MMI 188 Medical Microbiology and Immunology School of Medicine HUMAN IMMUNOLOGY Spring Quarter 2020 CRN: 73239 Online Instructor: José V. Torres, PhD Professor Medical Microbiology and Immunology School of Medicine 3226 Tupper Hall (530) 752-3157 jvtorres@ucdavis.edu Educator, Scientist, Tortoise Conservationist, Biotechnology Entrepreneur Teaching Assistant: Alicia Werner awerner@ucdavis.edu Molecular, Cellular and Integrative Physiology Graduate Group Office Hours by Zoom: Fridays from 4-6 PM Wednesdays from 4-6 PM on the week before each exam (April 15, May 13 and June 3) Elements of the Immune System and their Roles in Defense Based on: Chapter 1 of the Parham Textbook (4th Edition) MMI 188 Human Immunology José V. Torres, PhD Professor Medical Microbiology & Immunology School of Medicine University of California Davis, CA 95616 jvtorres@ucdavis.edu Elements of the Immune System and Their Roles in Defense Learning Objectives for this Lecture: Ø Understand the purpose of the immune system Ø Learn how the body discriminates between self and non-self Ø Learn the differences between commensal and pathogenic organisms Ø Recognize the main elements of the humoral and cellular immune responses Ø Become familiar with specialized lymphoid tissues Ø Learn the main differences between innate and adaptive immunity The purpose of the immune system To defend the body against foreign invaders by: ØRecognition of foreign organisms ØPrevention of spread of pathogens ØClearing invaders from body ØHelping with the healing process To keep you alive! Introduction to Immunology Important concepts and distinctions: ØDiscrimination between self and non-self ØAntigens versus immunogens ØHumoral versus cell-mediated immunity ØInnate versus adaptive immunity ØGeneration of diversity and clonal selection Discrimination between self and non-self Ø Discrimination between self and non-self is fundamental to survival. Ø Clones of cells which have the capacity to recognize self antigens are eliminated early in development. Ø Tumor cells can be destroyed by immune processes if they express antigens that are not present on normal cells (tumor antigens). Ø The magnitude of the immune response against an antigen is proportional to the difference between its structure and that of host antigens. Antigen versus Immunogen Antigen is the target of an adaptive immune response Immunogen induces an adaptive immune response How to make a small antigen more immunogenic? -Conjugate it to a big foreign protein Cell-mediated immune response to the carrier helps in the induction of a humoral immune response to the hapten. Humoral versus Cell-mediated Immunity Adaptive immune response consists of two major branches: • Humoral immunity: antibodies and associated accessory systems • Cell-mediated immunity: T lymphocytes and associated accessory systems Ø B lymphocytes secrete antibodies so are under humoral. Ø Some components of the innate immune response such as complement and cytokines may also be involved in both branches of the adaptive immune response. Ø The major difference is whether the antigen specificity is primarily determined by antibodies or T lymphocytes. Success of Vaccination Ø Best and more economical solution to reduce infectious diseases Ø Protects against disease and not against infection Ø A vaccine induces memory that is boosted by infection Ø Reduced vaccination causes increased susceptibility for everyone! Commensals are beneficial organisms that inhabit the healthy human body Ø Over 500 microbial species live in the healthy adult human gut Ø The community of microbial species that inhabits a specific niche in the body is called the commensal flora Ø Commensal organisms enhance human nutrition by digesting food elements and making several vitamins Ø They also protect against disease by competing with pathogens for space Ø E. coli (a commensal) secretes colicins, compounds that inactivate other bacteria Ø Eradication of commensals can have serious consequences (colonization by pathogens) Antibiotics kill beneficial bacteria Example: Clostridium difficile – toxin – diarrhea – colitis – death Time to appreciate the extensive diversity of human pathogens… Pathogen: an organism with the potential to cause disease Opportunistic Pathogen: can colonize the body without ill effects but can cause illness in the wrong tissue or when defenses are weak lombrices Innate immunity involves: Ø physical barriers Ø nonspecific responses to foreign invaders Innate Immune System Nonspecific recognition of pathogen followed by destruction Example: the complement system Innate Immunity: inflammation Cells of the immune system appear in tissue during inflammation Innate versus Adaptive Immunity Recognition mechanisms Innate Adaptive Adaptive Immunity Based on Clonal Selection: ØActivation of lymphocytes by a pathogen • Specific clones develop before antigen exposure • Self-reactive cells are deleted • Cells that