small molecules that bind with self proteins

small molecules that bind with self proteins

small molecules that bind with self proteins

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hapten, also spelled haptene, small molecule that stimulates the production of antibody molecules only when conjugated to a larger molecule, called a carrier molecule.

The term hapten is derived from the Greek haptein, meaning “to fasten.” Haptens can become tightly fastened to a carrier molecule, most often a protein, by a covalent bond. The hapten-carrier complex stimulates the production of antibodies, which the unbound hapten cannot do, and becomes immunogenic (capable of eliciting an immune response). The hapten then reacts specifically with the antibodies generated against it to produce an immune or allergic response.

small molecules that bind with self proteins
small molecules that bind with self proteins

Thus, although the hapten cannot elicit an antibody response on its own, it can bind with antibodies and act as an antigen. In the early part of the 20th century, immunologist Karl Landsteiner exploited the antigenic quality of synthetic haptens to study the highly specific way in which antibodies bind to antigens.

Many drugs that cause allergic reactions, such as penicillin, act as haptens. When injected or ingested, penicillin reacts chemically with proteins in the body to form a hapten-carrier complex that can lead to the life-threatening syndrome called anaphylaxis. Other haptens include synthetic substances, such as the organic compounds benzene arsonate or trinitrophenol, and naturally occurring polysaccharides, such as lactose. Researchers have used haptens to construct synthetic vaccines to immunize people against various infectious organisms.

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Hapten–Gelatin Gels Used as Adsorbents for Separation of Hapten-Specific B Lymphocytes

D Treatment of Separated Cells with Collagenase

Hapten–gelatin remains bound to cells recovered from hapten-gelatin layers by melting and cannot be removed from the cells by washing through FCS. However, hapten–gelatin may be removed from the cell surface after treatment with trypsin or collagenase. For most purposes, the use of highly purified collagenase (A grade) is required, which does not affect any cell-surface proteins. Up to 107 cells are suspended in 0.9 ml of EBSS (or PBS) and 0.1 ml of collagenase (1 mg/ml) is added.

Much lower collagenase concentrations may be sufficient depending on the activity of the collagenase preparation. The mixture is kept for 10 min at 37°C and the cells are then washed twice through 1-ml underlayers of FCS. Siliconized glass tubes should be used to avoid a substantial loss of cells during the washing procedure. For some purposes it may be advantageous to treat the cells with collagenase at 4°C for 20 min. This procedure also effectively removes all hapten–gelatin from the cells.

small molecules that bind with self proteins
small molecules that bind with self proteins

T Cells and MHC Proteins

The diverse responses of T cells are collectively called cell-mediated immune reactions. This is to distinguish them from antibody responses, which, of course, also depend on cells (B cells). Like antibody responses, T cell responses are exquisitely antigen-specific, and they are at least as important as antibodies in defending vertebrates against infection. Indeed, most adaptive immune responses, including antibody responses, require helper T cells for their initiation. Most importantly, unlike B cells, T cells can help eliminate pathogens that reside inside host cells. Much of the rest of this chapter is concerned with how T cells accomplish this feat.

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Types of Antigens

Antigens are categorized into broad classes of antigens based on their origin. So many different molecules can function as an antigen in the body, and there is considerable diversity even within these categories.

These are the main classes of antigens that are involved in immune system activation. Their diversity is analogous to the immense diversity of the diseases that the immune system works to overcome.

Exogenous Antigens

Exogenous antigens are antigens that have entered the body from the outside.

for example by inhalation, ingestion, or injection. also Exogenous antigens are the most common kinds of antigens, and includes pollen or foods that may cause allergies, as well as the molecular components of bacteria and other pathogens that could cause an infection.

Endogenous Antigens

Endogenous antigens are that have been generated within previously-normal cells as a result of normal cell metabolism or because of viral or intracellular bacterial infection (which both change cells from the inside in order to reproduce). The fragments are then presented on the surface of the infected cells in the complex with MHC class I molecules.

 Autoantigens

Autoantigens are normal “self” protein or complex of proteins or nucleic acid that is attacked by the host’s immune system, causing an autoimmune disease.

These antigens should, under normal conditions, not be the target of the immune system.

but due to mainly genetic and environmental factors, the normal immunological tolerance for such an antigen has been lost.

small molecules that bind with self proteins
small molecules that bind with self proteins

Tumor Antigens (Neoantigens)

These antigens are presented by MHC I or MHC II molecules on the surface of tumor cells.

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These antigens result from a tumor-specific mutation during malignant transformation of normal cells into cancer cells. Despite expressing this antigen, many tumors have developed ways to evade antigen recognition and immune system killing.

Native Antigens

A native antigen is an antigen that is not yet processed by an APC to smaller parts. T cells cannot bind native antigens, but require that they be digested and processed by APCs.

whereas B cells can be activated by native ones without prior processing.

Complete Antigens and Haptens

Haptens are molecules that create an immune response when attached to proteins.

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