Immunology_overview.ppt
Download as PPT, PDF0 likes581 views
The document provides an introduction to immunology, covering the following key points: - Immunology is the study of the body's protection from foreign substances and invading organisms. The immune system protects against pathogens and eliminates damaged or malignant cells. - Key events in the history of immunology include Jenner's development of the smallpox vaccine in 1798 and Pasteur's application of vaccines for anthrax and rabies in the late 1800s. - The immune system consists of innate (non-specific) immunity and acquired (adaptive/specific) immunity. Innate immunity provides immediate defense while adaptive immunity provides long-term, pathogen-specific memory and protection.
Immunology_overview.ppt
- 2. Immunology • Immunology is the study of our protection from foreign macromolecules or invading organisms and our responses to them. • Host – e.g. me!!!! • Foreign macromolecule, antigen – e.g. virus protein, worm, parasite (Everything that should not be in my body) 2 Dr.T.V.Rao MD
- 3. Immunity The Latin term “IMMUNIS” means EXEMPT, referring to protection against foreign agents. • DEFINITION: - The integrated body system of organs, tissues, cells & cell products that differentiates self from non – self & neutralizes potentially pathogenic organisms. • (The American Heritage Stedman's Medical Dictionary) Designed by Dr.T.V.Rao MD 3
- 4. • Protect against pathogens • Eliminate damaged or malignant cells 4 Dr.T.V.Rao MD
- 5. A Short History of Immunology • ~ 430 B.C: Peloponesian War, Thucydides describes plague – the ones who had recovered from the disease could nurse the sick without getting the disease a second time • 15th centurry: Chinese and Turks use dried crusts of smallpox as ”vaccine” • 1798: Edward Jenner – smallpox vaccine 5 Dr.T.V.Rao MD
- 6. Jenner - Smallpox vaccine • Noticed that milkmades that had contracted cowpox did NOT get smallpox • Test on an 8 year old boy, injected cowpox into him (NOT very nice……) • Follwed by exposure to smallpox • Vaccine was invented (latin vacca means ”cow”) 6 Dr.T.V.Rao MD
- 7. Immunology is a Complex Subject 7 Dr.T.V.Rao MD
- 8. Bacteria Tubercule bacillus Staphylococci Fungi Candida albicans Viruses Influenza Polio mellitus Parasites Tapeworms Malaria Helminths Role of the immune system is to protect from: 8 Dr.T.V.Rao MD
- 9. PRINCIPAL FUNCTION OF THE IMMUNE SYSTEM • To protect humans from pathogenic microorganisms • Pathogenic microorganisms (Pathogens) – Microorganisms capable of causing infection and/or disease • Infection – Ability of pathogen to enter host, multiply and stimulate an immune response • Disease – Clinical manifestations associated with infection 9 Dr.T.V.Rao MD
- 10. General Immunology Immunology stems from L.- immunis = “exempt;” Eng. = protection from disease *Protective adaptations in higher organisms to rid the body of foreign particles (microbial and otherwise) and abnormal cells Our Immune system involves the interplay between our Non-specific and our Specific Immune responses Non-specific immunities collectively referred to as our Innate immunity Specific immunities are referred to as our Adaptive immunity for which there are 2 branches: Humoral immunity Cell-mediated immunity 10 Dr.T.V.Rao MD
- 11. Subjects In Immunology • Cell mediated host defense functions • Antibody related defense mechanisms • Hypersensitivity reactions ( Including Allergy ) • Auto Immunity • Immunodeficiency • Transplantation 11 Dr.T.V.Rao MD
- 13. Definitions • Immune system = cells, tissues, and molecules that mediate resistance to infections • Immunology = study of structure and function of the immune system • Immunity = resistance of a host to pathogens and their toxic effects • Immune response = collective and coordinated response to the introduction of foreign substances in an individual mediated by the cells and molecules of the immune system 13 Dr.T.V.Rao MD
