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GLOSSARY (I-K)

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I


Immunoassay

A biochemical test that measures the presence or concentration of a macromolecule in a solution through the use of an antibody or immunoglobulin. The macromolecule detected by the immunoassay is often referred to as an “analyte” and is in many cases a protein.

Immunoassays are quick and accurate tests that can be used on-site and in the laboratory to detect specific molecules. They rely on the inherent ability of an antibody to bind to the specific structure of a molecule.


Immunogen

A substance that provokes an immune response. An immunogen is any antigen that is capable of inducing humoral and/or cell-mediated immune response rather than immunological tolerance. This ability is called immunogenicity. The term is sometimes used interchangeably with the term antigen, but only an immunogen can evoke an immune response


Immunogenicity

The ability of a substance to provoke an immune response or the degree to which it provokes such a response.

See: Immunogen


Immunoglobulin

An Immunoglobulin, also known as Antibody, is a protein produced by plasma cells that fight infection or are part of an immune response. Immunoglobulins bind with other molecules with a high degree of specificity.

On the basis of structural and biological activity, immunoglobulins are divided in 5 classes:

  • Immunoglobulin M (IgM)

Found in blood and lymph fluid, and making up about 5-10% of antibodies in the body, these immunoglobulins are a basic antibody and is produced by B cells. IgM is by far the physically largest antibody in the human circulatory system and the first type of antibody appearing early in the course of an infection. They usually reappear, to a lesser extent, after further exposure.  They also cause other immune system cells to destroy foreign substances.

  • Immunoglobulin G (IgG)

Found in all body fluids, these antibodies are the smallest but most common antibody (75% to 80%) isotope found in blood and extracellular fluid allowing it to control infection of body tissues.  They are very important in fighting bacterial and viral infections. IgG antibodies are the only type of antibody that can cross the placenta in a pregnant woman to help protect her baby (fetus). By binding many kinds of pathogens—representing viruses, bacteria, and fungi—IgG protects the body from infection. It does this via several immune mechanisms: IgG-mediated binding of pathogens causes their immobilization and binding together via agglutination; IgG coating of pathogen surfaces (known as opsonization) allows their recognition and ingestion by phagocytic immune cells; IgG activates the classical pathway of the complement system, a cascade of immune protein production that results in pathogen elimination; IgG also binds and neutralizes toxins. IgG also plays an important role in antibody-dependent cell-mediated cytotoxicity (ADCC) and intracellular antibody-mediated proteolysis, in which it binds to TRIM21 (the receptor with greatest affinity to IgG in humans) in order to direct marked virions to the proteasome in the cytosol. IgG is also associated with Type II and Type III Hypersensitivity.

  • Immunoglobulin A (IgA)

Also referred to as sIgA, Immunoglobulin A (IgA) is an antibody that plays a critical role in mucosal immunity and is found in tears, saliva, sweat, colostrum and secretions from the genitourinary tract, gastrointestinal tract, prostate and respiratory epithelium.  It is also found in small amounts in blood. IgA antibodies protect body surfaces that are exposed to outside foreign substances. About 10% to 15% of the antibodies present in the body are IgA antibodies.  The secretory component of sIgA protects the immunoglobulin from being degraded by proteolytic enzymes, as a result, sIgA can survive in the harsh gastrointestinal tract environment and provide protection against microbes that multiply in body secretions. sIgA can also inhibit inflammatory effects of other immunoglobulins.

  • Immunoglobulin D (IgD)

Found in small amounts in the tissues that line the belly or chest. Immunoglobulin D (IgD) is an antibody isotype that makes up about 1% of proteins in the plasma membranes of mature B-lymphocytes where it is usually coexpressed with another cell surface antibody called IgM. IgD is also produced in a secreted form that is found in very small amounts in blood serum. Secreted IgD is produced as a monomeric antibody with two heavy chains of the delta (δ) class, and two Ig light chains. Since the discovery in 1964, the function has always been a puzzle. However recently, IgD was found to bind to basophils and mast cells and activate these cells to produce antimicrobial factors to participate in respiratory immune defense in humans. It also stimulates basophils to release B-cell homeostatic factors. This is consistent with the reduction in the number of peripheral B cells, reduced serum IgE level and defective primary IgG1 response in IgD knockout mice.

  • Immunoglobulin E (IgE)

These antibodies are found in the lungs, skin, and mucous membranes. They cause the body to react against foreign substances, including pollen, fungus spores, and animal dander. IgE antibodies are involved in allergic reactions to milk, some medicines, and some poisons. In people with allergies, levels of IgE antibody levels are often high.

Also see: Immunoglobulin G (IgG) Antibody Isotypes


Immunohistochemistry

The staining of histology preparations using chromatin linked antibodies to specifically stain for specific proteins in a histology section or slide.


