Baines, M.G. INTRODUCTORY IMMUNOLOGY MIMM211. HOW MUCH IMMUNOLOGY DO I NEED TO KNOW FOR THE FINAL EXAM? REQUIRED TEXT FOR INTRODUCTORY MICROBIOLOGY AND IMMUNOLOGY Text: Prescott, Harley and Klein, Microbiology, 6th Edition, McGraw-Hill Publishing, New York, NY. Read this first, The following is not a collection of lecture notes but an overview of the words, concepts and theories related to the subject of Immunology with which you must be familiar to do well in the final exam. Use this as a study guide to check your understanding of immunology by reviewing what you know about the bold face words in the following text. The visual Power-point presentation images and audio recordings of my lectures can be found on the MIMM211 course Web-CT website. You can also find sample exam questions on Professor Cousineaus’ web pages that will help you to develop strategies for answering multiple-choice questions. First consult your textbook if you have difficulties with the concepts in this outline or in my lectures. Second, send an e-mail the teaching assistant for this course for help if you are still confused. Finally, if all else fails, you or the teaching assistant can phone of e-mail your questions to me. However, do not leave your questions until the last week of the course, as I may not be in my office when you need me most. Good luck in the immunology component of the course and the final exam. Malcolm Baines ============================================================================ Introductory Immunology (Antigens and Immunity): The science of immunology is concerned host defences against infection that includes both natural resistance and specific acquired immunity to infectious disease microorganisms and artificial substances that are foreign to our body. The term antigen simply denotes any material that is foreign to the immune system of the body and activates the host defences while those antigens that provoke a specific active immune response are termed immunogens. The immune response thereby produced has as its effectors both specific antibodies and specifically activated lymphocytes. Both immune antibodies and lymphocytes have the specific capability of binding the specific antigen. The first or primary immune response to most immunogens is invariably slower and smaller than a secondary immune response that is faster and larger. Immune responses demonstrate four primary characteristics or rules. They are: (1) discrimination (non-self from self), (2) specificity (for the immunogen), (3) anamnesis (immunological memory, accelerated second responses), (4) Transferability (active immunity can be permanently transferred only by specifically immune lymphocytes). (The corollary to this concept is that passive immunity can be temporarily transferred by a specific immune antibody or hyper immune serum). 1 October, 2009 @ M.G. Baines, Room: 404. Phone: 514-398-4443, [email protected] 1 Baines, M.G. INTRODUCTORY IMMUNOLOGY MIMM211. Innate Resistance Mechanisms: Many non-immunological factors determine the natural resistance of a host to infectious disease. Non-specific phagocytosis and cellular cytotoxicity during an inflammatory response are important resistance mechanisms. Polymorphonuclear (PMN) leukocytes and monocytes can spontaneously phagocytose microorganisms. PMNs are acute response cells which live only 6-13 hours while tissue macrophages may live up to 3 months. This function is greatly augmented by antibody (opsonisation) and complement (immune adherence) due to the presence of Fc and C3b receptors on the leukocytes that bind these components on the microbial surface. Phagocytosis is accompanied by cell activation and a respiratory burst resulting in the generation of toxic forms of oxygen that kill microbes (e.g.: nitric oxide NO, - superoxide O 2, peroxide H2O2, singlet oxygen O and hydroxyl radical OH.). Enzymes subsequently degrade the dead microbial residues within the phagocytic vacuole or phagosome. PMN and macrophages can also cause extracellular cytostatic and cytolytic reactions. This is particularly obvious for the activated macrophage that can also kill cells they have not engulfed. The release of the soluble protein lymphotoxins or tumour necrosis factors mediates this reaction. This mechanism usually requires the presence of specific antibody to mark the target cells for attachment by macrophages and natural killer lymphocytes leading to target cell lysis and this is referred to as antibody dependent cellular cytotoxicity (ADCC). Natural cytotoxicity refers to a very powerful first-line defence mechanism. These natural killer (NK) lymphocytes are non-specific and non-immune yet they are capable of selectively and instantly killing virally infected cells and cancer cells in vivo directly