Immunology Chapter 1 Syllabus PDF

Course Syllabus Course Title: Immunology Course code: 240337 Course Level: Undergraduate Course prerequisite (s) and/or corequisite (s): Credit hours: 3 Lecture Time: Course Module Description This is an introductory course of immunology. It is intended for students in the Biotechnology and Genetic...

Course Syllabus Course Title: Immunology Course code: 240337 Course Level: Undergraduate Course prerequisite (s) and/or corequisite (s): Credit hours: 3 Lecture Time: Course Module Description This is an introductory course of immunology. It is intended for students in the Biotechnology and Genetic Engineering field. The course consists of interactive lectures that incorporate Power Point presentations that help the instructor present the intended ideas clearly. Additionally, the instructor uses the help of pre-made CD animations that come with the book. These animations are utilized throughout the material to extend the explanation of specific ideas. Furthermore, the instructor uses some pre-evaluated educational movies and presentations made and prepared by professional institutions. The instructor incorporated a new technique in this class that is currently used in most immunology laboratories world-wide; it is the flow cytometry, in which the instructor was trained on for quite long time in the recent past. Students are introduced to basic concepts of flow cytometry and are acquainted with its major applications. The textbook, Immunology Short course , 6th edition, is the most used text book in immunology at academic institutions in the US and Canada, both for undergraduate and graduate immunology courses. The instructor aims at preparing his students for graduate studies if they intend to do so. The book presents immunological concepts in an interesting and imaginative way that makes learning immunology both easy and exciting. Introduction, basic concepts in immunology, components of the immune system, principles of innate and adaptive immunity 2. Innate immunity, Different lines and layers of defense, Pattern recognition in innate immune system, The complement system, Induced innate responses to infections 3. Antigen recognition by B-cells, The structure of a typical antibody molecule, Interaction between the antibody and specific antigen, Diversity of Immunoglobulins: VDJ Recombination 4. Antigen recognition by T cells, Antigen processing and presentation:MHC, 5. Development and survival of lymphocytes, Lymphocytes in bone marrow and thymus, Positive and negative selection of lymphocytes, Survival and maturation of lymphocytes, 6. The Adaptive Immune Response, T Cell- Mediated Immunity and cytotoxicity,Macrophage activation by armed CD4 TH1 cells, Humoral Immune Response 7. Adaptive Immuni ty to Infection, Infect ious agents and how they cause disease, The course of the adaptive response to infection, The mucosal immune system, Immunological memory 8. Failures of Host Defense Mechanisms, How do pathogens evade the immune system, Inherited immunodeficiency diseases, Acquired immune deficiency syndrome 9. Allergy and Hypersensitivity, Effector mechanisms in allergic reactions and IgE, Hypersensitivity diseases 10. Autoimmunity and Transplantation, Autoimmune responses are directed against self antigens, Responses to alloantigens and transplant rejection, Self- tolerance and its loss 11. Manipulation of the Immune Response, Extrinsic regulat ion of unwanted immune responses, Using the immune response to fight infections and attack tumors  Assessment instruments Allocation of Marks Assessment Instruments Mark Midter examination 30 Verbal quizzes and short exam, Presentation 30 Final examination: 50 marks 40 Total 100 Make-up exams will be offered for valid reasons only with consent of the Dean. 8  Chapter 1 Basic Concepts In Immunology This chapter introduces the cellular and molecular players of the immune system (based mainly on our understanding of the immune systems of mice and humans) Components of the immune system (organs, cells, molecules) Principles of innate and adaptive immunity Recognition and effector mechanism This chapter is a summary of immunology. It provides the framework upon which the remainder of the course is built. If you do not have a solid understanding of this chapter, you will have significant difficulty following the subsequent chapters. The earliest written reference to the phenomenon of immunity can be traced back to Thucydides, the great historian Of the Peloponnesian War. In describing a plague in Athens, he wrote in 430 BC that only those who had recovered from the plague could nurse the sick because they would not contract the disease a second time. The first recorded attempts to induce immunity deliberately were performed by the Chinese and Turks in the fifteenth century. Various reports suggest that the dried crusts derived from smallpox pustules were either inhaled into the nostrils or inserted into small cuts in the skin (a technique called variolation). In 1718, Lady Mary Wortley Montagu, the wife of the British ambassador to Constantinople, observed the positive effects of variolation on the native population and had the technique performed on her own children. In 1796 Edward Jenner infects a boy with cow pox to protect against small pox (before germ theory of disease) vacca=cow Mid-late 1800s Robert Koch showed that microorganism cause infectious diseases and that different organisms cause different diseases Louis Pasteur first showed how vaccines could be made to a variety of it was possible to attenuate, or weaken, a pathogen and administer the attenuated strain as a vaccinepathogens. 