1 / 97

Immune System

Immune System. Dispersed throughout the body Protects against infection and cancer Tightly regulated, self-limited and promptly terminated Lack of regulation could lead to inadequate response and failure to protect Failure to regulate could also lead to autoimmune disease.

shauna
Download Presentation

Immune System

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Immune System • Dispersed throughout the body • Protects against infection and cancer • Tightly regulated, self-limited and promptly terminated • Lack of regulation could lead to inadequate response and failure to protect • Failure to regulate could also lead to autoimmune disease

  2. Beginnings of immunology • Edward Jenner-1796 Cowpox vaccine • Robert Koch-19th century-microorganisms • Louis Pateur-1880s-vaccines for chicken cholera and rabies • Emil von Behring & Shibasaburo Kitasato-1890 Antibodies • Elie Metchnikoff-Macrophages

  3. Fig. 1.2 The eradication of smallpox by vaccination

  4. Components of the immune system Objectives: 1. Organization of the immune system 2. Origin of cells of the immune system 3. Central/peripheral lymphoid systems 4. Pattern recognition 5. Antigen presentation

  5. Organization of the lymphoid system • Lymphoid system is organized into: • Central/primary lymphoid organs • Peripheral/secondary lymphoid organs. • The central lymphoid organ: consists of thymus and bone marrow where T cells and B cells undergo maturation respectively • The peripheral lymphoid organs: Designed to trap Ag Allow initiation of adaptive immune response Sustain re-circulating lymphocytes

  6. Fig. 1.7 The distribution of lymphoid tissues in the body

  7. All cells in the blood originate from a common precursor Pluripotent hematopoietic stem cell: Common myeloid progenitor gives raise to: Erythrocyte progenitor: Platelets Red blood cells Granulocyte/macrophage progenitor Neutrophils Eosinophils Basophils Macrophages Mast cells Dendritic cells Common lymphoid progenitor gives raise to: T lymphocytes B lymphocytes

  8. Fig. 1.4 Myeloid cells in innate and adaptive immunity

  9. Fig. 1.5 Lymphocytes are mostly small and inactive cells

  10. Fig. 1.6 Natural killer cells

  11. Properties of lymphocytes • Resting B and T cells have large nuclei with very little cytoplasm • Upon Ag encounter lymphocytes proliferate and differentiate. • They mount specific immune responses against virtually all foreign Ags • They recognize Ags through cell surface receptors. • B cells have membrane immunoglobulins, which serve as BCRs • T cell antigenic receptors are called T cell receptors (TCRs) • BCR and TCR are structurally related but are distinct • NK cells lack Ag receptor-therefore, are part of the innate immune system.

  12. Fig. 2.2 Pathogens infect the body through a variety of routes

  13. Fig. 1.8 Organization of a lymph node

  14. Fig. 1.9 Organization of the lymphoid tissues of the spleen

  15. Fig. 1.10 Organization of typical gut-associated lymphoid tissue

  16. Fig. 1.11 Circulating lymphocytes encounter antigen in peripheral lymphoid organs

  17. Fig. 2.1 The response to an initial infection occurs in three phases

  18. Innate Immunity • Physical barriers • Chemical barriers • Phagocytosis • Complement activation • Receptors of the innate system • Induction of innate immunity • Cytokines and chemokines • NK cells • IgM antibodies

  19. Fig. 2.3 An infection and the response to it can be divided into a series of stages

  20. Fig. 2.4 Surface epithelia provide mechanical, chemical, and microbiological barriers to infection

  21. Fig. 2.6 Bactericidal agents produced or released by phagocytes on the ingestion of microorganisms

  22. Fig. 1.12 Bacterial infection triggers an inflammatory response

  23. Fig. 1.13 Dendritic cells initiate adaptive immune responses

  24. Immune system is dispersed in the body All cells arise from a common precursor Different cells have specialized functions Some provide 1st line of defense Others provide memory function for recall Cell-cell interactions required for response Soluble mediators play a key role Summary

  25. Lecture-II: Objectives • Receptors of the innate immune system • Induced innate responses: Cytokines and Chemokines • Summary of Innate immunity • Adaptive immune responses • Clonal selection • Antibody structure

