Introduction To Immunology PDF

INTRODUCTION TO IMMUNOLOGY Block: Foundations Block Director: James Proffitt, PhD Session Date: Wednesday, July 31, 2024 Time: 11:00 - 12:00 pm Instructor: Lonnie Lybarger, PhD Department: Cellular & Molecular Medicine Email: lybarger@ar...

INTRODUCTION TO IMMUNOLOGY Block: Foundations Block Director: James Proffitt, PhD Session Date: Wednesday, July 31, 2024 Time: 11:00 - 12:00 pm Instructor: Lonnie Lybarger, PhD Department: Cellular & Molecular Medicine Email: [email protected] INSTRUCTIONAL METHODS Primary Method: IM13: Lecture ☐ Flipped Session ☐ Clinical Correlation Resource Types: RE18: Written or Visual Media (or Digital Equivalent) INSTRUCTIONS Please read the session objectives and notes prior to session. The notes give additional depth and can be used to supplement the lecture, if needed. Likewise, the recommended readings indicated below can be used as a supplement. READINGS Recommended Reading: Additional information can be found primarily in chapter 1 of Basic Immunology: Functions and Disorders of the Immune System, 7th ed. (Abbas, Lichtman, and Pillai), 2024. This textbook is available electronically through the Health Sciences library. LEARNING OBJECTIVES: 1. Describe the general features that distinguish innate versus adaptive immunity (major cell types, kinetics of response, features of response, receptor families important for response). 2. Describe the properties and roles in immunity of key innate cells such as neutrophils and macrophages. 3. Define the general functions of the major cell types involved in adaptive immune response (B cells, T cells, and antigen-presenting cells). 4. Explain the clonal selection model of adaptive immunity. 5. Explain the difference between primary and secondary lymphoid organs. 6. Outline the path of lymph flow and explain its importance in immunity. CURRICULAR CONNECTIONS Below are the competencies, educational program objectives (EPOs), disciplines and threads that most accurately describe the connection of this session to the curriculum. Block: Foundations | LYBARGER [1 of 13] INTRODUCTION TO IMMUNOLOGY Related Related Competency\EPO Disciplines Threads COs LOs CO-01 LO #1 MK-02: The normal structure and Immunology N/A function of the body as a whole Microbiology and of each of the major organ systems CO-01 LO #2 MK-02: The normal structure and Immunology N/A function of the body as a whole and of each of the major organ systems CO-01 LO #3 MK-02: The normal structure and Immunology N/A function of the body as a whole and of each of the major organ systems CO-01 LO #4 MK-02: The normal structure and Immunology N/A function of the body as a whole and of each of the major organ systems CO-01 LO #5 MK-02: The normal structure and Immunology N/A function of the body as a whole Gross anatomy and of each of the major organ systems CO-01 LO #6 MK--03: The molecular, cellular Immunology N/A and biochemical mechanisms of Gross anatomy homeostasis CONTEXT: The immune system is a sophisticated set of tissues, cells, and their molecular products that collaborate to keep ‘foreign’ invaders from entering the body, and to neutralize invaders if they do enter. We consider immune system with blood (since many of the major cellular players in immunity are white blood cells) and mechanisms of disease (since pathology often arises from ineffective or inappropriate immune responses). The immune system and immunopathology will be the focus of several lectures and application exercises in Foundations. Nonetheless, this will just be a broad overview of a very complex subject. This material on the immune system will be revisited and greatly amplified in the Immunity and Infection Block (Year 2). It is important that you be introduced to it in Foundations, since immune responses are critical for defense against pathogens and cancer, and dysregulation of immune pathways results in autoimmune disease and many other pathologies you will encounter in all blocks of the curriculum. Furthermore, immune-related pathways are among the most common targets of therapeutic intervention. Block: Foundations | LYBARGER [2 of 13] INTRODUCTION TO IMMUNOLOGY LECTURE NOTES: - The immune system protects us from dangerous microbes and contributes to protection from cancer. This is clearly shown in cases of immunodeficiency. - Note that microbes are ubiquitious in the environment and on our body surfaces, and