4 broad categories of pathogens (disease causing organisms): viruses, bacteria, fungi, and “parasites” (eukaryotes including protozoans and worms) Emil Von Behring and Shibaaburo Kitasato sfound, in the blood of immune individuals, a substance that bound to the bacteria to which they were immune. Called the substance ANTIBODY  in 1881, Pasteur first vaccinated one group of sheep with heat-attenuated anthrax Bacillus (Bacillus anthracis); he then challenged the vaccinated sheep and some unvaccinated sheep with a virulent culture of the bacillus. All the vaccinated sheep lived, and all the unvaccinated animals died. These experiments marked the beginnings of the discipline of immunology 1885, Pasteur administered his first vaccine to a human, a young boy who had been bitten repeatedly by a rabid dog (Figure 1-1). The boy, Joseph Meister, was inoculated with a series of attenuated rabies virus preparations. He lived and later became a custodian at the Pasteur Institute. FIGURE 1-1 Wood engraving of Louis Pasteur watching Joseph Meister receive the rabies vaccine. [From Harper’s Weekly 29:836; courtesy of the National Library of Medicine. The experimental work of Emil von Behring and Shibasaburo Kitasato in 1890 gave the first insights into the mechanism of immunity, earning von Behring the Nobel prize in medicine in 1901. Von Behring and Kitasato demonstrated that serum (the liquid, noncellular component of coagulated blood) from animals previously immunized to diphtheria could transfer the immune state to unimmunized animals. In search of the protective agent, various researchers during the next decade demonstrated that an active component from immune serum could neutralize toxins, precipitate toxins, and agglutinate (clump) bacteria. In each case, the active agent was named for the activity it exhibited: antitoxin, precipitin, and agglutinin, respectively. Adaptive Immunity: Specific Immune Response (e.g., antibody) against a particular microorganism is an adaptive immune response. That is, it occurs during one’s lifetime as an adaptation to the presence of that particular organism. (usually, the term specific means the ability to distinguish one organism from another) An adaptive immune response might provide lifelong protective immunity to a given pathogen. These are central principles of adaptive immunity Specific immunity can be induced by a variety of substances. Things that are targets of adaptive immunity are called ANTIGENS* Antigen-specific responses are mediated by lymphocytes *Things that induce an adaptive immune response are immunogens In 1883, even before the discovery that a serum component could transfer immunity, Elie Metchnikoff demonstrated that cells also contribute to the immune state of an animal. He observed that certain white blood cells, which he termed phagocytes, were able to ingest (phagocytose) microorganisms and other foreign material. Noting that these phagocytic cells were more active in animals that had been immunized, Metchnikoff hypothesized that cells, rather than serum components, were the major effector of immunity. The active phagocytic cells identified by Metchnikoff were likely blood monocytes and neutrophils Innate immunity is the immunity that is immediately available without having to adapt to the specific pathogen that is present. It is not specific to a particular organism such that identical responses can protect against several organisms. Innate immunity is germline encode (evolved on an evolutionary time scale). Innate immunity is mediated by phagocytes (cell that ingest bacteria or other particulate matter) such as macrophages and neutrophils. It is also mediated by chemical compounds and physical barriers that will be described later. Together, innate and adaptive immunity prevent most infectious diseases (no symptoms from exposure to the microorganisms) or cure infections This course mostly deals with adaptive immunity. However, you must understand innate immunity and how adaptive immunity works together with innate immunity to prevent or cure infections. Definition of Immunity Protection against disease, usually infectious disease, mediated by a collection of molecules, cells, and tissues collectively called the immune system. In a broader sense, immunity refers to the ability to respond to foreign substances, including microbes or molecules. Immune = Latin mean exempt  Innate immunity Inbuilt immunity to resist infection Present from birth Not antigen-specific Not enhanced by second exposure Has no memory Uses cellular and humoral components Is poorly effective without adaptive immunity Also involved in the triggering and amplification of adaptive immune responses  Innate immunity Conferred by adverse array of cellular and sub cellular components includes: 1. Chemical influences such as pH, and secreted fatty acid part of it. 2. Complement system is another non- cellular part of it. 3. Fever 4. Interferon 5. Phagocyte, granulocytes, macrophage etc.  