Ibandronate A bisphosphonate licensed for the treatment of postmenopausal osteoporosis. The drug can be administered orally or by slow intravenous injection. Orally, it is given before meals and washed down with a cup of water; afterwards, the patient must sit and not lie down for 30 min. The oral dose of 150 mg is given once a month, a regimen thought to improve compliance. It can also be administered by slow intravenous injection at a dose of 3 mg in 3ml every 3 months. This is particularly useful in patients with gastrointestinal intolerance of bisphosphonates.

ICAM – see Intercellular adhesion molecule (ICAM).

ICF – see International classification of functioning (ICF).

Idiopathic infantile hypercalcaemia Patients resemble children with Williams syndrome; some of them can have heart disease, facial dysmorphism, hypertension and radioulnar synostosis. Further, there can be strabismus (squint), inguinal hernia and hyperacusis, which are persistent. Polyuria and polydipsia are frequent. In some patients, an elevated PTHrP (parathyroid hormone-related protein) level can be detected. The hypercalcaemia persists much longer than in Williams syndrome and sometimes requires limitation of the calcium intake, exclusion of vitamin D and administration of glucocorticoids.

Idiotope An idiotope is a unique set of antigen determinants found in variable domains of immunoglobulin polypeptide chains.

Idiotype It is a shared characteristic between a group of immunoglobulin or T cell receptor (TCR) molecules based upon the antigen-binding specificity and therefore structure of their variable region. Also it is a set of idiotopes at the binding site for a certain antibody. Anti-idiotypic antibodies that are one’s own anti-antibodies can develop against the idiotypes. Their binding site is complementary to the binding site of the first antibodies and so it has a spatial structure identical to the antigen determinant that is specific for this first antibody. These anti-idiotypic antibodies are therefore referred to as the inner antigen picture of homoantibodies. It is assumed that the idiotypes and anti-idiotypes form a regulatory network in the body.

IgD Immunoglobulins with a less well-understood biological function. IgD molecules are, together with IgM monomers, most frequently incorporated in the cytoplasmic membrane of B lymphocytes, having a discriminative function of the antigen receptor component.

IgE In physiological circumstances, their serum concentration is the lowest of all immunoglobulins. These antibodies participate in the protection of the body against parasitic infections and, just like reagins, are responsible for early hypersensitive reactions (allergies, anaphylaxis). Serum IgE levels are raised in parasitic infections and are especially high in allergic reactions.

IGF – see Insulin-like growth factor (IGF).

IgG This class of immunoglobulins is the most widespread in extracellular fluids. Their molecules consist of two identical light and two identical heavy chains that are spatially organised into domains. There are four known heavy chains γ distinct in antigens, which form the four subclasses IgG1, IgG2, IgG3 and IgG4. The antibodies of IgG class are formed mainly during the response to the repeated administration of soluble antigens. They are the only antibodies to cross the human foetal–maternal barrier in the placenta. They activate complement after binding with the antigen (immune complexes) or in the form of self-aggregates (clusters of one’s own molecules).

IgM They have the biggest relative molecular weight (900,000 kDa) and sedimentation coefficient (19S). Their molecule consists of five identical subunits (each with 180 kDa and 8S), thus forming a pentamere that aside from 10 light chains and 10 heavy chains contains also one J-chain. A small amount of circulating IgM (up to 5 %) forms a hexamere. The basic subunit 8S of IgM is not circulating but remains in membrane form as a component of the antigen receptor on the surface of B lymphocytes. Antibodies belonging to the IgM class are produced mainly upon first contact of the organism with a corpuscular antigen. They have the greatest additive effect of multivalency, which makes them particularly effective in the agglutination of bacteria and in activating complement via the classical pathway (after formation of immune complexes or aggregates).

IIF (indirect immunofluorescence) A laboratory test used to detect antibodies in serum or other body fluids. IIF uses two antibodies. The primary antibody is unconjugated, and a fluorophore-conjugated secondary antibody directed against the primary antibody is used for detection. The IIF Test on Hep-2 cells is the recommended gold standard to detect antinuclear antibodies (ANAs).