  26. Receptors of the innate immune system • They are pattern recognition molecules • Expressed by all cells of a particular type • Recognize broad classes of pathogens • Examples include: • Macrophage mannose receptor • Mannan binding lectin • CD-14/TLRs-involved in signaling

  27. Fig. 2.27 The characteristics of receptors of the innate and adaptive immune systems are compared

  28. Fig. 2.5 Phagocytes bear several different receptors that recognize microbial components and induce phagocytosis

  29. Fig. 2.28 Mannan-binding lectin (MLB) binds to patterns of carbohydrate groups in the correct spatial orientation

  30. Fig. 2.29 Bacterial lipopolysaccharide signals through the Toll-like receptor TLR-4 to activate the transcription factor NFκB

  31. Fig. 2.30 Bacterial LPS induces changes in Langerhans’ cells, stimulating them to migrate and initiate adaptive immunity to infection by activating CD4 T cells

  32. Induced Innate responses • Pathogens induce macrophage activation • They produce cytokines and chemokines • Different molecules have different effects • Local effects: cell activation/recruitment • Systemic effects: Fever, shock, mobilize metabolites, acute-phase protein prodn • Follows initial innate immune response • Lacks memory and is not long lasting

  33. Fig. 2.31 Important cytokines secreted by microphages in response to bacterial products include IL-1, IL-6, IL-8, IL-12 and TNF-α

  34. Fig. 2.33 Properties of selected chemokines

  35. Fig. 2.36 Neutrophils leave the blood and migrate to sites of infection in a multistep process mediated through adhesive interactions that are regulated by macrophage-derived cytokines and chemokines

  36. Inflammation • Inflammation: Heat, Pain, Redness and Swelling • Reflect effects of inflammatory mediators on blood vessels • Results in increased blood flow • Results in increased permiability • Leakage of fluid from blood vessels and tissues causes edema • Leukocytes migrate into the site through endothelial wall • Initially neutrophils-the principal cells that engulf and destroy bacteria appear • Later in the process monocytes migrate and differentiate into macrophages • Further down in the process lymphocytes might be involved • This increases lymph flow into the lymph node • Lymph brings Ag into the lymph node where it is trapped • Activates adaptive immune system via dendritic cells

  37. Fig. 2.38 The cytokines TNF-α, IL-1, and IL-6 have a wide spectrum of biological activities that help to coordinate the body’s responses to infection

  38. Fig. 2.40 Interferons are antiviral proteins produced by cells in response to viral infection

  39. Fig. 2.41 Natural killer cells (NK cells) are an early component of the host response to virus infection

  40. Fig. 2.42 Possible mechanisms by which NK cells distinguish infected from uninfected cells

  41. Fig. 2.43 CD5 B cells might be important in the response to carbohydrate antigens such as bacterial polysaccharides

  42. Summary • Physical, Chemical and Mechanical barriers provide the first line of defense • Cells of the innate immune system are rapidly deployed and can clear infections • Sometimes they cannot completely clear infection • Cells of the innate immune system are involved in activating adaptive immune system • This is facilitated through Ag presentation and cytokine production • Adaptive immune system is more versatile but there is 4-7 day delay in deployment • Therefore, cells of the innate immune system play a critical role in host defense

  43. Summary: Innate immune system-2 • Phagocytic cells recognize patterns on microbes • Macrophages engulf bacteria, which in turn induce cytokines • Cytokines are proteins that affect cells that express their cognate receptor • Macrophages also release chemokines • Chemokines attract neutrophils and monocytes from blood • Inflammation is initiated by Chemokines • Inflammation can also be initiated by activation of complement

  44. Adaptive Immunity • Activated upon exposure to a pathogen/Ag • Requires help from the innate immune system • Depends on clonal selection from a repertoire of lymphocytes with diverse Ag specificity • Ag specific lymphocytes proliferate/differentiate into effector cells and help eliminate pathogens • Generates memory cells that allow rapid effective response to re-infection- Vaccination

  45. Clonal selection • Clonal Selection is the Central Principal of Adaptive Immunity: • T cells are selected in the thymus • B cells are selected in the BM • When cells encounter self-antigens- • clonal deletion occurs. • This is known as negative selection. • When cells are positively selected it is called clonal selection and these cells populate the peripheral lymphoid organs

More Related