most are not dangerous and can even be beneficial. The immune system has the challenging task of deciding what is dangerous and what can be ignored. INTRODUCTORY TERMS: Immunity = Resistance or protection against infectious agents (e.g. bacteria, fungi, viruses) Immunogen = Something (antigen) that can evoke an immune response such as the production of antibodies Immunology = The study of the cellular and molecular events that occur during the host response to a foreign substance Immune response = The combined repertoire of cellular and molecular events that occur during exposure to foreign substances CELLS OF THE IMMUNE SYSTEM: Block: Foundations | LYBARGER [3 of 13] INTRODUCTION TO IMMUNOLOGY Below is a simplified diagram of hematopoietic cell lineages. These cell types figure prominently in immune responses; all are derived from hematopoietic stem cells in the bone marrow. B cells mature in the bone marrow and T cells mature in the thymus. The developmental intermediates of each lineage are not shown. I. IMMUNITY CAN BE CLASSIFIED AS INNATE OR ADAPTIVE INNATE IMMUNITY “Born with it” - Immunity that exists prior to exposure to a foreign substance or pathogen (antigen) and is not improved by repeated exposure to the same antigen. There is no/little immunological “memory” ADAPTIVE IMMUNITY State of immunity that is developed as a result of exposure to a foreign substance or pathogen (antigen). It is specific for the particular antigen and is enhanced following repeated exposure to the same antigen. Immunological “memory”. This form is mediated primarily by lymphocytes. Adaptive immunity will be explored in detail in subsequent sessions. *NOTE: these systems exhibit extensive crosstalk! INNATE VERSUS ADAPTIVE IMMUNITY Block: Foundations | LYBARGER [4 of 13] INTRODUCTION TO IMMUNOLOGY Figure: Comparison of the cell types, effector pathways, and kinetics associated with the innate and adaptive immune responses. Different ways to recognize “non-self” Self quiz: after completion of these basic immunology sessions in Foundations, you should be able to explain the differences between innate and adaptive in each category. A related table/figure with additional details can be found in the textbook (Basic Immunology; Figure 2.1) Block: Foundations | LYBARGER [5 of 13] INTRODUCTION TO IMMUNOLOGY Block: Foundations | LYBARGER [6 of 13] INTRODUCTION TO IMMUNOLOGY II. INNATE IMMUNITY MECHANISMS: Physical Barriers - epithelial surfaces: -skin, lungs, GI tract, reproductive tract - physical barriers with anti-microbial properties Complement system: - plasma proteins with anti-microbial properties, which are activated in response to infection Tissue-resident and circulating immune cells: - macrophages, neutrophils, dendritic cells, etc., with capacity to kill microbes and initiate an inflammatory response NOTE: the innate immune system can work with - and be augmented by - adaptive immunity components. Further, most cells in the body perform innate immune functions. Block: Foundations | LYBARGER [7 of 13] INTRODUCTION TO IMMUNOLOGY III. (SOME) CELLS OF THE INNATE IMMUNE SYSTEM: Macrophages - tissue-resident (derived from monocytes) in connective tissues, mucosal tissues, liver, etc. - long-lived and present at the outset of infection; more can also be recruited - initiate responses and serve many other roles, including direct killing of microbes and facilitating adaptive immunity Neutrophils - often called polymorphonuclear (PMN) leukocytes - short-lived (≈2-3 days), abundant cells of the circulation - “flood” into sites of infection (inflammation), and engulf and kill microbes * both cell types possess multiple mechanism to kill microbes: digestive enzymes, low pH, reactive oxygen species, etc. IV. DISTINGUISHING FEATURES OF THE ADAPTIVE IMMUNE RESPONSE Specificity: - Response is directed only against the stimulating antigen Adaptability: - Responses can be made against an immense variety of antigens, even those that are not naturally occurring Self/non-self discrimination: - Responses are made against foreign (“non-self”) antigens and not usually against “self” antigens Memory: Block: Foundations | LYBARGER [8 of 13] INTRODUCTION TO IMMUNOLOGY - Ability to recall previous contact with a foreign antigen and to respond in a “learned” way by initiating a rapid and vigorous response following re-exposure to the antigen - Invoked during the secondary immune response, but