AGENCY FOR TOXIC SUBSTANCES AND DISEASE REGISTRY

Immune response

The Immune response is the body's response caused by its immune system being activated by antigens. The immune response can include immunity to pathogenic microorganisms and its products, allergies, graft rejections, as well as autoimmunity to self-antigens. In this process the main cells involved are T cells and B cells (sub-types of lymphocytes), and macrophages (a type of leucocyte or white blood cell). These cells produce lymphokines that influence the other host cells' activities. B cells, when activated by helper T cells undergo clonal expansion. B cells differentiate into plasma cells, which are short lived and secrete antibodies, and memory B cells, which are long lived and produce a fast, remembered response when exposed to the same infection in the future. B cells mature to produce immunoglobulins (also known as antibodies), that react with antigens. At the same time, macrophages process the antigens into immunogenic units which stimulate B lymphocytes to differentiate into antibody-secreting plasma cells, stimulating the T cells to release lymphokines.

Innate response is evolutionary more conserved than adaptive immune response. It is the first line of defense when it comes to defending an organism from an foreign invader. Foreign invaders include bacteria, viruses, and parasites. Innate immunity responses are not specific to particular pathogen. They are rather limited to conserved features amongst pathogens. They depend on a group of proteins (complement, interferons, lectins) and phagocytic cells. The protection an innate response offers is beneficial because it attacks all foreign invaders that are not part of the cell's self. Innate response is very quick - the pathogen is eliminated within minutes. Moreover, the innate immune responses in vertebrates are required to activate adaptive immune responses.

The innate immune response is "the response by the host that comprises the cells and mechanisms that defend the host from infection by other organisms or is activated by endogenous molecules, in a nonspecific manner." The innate immune response is quick and is the body's initial response to unwanted invaders. It consists of the body's non-specific external and internal defense mechanisms. An example of the body's external defense mechanisms are mucus and skin. Skin consists of epithelial and endothelial cells which acts a sort of barrier against infection, invading antigens would have to pass through the initial skin barrier in order to actually get inside the host. Mucous acts similarly to skin, in that it is a barrier of sorts. Mucus traps invading pathogens and sometimes degrades them, preventing them from going any further into the body. Non-specific internal defense mechanisms are put in place in case the invading pathogens gets past the external defenses and actually makes it inside the body. Things such as phagocytes, and Natural Killer (NK) cells attack the pathogen and destroys it before further infection takes place.

Almost all cells in our body are capable of presenting antigen through the function of major histocompatibility complex molecules. Moreover, some cells are specially equipped to present antigen, and to prime naive T cells. Dendritic cells, B-cells, and macrophages are termed professional antigen-presenting cells (APCs). Plus they are equipped with special "co-stimulatory" ligands recognized by co-stimulatory receptors on T cells. Adaptive immune response would be inefficient without those costimulatory signals as the T cells would become anergic. Several T cells subgroups can be activated by professional APCs, and each type of T cell is specially equipped to deal with each unique toxin or microbial pathogen. The type of T cell activated, and the type of response generated, depends, in part, on the context in which the APC first encountered the antigen.

NK cells attack self cells that have become infected or more specifically compromised host cells (such as tumor cells or virus-infected cells) rather than attack foreign invaders. They distinguish cells with abnormally low levels of a cell-surface marker called MHC I (major histocompatibility complex). They were named "natural killer" because of the initial notion that they do not require activation in order to kill cells that are "missing self." NK cells have cytotoxic chemicals which recognize a broad spectrum of foreign invaders in a non-specific manner. NK cells are bound to foreign substances and insert their cytotoxic chemical which results in the death of foreign cells. NK cells are a type of lymphocyte. In an organism, B and T lymphocytes are present. They grow in the bone marrow and in the liver and produce hematopoetic stem cells.

Natural killer T cells are a branch of T cells and a lymphocyte that is involved in the innate response. NKT cells can pinpoint nonpeptide antigens using MHC molecules from CD1 on the cell surface. NKT constantly express T-cell and NK cell antigens. Invariant NKT cells express a unique TCRa rearrangement, Va24-Ja18 with Vb11 that is expressed that characterizes many NKT cells. When NKT cells are activated, cytokines are rapidly produced. IL-4 is associated in allergy pathogenesis. Ulcerative colitis, UC, is a form of inflammatory bowel disease. It has recently been found that natural killer T cells can play a key role in the disease. According to a recent study, by manipulating natural killer T cells, it may be possible to modify the abnormal immunoresponse activity characteristic within UC.

One of the most important regulatory mechanisms. Cytokines influence for example the development and differentiation of various T cell subpopulations. The influence of cytokines can be inhibit by endocytosis of receptors able to bind them or by inhibitors binding directly to the receptor instead. Intercellular synapse is a key part of immune responses. The immune response wont be activated without proper communication between cells. Moreover, effector cells need costimulation in order to be actually activated nad to avoid anergy.