Immunology Lecture Notes PDF

Immunology Dr. Kiran C. Patel College of Osteopathic Medicine Kelley Davis, Ph.D. Professor of Microbiology & Immunology Dr. Kiran C. Patel College of Allopathic Medicine Director – M.S. in Disaster & Emergency Management Dr. Kiran C. Patel College of Osteopathic Medicine Office hours: https://cal...

Immunology Dr. Kiran C. Patel College of Osteopathic Medicine Kelley Davis, Ph.D. Professor of Microbiology & Immunology Dr. Kiran C. Patel College of Allopathic Medicine Director – M.S. in Disaster & Emergency Management Dr. Kiran C. Patel College of Osteopathic Medicine Office hours: https://calendly.com/drkdavis or by appt. 1 Learning Objectives Abbas: Cellular and Molecular Immunology, 2018 1.Describe the two branches of the immune system. 2.Distinguish between the two branches of the immune system. 3.Understand how the innate and adaptive immune responses interact with each other in the human body. 4.Identify the importance of blood and the lymphatic system and their roles in the immune system. Overview and Key Concepts 3 Purpose of the immune system Abbas: Basic Immunology: Functions and Disorders of the Immune System, 2020 • Prevent infections • Control infections when they occur • Eliminate pathogens & their products • Tumor surveillance • Immunopathology • Hypersensitivity • Autoimmunity • Transplant rejection • These functions are carried out by cells, organs, tissues, & molecules 4 Layering • Two “types” of immunity o innate o adaptive (AKA: acquired) • Within each “type” there are multiple o means of protection o effector mechanisms o components which carry out these functions (cells, molecules, organs) 5 Layering • Means of protection within a layer (e.g.) o innate – phagocytosis, barriers, enzymes, opsonization, complement, inflammation o adaptive – antibodies, complement, CMI • Effector mechanisms o innate – PAMP recognition, 2 complement pathways (opsonization or pathogen lysis) o adaptive – antibody neutralization, antibodymediated ADCC, antibody- & complementmediated opsonization, complement lysis, cell-mediated killing of infected host cells 6 Layering Abbas: Cellular and Molecular Immunology, 2018 7 Redundancy • Multiple ways for the immune system to protect against a single type of pathogen (e.g. Staphylococcus aureus) o cellular components (mΦs, PMNs, receptors) o soluble components (antibodies, complement proteins, PRRs, cytokines) o intracellular (oxidative burst, CMI) o extracellular (clotting, lysis, opsonization, inflammation, induced hypoferremia) 8 Single most important attribute of the immune system • Being able to tell the difference between “us” and “them”: self from non-self o pathogen motif receptors (PRRs) o antigen-specific receptors (antibodies, TCRs, MHCs) • If this mechanism fails, disease results o What happens if we fail to recognize non- self antigens? o What happens if we react to self-antigens? 9 Immune response has 2 parts • In order for the immune system to work, a response must be activated • The response has two parts/activities o recognition of antigen o effector mechanisms (contain/remove it) 10 Importance of blood • The cells & proteins involved in immunity circulate in/out of the bloodstream & lymphatic system • Leukocytes (myeloid cells – PMN, mΦ, etc.) • Lymphocytes (T cells, B cells, NK cells) • Proteins (complement, clotting factors) 11 Importance of blood 12 Lymphatic System • Network of vessels & nodes that circulate & filter plasma-derived fluid (lymph) • Interstitial fluids o fluids found in the spaces between body tissues – this fluid bathes the tissues o fluid drains into the lymphatic tissues (where it is called lymph), is filtered (by lymph nodes), & returned to the bloodstream • The difference between lymph & interstitial fluid is location 13 Lymphatic System https://medicine.missouri.edu/2017/03/limiting-protein-reduces-postheart-attack-injury-in-mice/ Abbas: Cellular and Molecular Immunology, 2018 14 Lymphatic System • Lymph nodes o filter the interstitial fluids/lymph & remove antigens o antigens are presented to T cells o provide a location where an immune response to foreign antigens can be initiated o allow B & T cell interactions to carry out the immune response o place for B cells to make antibodies 15 Lymphatic System Abbas: Cellular and Molecular Immunology, 2018 16 Branches of the Immune System Abbas: Basic Immunology: Functions and Disorders of the Immune System, 2020 17 Innate Immunity Abbas: Basic Immunology: Functions and Disorders of the Immune System, 2016 18 Innate Immunity • Non-specific (grenade) o responds to non-self antigens rather than specific pathogens (bacteria rather than S. aureus) o responds to conserved structures found on many pathogens but not on self • Already present at birth • Always “on” & present at basal levels • Does not develop memory for future responses 19 Innate Immunity • Initiates inflammatory responses o inflammation is a coordinated reaction between cells, cytokines, & proteins found in the tissues or recruited from circulation o