- 14. March towards modern times… 1718- Lady Montague became aware of a practice, called variolation or inoculation, and introduced it to Britain after first having her own children treated. 1774 – Benjamin Justy 1776- Geo. Washington 1798 –Edward Jenner noticed immunity bestowed to milkmaids – injected fluid from cowpox blister into skin of patient (orphan or prisoner) 1989- WHO announced smallpox was eradicated from the world Lady Mary Wortley Montague (1689-1762) War on smallpox… 14 Dr.T.V.Rao MD
- 15. Jenner - Smallpox vaccine • Noticed that milkmades that had contracted cowpox did NOT get smallpox • Test on an 8 year old boy, injected cowpox into him (NOT very nice……) • Follwed by exposure to smallpox • Vaccine was invented (latin vacca means ”cow”) 15 Dr.T.V.Rao MD
- 16. Pasteur inoculating sheep at Msr. Rossignol’s farm – May, 1881 1879- discovered that aged bacterial cultures of Pasteurella lost virulence. Referred to injection of weakened culture a “vaccine” in honor of Jenner 1881- He applied the same technique vs. anthrax ….and then rabies Louis Pasteur 16 Dr.T.V.Rao MD
- 17. Louis Pasteur watching as Joseph Meister receives attenuated rabies vaccine (1885) 17 Dr.T.V.Rao MD
- 18. First insights into mechanics of immunity… 1880’s- Metchnikoff discovered phagocytic cells that ingest microbes and particles cells conferred immunity 1890- von Behring and Kitasato discovered blood sera could transfer immunity liquid of blood conferred immunity Q: Which confers immunity… cells or serum? Emil von Behring S. Kitasato Elie Metchnikoff 18 Dr.T.V.Rao MD
- 19. Types Of Immunity • Inborn or innate immunity: It is present at birth; This is our First Line Of Defense. • Acquired or specific: It is not present at birth but becomes part of our immune system as the lymphoid system develops. • 1970: WHO defined immunity as immune response to antigen ( Foreign body) in form of • Humoral ( activation of B-lymphocytes) • Cellular (by activation of T-lymphocytes 19 Dr.T.V.Rao MD
- 20. Different types of Immunity A - Non specific 1 Species 2 Racial 3 Individual B Specific 1.Species 2 Racial 3 Individual 20 Dr.T.V.Rao MD
- 21. Basic classification of Immunity Designed by Dr.T.V.Rao MD 21
- 22. Two types of immunity 1. Innate (non-adaptive) – first line of immune response – relies on mechanisms that exist before infection 2. Acquired (adaptive) – Second line of response (if innate fails) – relies on mechanisms that adapt after infection – handled by T- and B- lymphocytes – one cell determines one antigenic determinant 22 Dr.T.V.Rao MD
- 23. Distinction Between Innate and Adaptive Immune Responses • Innate immunity is non-adaptive and helps to initiate adaptive immune responses (= first line of defense – but LIMITED) – Immediate (0-4 hours) • Adaptive immunity provides a more universal line of defense and has long-lived memory to provide protection upon re-infection – Second line of defense – Generation of Ag-specific effector cells – Early (4-96 hours) – Late (>96 hours) 23 Dr.T.V.Rao MD
- 24. Immunology Overview • Lymphocytes •Antigen-presenting cells •Effector cells • Responses •The innate immune response •Capturing and displaying antigens •Cell-mediated immunity •Humoral immunity •Immunologic memory 24 Dr.T.V.Rao MD
- 25. THE EVOLUTION OF IMMUNITY 25 Immunity Innate immunity Acquired immunity Non-specific Specific Immediate onset Delay onset Humoral Immune Response Cellular Immune Response Antibodies production T-cell activation Dr.T.V.Rao MD
- 26. DEFENSE MECHANISMS OF THE HUMAN HOST • Innate Mechanisms (Innate immunity) – First line of defense – Non-specific • Adaptive Mechanisms (Adaptive immunity) – Second line of defense – Highly specific with memory • Cooperation between mechanisms 26 Dr.T.V.Rao MD