recognize foreign antigens remain and are expanded and differentiate following exposure • Immunological memory – faster and stronger second reaction to pathogens Relative importance of innate and adaptive immunity Innate immunity is required for survival. We can survive even if some elements of the adaptive immunity are defective. Cells of the immune system B cells – become Plasma cells that secrete antibodies T cells – helper and cytotoxic Dendritic cells: ØIn tissues act as cellular messengers that call up an adaptive immune response when needed. ØMigrate from tissues to lymphoid organs to deliver antigens from pathogens. They are antigen-presenting cells (APC). Neutrophil – phagocytic, small, short life, white pus Macrophage – phagocytic, large, long life Ø first to detect infection Ø secretes cytokines that recruit neutrophils and other leukocytes Ø Antigen presenting cell (APC) Eosinophil – parasite killer. Ø In allergy, activated eosinophils secrete enzymes that damage the respiratory epithelium. Ø They also release active oxygen that injures cells. Parasite control trio (mast cell, eosinophil, basophil) now associated with allergy. Megakaryocyte – platelet producer (to stop bleeding) Hematopoiesis The generation of cellular elements of blood: -Red blood cells -White blood cells -Platelets The site of hematopoiesis changes during human development Cells of the immune system arise from a common hematopoietic stem cell. Hematopoietic stem cells divide for self-renewal. Relative abundance of white blood cells in human peripheral blood Neutrophils are the most abundant white blood cells Bacterial receptors on macrophages: Bacterial binding induces: Ø engulfment for degradation (phagocytic receptors) Ø production of inflammatory cytokines (signaling receptors) Structure of B and T cell Receptors and Antibodies Ø No secreted form for the T cell receptor Neutralization and Opsonization by Antibodies Mechanisms by which antibodies fight infection. Neutralization: When antibodies bind to a bacterial toxin and neutralize its toxic activity by preventing the toxin from interacting with its receptor on human cells. Opsonization: When a bacterium is coated with IgG antibodies the constant regions point outward and can bind to receptors on a macrophage, which then ingests and degrades the bacterium. Major sites of lymphoid tissues within the human body Primary lymphoid tissues: Ø Bone marrow Ø Thymus Secondary lymphoid tissues: Ø Spleen Ø Lymph nodes Lymphocytes travel in the blood and lymph Left subclavian vein: Ø lymph returns to blood Lymphocytes that encounter pathogens in lymph nodes stop circulating. Lymph contains fluid that leaks from blood vessels. It transports cells and proteins associated with the immune system. The draining lymph nodes serve as specialized meeting places for circulating lymphocytes and pathogens 4 1 3 2 Lymph nodes are highly organized and dynamic structures that optimize interactions of lymphocytes and pathogens Activation of adaptive immunity in a draining lymph node During an infection, lymphocytes proliferate in lymph nodes, resulting in swollen or enlarged lymph nodes. Ø Pathogens, pathogen components, and dendritic cells carrying pathogens and molecules derived from them arrive in the afferent lymph draining the site of infection. Ø The dendritic cells specifically stimulate the division and differentiation of pathogen-specific small lymphocytes (green) into effector lymphocytes (blue). Ø Some helper T cells and cytotoxic T cells leave in the efferent lymph and travel to the infected tissue via the lymph and blood. Ø Other helper T cells remain in the lymph node and stimulate the division and differentiation of pathogen-specific B cells into plasma cells (yellow). Ø Plasma cells move to the medulla of the lymph node, where they secrete pathogen-specific antibodies, which are taken to the site of infection by the efferent lymph and subsequently the blood. Ø Some plasma cells leave the lymph node and travel via the efferent lymph and the blood to the bone marrow, where they continue to secrete antibodies. Green: Pathogen-specific small lymphocytes Blue: Effector lymphocytes Spleen: has aggregations of lymphocytes similar to those in lymph nodes The red pulp is where old or damaged red cells are removed from the circulation. The white pulp is secondary lymphoid tissue, in which lymphocyte responses to bloodborne pathogens are made. Lymphoid follicle Much of the secondary lymphoid tissue is associated with the gut ØRegions of organized GALT such as Peyer’s patches You Should Now Be Familiar With: 1) How and why the body distinguishes self from nonself 2) The difference between commensal and pathogenic organisms 3) The differences between humoral and cellular immune responses 4) The main differences between innate and adaptive immunity 5) The major lymphoid tissues of the body 6) The major types of cells involved with innate and adaptive immunity