established after the primary immune response ***permits vaccines to work! V. LYMPHOCYTES - KEY PLAYERS OF THE ADAPTIVE RESPONSE B lymphocytes: make immunoglobulins (antibodies) that act as antigen receptors. Upon activation they differentiate into antibody-secreting cells known as plasma cells. T lymphocytes: express T cell receptors (TCRs) that bind antigen (in the form of peptides) and can be subdivided into: i. T helper (Th) cells (CD4+) - secrete numerous cytokines, activate dendritic cells and macrophages, and “help” B lymphocytes in producing antibodies. ii. T cytotoxic (Tc) (CD8+) cells - destroy virus-infected cells and tumor cells. iii. T regulatory (Treg) cells - regulate immune responses by controlling the activities of other immune cells including T cells – typically suppressive. Natural Killer cells: arise from the lymphocyte lineage and can kill virus- infected cells. They do NOT have antigen receptors like T and B cells. NK cells will be discussed later, in the Immune Response lecture…. Block: Foundations | LYBARGER [9 of 13] INTRODUCTION TO IMMUNOLOGY VI. ANTIGEN RECEPTORS AND CLONAL SELECTION The Clonal Selection model was developed to explain the features of the adaptive immune response. The essential elements are: 1. Every individual possesses numerous clonally-derived naïve lymphocytes (T and B) with distinct antigenic specificities that exist PRIOR to contact with antigens. Specificities arise by a random DNA rearrangement of antigen receptor genes. - millions of distinct lymphocyte ‘clones’ circulating in the body at any given time 2. The lymphocytes have antigen-specific receptors (immunoglobulin; Ig) for B cells and T cell receptors (TCR) for T cells, on their surface. 3. Each lymphocyte clone has many copies of an antigen receptor of a ≈single specificity on its membrane. 4. Antigen “selects” and binds to the lymphocyte with a receptor with specificity for that antigen. Block: Foundations | LYBARGER [10 of 13] INTRODUCTION TO IMMUNOLOGY 5. Binding to specific antigen stimulates that lymphocyte clone to proliferate. In the case of B lymphocytes, they differentiate into plasma cells that secrete antibodies that will bind that antigen. In the case of T cells, they differentiate into effector (helper or cytotoxic) cells. Some of these cells are set aside as long-lived “memory” cells in anticipation of re-exposure to the same antigen. 6. Cells capable of responding to self-antigens (auto-reactive) are destroyed following contact with self-antigen (during development) or are rendered unresponsive (in adults). Clonal Selection model - B cell example: Block: Foundations | LYBARGER [11 of 13] INTRODUCTION TO IMMUNOLOGY B cell example: In panel A, the B cell in the center has an antigen receptor that can bind the virus (whereas the other two B cells are incapable of binding the virus). In panel B, events (antigen binding plus other events [not shown]) on the center B cell causes the B cell clone to proliferate and begin to secrete the antigen receptor (antibody). The antibody can travel throughout the body via the circulation to find the antigen. VII. ANATOMY OF THE IMMMUNE SYSTEM Virtually all cells and tissue of the body have some capacity for immune defense, but our focus will be on lymphoid organs and tissues. These include bone marrow, thymus, spleen, lymph nodes, appendix, tonsils, and others. Lymphoid tissues can be categorized as primary or secondary. Primary lymphoid organs - sites of lymphocyte development - bone marrow (B lymphopoiesis) and thymus (T lymphopoiesis) Secondary lymphoid organs - sites where immune response begins - spleen, lymph nodes, tonsils, and others - The spleen is a filter of the blood, while lymph nodes filter an survey lymph (see below) Blood and lymphatic vessels are used as ‘highways’ to move cells throughout the body Block: Foundations | LYBARGER [12 of 13] INTRODUCTION TO IMMUNOLOGY Fluid leaks out of the vasculature under pressure and enters tissues. This fluid finds it way into lymphatic capillaries that gather into ever-large vessels. Lymphatic vessels return the fluid (lymph) to the blood at the great veins of the neck. Along the way, lymph passes through lymph nodes where it is surveilled by the adaptive immune system for the presence of anything ‘dangerous’ draining out of the surrounding tissues. If necessary, an immune response can be generated. Block: Foundations | LYBARGER [13 of 13]