Complications arise when the immune system does not function properly. Some issues are less pervasive, such as pollen allergy, while others are extensive, such as genetic disorders that wipe out the presence or function of an entire set of immune cells. Immune Deficiencies Immune deficiencies may be temporary or permanent. Temporary immune deficiency can be caused by a variety of sources that weaken the immune system. Common infections, including influenza and mononucleosis, can suppress the immune system. When immune cells are the target of infection, severe immune suppression can occur. For example, HIV specifically infects T cells, and their elimination allows for secondary infections by other pathogens. Patients receiving chemotherapy, bone marrow transplants, or immunosuppressive drugs experience weakened immune systems until immune cell levels are restored. Pregnancy also suppresses the maternal immune system, increasing susceptibility to infections by common microbes. Primary immune deficiency diseases (PIDDs) are inherited genetic disorders and tend to cause chronic susceptibility to infection. There are over 150 PIDDs, and almost all are considered rare (affecting fewer than 200,000 people in the United States). They may result from altered immune signaling molecules or the complete absence of mature immune cells. For instance, X-linked severe combined immunodeficiency (SCID) is caused by a mutation in a signaling receptor gene, rendering immune cells insensitive to multiple cytokines. Without the growth and activation signals delivered by cytokines, immune cell subsets, particularly T and natural killer cells, fail to develop normally. The NIAID Primary Immune Deficiency Clinic was established with the goal of accepting all PIDD patients for examination to provide a disease diagnosis and better treatment recommendations. Allergy Allergies are a form of hypersensitivity reaction, typically in response to harmless environmental allergens like pollen or food. Hypersensitivity reactions are divided into four classes. Class I, II, and III are caused by antibodies, IgE or IgG, which are produced by B cells in response to an allergen. Overproduction of these antibodies activates immune cells like basophils and mast cells, which respond by releasing inflammatory chemicals like histamine. Class IV reactions are caused by T cells, which may either directly cause damage themselves or activate macrophages and eosinophils that damage host cells. Autoimmune Diseases Autoimmune diseases occur when self-tolerance is broken. Self-tolerance breaks when adaptive immune cells that recognize host cells persist unchecked. B cells may produce antibodies targeting host cells, and active T cells may recognize self-antigen. This amplifies when they recruit and activate other immune cells. Autoimmunity is either organ-specific or systemic, meaning it affects the whole body. For instance, type I diabetes is organ-specific and caused by immune cells erroneously recognizing insulin-producing pancreatic β cells as foreign. However, systemic lupus erythematosus, commonly called lupus, can result from antibodies that recognize antigens expressed by nearly all healthy cells. Autoimmune diseases have a strong genetic component, and with advances in gene sequencing tools, researchers have a better understanding of what may contribute to specific diseases. Sepsis Sepsis may refer to an infection of the bloodstream, or it can refer to a systemic inflammatory state caused by the uncontrolled, broad release of cytokines that quickly activate immune cells throughout the body. Sepsis is an extremely serious condition and is typically triggered by an infection. However, the damage itself is caused by cytokines (the adverse response is sometimes referred to as a "cytokine storm"). The systemic release of cytokines may lead to loss of blood pressure, resulting in septic shock and possible multi-organ failure. Cancer Some forms of cancer are directly caused by the uncontrolled growth of immune cells. Leukemia is cancer caused by white blood cells, which is another term for immune cells. Lymphoma is cancer caused by lymphocytes, which is another term for adaptive B or T cells. Myeloma is cancer caused by plasma cells, which are mature B cells. Unrestricted growth of any of these cell types causes cancer. In addition, an emerging concept is that cancer progression may partially result from the ability of cancer cells to avoid immune detection. The immune system is capable of removing infectious pathogens and dangerous host cells like tumors. Cancer researchers are studying how the tumor microenvironment may allow cancer cells to evade immune cells. Immune evasion may result from the abundance of suppressive, regulatory immune cells, excessive inhibitory cytokines.