Immunology: Basis of Traditional Vaccinology

1. Immunology: Basis of Traditional Vaccinology

3. THE IMMUNE SYSTEM Comprised of host cells and molecules which can be stimulated by non-self agents to protect against disease. The function of the Immune System can be divided into two categories: Innate immunity and adaptive immunity

4. Characteristics of Immunity Innate immunity -1st line of defense -provides initial defense against infection -relatively nonspecific -not enhanced by immunization -necessary for the establishment and enhancement of adaptive immunity

5. Adaptive immunity -develops slowly -broad activity -high degree of specificity -enhanced by immunization -activity heightened by cross talk with the innate immune system via cytokines (chemical signals that change the behavior of other cell types)

6. Components of the Innate Immune system Complement components Interferons Acute phase proteins Cytokines Platelets Polymorphonuclear leukocytes NK cells, NKT cells Monocytes/macrophages Dendritic cells

7. Components of the Adaptive Immune System Cells B lymphocytes T lymphocytes Molecules Antibodies Cytokines

8. The Immune Response Inductive phase Productive phase Effector phase Memory phase Contraction phase

9. Inductive Phase

10. Activating Agents Immunogens Molecules Peptide/proteins, Polysaccharides Nucleic acids, Lipids Microrganisms Bacteria, Viruses, Fungi, Protozoa, Metazoa

11. Recognition of Microbes by the Innate Immune System Structures that are shared by various classes of microbes and are not present on host cells (PAMPS- pathogen associated molecular patterns) Pattern recognition receptors encoded in germline genes express proteins called Toll-like receptors on the surface of cells that recognize PAMPS Innate immune system does not recognize self molecules

12. Activation of INNATE IMMUNE Cells

13. Changes in Cells of the Innate Immune System During Productive Phase Binding of PAMPS Leads to intracellular signaling events, gene transcription and translation resulting in: 1/changes in cell behavior 2/expression of surface markers 3/production and secretion of pro- inflammatory cytokines 4/antigen processing and presentation

14. Adaptive Immunity Organization of lymphocytes in organs and tissue - Central lymphoid organs bone marrow & thymus - Peripheral lymphoid organs lymph nodes, spleen, tonsils, appendix, Peyers patches, diffuse lymphoid tissue

15. Distribution of lymphoid tissuesParham Fig.1.11

16. Lymphocytes Two major populations, T cells and B cells, in peripheral lymphoid organs based on the central lymphoid organs where differentiation of precursor cells occurs. They are identified by the expression of surface markers and receptors which enable them to recognize and bind specific antigenic epitopes. T cells express costimulation molecules

17. T & B cell receptorsParham Fig. 1.16

18. Receptor molecules Both T and B lymphocytes have receptors molecules that allow for the recognition of small areas of antigens called antigenic epitopes These receptors are made up of constant and variable regions Different variable regions form biding sites for Ag epitopes Constant region determines function of secreted antibody molecule B cell receptor (antibody) secreted: T cell receptor not secreted

19. Receptor diversity is necessary to defend against the enormous numbers of pathogens we encounter Receptor diversity is generated through the process of gene rearrangement B cell receptors diversify further via somatic hypermutation

20. Activation of the Adaptive Immune System During the Inductive Phase of the Immune Response

21. Major histocompatibility(MHC) molecules & Ag presentationParham Fig.1.20

22. Antigen recognition B cells recognize Ag epitopes on native proteins T cells cells recognize processed peptide Ag epitopes complexed with MHC molecules on antigen presenting cells Ag recognition initiates clonal expansion

23. Clonal selectionParham Fig.1.18

24. Productive Phase of the Immune Response

26. Primary & Secondary Antibody Responses Antibody Isotype Switching

27. Immunologic Memorythe basis for prophylactic immunization

28. Effector Phase of the Immune Response

29. Innate Immune Responses Antigen presentation Phagocytosis and killing by neutrophils, monocytes/macrophages, dendritic cells NK cell-mediated cytotoxicity Inflammation Modulation of immune responses by cytokines produced by cells of the innate immune system.

31. Adaptive Immune Functions Antibody-mediated responses Cell-mediated responses

32. Antibody mediated immunityParham Fig. 1.23

33. T cell Effector Functions CD4+ T cell functions mediated via cytokines. -recruitment and activation of other cell types -immunoregulation -helper function CD8+ T cell functions -activation of other cell types via cytokine secretion -cytotoxicity against infected cells -immunoregulation

34. Tuberculin Reaction

35. Cell Mediated Immunity in Tuberculosis

36. Cell- mediated Immunity to Tubercule Bacilli

37. Sources The Vaccine Book. Ed. Barry Bloom and Paul-Herri Lambert Kuby-Immunology 6ed The Immune System 2nd ed