Educational Appendix

A measure of the binding constant between a single antigen combining site on an antibody and a monovalent antigenic determinant.

The ability of heterozygous lymphoid cells to produce only one allelic form of antigen-specific receptor when they have the genetic endowment to produce both. Genes other than those for the specific receptors are usually expressed codominantly. In B lymphocytes, successful heavy chain gene rearrangement of the genetic material from one chromosome results in the shutting down of rearrangement of genetic material from the second chromosome. If no successful rearrangement occurs, rearrangement of genetic material on the second chromosome takes place. If no successful rearrangement occurs on either chromosome, the cell dies. As a result of allelic exclusion, all the antigen receptors on an individual lymphocyte will have the same amino acid sequence in the variable domain of the heavy chain protein. As the specificity of the antigen receptor is modulated by the variable domain of the light chain encoded by one of the immunoglobulin light chain loci, the specificities of B cells containing the same heavy chain recombination event can differ according to their light chain recombination event.

An allergen is a type of antigen that produces an abnormally vigorous immune response in which the immune system fights off a perceived threat that would otherwise be harmless to the body. Such reactions are called allergies. Specifically, an allergen is an antigen capable of stimulating a type-I hypersensitivity reaction in atopic individuals through Immunoglobulin E (IgE) responses. Most humans mount significant IgE responses only as a defense against parasitic infections. However, some individuals may respond to many common environmental antigens. This hereditary predisposition is called atopy. In atopic individuals, non-parasitic antigens stimulate inappropriate IgE production, leading to type I hypersensitivity.

Allergies are a number of conditions caused by hypersensitivity of the immune system to something in the environment that usually causes little problem in most people. These diseases include hay fever, food allergies, atopic dermatitis, allergic asthma, and anaphylaxis. In the early stages of allergy, a type I hypersensitivity reaction against an allergen encountered for the first time and presented by an antigen-presenting cell causes a response in an immune cell called a TH2 lymphocyte. These TH2 cells interact with B cells and stimulate production of a large amount of IgE antibodies. Secreted IgE circulates in the blood and binds to immune cells called mast cells and basophils, which are both involved in the acute inflammatory response. The IgE-coated cells, at this stage, are sensitized to the allergen. If later exposure to the same allergen occurs, the allergen can bind to the IgE molecules held on the surface of the mast cells or basophils, cross-linking them and activating the sensitized cell. Activated mast cells and basophils undergo a process called degranulation, during which they release histamine and other inflammatory chemical mediators (cytokines, interleukins, leukotrienes, and prostaglandins) from their granules into the surrounding tissue causing several systemic effects, such as vasodilation, mucous secretion, nerve stimulation, and smooth muscle contraction. After the acute response subsides, late-phase responses can often occur due to the migration of other leukocytes such as neutrophils, lymphocytes, eosinophils and macrophages to the initial site. This reaction is usually seen 2-24 hours after the original reaction. Cytokines from mast cells may play a role in the persistence of long-term effects.

Having a genetic dissimilarity within the same species.

A tissue transplant (graft) between two genetically nonidentical members of a species.

Antigenic determinants that are present in allelic (alternate) forms. When used in association with immunoglobulin, allotypes describe allelic variants of immunoglobulins detected by antibodies raised between members of the same species.

 The mechanism of complement activation that does not involve activation of the C1, C4, C2 pathway by antigen-antibody complexes, and begins with the activation of C3.

Substance capable of releasing histamine from mast cells.

Immediate hypersensitivity response to antigenic challenge, mediated by IgE and mast cells. It is a life-threatening allergic reaction, caused by the release of pharmacologically active agents.

Serum protein formed in response to immunization; antibodies are generally defined in terms of their specific binding to the immunizing antigen.

A phenomenon in which target cells, coated with antibody, are destroyed by specialized killer cells (NK cells and macrophages), which bear receptors for the Fc portion of the coating antibody (Fc receptors). These receptors allow the killer cells to bind to the antibody-coated target.

 Any foreign material that is specifically bound by specific antibody or specific lymphocytes; also used loosely to describe materials used for immunization. Antigens may also be immunogens if they are able to trigger an immune response, or haptens if not.

Large molecules are broken down (processed) within macrophages into peptides and presented within the groove of MHC molecules.

The specific antigen-binding receptor on T or B lymphocytes; these receptors are transcribed and translated from rearrangements of V genes.

 The part of an immunoglobulin molecule that binds antigen specifically.

An antigen-presenting cell or accessory cell is a cell that processes antigens and presents them on their cell surface complexed with major histocompatibility complexes (MHCs) for T cells to recognize using their T cell receptors (TCRs). Almost all cell types can serve as some form of APC, and they are found in a variety of tissue types. Professional antigen-presenting cells, including macrophages, B cells and dendritic cells, present foreign antigens to helper T cells, while other cell types can present antigens originating inside the cell to cytotoxic T cells. Antigen-presenting cells are vital for an effective adaptive immune response that is specific and can be directed against either intracellular and extracellular pathogens. It is also involved in defense against tumors.

A term used by allergists to describe IgE-mediated anaphylactic responses in humans, usually genetically determined.

A tissue transplant from one area to another on a single individual.

An immune response to "self" tissues or components. Such an immune response may have pathological consequences leading to autoimmune diseases.

In antibody-antigen interactions multiple antigen-binding sites simultaneously interact with the target antigenic epitopes, often in multimerized structures. Individually, each binding interaction may be readily broken, however, when many binding interactions are present at the same time, transient unbinding of a single site does not allow the molecule to diffuse away, and binding of that weak interaction is likely to be restored. Each antibody has at least two antigen-binding sites, therefore antibodies are bivalent to multivalent. Avidity (functional affinity) is the accumulated strength of these multiple affinities. For example IgM is said to have low affinity but high avidity because it has 10 weak binding sites for antigen as opposed to the 2 stronger binding sites of IgG, IgE and IgD with higher single binding affinities.

AXL is a member of the TAM receptor tyrosine kinase subfamily (TYRO3, AXL and MER). AXL transduces signals from the extracellular matrix into the cytoplasm by binding growth factors like vitamin K-dependent protein growth-arrest-specific gene 6 (GAS6). It is involved in the stimulation of cell proliferation; Axl is a chronic myelogenous leukemia-associated oncogene and also associated with colon cancer and melanoma. This receptor can also mediate cell aggregation by homophilic binding. The Axl gene is evolutionarily conserved between vertebrate species, and has two different alternatively spliced transcript variants.