1. Microbiology 532: Immunology Dennis E. Lopatin, Ph.D. Dept. of Biologic and Materials Sciences 4209 Dental Building Office Hours by Appointment Phone: 647-3912 Electronic mail: lopatin@umich.edu

2. Helpful Hints Readings in text are optional - I don’t test from the book. Readings in text are optional - I don’t test from the book. Understanding the concepts is not optional Understanding the concepts is not optional Think, rather than memorize Think, rather than memorize Test questions are based on concepts Test questions are based on concepts Ask questions Ask questions Don’t wait until the last minute to study for the exam Don’t wait until the last minute to study for the exam Check the website Check the website

3. What is immunity? Distinguishes “self” from “non-self” Distinguishes “self” from “non-self” Danger Hypothesis Danger Hypothesis “Protection” from infection, tumors, etc. “Protection” from infection, tumors, etc. A response that may result in host tissue damage A response that may result in host tissue damage

4. The Beginning of Immunology Edward Jenner discovered that cowpox vaccination protected against smallpox in 1796. Officially eradicated in 1979.

5. Two types of immunity Innate immunity (not antigen-specific) Innate immunity (not antigen-specific) Anatomical barriers Anatomical barriers Mechanical Mechanical Biochemical Biochemical Non-specific (eg. Low pH in stomach) Non-specific (eg. Low pH in stomach) Receptor-driven (eg. PAMP-recognition) Receptor-driven (eg. PAMP-recognition) Adaptive immunity (antigen-specific) Adaptive immunity (antigen-specific) Receptor-driven Receptor-driven Pre-existing clones programmed to make a specific immune response (humoral/cellular) Pre-existing clones programmed to make a specific immune response (humoral/cellular)

6. Antigen A substance (antigen) that is capable of reacting with the products of a specific immune response, e.g., antibody or specific sensitized T-lymphocytes. A substance (antigen) that is capable of reacting with the products of a specific immune response, e.g., antibody or specific sensitized T-lymphocytes. A “self” component may be considered an antigen even though one does not generally make immune responses against those components. A “self” component may be considered an antigen even though one does not generally make immune responses against those components.

7. Characteristics of Adaptive Immunity Immune response is highly specific for the antigen that triggered it. Immune response is highly specific for the antigen that triggered it. Receptors on surface of immune cells have same specificity as the antibody/effector activity that will be generated Receptors on surface of immune cells have same specificity as the antibody/effector activity that will be generated Exposure to antigen creates an immunologic “memory.” Exposure to antigen creates an immunologic “memory.” Due to clonal expansion and creation of a large pool of cells committed to that antigen Due to clonal expansion and creation of a large pool of cells committed to that antigen Subsequent exposure to the same antigen results in a rapid and vigorous response Subsequent exposure to the same antigen results in a rapid and vigorous response

8. Exposure to Antigen (Naturally-acquired or artificial) Exposure to Antigen (Naturally-acquired or artificial) Virgin lymphocyte pool PRIMARY RESPONSE SECONDARY RESPONSE effector cells memory cell pool effector cells memory cell pool B lymphocytes T lymphocytes B lymphocytes T lymphocytes Activated T lymphocytes Plasma cells Activated T lymphocytes Plasma cells RegulatoryCytotoxicRegulatoryCytotoxic AntibodiesAntibodies What happens upon antigen exposure?

9. Cell-MediatedCell-Mediated Antibody-MediatedAntibody-Mediated Cytotoxic T-LymphocyteCytotoxic T-Lymphocyte Natural Killer CellsNatural Killer Cells Antibody-mediated cellular cytotoxicity (ADCC)Antibody-mediated cellular cytotoxicity (ADCC) Cytotoxic T-LymphocyteCytotoxic T-Lymphocyte Natural Killer CellsNatural Killer Cells Antibody-mediated cellular cytotoxicity (ADCC)Antibody-mediated cellular cytotoxicity (ADCC) Complement activationComplement activation AgglutinationAgglutination NeutralizationNeutralization Mask receptorsMask receptors Antibody-mediated cellular cytotoxicity (ADCC)Antibody-mediated cellular cytotoxicity (ADCC) Opsonization and phagocytosisOpsonization and phagocytosis Complement activationComplement activation AgglutinationAgglutination NeutralizationNeutralization Mask receptorsMask receptors Antibody-mediated cellular cytotoxicity (ADCC)Antibody-mediated cellular cytotoxicity (ADCC) Opsonization and phagocytosisOpsonization and phagocytosis What are the effector functions?