- 27. Organs Of Immune System • Primary Lymphoid Organs –Bone Marrow and Thymus –Maturation Site • Secondary Lymphoid Organs –Spleen, lymph nodes, –MALT (mucosal associated lymph tissue) –GALT (gut associated lymph tissue) –Trap antigen, APC, Lymphocyte Proliferation 27 Dr.T.V.Rao MD
- 28. ORIGIN OF CELLS OF THE IMMUNE SYSTEM • Derived from common progenitor cell in bone marrow – Pluripotent hematopoietic stem cell • Progenitor Stem Cells – Erythroid lineage • Erythrocytes and Megakaryocytes – Myeloid lineage • Monocyte/macrophage, dendritic cells, PMN’s, mast cells –Lymphoid lineage • Small and large lymphocytes 28 Dr.T.V.Rao MD
- 30. The immune system 30 Immune system •Anatomic barriers (Skin, mucous membranes) •Physiological barriers (temperature, pH) •Phagocytic Barriers (cells that eat invaders) •Inflammatory barriers (redness, swelling, heat and pain) •Antigen specificity •Diversity •Immunological memory •Self/nonself recognition Innate (non-specific) immunity Adaptive (specific) immunity Dr.T.V.Rao MD
- 31. 31 Dr.T.V.Rao MD
- 32. Central Immune organs Central Immune Organs are the sites of generation, differentiation and maturation of immunocytes. Bone marrow Thymus Bursa of Fabricius (the site of B cells maturation in birds) But absent in Humans 32 Dr.T.V.Rao MD
- 33. Innate Immunity • Nonspecific host defenses that exist prior to exposure to an antigen. Involves the following components: –Anatomic –Physiologic –Phagocytic –Inflammatory 33 Dr.T.V.Rao MD
- 34. Barriers to Antigenic Insult • Anatomic –Skin –Mucous membranes • Physiologic –Temperature –pH –Chemical mediators 34 Dr.T.V.Rao MD
- 35. THE INNATE IMMUNE RESPONSE • Mediated (initiated) by phagocytes, NK cells and soluble proteins • Phagocytes – Cells specialized in the process of phagocytosis • Macrophages – Reside in tissues and recruit neutrophils • Neutrophils – Enter infected tissues in large numbers – Recognize common molecules of bacterial cell surface using a few surface receptors • Phagocytosis – Capture, engulfment and breakdown of bacterial pathogen 35 Dr.T.V.Rao MD
- 36. 36 Important components of innate immunity Factors that limit growth of microorganisms within the body • Natural killer cells • Neutrophils • Macrophages and dendritic cells • Interferons • Complement • Transferrin and Lactoferrin • Fever • Inflammatory response • APOBEC3G (apolypoprotein is RNA editing enzyme) • Kill virus infected cells • Ingest and destroy microbes • Ingest and destroy microbes, and present antigen to helper T-cells • Inhibit viral replication • C3b is an opsonin, membrane attack complex creates holes in bacterial membranes • Sequester iron required for bacterial growth • Elevated temperature retards bacterial growth • Limits spread of microbes • Causes hyper mutation in retroviral DNA and mRNA Dr.T.V.Rao MD
- 37. 37 Main Components of Innate and acquired Immunity that contribute to humoral ( antibody-mediated ) immunity and cell mediated immunity Humoral Immunity Cell mediated Immunity Innate Complement Neutrophil Macrophages Natural killer cells Acquired B cells Antibodies Helper Tcells Cytotoxic T cells Dr.T.V.Rao MD
- 38. 38 Major Functions Of T Cells and B cells Antibody-Mediated Immunity (B Cells) 1) Host defense against infection 2) (Opsonize bacteria, neutralize toxins and viruses) 3) Allergy (hypersensitivity) eg, hay fever anaphylactic shock 4) Autoimmunity Cell Mediated Immunity 1) Host defense against infection (especially M.tuberculosis, fungi and virus infected cells) 2) Allergy (hypersensitivity )eg poison oak 3) Graft and tumor rejection 4) Regulation of antibody response (help and suppression) Dr.T.V.Rao MD