IL 1–18 – see Interleukin 1–18.

IL-1R The IL-1 receptor occurs in two isotypes: I and II. Type II has a shorter cytoplasmic part compared to type I which consequently causes insufficient intracellular transmission of the signal after binding IL-1.

IL-1RA An antagonist of the IL-1 receptor. IL-1 is a cytokine participating in normal physiological processes as well as regulation of the inflammatory responses. IL-1RA occurs in three isoforms: one secretory (sIL-1RA) and two intracellular (icIL-1RAI and icIL-1RAII). The function of secretory IL1RA consists in local inhibition of IL-1 and blockade of acute phase proteins, whilst the function of the intracellular IL-1RA is unknown.

Immune complexes Complexes arising from the reaction between an antigen and an antibody. They can occur either in vitro (where they are the essence of immunochemical assays and diagnostic methods) or in vivo (in which case they facilitate phagocytosis of bacteria or other particles opsonised by the antibodies or can induce immune complex disorders if the immune complexes are soluble or autoimmune disorders when the reaction between an autoantibody and autoantigen occurs in an organ). With in vivo conditions or in the presence of blood serum, the immune complexes can also bind to certain components of complement.

Immune-mediated necrotising myopathy A subtype of a statin-induced myopathy, characterised by muscle fibre necrosis without presence of a significant lymphocytic inflammatory infiltrate. Pathogenesis is autoimmune. Antibodies against HMG CoAR (3-hydroxy-3-methylglutaryl-coenzyme A reductase) are detected in patient serum. Discontinuation of a statin is not a sufficient therapy. Treatment consists of immunosuppression.

Immune system (IS) This is a diffuse (not strictly delineated) organ that weighs around 1000 g in an adult and consists of multiple tissues, cells and molecules. It is a component of the neuro–endocrine–immune supersystem, ensuring the input and processing of all information necessary for the survival of humans and other superior organisms. The fundament component of the IS is lymphatic tissue either condensed in lymphoid organs or existing in the form of free cells (lymphocytes, leukocytes). The lymphoid organs are divided into central (primary) or peripheral (secondary). As well as lymphocytes, the other important cells include antigen-presenting cells and phagocytes (especially macrophages and neutrophils). Essential molecules involved in the reactions of the IS include antibodies (immunoglobulins), components and factors of the complement system (complement), various immunohormones, cytokines and other immunoregulatory substances, and numerous receptors on the surface of immunologically active cells, such as antigen and immunoadherence receptors, Fc receptors etc. The basic function of the IS is to obtain information from the internal and external environment, their logical processing and response (immune response), the result of which is usually a defence-adaptation reaction (induction of immunity) but can also sometimes cause damage to one’s own tissues, cells and their structure in the autoimmune or other immunopathological responses (immunopathology). In this respect, the immune system is similar to the neuroendocrine system, with which it is closely linked, thus forming a single superinformation system that is a prerequisite for the existence of all superior animals. The most important property of the IS is its ability to differentiate its own molecular structures from foreign ones (antigen). Proper and fully functioning antigens are normally tolerated; heterogeneous (on the surface of microorganisms or transplanted cells) or proper but functionally altered (estranged as, e.g. on tumour-transformed or virus-infected cells) are inactivated and destroyed in the course of an immune response.

Immunity The capability of an organism to withstand infectious germs (viruses, bacteria, fungi, cytozoon), foreign and estranged cells (cells transplanted from a genetically different individual and one’s own altered cells (cancerous) or cells invaded by viruses) and their products, producing the ability to react against the antigen by the immune response to the benefit of the body. This immunity can be either non-specific (natural, innate) or specific (acquired, adaptive). Both are determined by an individual’s genetic makeup (genome).

Immunity – cellular immunity Immunity executed by cells belonging to the immune system (lymphocytes and professional phagocytes for specific and natural or non-specific cellular immunity, respectively).