Adaptive immunity Immunity established to adapt to infection Presents only in vertebrate Learnt by experience Confers pathogen-specific immunity Enhanced by second exposure Has memory Uses cellular and humoral components Is poorly effective without innate immunity Antibodies reflect infections to which an individual has been exposed - diagnostic for infection  Active, Passive and Adoptive immunization Active immunization: refers to immunization of an individual by administration of antigen. Passive Immunization: refers to immunization through the transfer of specific antibody from an immunized individual to non immunized one. Adoptive immunization: refers to the transfer of immunity by the transfer of immune cells Property Innate Adaptive Characteristics Antigen none Antigen specific specific Rapid response Slow response (minutes-hours0 (days) No Memory Memory Immune Natural Barriers Lymphocyte components (e.g. skin, mucous membranes) Phagocytes and Antigen recognition natural killer cells molecules (B- and T- cell receptors Soluble mediators Secreted Molecules (e.g. complement) (e.g. Antibody) Pattern recognition  Characteristics of Acquired immune response 1. Specificity: ability to discriminate among different molecular entities and respond only to those. 2. Adaptiveness: is the ability to previously responded to unseen molecule. 3. Discrimination between self and nonself molecule. 4. Memory: ability to recall previous contact with foreign molecule and respond to it in learned manner. Innate immunity is mediated by phagocytes such as macrophages and neutrophils. It is also mediated by chemical compounds and physical barriers that will be described later table 1-2.  Innate Immunity: 1.1 Physical Barriers: - skin acts as a physical barrier - mucous membranes in the respiratory, gastrointestinal, urogenital tract trap bacteria which are subsequently removed by ciliated cells. 1.2 Physiological Barriers: - acid pH on skin, in stomach, and in the urogenital tract inhibit bacterial growth - detergent-like activity on skin (fatty acids from sebaceous glands), bile (small intestine) inhibit bacterial growth - hydrolytic activity of lysozyme in saliva, tears, vaginal secretions destroys bacterial cell walls - Interferons and complement are proteins that can be activated by infected/damage cells that participate in cell killing. Complement kills by forming pores in membranes. A variety of soluble factors contribute to innate immunity, among them the Soluble proteins lysozyme, interferon, and complement. Lysozyme, a hydrolytic enzyme found in mucous secretions and in tears, is able to cleave the peptidoglycan layer of the bacterial cell wall. Interferon comprises a group of proteins produced by virus- infected cells. Among the many functions of the interferons is the ability to bind to nearby cells and induce a generalized antiviral state. Complement, is a group of serum proteins that circulate in an inactive state. 1.3 Cellular Barriers: - Ingestion of foreign material by cells leads to its destruction (primary outcome) and to the development of acquired immunity (secondary outcome). Phagocytes include leukocytes, macrophages, and dendritic cells. Modes of ingestion are: 1. - Pinocytosis: ingestion of fluid surrounding cells 2. - Receptor-mediated endocytosis: Molecules bound to membrane receptors is Internalized. 3. - Phagocytosis: Intact particles (e.g. bacteria) are internalized whole. Receptor-mediated endocytosis & phagocytosis are an important step in the generation of acquired immunity. These processes are also facilitated by opsonination (e.g. coating of bacteria or virus with antibodies or other proteins (C-reactive Protein)  Cellular Fate of Ingested Material: 1. - In the case of pinocytosis and receptor-mediated endocytosis the ingested membrane vesicles first fuse with endosomes. The endosomes fuse with lysosomes to give secondary lysosomes. 2. - In the case of phagocytosis, the phagosome, containing the particle, fuses with lysosomes to give a phagolysosome. 3. - Killing occurs because the secondary lysozomes/phagolysosome contain hydrolytic enzymes, reactive oxygen species (e.g. superoxide anion, hydrogen peroxide), reactive nitrogen species (nitrous acid). 4. - Digested material is exocytosed out of the cell. 5. - A small number of peptides from the foreign substance bind to surface receptors. These antigens are presented on the surface of the cell by macrophages and dentritic cells.  1.4 Direct Cellular Killing: Natural-killer (NK) cells are lymphocytes that can recognize and destroy viral or cancerous cells. NK cells contact other cells. If the other cell appears to be abnormal (i.e. virally infected or cancerous) then the NK cell releases cytotoxic molecules that cause the abnormal cell to undergo apoptosis. NK cells respond to levels of class I MHC (major histocompatibility antigen) molecules on cell surface. Reduced levels in viral and cancerous cells result in killing. 1. The target cell is made permeable by a pore-forming protein called perforin. 2. - Apoptosis may be initiated by TNF-a (tumor necrosis factor α)  Apoptosis-programmed cell death without release of cellular contents. 1. - DNA degradation 2. - Cell fragments into apoptotic bodies that enclose intercellular contents 3. - Apoptotic bodies are rapidly removed by macrophages.