- 39. Cellular and Inflammatory Components of Innate Immunity • Cellular –Phagocytic cells • Inflammatory –Vasodilation –Capillary permeability 39 Dr.T.V.Rao MD
- 40. CELLS OF INNATE AND ADAPTIVE IMMUNITY • Myeloid Lineage – Neutrophil • Principal phagocytic cell of innate immunity – Eosinophil • Principal defender against parasites – Basophil • Functions similar to Eosinophils and mast cells – Referred to as • Polymorph nuclear leukocytes (PMN’s) – Nuclei are multilobed (2 to 5) • Granulocytes – Cytoplasmic granules 40 Dr.T.V.Rao MD
- 41. CELLS OF INNATE AND ADAPTIVE IMMUNITY • Myeloid lineage – Monocytes • Leukocytes with bean shaped or brain-like convoluted nuclei • Circulate in blood with half life of 8 hours • Precursors of tissue macrophages – Macrophages • Mononuclear phagocytic cells in tissue • Derive from blood monocytes • Participate in innate and adaptive immunity 41 Dr.T.V.Rao MD
- 42. CELLS OF INNATE AND ADAPTIVE IMMUNITY • Myeloid lineage – Dendritic cells • Cells with dendriform (star shaped) morphology • Interdigitating reticular cells (synonym) • Capture and present antigens to T lymphocytes – Mast cells • Located in mucous membrane and connective tissue throughout body • Major effector cell in allergy • Modulation of initial immune response 42 Dr.T.V.Rao MD
- 43. CELLS OF INNATE AND ADAPTIVE IMMUNITY • Lymphoid Lineage – Large lymphocytes (large granular lymphocytes) • Natural killer (NK) cells (CD16, CD56) • Innate immunity to viruses and other intracellular pathogens • Participate in antibody-dependent cell-mediated cytotoxicity (ADCC) – Small lymphocytes • B cells (CD19) • T cells (CD3, CD4 or CD8) • Adaptive immunity – Lymphocytes refers to small lymphocytes 43 Dr.T.V.Rao MD
- 44. THE CLUSTER OF DIFFERENTIATION (CD) • A protocol for identification and investigation of cell surface molecules • CD number assigned on basis of 1 cell surface molecule recognized by 2 specific monoclonal antibodies • CD nomenclature established in 1982 –1st International Workshop and Conference on Human Leukocyte Differentiation Antigens (HLDA) 44 Dr.T.V.Rao MD
- 45. THE CLUSTER OF DIFFERENTIATION (CD) • CD markers on leukocytes Granulocyte CD45+, CD15+ Monocyte CD45+, CD14+ T lymphocyte CD45+, CD3+ T helper lymphocyte CD45+, CD3+, CD4+ T cytotoxic lymphocyte CD45+, CD3+, CD8+ B lymphocyte CD45+, CD19+ Natural killer cell CD45+, CD16+, CD56+, CD3- 45 Dr.T.V.Rao MD
- 46. Physiologic Mediators of Innate Immunity • Chemical mediators –Enzymes –Interferon –Complement • Three pathways – Classical – MB Lectin – Alternative 46 Dr.T.V.Rao MD
- 47. Physiologic Mediators of Innate Immunity(cont’d) • Chemical mediators –Collections –Toll-like receptors –Acute phase proteins 47 Dr.T.V.Rao MD
- 48. Mechanism's of Immunity • Epithelial surfaces Skin and Epithelial surfaces cover the body and protects the individuals Healthy skin poses bactericidal influence, salt, drying sweat , Long fatty acids Wet hand predisposes to Mycotic and pyogenic infections 48 Dr.T.V.Rao MD
- 50. 50 Dr.T.V.Rao MD
- 51. 51 White Blood Cell Development Dr.T.V.Rao MD
- 52. LYMPHOCYTES, LYMPHOID TISSUES AND ORGANS • Lymphocytes originate in bone marrow • Lymphoid tissues and organs – Primary • Development and maturation of lymphocytes • Bone Marrow (B cells) and thymus gland (T cells) – Secondary • Mature lymphocytes meet pathogens • Spleen, adenoids, tonsils, appendix, lymph nodes, Peyer’s patches, mucosa-associated lymphoid tissue (MALT) 52 Dr.T.V.Rao MD
- 53. THE LYMPHATIC SYSTEM • Lymph – Fluid and cells in lymphatic vessels • Lymphatic vessels – Collect and return interstitial fluid to blood – Transport immune cells throughout body – Transport lipid from intestine to blood • Lymph nodes – Kidney shaped organs at intervals along lymphatic vessels • Other secondary lymphatic tissues and organs 53 Dr.T.V.Rao MD
- 54. 54 Dr.T.V.Rao MD