Immunity – humoural immunity The immunity mediated by executive molecules belonging to the immune system and often found in body fluids (humours). These molecules are mostly antibodies. This type of immunity is also called antibody-mediated immunity.

Immunity – non-specific immunity This is a set of reactions at the tissue, cellular and molecular cellular level that are congenitally present in the body and whose activity is independent of prior contact with the antigen. This allows them to respond immediately after contact of the body with an infectious agent. Non-specific immunity is activated predominantly in the elimination of heterogeneous substances from tissues and in anti-infectious and antineoplastic defence.

Immunity – specific immunity It is also referred to as acquired immunity. It is the ability of the body to react against a heterogeneous antigen with a specific immunological response. Specific antibodies, executive lymphocytes and lymphocytes with an immunological memory able to react solely with the antigen that has induced their production occur in specific immunity. They do not exert action immediately after contact of the immune system with a specific antigen but instead require a latent period of several days during which the relevant clones of cells proliferate and differentiate and the production of antibodies is induced.

Immunity – transplantation immunity An acquired immunity against the cells, tissues and their antigens (major histocompatibility antigens) induced following their transfer from a genetically nonidentical donor. There can be two responses to heterogeneous histocompatibility antigens: host versus graft rejection (HvG) or graft versus host reaction (GvHR). The host versus graft rejection can be hyperacute (executed by the antibodies, e.g. in blood group differences or xenotransplantations), acute (reaction of cytotoxic T lymphocytes against heterogeneous HLA antigens) or chronic (participation of antibodies against weak histocompatibility antigens).

Immunoadherence This is the ability of professional phagocytes to adhere to their immunoadherent receptors (FcR or CR) of bacteria or other particles opsonised by antibodies or the C3b fragment of complement.

Immunoadherent receptors These are present particularly on the surface of professional phagocytes where they are involved in phagocytosis with the binding and ingestion of bacteria, immune complexes and other particles covered by antibodies or C3b, iC3b or possibly C4b fragments of complement. The particles covered by antibodies are recognised by Fc receptors, whilst particles opsonised by C3b or C4b fragments are bound to CR1 and CR3. In primates, the CR1 is present on erythrocytes and is involved in the clearance of immune complexes from the circulation.

Immunoadsorbent An insoluble substance (carrier) with a bound antigen or antibody used as a functional ligand. If the antibody is bound to the carrier, a simple separation of a specific antigen is possible or vice versa (immunoadsorbent chromatography).

Immunoassay, chemiluminescence An immunochemical method used to measure the concentration of antigen (hapten) or antibody, in which one of these reactants is labelled by a chemiluminophore (chemiluminescence).

Immunoassay, enzymatic An immunochemical method used for determining the concentration of a certain antigen (hapten) or antibody in which one of these reacting components is labelled with an enzyme. After interaction, the resultant immune complex is also labelled with this enzyme and the precise level of immune complexes can be quantified by an enzymatic reaction with a suitable, usually coloured substrate.

Immunoassay, fluorescence Fluoroimmunoanalysis is an immunochemical method for determining the concentration of antigen (hapten) or antibody in a compound mixture of different substances in which the antigen or antibody is labelled by a fluorescent agent (a fluorophore). The level of analysed substance is then measured by fluorimetry or photon absorptiometry.

Immunoassay, particle-enhanced An immunochemical method for determining the concentration of antigen (hapten) or antibody in which one of these reactants is adsorbed or chemically linked to the surface or a particle (erythrocyte, latex particles, colloid gold, etc.). Following interaction with the other reactant, agglutination or particle lysis occurs, which can be measured by various techniques.

Immunoassay, radioisotope An immunochemical method used to determine the concentration of an antigen or hapten, in which added external antigen is labelled by a radioactive isotope giving rise to the term, radioimmunoassay (RIA). Conversely, if the antibody is labelled with the radioactive isotope, the method is called an immunoradiometric assay (IRMA).

