Immunodeficiency

Immunology IMMUNODEFICIENCY Immunodeficiency (or immune deficiency) is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. A person who has an immunodeficiency is said to be immuno-compromised and becomes very vulnerable to opportunistic infections. An efficient immune system provides protection to body against a wide range of agents. Defects in these mechanisms may increase the chance of acquiring infection or increase the severity of eventual lesion. Such defects may be genetically determined (congenital or primary immunodeficiency) and present from birth or may be acquired by way of some disturbance in the internal or external milieu of the individual (acquired or secondary immunodeficiency). Primary Immunodeficiency Physiological Primary Immunodeficiency This presents as hypo-gammaglobulinaemia of newborn who have to commence synthesis of their own immunoglobulin by the age of 4-5 months with the waning of passive acquired antibody from mother. Pathological Primary Immunodeficiency This is rare, but can result from defects in either natural or adaptive immunity. Deficiencies can occur at various levels, from stem cells to more differentiated precursors resulting in neutropenias or, for lymphocytes, severe combined immunodeficiencies which include following syndromes: • Swiss type agammaglobulinaemia • Nezelof's syndrome • Adenosine deaminase deficiency • Reticular dysgenesis Classification of primary immunodeficiency syndromes: B cell deficiencies · X-linked agammaglobulinaemia · Selective immunoglobulin deficiency T cell deficiencies · DiGeorge's syndrome (Thymic aplasia) · Chronic mucocutaneous candidiasis · Hyper-IgM syndrome · Interleukin-12 receptor deficiency Combined T cell and B cell abnormalities · Severe combined immunodeficiency disease (SCID) · Wiskott-Aldrich syndrome · Ataxia-telangiectasia Complement deficiencies · Hereditary angioedema or hereditary angioneurotic edema · Recurrent infections · Autoimmune-like diseases Phagocyte deficiencies · Leucocyte adhesion deficiency · Chronic granulomatous disease (CGD) · Chediak-Higashi syndrome · Job's syndrome (Hyper-IgE syndrome) · Cyclic neutropenia · Myeloperoxidase deficiency · Glucose-6-phosphate dehydrogenase deficiency · Interferon-y deficiency Various/unknown · Common variable immunodeficiency (CVID) Secondary Immunodeficiency (Acquired)

Nutritional Immune responsiveness can be depressed nonspecifically by many factors. Cell mediated immunity in particular may be impaired in a state of malnutrition. Physical Immunosuppression Exposure to X-rays result into an extended latent period for production of immune response, prolonged antigen elimination and decreased antibody titre. B cells are more sensitive to irradiation than T cells. Chemical Immunosuppression Chemicals that act as immunosuppressants include corticosteroids, anticancer agents (cyclophosphamide), antibiotics, enzymes and plant alkaloids. The immunosuppressant antibiotics include actinomycin D, mitomycin C, puromycin, cyclosporin and chloramphenicol. Ribonuclease and asparaginase enzymes have also got immunosuppressive actions. Biological Immunosuppression Antilymphocyte serum (ALS) also known as antilymphocyte globulin (ALG), antithymocyte serum or globulin (ATS or ATG) is prepared by immunization of a heterologous species with cells from the lymph nodes, blood, thymus or spleen of donor. ALS is administered as a passive immunization of the donor species before, at the end or after the exposure to the antigen. Microbial Infections Various infections frequently produce immunosuppression. Most important example is measles in man which results into direct cytotoxic effect of virus on the lymphoid cells. Macrophage functions get aberrant in malaria and diminished immune response is a feature of lepromatous leprosy. The most notorious of all microbes is HIV which causes acquired immunodeficiency syndrome (AIDS) in which attack by virus on CD4 helper cells destroys the ability to give a CMI response and leaves the patient open to infection with opportunistic organisms such as Pneumocystis carinii and CMV which can lead to death. Infections that cause immunosuppression Viral Measles Mumps Congenital rubella Epstein Barr virus Cytomegalovirus Human immunodeficiency virus

Bacterial Mycobacterium tuberculosis Mycobacterium leprae Brucella species

Malignancies Lymphoproliferative disorders like chronic lymphatic leukaemia, myeloma and Waldenstrom's macroglobulinemia are associated with varying degrees of hypogammaglobulinaemia and impaired antibody response Chronic Diseases Many a times it is difficult to pinpoint the site of the deficiency but association with certain ailments has been seen too often. These diseases include diabetes mellitus, renal failure, autoimmune diseases and various malignancies. Treatment Induced Deficiency Many of the components of treatment have been described earlier also for e.g. corticosteroids, immunosuppressants, antilymphocytic globulin and splenectomy. Infections and Immunodeficient Patients Apart from known pathogens, the opportunistic organisms also produce diseases in patients who are immunologically compromised. Infections of skin and soft tissues are common. Infections of respiratory tract and central nervous systems are also common whereas septicaemia is the most serious complication and may prove fatal.

Microbes producing infections in hosts with defective immunity Bacteria · Gram-negative aerobic bacilli, e.g Esch coli · Klebsiella sp., Pseudomonas aeruginosa · Streptococcus and Staphylococcus · Mycobacteria including atypical mycobacteria · Listeria monocytogenes, Nocardia Viruses · Herpes simplex · CMV, EB virus · Varicella zoster · Vaccinia virus · Measles virus · Papovavirus, Papilloma virus Fungi · Candida albicans · Cryptococcus neoformans · Histoplasma capsulatum · C. immitis · Blastomyces dermatitidis · Aspergillus, Mucor, Rhizopus Parasites · P. carinii · Toxoplasma gondii · Cryptosporidium · Isospora belli · Strongyloides infection (extra intestinal) Diagnosis of Immunodeficiencies: Repeated occurrence of acute infections or isolation of opportunistic organisms should raise suspicion of immunodeficiency and investigations should proceed to assess various components of the immune response. Defects in immunoglobulins can be assessed by several immunological quantitative estimations. The humoural immune response can be assayed by screening serum for natural antibody. T cell deficiency can be confirmed by the absence or reduced response in skin tests to antigens like tuberculin, Candida, and dinitrochlorobenzene (DNCB). Important points regarding Immunodeficiency • Immunodeficiency may lead to repeated microbial infections. • Enhanced susceptibility to malignancies. • It may involve AMI, CMI or both and also non-specific immune mechanisms. • Though primary immunodeficiencies are classified as affecting B-cells and T-cells, but there is always an overlap. • Secondary immunodeficiencies are much more common than primary deficiencies. • Nutritional deprivation and ageing also cause waning in the efficiency of acquired immunity.