Immunodeficiency

Immunodeficiency results from a failure or absence of elements of the immune system, including lymphocytes, phagocytes, and the complement system. These immunodeficiencies can be either primary, such as Bruton disease, or secondary, as the one caused by HIV infection. X- linked Agammaglobulinemia (Bruton disease): First described by Bruton. X-linked disorder. Found in male babies expressed around 5 to 6 months of age (maternal IgG disappears). In boys, pre-B cells did not differentiate into mature B lymphocytes. There is a mutation in the gene that encodes for a tyrosine kinase protein. A low level of all immunoglobulins (IgG, IgA, IgM, IgD, and IgE) is present. Infants with X-linked agammaglobulinemia suffer from recurrent bacterial infections: otitis media, bronchitis, septicemia, pneumonia, and arthritis, and Giardia lamblia causes intestinal malabsorption. Intermittent injections of large amounts of IgG keep the patient alive, but a patient may die at a younger age if infection with antibiotic-resistant bacteria occurs. Bone marrow transplantation is critical. IgA deficiency is more common than other deficiencies of immunoglobulins. These patients are more prone to recurrent sinus and lung infections. A malfunctioning in heavy-chain gene switching may cause this problem. Treatment should not include gammaglobulin preparations to prevent hypersensitivity reactions. . Congenital thymic aplasia (DiGeorge syndrome): Tetany is present. Fungal and viral infections are common. A transplant of the fetal thymus is needed to correct this deficiency.  Chronic Mucocutaneous Candidasis: Selective defect in the functioning of T-cells. . Patients with this disorder usually have a normal T-cell mediated immunity to microorganisms other than Candida. B-cell function is normal. Disorders affect both genders, and it is inherited. Patients, in addition to the above, will have other disorders like parathyroid deficiencies. Antifungals are useful.  Hyper-IgM syndrome: This disorder is characterized by bacterial infections, including pneumonia, meningitis, otitis, among others that start in early childhood. High levels of IgM. Other immunoglobulins are defective. Lymphocytes are normal in numbers. The gene encoding the CD40 ligand on T lymphocytes is faulty. B and T lymphocyte cooperation in the immune response are compromised. The failure to interact with CD40 results in an inability of the B cell to switch from the production of IgM to the other classes of antibodies. Immunoglobulin therapy is recommended. Interleukin-12 receptor deficiency: Mycobacterial infections are frequent due to the lack of the interleukin-12 receptor. Treatment involves selective antimicrobials. Severe combined immunodeficiency disease (SCID): There is a failure of early stem cells to differentiate into T and B lymphocytes.  . Deficiency of the interleukin-2 receptor is the most prevalent.  . Other problems are due to defective genes encoding ZAP-70, Janus kinase 3, and the genes involved in the DNA recombination of immune cells receptors: RAG1 and RAG2. Clinically characterized by a variety of infections, including those caused by opportunistic pathogens. Selective antibiotics, antivirals, and antifungals are available after the pathogen identification. Immunosuppressive therapy is not needed after allograft transplantation. Wiskott-Aldrich syndrome: This syndrome is associated with normal T-cell numbers with reduced functions, which get progressively worse. IgM concentrations are reduced, but IgG levels are normal. Both IgA and IgE levels are elevated. These patients have a defective WASP, which is involved in actin filament assembly. Immunodeficiency with ataxia-telangiectasia: This is a deficiency of T-cells associated with a lack of coordination of movement (ataxia) and dilation of small blood vessels of the facial area (telangiectasis). T-cells and their functions are diminished to various degrees. B-cell numbers and IgM concentrations are normal to low. . IgG is often reduced, and IgA is considerably reduced. There is a high incidence of malignancy, especially leukemias, in these patients. MHC deficiency (Bare leukocyte syndrome): This subjects have fewer CD4+ or CD8+ T lymphocytes that predispose these individuals to be prone to recurrent infections. Antibody production is affected and predispose to bacteremia. Hereditary angioedema: This disease has an autosomal dominant genetic pattern. Caused by C1 inhibitor deficiency. Clinically characterized by generalized edema including the one leading to acute suffocation. Therapy with oxymetholone and danazol can be helpful in correcting the defect. Recurrent infections: Frequent infections by extracellular bacteria may be caused by C3 deficiency. C5 deficiency predisposes to viral infections. . Patients with a deficiency of the membrane attack complex (MAC) are particularly susceptible to bacteremia caused by Neisseria species.  . Autoimmune diseases: This is caused by C2 and C4 deficiencies and mimics systemic lupus erythematosus.   Chronic granulomatous disease (CGD): It is mostly an X-linked disorder.   . It is clinically characterized by a defective NADPH that interferes with the intracellular ability of neutrophils to kill engulfed bacteria species. NADPH oxidase is required for the generation of peroxidase and superoxides that will kill the organisms. The intracellular survival of the organisms leads to the formation of a granuloma, an organized structure consisting of mononuclear cells. These granulomas can become large enough to obstruct the stomach, esophagus, or bladder. Patients with this disease are very susceptible to opportunistic infections by certain bacteria and fungi, especially with Serratia and Burkholderia.  . Nitroblue tetrazolium (NBT) dye reduction test confirms the diagnosis of CGD and the dichlorofluorescein (DCF) test is also useful. . Aggressive therapy with wide-spectrum antibiotics and antifungal agents is required. . Leukocyte adhesion deficiency syndrome: It is characterized by pyogenic infections, including pneumonia and otitis. It is an autosomal recessive disease, and the faulty gene encodes for an integrin. There is an impaired adhesion and defective phagocytosis of bacteria. Treatment involves the use of selective antibiotics. Administration of steroids has direct effects on immune cell traffic and functions. T cells are more affected than B cells. Cytokine synthesis is inhibited. They are associated with an impaired immune system. Affects cell-mediated immunity, antibody production, phagocyte function, complement system, and cytokine synthesis. Aggravated by infections. Multiple enzymes with important roles require zinc, iron, and other micronutrients. It may cause impaired immune responses. There is altered NK function. Cytotoxicity is compromised and the ability of phagocytes to kill microorganisms. Caused by the human immunodeficiency virus (HIV), which is a retrovirus transmitted sexually, perinatally, or blood products. Immune dysfunction results from the direct effects of HIV and the impairment of CD4 T cells. HIV proteins may act as superantigens. There are decreased responses to antigens and mitogens. Interleukin-2  and other cytokines are decreased. Infected cells may be killed by HIV-1 specific CD8+ T cells. In HIV-1 infection, neutralizing antibodies appear to be ineffective in controlling viral replication and infection.