In Silico

An expression used to mean performed on computer or via computer simulation. The phrase was originally coined in 1989 as an analogy to the Latin phrases commonly used in biology including: in vivo (experiments done in living organisms), in vitro (experiments outside of living organisms), and in situ (where they are found in nature).


In vitro

An expression used to mean outside of living organisms, using laboratory equipment


In vivo

An expression used to mean in living organisms. Experiments involve living animals or humans as test subjects.


IND

Also: Investigational New Drug application

A process by which a sponsoring pharmaceutical company requests the U.S. Food and Drug Administration (FDA) for permission to expose patients or healthy volunteers to its experimental (trial) drug.  The application needs to be files for each individual clinical Phase I – III study.


Inotuzumab ozogamicin (CMC-544)

Inotuzumab ozogamicin is an investigational antibody-drug conjugate comprised of a monoclonal antibody targeting CD22, a cell surface antigen expressed on approximately 90% of B-cell malignancies, linked to a cytotoxic agent. The drug is being developed by Pfizer, Inc.

When inotuzumab ozogamicin binds to the CD22 antigen on malignant B-cells, it is absorbed into the cell, at which point the cytotoxic agent calicheamicin,  a natural product of bacteria that was first discovered in caliche clay and was found to be toxic to normal and cancerous cells, is released to destroy the cell.

Pfizer is exploring a clinical development program to determine which patients may benefit from inotuzumab ozogamicin in different B-cell malignancies:

Phase III:  INO-VATE NHL (INotuzumab Ozogamicin trial to inVestigAte Tolerability and Efficacy)

Study 1008 – A multicenter, open-label, randomized, Phase III study of inotuzumab ozogamicin administered in combination with rituximab compared to defined investigator’s choice therapy in subjects with relapsed or refractory CD22-positive aggressive NHL who are not candidates for intensive high-dose chemotherapy.

Study 1022 – An open-label, randomized, Phase III study of inotuzumab ozogamicin compared to a defined investigator’s choice of chemotherapy in adult patients with relapsed or refractory CD22+ acute lymphoblastic leukemia (ALL).

Phase II

Study 2005 – An open-label, single-arm Phase 2 study of inotuzumab ozogamicin plus rituximab in subjects with relapsed/refractory CD22-positive diffuse large B-cell lymphoma, eligible for autologous stem cell transplantation.

Study 2001 – A Phase II study of inotuzumab ozogamicin in subjects with indolent NHL that is refractory to or has relapsed after rituximab and chemotherapy or radioimmunotherapy.

Phase I

Study 1010 – An open-label, Phase I study of inotuzumab ozogamicin in subjects with relapsed or refractory CD22-positive ALL.


Interleukins

A group of naturally occurring cytokines (secreted proteins and signaling molecules) produced by lymphocytes or macrophages that mediate communication between cells. They modulate the immune response and regulate cell growth, differentiation, and motility.

The function of the immune system depends in a large part on interleukins, and rare deficiencies of a number of them have been described, all featuring autoimmune diseases or immune deficiency. The majority of interleukins are synthesized by helper CD4 T lymphocytes, as well as through monocytes, macrophages, and endothelial cells. They promote the development and differentiation of T and B lymphocytes, and hematopoietic cells.


Intermediates

An organic compound or substance that is formed in a stage between the parent substance and the final pharmaceutical compound. Generally a considered to be a stepping stone in the synthesis of the final pharmaceutical product.


K


kDa

Abbreviation of kiloDalton; a thousand Daltons

The unified atomic mass unit (symbol: u) or Dalton (symbol: Da) is the standard unit that is used to indicate mass on an atomic or molecular scale (atomic mass). One unified atomic mass unit is approximately the mass of one nucleon (either a single proton or neutron) and is equivalent to 1 g/mol.  This is defined as one twelfth of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state, and has a value of 1.660538921(73)×10−27 kg. The International Committee for Weights and Measures (CIPM) has categorised it as a non-SI unit accepted for use with the SI (International System of Units) , and whose value in SI units must be obtained experimentally.


Knockout

In gene targeting, a knockout mouse is a genetically engineered mouse in which researchers have inactivated, or knocked out, an existing gene by replacing it or disrupting it with an artificial piece of DNA. The loss of specific gene activity, while leaving other genes unaffected, causes changes in a mouse’s phenotype, which includes appearance, behavior and other observable physical and biochemical characteristics. This method provides the best way to delineate the function of a gene.

Knockout mice are important animal models for studying the role of genes which have been sequenced but whose functions have not been determined. By causing a specific gene to be inactive in the mouse, and observing any differences from normal behaviour or physiology, researchers can infer its probable function.


 

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