- 55. SECONDARY LYMPHOID TISSUES ASSOCIATED WITH MUCOUS MEMBRANES • Primary portals of entry for pathogens – Respiratory tract – Gastrointestinal tract • Secondary lymphoid tissues – Bronchial-associated lymphoid tissue (BALT) – Gut-associated lymphoid tissues (GALT) • Tonsils, adenoids, appendix, Peyer’s patches • Pathogens are directly transferred across mucosa by “M” cells 55 Dr.T.V.Rao MD
- 56. Innate immunity: mechanisms • Mechanical barriers / surface secretion – skin, acidic pH in stomach, cilia • Humoral mechanisms – lysozymes, basic proteins, complement, interferons • Cellular defense mechanisms – natural killer cells neutrophils, macrophages,, mast cells, basophils, Eosinophils Neutrophil NK Cell Monocyte Macrophage Basophils & Mast cells Eosinophils 56 Dr.T.V.Rao MD
- 57. Adaptive immunity: second line of response • Based upon resistance acquired during life • Relies on genetic events and cellular growth • Responds more slowly, over few days • Is specific – each cell responds to a single epitope on an antigen • Has anamnestic memory – repeated exposure leads to faster, stronger response • Leads to clonal expansion 57 Dr.T.V.Rao MD
- 58. Adaptive immunity: mechanisms • Cell-mediated immune response (CMIR) – T-lymphocytes – eliminate intracellular microbes that survive within phagocytes or other infected cells • Humoral immune response (HIR) – B-lymphocytes – mediated by antibodies – eliminate extra-cellular microbes and their toxins Plasma cell (Derived from B-lymphocyte, produces antibodies) 58 Dr.T.V.Rao MD
- 59. Cell-mediated immune response 1.T-cell – recognizes peptide antigen on macrophage in association with major histo-compatibility complex (MHC) class – identifies molecules on cell surfaces – helps body distinguish self from non-self 2. T-cell goes into effectors cells stage that is able to kill infected cells 59 Dr.T.V.Rao MD
- 60. Cell mediated immune response Primary response – production of specific clones of effector T cells and memory clones – develops in several days – does not limit the infection Secondary response – more pronounced, faster – more effective at limiting the infection Example - cytotoxic reactions against intracellular parasites, delayed hypersensitivity (e.g., Tuberculin test) and allograft rejection Dr.T.V.Rao MD 60
- 61. Humoral immune response 1. B lymphocytes recognize specific antigens – proliferate and differentiate into antibody-secreting plasma cells 2. Antibodies bind to specific antigens on microbes; destroy microbes via specific mechanisms 3. Some B lymphocytes evolve into the resting state - memory cells Dr.T.V.Rao MD 61
- 62. Antibodies (immunoglobulin's) •Belong to the gamma-globulin fraction of serum proteins •Y-shaped or T-shaped polypeptides –2 identical heavy chains –2 identical light chains • All immunoglobulin's are not antibodies •Five kinds of antibodies –IgG, IgM, IgA, IgD, IgE
- 63. Acute Phase proteins too play a great role in Immunity • Infection and Injury produces Acute phase proteins • C- Reactive proteins CRP • Mann in binding proteins • CRP activates alternative pathway • Increases host defenses • Prevents issue injury • Repair inflamed lesions. 63 Dr.T.V.Rao MD
- 64. Natural Killer cells NK cells 64 Dr.T.V.Rao MD
- 65. Role of Natural killer Cells • Natural killer cells (or NK cells) are a type of cytotoxic lymphocyte that constitute a major component of the Innate immune system. NK cells play a major role in the rejection of tumours and cells infected by viruses. The cells kill by releasing small cytoplasmic granules of proteins called perforin and granzyme that cause the target cell to die by apoptosis 65 Dr.T.V.Rao MD
- 66. • Programme created by Dr.T.V.Rao MD for Medical and Paramedical Students in the Developing World • Email • doctortvrao@gmail.com 66 Dr.T.V.Rao MD