inflammation helps to remove a pathogen, or limit its spread (contain it) o inflammation is also involved in tissue repair Rapid but generalized response 20 Adaptive Immunity Abbas: Basic Immunology: Functions and Disorders of the Immune System, 2020 21 Adaptive (Acquired) Immunity • Specific (sniper/expert marksman) o targeted response – only cells specific to that pathogen will respond • Acquired o activated only when a specific pathogen is encountered • Adaptive o gets better with each encounter • Provides memory for next encounter Specific but slower response 22 Adaptive Immunity • Must be upregulated/induced based on recognition of the specific pathogen o pathogen specific o slower to develop o mediated by lymphocytes • Three types o humoral o cell-mediated o mucosal 23 Abbas: Basic Immunology: Functions and Disorders of the Immune System, 2020 Clonal expansion (Proliferation) • Increases the number of lymphocytes • All lymphocytes that arise from a single activated cell will be identical clones of the original Original cell Clonal Expansion Kuby: Immunology, 2013 Clones of original cell 24 Adaptive Immunity • Humoral immunity o protects against extracellular pathogens o involves the production of antibodies from specialized differentiated B cells called plasma cells • Cell-mediated immunity o protects against intracellular pathogens o is carried out by specialized differentiated T cells which kill host cells that have become infected 25 Adaptive Immunity • Mucosal immunity o protects against pathogens at the interface with mucosal tissues or within mucosal tissues o some of the mechanisms, processes, & molecules are the same as systemic adaptive immunity, but there are significant differences & unique components not found in systemic immunity o mucosal immunity makes up most of our adaptive immune responses in the body 26 Adaptive Immunity • Cellular components o Lymphocytes (B & T cells) o Leukocytes (granulocytes) o Antigen presenting cells (APCs) Immunology, Infection, and Immunity , 2004 27 Adaptive Immunity • Lymphocytes exist in various states of readiness o naïve cells – before pathogen encounter & activation clonal proliferation differentiation o effector cells – activated, carry out immune function/activity o memory cells – activated but resting, quickly become effector cells upon next encounter with the same antigen 28 Adaptive Immunity Terminal Original cell Clonal Expansion Clones of original cell will differentiate Kuby: Immunology, 2013 Clones of original cell 29 Adaptive Immunity • Non-cellular components of adaptive immunity o antibodies (B cells) o cytokines (T cells) o complement (serum proteins) 30 Humoral Immunity • Production of antibodies by a type of terminally differentiated B cell → plasma cells • Protects against extracellular pathogens & products • B cells • T helper cells 31 Cell-Mediated Immunity • Protects against intracellular pathogens • T cytotoxic cells 32 Mucosal Immunity • Protects against pathogens in our mucosal tissues o mouth, respiratory system, GI, urogenital, eyes, ears • Involves both humoral & cell-mediated mechanisms • Includes additional mechanisms, cells, receptors, & tissues 33 Adaptive Immunity • These characteristics allow adaptive immunity to be protective o diversity – different types of cells & soluble molecules allow different ways to protect against many types of pathogens o specific/targeted response – only activated for a specific pathogen (e.g. S. aureus) o memory – memory cells are created, allowing for a more specific & rapid response upon next encounter → once reactivated, they become effector cells 34 Interactions between branches 35 Innate & Adaptive Interact • The two branches do not act in isolation • Innate generally responds first (always if this is a first encounter with the pathogen) • Lag time for upregulation of the adaptive response makes it inefficient for responding to continuous low-level exposures • Memory of the adaptive response is useful for infrequent re-exposures 36 Innate & Adaptive Interact • The innate response can inform & regulate the adaptive response & vice versa Immunology, Infection, and Immunity , 2004 37 Innate immunity regulates adaptive immunity • Complement proteins can activate B cells • Phagocytes & infected cells produce cytokines that affect activation & differentiation of B cells & T cells • Cytokines produced by innate immune cells can “guide” the type of adaptive response that occurs or cause upregulation of important molecules needed for the adaptive system to function 38 Adaptive immunity regulates innate immunity • T cells produce cytokines that increase phagocytic activity & intracellular killing by innate cells • Antibodies bound to an antigen provide “handles” for the phagocyte to engulf (opsonize) & remove/kill the pathogen 39 Innate vs. Adaptive Innate Adaptive Antigen non-specific Antigen specific Rapid Slow No memory Memory Always on/present, chemical & cell barriers Humoral ,Cell-mediated, Mucosal Phagocytes, NK cells, etc. Antibodies, Lymphocytes, etc. 40