Immunoblotting A method used to detect a specific protein in a given sample of tissue homogenate or extract.

Immunocompetence A genetically determined ability of certain lymphocytes to react against an antigen with a specific immune response in a quantitative and qualitative sense. This is the ability of the body to produce a normal immune response following exposure to an antigen. When applied to lymphocytes, it means that a B or T lymphocyte is mature and can recognise antigens and is capable of mounting an immune response.

Immunodiffusion A diffuse movement of the antigen and antibody molecule, usually in agar or agarose gel. The movement velocity depends on the concentration of both components and diffusion constants. A gel precipitate can be seen in the presence of the sought antigen or antibody at the point where they meet and their concentration is approximately equal. Under the correct conditions, it is also possible from the surface of the precipitate to determine the concentration of the evaluated component, in a similar fashion to simple radial immunodiffusion. Immunodiffusion methods are used for confirmation of diagnostically significant antigens (where a specific antibody is available) or antibodies (where a specific antigen is available).

Immunoelectrophoresis This laboratory technique is a combination of electrophoresis and immunodiffusion in agar or agarose gel. Using immunoelectrophoresis techniques, it is possible to determine the presence and amount (concentration) of antigens substantially faster than by a simple immunodiffusion method. Depending on technique, immunoelectrophoresis can be subdivided into five groups: classical immunoelectrophoresis according to Grabar and Williams (used especially for confirming multiple myeloma immunoglobulins), rocket immunoelectrophoresis, counterimmunoelectrophoresis, two-dimensional immunoelectrophoresis and immunofixation.

Immunofixation An immunoelectrophoresis method in which the separated antigens are detected directly in the gel on the basis of their precipitation with a specific antibody.

Immunofluorescence A property of certain molecules to absorb light or other form of energy and show it in the form of a photon (light with longer wavelength than that of absorbed light). It is used in immunohistochemistry and immunoassay techniques. Using the antibodies labelled by an immunofluorescent stain, it is possible to localise the applicable antigens in histological slides or study the fluorescent immune complexes through a fluorescent microscope. The same principle is also applied in sensitive fluorescent immunoassays (immunoassay, fluorescent).

Immunogenetics A branch of science representing the boundary between immunology and genetics and dealing with the genetic analysis of executive and regulatory molecules of the immune system (especially antigens of the major histocompatibility complex, immunoglobulins, cytokines and components and factors of complement) as well as the genetic regulation of immune responses.

Immunoglobulin deficiency This can be induced by abnormal function of B lymphocytes or both B and T lymphocytes. Affected individuals manifest with a low level of immunoglobulins (hypogammaglobulinaemia), abnormal function of immunoglobulins (gammopathy), hypercatabolism (excessively rapid degradation of the immunoglobulin molecules), excessive loss (upon heavy haemorrhage) or damage to lymphocytes (e.g. by drugs or lymphocytotrophic viruses). These can all lead to diseases in which the pathogenesis is a decreased immunity against most infectious agents. Subsequent severe recurrent infections are usually resistant to conventional antibiotic treatment. Primary immunoglobulin deficiencies include agammaglobulinaemia and selective deficiency of IgA or also other immunoglobulin classes and subclasses, severe combined immunodeficiency and hereditary ataxia-telangiectasia.

Immunoglobulin, normal human Intravenously applicable immunoglobulin preparation made from the blood plasma of at least 1000 healthy donors. It contains predominantly IgG and is used for substitution treatment (in deficiencies of antibody production), for prophylaxis and the treatment of certain infectious and autoimmune disorders (immunoglobulins, therapeutic preparations).