or by ADCC. The nature of the NK recognition step and cytolytic mechanism are very different from immune cells allowing a broad recognition of cancers and infected cells. The activity of these cells is augmented by interferon and suppressed by prostaglandins and they appear to be an important early defence mechanism during viral disease. They may also be involved as non-specific effectors in other microbial diseases, transplant rejection, cancer resistance and autoimmune disease. Cell biology and Anatomy of the Immune System: The cells responsible for producing the immune response are called lymphocytes. These are found in blood, lymph nodes, spleen, thymus and bone marrow. The bone marrow is the source of the stem cells for both the red and white blood cell populations including the lymphocyte precursors. The bone marrow and thymus are central or primary lymphoid organs responsible for the production of B-lymphocytes and T-lymphocytes respectively. These lymphocytes populate the peripheral or secondary lymphoid organs (spleen, lymph nodes) where the immune responses subsequently occur. The spleen primarily responds to antigens in the central blood circulatory system (bacteraemia and viremia), whereas the lymph nodes respond to antigens and infectious agents that enter the through the skin and mucous membranes infecting the subcutaneous areas and move via the extracellular or lymphatic fluid flowing into the lymphatic system and back into the circulatory system. The Humoral Immune Response: As previously stated, immunogens are materials that are capable of stimulating the production of a specific antibody or a specifically activated lymphocyte. Immunogenic materials are natural or artificial (man-made), particulate or soluble, and living or non-living. Occasionally, autologous (self) materials such as proteins that have become denatured or mutated can also be seen as foreign by the immune system. The concept of a 1 October, 2009 @ M.G. Baines, Room: 404. Phone: 514-398-4443, [email protected] 2 Baines, M.G. INTRODUCTORY IMMUNOLOGY MIMM211. complete antigen (or immunogen) refers to a material (usually protein or polysaccharide) that has both immunogenicity and specificity and is usually greater than 10,000 Da in size. In other words, the foreign immunogenic molecule (carrier or backbone) is of sufficient size to be recognised by the immune system as being foreign and expresses antigenic determinants or epitopes to which the induced antibodies bind. Free antigenic epitopes, or haptens, are usually too small to be immunogenic but they express specificity, as they will react with the specific effectors generated by an immune response (antibodies and immune lymphocytes). Therefore, haptens have specificity but are not immunogenic and are termed incomplete antigens. The immune antibodies generated by an immune response are capable of recognising several ranges of epitope specificity. This epitope specificity is determined by the origin of the antigens with which the antibody is specifically reactive. Antibodies may react (a) with epitopes specific (unique) for a particular individual (idiotypic specificity), (b) with a group of individuals within a species (type or allele specific) or (c) react with all the members of a particular species (species specificity). In addition, (d) there are a number of ubiquitous antigens found in many sources (heterophile antigens) that induce antibodies that will cross- react with many interspecies antigens (e.g. Forssman antigens). The peripheral immune system contains both bone marrow derived antibody forming precursor lymphocytes (B-cells) and thymus derived antigen reactive lymphocytes (T-cells). The B-cells have common B-cell markers and a unique membrane immunoglobulin receptor on their surface representative of the single antibody specificity that they will be able to produce once they are activated. The T- lymphocytes have common markers peculiar to thymus derived lymphocytes (Thy-1, CD3) and have an antigen specific T-cell receptor (TCR). Some of the T-lymphocytes help B-lymphocyte activation (Th- cells) and amplify the production of antibodies while others are involved in the generation of cell-mediated immunity (described below). Most antigens recognized by B-cells require help by Th-lymphocytes to produce antibodies and are called thymus dependent antigens. A few polymeric antigens that do not require Th-cell help to activate the antibody forming B-lymphocytes are termed thymus independent (e.g. bacterial polysaccharides and polymeric proteins). The clonal selection theory states that the specific cells of the immune system are created in an antigen independent manner and are subsequently selected and activated by an immunogen to form the basis of the immune response.