10. The Adaptive Response is a “Two-Edged Sword” Protection Protection Damage to the host (hypersensitivities) Damage to the host (hypersensitivities) Allergies Allergies Cell and tissue damage due to autoimmunity Cell and tissue damage due to autoimmunity

11. Hypersensitivity Reactions Reactions that are detrimental to the host Reactions that are detrimental to the host Autoimmunity Autoimmunity Atypical immune responses (allergies) Atypical immune responses (allergies) Inability to eliminate a pathogen (granulomas) Inability to eliminate a pathogen (granulomas) The tissues become a carrier for a hapten (poison ivy, nickel, penicillin The tissues become a carrier for a hapten (poison ivy, nickel, penicillin Rejection of transplanted tissues Rejection of transplanted tissues

12. Why Does a Dentist Need to Understand Immunology? Many of the oral diseases have an immune component Many of the oral diseases have an immune component Periodontal disease Periodontal disease Caries Caries Sjögren’s Syndrome Sjögren’s Syndrome Current and future therapeutics affect the immune system and oral health Current and future therapeutics affect the immune system and oral health Systemic and Oral diseases are interrelated Systemic and Oral diseases are interrelated Cooperation with other health care professional requires a common language Cooperation with other health care professional requires a common language

13. The products of the immune response may be used To diagnose disease To diagnose disease To monitor disease progress To monitor disease progress As reagents in assays to detect and quantify other substances As reagents in assays to detect and quantify other substances

14. Components of the immune system

15. Cells involved in immunity platelets megakaryocyte eosinophil neutrophil basophil mast cell common myeloid progenitor monocyte macrophage Natural Killer cell plasma cell B Lymphocyte T Lymphocyte common lymphoid progenitor Pluripotenthematopoietic stem cell

16. BloodBlood Serum or Plasma Leukocytes, Platelets and RBC Serum Proteins Mononuclear Cells Polymorphonuclear leukocytes (or Granulocytes) ImmunoglobulinsImmunoglobulins ComplementComplement Clotting factorsClotting factors Many othersMany others ImmunoglobulinsImmunoglobulins ComplementComplement Clotting factorsClotting factors Many othersMany others NeutrophilsNeutrophils EosinophilsEosinophils BasophilsBasophils NeutrophilsNeutrophils EosinophilsEosinophils BasophilsBasophils Lymphocytes (T cells, B cells & NK cells)Lymphocytes (T cells, B cells & NK cells) MonocytesMonocytes Lymphocytes (T cells, B cells & NK cells)Lymphocytes (T cells, B cells & NK cells) MonocytesMonocytes Where is that stuff?

17. Lymphoid Organs Primary or central lymphoid organs Primary or central lymphoid organs bone marrow and thymus bone marrow and thymus where lymphocytes are generated where lymphocytes are generated Secondary or peripheral lymphoid organs Secondary or peripheral lymphoid organs where adaptive immune responses are initiated where adaptive immune responses are initiated

18. Distribution of Lymphoid Tissues

19. Mucosal-associated lymphoid tissues (MALT) Will be discussed in the Spring Salivary Gland Course Will be discussed in the Spring Salivary Gland Course

20. What’s the bottom line? Innate immunity is a function of anatomical, mechanical and biochemical factors. Innate immunity is a function of anatomical, mechanical and biochemical factors. No requirement for prior exposure/memory No requirement for prior exposure/memory Biochemical response may involve pattern recognition Biochemical response may involve pattern recognition Lacks the specificity of the adaptive immune system Lacks the specificity of the adaptive immune system Adaptive immune system recognizes foreign agents via receptors and develops memory. Adaptive immune system recognizes foreign agents via receptors and develops memory. Triggering the adaptive immune response results in activated T cells and antibodies specific for the substance (antigen) that triggered it. Triggering the adaptive immune response results in activated T cells and antibodies specific for the substance (antigen) that triggered it. Antibodies react with antigen Antibodies react with antigen Block or neutralize Block or neutralize Activate complement system Activate complement system Bind to Fc receptors on cells providing specificity to the effector activity of those cells Bind to Fc receptors on cells providing specificity to the effector activity of those cells Activated T cells Activated T cells Cytotoxic against foreign agent (tumor cell, transplant, virus-infected cell) Cytotoxic against foreign agent (tumor cell, transplant, virus-infected cell) May influence other cells (Helper/Suppressor T cells, cytokines) May influence other cells (Helper/Suppressor T cells, cytokines)

21. Host Defense DefenseMechanisms Innate Inborn independent of previous experience Acquired Naturallyacquired Active Adoptive Passive Active Adoptive Passive after natural exposure to a foreign agent placental transfer immune cells in colostrum Artificiallyacquired Specificimmunization administration of preformed antibodies Bone marrow transplant immune cells in colostrum

22. Subsequent lectures Immunoglobulin structure Immunoglobulin structure Antibody/antigen reactions Antibody/antigen reactions T cell-mediated immunity T cell-mediated immunity Humoral immunity Humoral immunity Host defense against infection Host defense against infection Hypersensitivity reactions Hypersensitivity reactions Autoimmunity Autoimmunity