Immune System-Basics of Immunology-Lecture Handout, Exercises of Immunology

Download Immune System-Basics of Immunology-Lecture Handout and more Exercises Immunology in PDF only on Docsity! AN OVERVIEW OF THE IMMUNE SYSTEM Recommended reading Abbas et al. 4th ed. Chapter 1; Janeway et al., 5th ed. Chapter 1. The survival of members of most vertebrate species to an age at which they can reproduce depends critically on their ability to resist infection. The specialized cells and organs that protect these animals from infection and death make up the immune system. This system continuously monitors every tissue and organ in the body for invaders. When the presence of cells or molecules that "do not belong" is confirmed, the immune system activates a battery of weapons designed to eliminate or contain the source of the infection. Growing awareness about inherited and acquired immunodeficiency diseases has helped underscore how absolutely crucial this protective system is for our survival. docsity.com The study of immunology, as distinguished from other areas of biology, revolves around two central questions. How does the immune system recognize the enormous variety of foreign shapes that must be targeted in order to ensure survival? How do we manage to discriminate between self structures and shapes that are foreign? The explosion in our knowledge of immunology at the molecular and cellular level has considerably simplified our understanding of the immune system. As a result, it is now possible to describe immunological phenomena such as the "generation of diversity" and "self-nonself recognition" in fairly simple cellular and molecular terms. The primary goal of the immune system is to protect us from disease. One cannot seriously discuss this subject without reference to disorders that result either from the absence of an immune response or from an immune response gone awry. In this course we will briefly look at a number of diseases largely from a mechanistic point of view. Indeed there is little doubt that we are likely to witness a new era in which an increased understanding of immune function will contribute to novel therapeutic approaches to immunodeficiency diseases, organ transplantation and cancer. Understanding the immune system may open the door to a very exciting and intriguing world. Innate Immunity The immune system as we know it in its highly evolved form is extraordinarily versatile. A considerably simpler version existed before the evolution of vertebrates. This more ancient immune system represents the principal defense machinery in invertebrates (animals such as insects and worms, which lack a backbone). The basic elements of this early protective system have been preserved in all animals including man. This primitive system, now frequently described as the "innate" immune system, is made up primarily of proteins called agglutinins and cells called phagocytes. One of the underlying principles in nature's grand design for host defense is the requirement that the immune system should discriminate between self and "non-self". Agglutinins are multivalent proteins which recognize structures that are not found on host cells but which are commonly found on the surface of microorganisms. The term multivalent here refers to the presence of more than one recognition site in a single protein. Having more than one recognition site allows agglutinins to "agglutinate" or clump target cells such as bacteria with the appropriate coat sugar for instance. An agglutinin which recognizes carbohydrates is called a lectin. Lectins that are capable of specifically agglutinating certain microbes are secreted by cells of the host. These lectins do not recognize sugars on the surface of host cells and thereby discriminate between self and non-self. Phagocytes (phagos=to eat) are specialized cells which engulf invading microorganisms. They either use specific receptors which discriminate between self and foreign shapes or they recognize microbes that have been coated by host agglutinins. Another important component of the innate immune system is a set of circulating complement proteins. These proteins obtain their name from their ability to complement the function of antibody molecules in the immune system. They help destroy target cells coated by antibody proteins by punching holes in the cell membrane. The concentration of sodium chloride outside cells is relatively high - the holes in the membrane permit salt and water to rush into targets cells which swell up and burst, a process kmown as lysis.. Complement proteins however existed in invertebrates before the evolution of antibodies. A subset of complement proteins can directly coat certain bacteria, thus either lysing them or targeting them for ingestion by phagocytes. The complement system will be discussed in a subsequent lecture. docsity.com Once lymphocytes with a wide repertoire have been generated, the need exists to ensure that this repertoire is directed only against foreign antigens. The primary means by which self- nonself discrimination is achieved is by eliminating cells that make receptors directed against self antigens. When lymphocytes are generated in central lymphoid organs (the bone marrow for B cells and the thymus for T cells) they pass through a 'developmental window' during which time they respond to antigen not by proliferating but by being inactivated. Very tight binding to antigen during this time period leads to cell death. As lymphocytes pass through this developmental window the antigens that they usually encounter are self antigens. Those lymphocytes with receptors that bind very well to self antigens are thus eliminated. The process by which cells expressing self reactive receptors are eliminated is known as negative selection or clonal deletion or central tolerance. Following development in central lymphoid organs lymphocytes acquire the ability to leave these organs and to seed lymph nodes in the periphery . Rearrangement of immune receptor genes Elimination of self reactive cells Final repertoire in responders Central lymphoid organs Periphery "The death window"















































antigen receptor Proliferation and activation A simple overview of lymphocyte ontogeny. In summary, the immune system in vertebrates has two arms. Humoral immunity is the province of B cells and cell mediated immunity is generated by T lymphocytes. Individual lymphocytes have distinct antigen receptors that each recognize a specific shape. The tremendous diversity of antigen receptors is primarily achieved by gene rearrangement. During lymphocyte development most self reactive lymphocytes are tolerized by being triggered by self antigens during a narrow developmental window when cells are wired to be turned off. Beyond this window, cells respond to foreign antigens and divide and differentiate into effector cells of the immune system. Once activated by antigens the immune system exhibits a form of memory and subsequent antigenic challenges meet more aggressive responses. Additonal reading: Panum, P.L. (1847) Beobachtungen uber das Maserncontagium. Virchows Arch. 1, 497-502 The epidemiological argument for immunological memory was made before anyone had actually described the immune system. docsity.com GETTING YOUR BEARINGS This first lecture is meant to be an introduction. Many of the concepts will be reinforced in Lecture II. The terms listed in the glossary above should begin to make sense. In particular you should begin to get a feel for the differences between innate/natural immunity and adaptive/specific immunity Glossary for Lecture 1: Active immunity: Immunity conferred by immunization (as opposed to Passive Immunity) Adaptive Immunity: aka Specific Immunity. Lymphocyte dependent immune system which has very diverse antigen receptors and exhibits memory. Agglutinins: Multivalent proteins that recognize structures on cell surfaces or on other proteins. They can precipitate pathogens or coat them for removal by phagocytes. They may “fix” complement proteins on the surfaces of pathogens. Antibodies: Y shaped proteins of adaptive immunity, which are the bullets of the humoral immune system (B lymphocytes are the warriors). Antigens: Structures recognized by the immune system. May or may not be an immunogen. B lymphocytes: “Bursal” or “Bone-marrow” derived lymphocytes. Responsible for antibody mediated humoral immunity. Cell Mediated Immunity: Immune responses mediated by cells. Complement: Serum protein cascade which is generally activated either by certain pathogens or by agglutinin or antibody coated microbes. Humoral immunity: Immune responses mediated by circulating secreted molecules Immunogens: Antigens that can induce specific immune responses. Some antigens can be recognized by the immune system but do not induce responses – they are NOT immunogens. Innate Immunity: aka Natural Immunity. Immune system which responds in minutes and hours to noxious stimuli. Less specific than Adaptive immune system and does not exhibit memory. Natural Immunity: aka Innate Immunity Passive Immunity: Immunity that is passively obtained without immunization by the transfer of cells or serum Phagocytes: Cells which gobble up microbes and other particles Specific Immunity: aka Adaptive Immunity T lymphocytes: Thymus derived lymphocytes. Mediate cellular immunity during adaptive immune responses. docsity.com