Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that affect the patient's immune system. Examples of these extrinsic factors include HIV infection and environmental factors, such as nutrition. Immunocompromisation may also be due to genetic diseases/flaws such as SCID.
Chronic granulomatous disease (CGD), also known as Bridges–Good syndrome, chronic granulomatous disorder, and Quie syndrome, is a diverse group of hereditary diseases in which certain cells of the immune system have difficulty forming the reactive oxygen compounds used to kill certain ingested pathogens. This leads to the formation of granulomas in many organs. CGD affects about 1 in 200,000 people in the United States, with about 20 new cases diagnosed each year.
Myeloperoxidase deficiency is a disorder featuring lack in either the quantity or the function of myeloperoxidase–an iron-containing protein expressed primarily in neutrophil granules. There are two types of myeloperoxidase deficiency: primary/inherited and secondary/acquired. Lack of functional myeloperoxidase leads to less efficient killing of intracellular pathogens, particularly Candida albicans, as well as less efficient production and release of neutrophil extracellular traps (NETs) from the neutrophils to trap and kill extracellular pathogens. Despite these characteristics, more than 95% of individuals with myeloperoxidase deficiency experience no symptoms in their lifetime. For those who do experience symptoms, the most common symptom is frequent infections by Candida albicans. Individuals with myeloperoxidase deficiency also experience higher rates of chronic inflammatory conditions. Myeloperoxidase deficiency is diagnosed using flow cytometry or cytochemical stains. There is no treatment for myeloperoxidase deficiency itself. Rather, in the rare cases that individuals experience symptoms, these infections should be treated.
Respiratory burst is the rapid release of the reactive oxygen species (ROS), superoxide anion and hydrogen peroxide, from different cell types.
NADPH oxidase is a membrane-bound enzyme complex that faces the extracellular space. It can be found in the plasma membrane as well as in the membranes of phagosomes used by neutrophil white blood cells to engulf microorganisms. Human isoforms of the catalytic component of the complex include NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1, and DUOX2.
Cyclic neutropenia (CyN) is a rare hematologic disorder and form of congenital neutropenia that tends to occur approximately every three weeks and lasting for few days at a time due to changing rates of neutrophil production by the bone marrow. It causes a temporary condition with a low absolute neutrophil count and because the neutrophils make up the majority of circulating white blood cells it places the body at severe risk of inflammation and infection. In comparison to severe congenital neutropenia, it responds well to treatment with granulocyte colony-stimulating factor (filgrastim), which increases the neutrophil count, shortens the cycle length, as well decreases the severity and frequency of infections.
Severe congenital neutropenia (SCN), also often known as Kostmann syndrome or disease, is a group of rare disorders that affect myelopoiesis, causing a congenital form of neutropenia, usually without other physical malformations. SCN manifests in infancy with life-threatening bacterial infections. It causes severe pyogenic infections. It can be caused by autosomal dominant inheritance of the ELANE gene, autosomal recessive inheritance of the HAX1 gene. There is an increased risk of leukemia and Myelodysplastic cancers.
NADPH oxidase 2 (Nox2), also known as cytochrome b(558) subunit beta or Cytochrome b-245 heavy chain, is a protein that in humans is encoded by the NOX2 gene. The protein is a superoxide generating enzyme which forms reactive oxygen species (ROS).
WHIM syndrome is a rare congenital immunodeficiency disorder characterized by chronic noncyclic neutropenia.
C-C chemokine receptor type 1 is a protein that in humans is encoded by the CCR1 gene.
Neutrophil cytosol factor 2 is a protein that in humans is encoded by the NCF2 gene.
Neutrophil cytosol factor 1, also known as p47phox, is a protein that in humans is encoded by the NCF1 gene.
Cytochrome b-245 light chain is a protein that in humans is encoded by the CYBA gene involved in superoxide production and phagocytosis.
Moesin is a protein that in humans is encoded by the MSN gene.
Neutrophil cytosol factor 4 is a protein that in humans is encoded by the NCF4 gene.
p22phox Protein, also known as the human neutrophil cytochrome b light chain (CYBA), is an essential component of the membrane-associated enzyme phagocyte NADPH-oxidase This enzyme uses NADH or NADPH as the electron donor for the one electron reduction of oxygen to produce superoxide anion, a reactive oxygen species (ROS), and a functionally important step for the antimicrobial activity of phagocytic cells. p22phox is also expressed in many other human cells such as endothelial and vascular smooth muscle cells, including those within the coronary arteries. Specific polymorphisms of the CYBA gene have been identified that are associated with a decreased risk of coronary artery disease (CAD).
MonoMAC syndrome is a rare autosomal dominant syndrome associated with: monocytopenia, B and NK cell lymphopenia; mycobacterial, viral, fungal, and bacterial opportunistic infections; and virus infection-induced cancers. The disorder often progresses to the development of myelodysplasia, myeloid leukemias, and other types of cancer. MonoMAC is a life-threatening and precancerous disorder.
Neutrophil oxidative burst test is a measure of neutrophil oxidation and is a useful assay in the diagnosis of chronic granulomatous disease and is also a useful means to determine the overall metabolic integrity of phagocytosing neutrophils. The NADPH oxidase enzyme is missing in CGD. From total blood, neutrophils can be purified and the NADPH oxidase activity can be measured with different methods in these cells after activation. Phagocytosis by polymorphonuclear neutrophils and monocytes constitutes an essential arm of host defense against bacterial or fungal infections. The phagocytic process can be separated into several major stages: chemotaxis, attachment of particles to the cell surface of phagocytes, ingestion (phagocytosis) and intracellular killing by oxygen-dependent and oxygen-independent mechanisms.
Neutrophil-specific granule deficiency is a rare congenital immunodeficiency characterized by an increased risk for pyogenic infections due to defective production of specific granules and gelatinase granules in patient neutrophils.
