) levels can also be measured as they are quite low in these patients. SCID diagnosis can also be made in the utero (before baby is born), in case of family history (previously affected infant).
It should be given to SCID infants who are more that 3 months of age or/and who have aldready had infections. Ig therapy cannot restore the function of deficient lymphocytes, but can replace the missing antibodies.
Hematopoietic stem cell transplantation (HSCT)
In this therapy the bone marrow cells from a normal donor are given to an immunodeficient individual to replace the defective lymphocytes with the normal lymphocytes from the donor. The ideal donor is a perfectly matched (85% survival) HLA-type matched normal brother or sister. The patient must undergo immunotherapy before transplantation to reduce the chances of graft rejection. In the absence of a tissue matched sibling, patients can be given a T-cell depleted bone marrow transplant from (haploidentical) partially matched donor (mother or father).
Gene therapy has been successfully used in case of ADA and X-linked deficient SCID. The DNA is corrected (modified) in the sample of Tcells and the T cells are the returned to the deficient individual. But further research is being conducted to make it a safer treatment.
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