Basic Concepts In Immunity

Basic Concepts in Immunity ROSS UNIVERSITY SCHOOL OF MEDICINE Raymond F Adebiyi Professor Immunology and Medical Microbiology Resources Required Reading: Basic Immunology: Functions and Disorders of the Immune System. 5th edition, 2016. Abbas, AK, Lichtman, AH, & Pillai, S. Elsevier. St. Louis,...

Basic Concepts in Immunity ROSS UNIVERSITY SCHOOL OF MEDICINE Raymond F Adebiyi Professor Immunology and Medical Microbiology Resources Required Reading: Basic Immunology: Functions and Disorders of the Immune System. 5th edition, 2016. Abbas, AK, Lichtman, AH, & Pillai, S. Elsevier. St. Louis, MO. Chapter 1, pp 1-25 Suggested Reading: How the Immune System Works, 6th edition, 2019. Lauren Sompeyrac. Wiley-Blackwell, Lecture 1 Accessible through Canvas: Student Resources Resources  R2 Digital Library As the title suggests this is reference, but it is Immunology & Serology abyquick no means complete enough for this course… Any Questions? [email protected] Office Hours https://atge.webex.com/meet/radebiyi Learning Objectives 1. Name the cells of the immune system. Distinguish which are innate cells and which are adaptive cells. 2. Describe the function of the primary and secondary lymphoid organs. 3. In general terms, how do white blood cells get to the site of infection? 4. Where does activation of adaptive cells occur? How and where do activated adaptive cells perform their function? 5. Define the immune response. Explain how recognition and self-discrimination are important principles related to an immune response. 6. List the main characteristics of the innate immune response. Name the components of an innate response and discuss the roles of each component. Describe generally how innate immune cells recognize antigens. 7. List the main characteristics of the adaptive immune system. Contrast these characteristics with those of the innate immune system. Describe in general terms how innate recognition of antigen differs from adaptive recognition of antigen. Name the components and the roles of each component of the adaptive immune system. 8. Describe in general terms how innate recognition of antigen differs from adaptive recognition of antigen. 9. Compare and contrast humoral immunity and cell-mediated immunity. 10. Define the following terms: active immunity; passive immunity; natural immunity; artificial immunity. Recognize specific examples of each type of immunity. 11. Explain the role of apoptosis in immunity. Describe how Fas/FasL interactions induce apoptosis. 12. Describe how Fas/FasL interactions induce apoptosis. Scope of Immunology • • • • • • • • Infectious disease Tissue repair Allergy/hypersensitivity Autoimmunity Immunotherapy (mAbs) Transplantation Tumor immunology/treatment (CAR therapy) Neuroimmunology • Rapidly advancing! Journal of Reproductive Immunology 116(2016): 7–12 Definition  Effort to combat potentially hazardous materials Restoration of normal structure and function The immune system is predicated upon two central principles. • Recognition o The body must have the capacity to ‘recognize’ the invading material. o Achieved through cell surface receptors that bind ligands on invaders. • Self-Discrimination o An immune response must implicitly be directed at a ‘foreign’ substance to defend self from harm. o The generation of nonself immune cells occurs by the process of elimination of self-reactive precursors. Who How Immunity Where What When Cells of the Immune System Histology: Lymphoid Tissue from past lecture Tissues of the Immune System Histology: Lymphoid Tissue Lymphocyte Recirculation Histology: Lymphoid Tissue Roles of the Immune System Primary immunodeficiencies Prevention of disease through vaccination B cell acute lymphoblastic leukemia (ALL) - CAR therapy TNF- mAb for treatment of rheumatoid arthritis Cells of the Immune Responses Innate • Natural Barriers • Phagocytes o Dendritic cells o Neutrophils o Macrophages • Mast cells, eosinophils, basophils • Complement Adaptive • B cells • T cells Histology: Lymphoid Tissue Characteristics of Immune Responses Innate • Group-specific  Multiple, relatively specific antigen receptors per cell.  Recognize antigens based on common structural motifs.  