Institute of Immunology, MFCU, http://www.fmed.uniba.sk/index.php?id=2154
B lymphocytes are principal cells that mediate humoral adaptive immunity. After their maturation in the bone marrow, B cells enter peripheral lymphoid tissues, which are the sites of interaction with foreign antigens. Production of antibodies is initiated by the interaction of antigens with a small number of mature B cells specific for each antigen. An antigen binds to the membrane receptors on specific B cells and initiates a series of responses that lead to two principal changes: cell proliferation resulting in expansion of the clone, and differentiation to either plasma cells actively secreting antibodies or to memory cells.
Key words: B cells, subsets of B cells, memory B cells, plasma cells
Presentation provides basic facts on allergic reactions - mechanism, symptoms, allergens. Main accent is put on diagnostic possibilities, both laboratory and in vivo (skin tests). Basic information about anaphylaxis and its management is included as well.
Presentation provides basic information on the HLA-complex and transplantation immunology, with focus on kidney and haematopoetic stem cell transplantations. Most important HLA-typing methods are explained as well as other techniques used in donor-recipient pair selection.
Serological methods are basic diagnostic methods used to identify antibodies and antigens in patient sample (serum, plasma). Agglutination and precipitation belong to classical serological methods that are used in diagnosis of infectious diseases (antibodies screening), serotyping of microorganisms and human blood group typing. Agglutination is based on reaction of particular (insoluble) antigen with antibodies, whereas precipitation involves reaction of colloidal (soluble) antigen and antibodies. In the immunodiagnostics an agglutination method as Coombs test is used to determine anti Rh antibodies in pregnant women (diagnosis of hemolytic disease of newborn). Another agglutination method involves latex agglutination that is used to determine, i.e. rheumatoid factor (diagnosis of autoimmune diseases) and hemagglutination method that can be used in, i.e. antibodies screening against Treponema pallidum, the main cause of syphilis. Radial immunodiffusion assay belongs to the precipitation method. This quantitative assay is based on immunodiffusion of antigens and antibodies in the gel and can be used in level analysis of complement components (C3, C4), inflammation proteins (CRP) and immunoglobulins (IgG, IgM and IgA). Modern precipitation methods performed in fluid involve nephelometry and turbidimetry.
A principal biological role of the immune system is an eradication of both external as well internal violators of integrity of the organism. External „enemies“ are represented mainly by germs; those of internal origin belong especially to potentially malignant cells that appear in our organisms as the results of a breakdown of their replication mechanisms.Under certain circumstances, however, the immune response can have deleterious effects, resulting in significant tissue damage or even death. This inappropriate immune response is termed hypersensitivity. Although the word hypersensitivity implies an increased response, the response is not always heightened but may, instead, be an inappropriate immune response to an antigen.
Several forms of hypersensitive reaction can be distinguished, reflecting differences in the effector molecules generated in the course of the reaction. In immediate hypersensitive reactions different antibody isotypes induce different immune effector molecules. IgE antibodies, for example, induce mast cell degranulation with release of histamine and other biologically active molecules. IgG and IgM antibodies, on the other hand, induce hypersensitive reactions by activating complement. The effector molecules in these reactions are the membrane-attack complex and such complement split products as C3a, C4a and C5a. In delayed-type hypersensitivity reactions, the effector molecules are various cytokines secreted by T helper cells and macrophages. As it became clear that different immune mechanisms can give rise to hypersensitive reactions, P. G. H. Gell and R. R. A. Coombs proposed a classification scheme in which hypersensitive reactions are divided into four types, I, II, III, and IV, each involving distinct mechanisms; later type V was added. Antibodies mediate four types of hypersensitive reactions: IgE-mediated (type I), cytotoxic (type II), immune complex (type III), and stimulatory/inhibitory (type V) hypersensitivity, respectively. T cells initiate the last type of hypersensitivity (type IV) and clinical symptoms appear more days after exposure; it is therefore referred to as delayed-type hypersensitivity (DTH). However, a great deal of com¬plexity exists within each type of reactions that blurs the boundaries between them.
A success of pregnancy depends on a proper implantation and induction of immune tolerance. The immune system secures it by various mechanisms – special cells, cytokines, HLA molecules, peripheral tolerance take part in.
The immune system of the newborn has also its own specifics as it matures relatively long time till it reaches the same protective ability as characteristic for adults.
The lecture deals with primary and secondary immunodefeciencies. It gives an overview on general clinical manifestations and their divisions according to the type of the immune functions defects. Must of the lecture devotes to AIDS.
Type I hypersensitivity belongs to the most common disorder mediated by immune reactions; it affects app. more than 30% of all individuals in Caucasoid population. Type I hypersensitivity is commonly called allergy. It is characterised by rapid onset (hence the term immediate hypersensitivity), within minutes of antigen challenge, and results in conspicuous clinical symptoms.
Cytokines are soluble peptides that induce activation, proliferation and differentiation of cells of the immune system. Moreover, cytokines influence functions of cells of other tissues and organs, esp. of nervous and endocrine systems. They act in very low concentrations (10-10 M) what makes them to be like hormones. However, hormones tend to be produced constitutively and are produced by endocrine organs. Cytokines, on the contrary, are secreted after activation of particular cells and secretion is short-lived, generally ranging from a few hours to a few days and there are no specialised organs for their synthesis. Cytokines influence target cell in 4 different ways, synergistic, antagonistic, pleiotropic, and redundant way, respectively. They ca act in a autocrine, paracrine and endocrine manner. There are many cytokines that can be divided into those regulating innate and adaptive immunity, to the group of cytokines endowed by chemotactic properties and those supporting growth of hematopoietic and immune system cells.
Histocompatibility molecules are genetically determined proteins present in membranes of all nucleated cells. They form a unique system for which the term “Major Histocompatibility Complex (MHC)” was coined. Each vertebrate species is characterised by its own MHC; that of humans has an abbreviation HLA. This acronym is derived from the words: “human leucocyte antigens” as its fist molecules were discovered in membranes of leucocytes.