Immunoglobulin superfamily A complex of glycoprotein molecules coded for by genes with an evolutional homology, i.e. a common predecessor. The members of the immunoglobulin superfamily have several common sections of polypeptide chains in their molecules, with the same stereometric structure as the immunoglobulin chains (immunoglobulin domains). There are three types of stereometrically homologous domains identified amongst the members of the Ig superfamily: the variable (V), the constant (C) and the H domain. Currently, there are more than 40 known members of this superfamily whose basic functions are discriminative (immunoglobulins, antigenic receptors on T cells, antigens of class I and II of the major histocompatibility complex, differentiation antigens CD2, CD3, CD4, CD8 and receptors for Fc domain of immunoglobulins – FcR), adhesive (connecting) or regulatory interactions between cells. The group of adhesive molecules include ICAM-1 (CD54 – intercellular adhesion molecule-1), ICAM-2 (CD102), VCAM-1 (CD106 – vascular cell adhesion molecule) and PECAM-1 (CD31 – platelet-endothelial cell adhesion molecule). Besides the discriminative molecules, the receptor for polymeric immunoglobulins (p-IgR) and platelet-derived growth factor receptor also possess a regulatory function.

Immunoglobulins (Ig) These are glycoproteins of animal origin and include all antibodies. Their molecules consist of two identical light chains and two identical heavy polypeptide chains interconnected by disulphide bonds. The chains are spatially organised into domains (immunoglobulin domains) and modules. The first domains of the light and heavy chains are variable, whilst the others are constant. In the variable domains, the sequence of amino acids of the polypeptide chains changes amongst the antibody molecules with diverse specificity, whilst in the constant domains remains unchanged. The sections of variable domains with particularly intensive changes of amino acids in individual positions are called hypervariable sections. The hypervariable sections of the light and heavy chains are positioned in the Ig molecule side by side and form the antibody binding site, accounting for antibody-mediated specificity. There are two types of light chains (kappa and lambda). Heavy chain immunoglobulins are classified into five classes (IgA, IgD, IgE, IgG and IgM).

Immunoglobulins – chains Polypeptide chains constituting the immunoglobulin molecule. Each of the molecules contains at least two identical light (L) chains and two identical heavy (H) chains. There are two types of light chain: kappa (κ) or lambda (λ); they determine the type of immunoglobulin molecule (K or L). The heavy chains belong to five different isotypes: gamma (γ), mu (μ), alpha (α), delta (δ) and epsilon (ε); each of them determines membership to a specific immunoglobulin class. In addition to these two types of chains, the molecule of polymeric immunoglobulins (IgM and secretory IgA) also contains one joining (J) chain and the secretory IgA molecule a secretory component (SC).

Immunoglobulins – classes Isotypic variants that differ from one another by the antigenic structure of constant domains of the heavy chains of their molecules (immunoglobulins, chains). There are five known classes of immunoglobulins: IgG (having the heavy chain γ), IgM (μ), IgA (α), IgD (δ) and IgE (ε).

Immunoglobulins – effector functions All functions except those serving at the binding site. These include the ability to activate the complement, bind to the cellular Fc receptors, pass through the placenta, etc.

Immunoglobulins – genetics See Genetics of immunoglobulins.

Immunoglobulins – hypervariable regions This is the section of polypeptide chains in the variable domains where individual amino acids are able to a greater extent to change positions and thus allow immense diversity to generate millions of antigen-specific antibodies. There are six such sections in general – three on the light chain and three on the heavy chain. During the final stereometric arrangement of the immunoglobulin molecule, they become mutually close and form an antibody binding site. The hypervariable sections are also called complementary determining regions (CDR).

Immunoglobulins – idiotypes Immunoglobulin variants determined by a set of antigenic determinants, mainly in the hypervariable sections of both light and heavy chains. Such an idiotype represents the antigenicity of the antibody binding site. Some idiotypes can be found only in the organism of a certain individual (private idiotypes), whilst others can be confirmed in multiple individuals (common or cross-reacting idiotypes).

Immunoglobulins – isotypes These represent individual classes (subclasses) and types of immunoglobulins. They identify their antigenic determinants localised in the constant domains of heavy and light chains and are identical in all individuals of the given animal species. They are products of different structural genes and can be identified using xenogenic antisera (e.g. rabbit antiserum against human IgG will react with the IgG of all individuals of the human population, but not with the IgG of other biological species).