Recognize antigen marked by complement. • Always present/immediate response • Short-lived  No memory Adaptive • Antigen-specific  Cells express a unique antigen receptor. • Called upon only when necessary • Slow response • Long-lived  Second response against pathogen is better, faster, and stronger than first.  “Immunological Memory” Phases of Immunological Action Cognitive Phase Activation Phase Effector Phase Innate Immunity COGNITIVE Phase – INNATE Immunity Cognitive functions mediated by Pattern Recognition Receptors (PRRs): • • • • Limited in number (dozens) Specificity is predetermined and fairly broad (generally respond to groups of organisms). Same for all cells Little or no expansion upon stimulation Cognitive Phase – Innate Immunity Type 1 PRRs – Secreted PRRs: • Circulate in blood and lymph. • Mannan binding lectin, a collectin – binds to CHO on bacteria to initiate complement activation. • Other C-type lectin receptors and C-reactive protein function similarly. • Produced by the liver. • Induced by IL-6. Cognitive Phase – Innate Immunity Type 2 PRRs – Phagocytosis PRRs/scavenger receptors: • High affinity for mannose residues. • Bind to bacteria. • Facilitate phagocytosis. • Pathogen-derived proteins are presented to T cells (antigen processing and presentation). Cognitive Phase – Innate Immunity Type 3 PRRs – Signaling receptors: • TLRs (Toll-like receptors): o Homologous to toll receptors o On macrophages, dendritic cells, and epithelial cells (cell membrane and on endosomes) o Binding to pathogens results in activation of signal transduction and expression of cytokine genes • NLRs (Nod-like receptors): o Nucleotide oligomerization domain-like receptors (cytosolic) • RLRs (RIG-like receptors): o Retinoic acid-inducible gene-like receptors (cytoplasmic) Microbial Ligands Recognized by PRRs PRRs bind to unique microbial structures: • Pathogen-Associated Molecular Patterns – PAMPs • Microbe-Associated Molecular Patterns – MAMPs • Bacterial-Associated Molecular Patterns – BAMPs • Damage-Associated Molecular Patterns – DAMPs PAMPs: • Not shared with the host • Common to many pathogens • Invariant PRRs Recognize Specific PAMPs Adaptive Immunity COGNITIVE Phase –ADAPTIVE Immunity Cognitive functions mediated by unique cell surface receptor: • Specific to each cell (each B cell and T cell express receptors of only one specificity). • Receptor is generated by recombination of genes encoding the receptor (germline gene rearrangement). • Rearrangements are random and are antigen independent. • Allows for high degree of diversity in antigen receptors (many lymphocytes of only one specificity). • Expanded upon stimulation. COGNITIVE Phase – ADAPTIVE Immunity Take home message: protect • • from disease upon re-infection Specificity is guaranteed by having each cell only carry receptors specific for one antigen. Diversity is ensured by the staggering number of lymphocytes, each possessing specificity for only one antigen. COGNITIVE Phase – ADAPTIVE Immunity To illustrate: Adaptive Immune RecognitionCognitive Phase Comparison of BCR vs TCR Recognizes many different kinds of antigen Recognizes only peptides B cell receptor T cell receptor B cells and T cells express a unique antigen receptor. The Immune System Fig 3.4 Garland Science 2009 Characteristics of Receptors Adaptive Immunity B cells • How do they recognize antigen? B cell receptor (BCR, immunoglobulin, antibody) • What do they do in response to antigen? Secrete antibodies T cells • How do they recognize antigen? T cell receptor (TCR) • What do they do in response to antigen? Help other cells • Cytokines • Cell-surface interactions Kill infected cells Types of Adaptive Immunity Properties of Adaptive Immune System 1. 2. 3. 4. Specificity Diversity Clonal expansion Anamnestic reaction (secondary response) (booster response) 5. Memory Time Course of Adaptive Immune Response into effector cells Types of Immune Responses (Refinements) The Immune Response Lectures on B cells, antigens, & antibodies Lecture on cytokines Lecture on innate immunity Lecture on complement Lecture on antigen presentation & T cells INTEGRATIVE INTERACTIVE SESSION AT THE END Overview Innate Recognition. Antibodies & cytokines trigger additional functi ons. Lymph drains antigen and innate cells to secondary lymphoid tissue. Activation of B cells and T cells. Killer T cells kill infected cells. T cells become effector cells, B cells secrete antibodies. Effector T cells and antibodies traffic to site of infection. The End