Medical brain notes 12

  INITIATION OF THE IMMUNE RESPONSE The effector cells are really divided into two types: B cells and T cells. B cells are primarily responsible for antibody produc-tion, whereas T cells act as effector cells and may function as both helpers and suppres-sors, depending on the stimulus provided by APCs. The first step in initiation of the immune response to an antigen must necessarily involve modification of the antigen, and these specialized cells are called APCs. Without such processing, T cells cannot recognize antigen. Thus, it is the secretion of cytokines by APCs activated by antigen presentation that further activates antigen- specific T cells. This interaction between APCs and T cells is strongly influenced by a group of molecules called co-stimulators. For example, it is CD80 (B7-1) and CD86 (B7-2) on the APC cells with receptors CD28 and CTLA-4 on the T cell that pro-vides this interaction. The absence of these co-stimulators leads to T-cell unrespon-siveness. The importan...

  ANTIBODY PRODUCTION To achieve antibody production, at least four types of cells are required: APC, B cells, and two types of regulating cells. B Cells Antibodies are produced by naïve B cells and are called  plasma cells . These cells express immunoglobulins on their sur-face. In the early stages, B cells first show intracellular µ-chains and then surface IgM. Through the process described ear-lier, these cells can later express IgG, IgA, or IgE, a phenomenon known as isotype switching. The final type of surface immu-noglobulin determines the class of anti-body secreted. Isotype switching is mediated through two important protein interactions: CD40 on the B cell interacts with CD40L on acti-vated T cells (IL-4 induced) to stimulate B  cells to switch from IgM molecules to other isotypes.   Deficiencies in either molecule lead to severe immunodeficiency states with only IgM produced but no IgG or IgA antibodies. This syndrome is called the hyper-IgM syndrome, and i...

  FUNCTIONAL COMPONENTS OF THE  IMMUNE SYSTEM Each of the cells in the immune response has a particular role to play. While many of these cells will be discussed in detail in subsequent, a brief review of the functional capabilities is presented here. Macrophages These cells may be divided into two main groups: the dendritic cell and the mature macrophage. The dendritic cell’s major function is to present antigen to the lym-phocyte, and it is the earliest cell to recog-nize foreign antigen.   There are two forms of dendritic cells:  immature  and  mature . The induction of an   adaptive immune response begins when a pathogen is ingested by an immature den-dritic cell. These cells reside in most tissues and are relatively long-lived. As seen in Figure 1.1, they are derived from the same cell myeloid precursor as the macrophage. This immature cell carries receptors on its surface that recognize common features of many pathogens such as cell wall carbo-hy...

TISSUE DAMAGE PATHWAYS Although the major function of the com-ponents of the immune system is to neu-tralize or destroy the invading organisms or antigen, these reactions often cause “bystander” tissue damage as well. These are called  hypersensitivity reactions , and Gell and Coombs conveniently divided them into five types. Hypersensitivity Reactions TYPE I: IMMEDIATE These reactions are those that involve antigens that react with IgE bound to tissue mast cells or basophils. Activation of the mast cell results in the release of large amounts of pharmacologically active sub-stances. These reactions are rapid (hence immediate) and if injected into the skin a “wheel and flare” reaction can be seen within five to ten minutes. Most anti-gens stimulating IgE are either inhaled or ingested. A perfect example of the inhaled antigen is ragweed pollen. The IgE pro-duction requires helper T cells and T-cell-derived cytokines. IL-4 and IL-13 stimulate IgE production while IFN- γ  is inh...

  ANTIBODY PRODUCTION Antibodies for various tests can be pro-duced in a number of different ways, and we will discuss the prototype of each in turn. a.     Polyclonal antibodies : Many mammals   have been used to produce antibodies, ranging from the horse, sheep, and goat down to mice and guinea pigs. Often an animal species is selected for antibody production because it will produce less-cross-reactive antibodies to a given tis-sue. Larger mammals, such as goats and sheep, are used to obtain larger volumes of serum to be used therapeutically in humans. A recent fear has been that ani-mals such as sheep or cows may have eaten animal foddage contaminated with prion disease. Thus, polyclonal antibody production for therapeutic uses has often been limited to countries like Australia or New Zealand where there have been no recorded cases of prion disease in mammals.   b.     Monoclonal antibodies : Over the past   two decades, the revolutio...

  Measurements of Immunoglobulins The introduction of automated machines to measure immunoglobulins and other proteins has proceeded rapidly in recent decades. Most clinical immunology laboratories rely almost exclusively on these machines, and research labs are also intro-ducing these automated techniques at a rapid pace. Precise measurement of serum immunoglobulins is an essential corner-stone in this area and is important for repeated and serious infections secondary to immunosuppressive agents, immunode-ficiencies, in lymphoproliferate disorders, and for detection of autoantibodies. The main principle behind this test is related to the formation of immune com-plexes between the antibody and a given antigen. If the concentration of antigen– antibody complex is low, then the immune complexes remain in suspension as fine particles, which can disperse a beam of light. As the complexes increase with concentration of antibody, the complexes will precipitate, and light scattering will...