Introduction to immunity

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Introduction to immunity

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Introduction to immunity

  1. 1. Introduction to Immunology Science of Immunity Dr.T.V.Rao MD Dr.T.V.Rao MD 1
  2. 2. Immunology• Immunology: – Study of the molecules, cells, organs, and systems responsible for the recognition and disposal of foreign (nonself) material – Study of the MECHANISMS that protect an individual from injury from: • Exogenous microorganisms – bacteria, fungi, viruses • Exogenous chemicals – pollen, poison ivy, etc. • Endogenous cells – malignant or senescent cells – IMMUNE RESPONSE: Broad range of defense mechanisms including inflammation, phagocytosis, antibody synthesis, etc.
  3. 3. Edward Jenner, “ the founder of modern immunology” 1796- Introduction of protective vaccine against small pox: based on cow pox (in Latin - vaccinia )
  4. 4. What is the immune system?• The body’s defense against disease causing organisms, malfunctioning cells, and foreign particles
  5. 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
  6. 6. Dr.T.V.Rao MD 6
  7. 7. Immunology• Contains Basic science• Clinical Application Host defense reactions to foreign Antigen Substance is not self Antigen recognizing Cell Mediated Host defense functions Dr.T.V.Rao MD 7
  8. 8. 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”)Pierre Dönnes Andreas Hildebrandt Annette Höglundpierre@bioinf.uni-sb.de anhi@bioinf.uni-sb.de annette@bioinf.uni-sb.de
  9. 9. Subjects In Immunology• Cell mediated host defense functions• Antibody related defense mechanisms• Hypersensitivity reactions ( Including Allergy )• Auto Immunity• Immunodeficiency• Transplantation Dr.T.V.Rao MD 9
  10. 10. What is Response to Infection• Immunity can be Innate Nonadapative• Adaptive - Acquired. Dr.T.V.Rao MD 10
  11. 11. What is immunity?- Resistance to a disease causing organism or harmful substance- Two types - Active Immunity - Passive Immunity
  12. 12. Immunology is a Complex Subject Dr.T.V.Rao MD 12
  13. 13. Dr.T.V.Rao MD 13
  14. 14. The Invaders . . .• Bacteria http://www.hhs.gov/asphep/presentation/images/bacteria.jpg• Viruses• parasites such as fungi, http://www.skidmore.edu/academics/biology/plant_bio/lab13.FUNGI.html & worms worm trichura.jpg
  15. 15. Different types of ImmunityA - Non specific 1Species 2Racial 3IndividualB Specific1.Species2 Racial 3 Individual Dr.T.V.Rao MD 15
  16. 16. THE EVOLUTION OF IMMUNITY ImmunityNon-specific Immediate onset Specific Delay onset Innate immunity Acquired immunity Humoral Cellular Immune Response Immune Response Antibodies production T-cell activation Dr.T.V.Rao MD 16
  17. 17. Innate ImmunityInnate Immunity is resistance that ispreexisting and is not acquired throughcontact with a nonself ( Foreignknown as antigenIndividual has innate Immunity by geneticor constitutional Make UpNon related to prior contact withMicroorganisms or Immunization Dr.T.V.Rao MD 17
  18. 18. 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, MD Dr.T.V.Rao Lymphocyte 18 Proliferation
  19. 19. 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 Dr.T.V.Rao MD 19
  20. 20. It is Dependent on• Species• Race ( Racial )• Individual Dr.T.V.Rao MD 20
  21. 21. Species and Immunity• Immunity refers to total resistance to a Pathogen by all members of the species• Eg Human do not get plant diseases• Humans do not get some animal diseases• Dependent on Human configuration physiology ? Biochemical difference Dr.T.V.Rao MD 21
  22. 22. Immune system is distributed all over the Body 22 Dr.T.V.Rao MD
  23. 23. Dr.T.V.Rao MD 23
  24. 24. Race - Immunity• Genetic resistance Plasmodium falciparum malaria resistance in Africa• In sickle cell anemia immune to malaria Dr.T.V.Rao MD 24
  25. 25. Individual - Immunity• Twins homozygous twins exhibit similar resistance• Susceptibility similar in Leprosy• Tuberculosis similar resistance Dr.T.V.Rao MD 25
  26. 26. Factors Influencing Innate Immunity• Placenta prevent infection• But still can infected with Toxoplasmosis, Rubella, CMV and Herpes infection.• Can produce congenital malformations Dr.T.V.Rao MD 26
  27. 27. Immunity In Adults• Polio infection , and Chickenpox highly severe in adults.• Enlargement of prostate lead to UTI Dr.T.V.Rao MD 27
  28. 28. Hormonal Influces on Immunity• Diabetes mellitus• Hypothyroidism in adults• Adrenal dysfunction• Stress increases steroids predisposes to Infection Dr.T.V.Rao MD 28
  29. 29. Nutrition• Immunodefic iency• Some protection in some diseases Dr.T.V.Rao MD 29
  30. 30. Our 1st Line of Defense...• The Integumentary System… –Skin –Mucous membranes –Mucous• provides a physical barrier preventing microbial access
  31. 31. Mechanisms of Immunity• Epithelial surfaces Skin and Epithelial surfaces cover the body and protects the individualsHealthy skin poses bactericidal influence, salt, drying sweat , Long fatty acidsWet hand predisposes to Mycotic and pyogenic infections Dr.T.V.Rao MD 31
  32. 32. Mucous Membranes• Respiratory tract Shape of Nose, Nasal orifice Dr.T.V.Rao MD 32
  33. 33. • Cilia in Respiratory tract• Propel the foreign particles• Respiratory secretion contain Dr.T.V.Rao MD 33
  34. 34. Oral Cavity• Saliva• Stomach Hcl• Large intestine large number of bacteria Dr.T.V.Rao MD 34
  35. 35. Conjunctiva• Contain lachrymal secretions• Tears contains antibacterial substances• Lysozyme present except in CSF, Sweat, Urine Dr.T.V.Rao MD 35
  36. 36. The First Line of Defense What’s the first thing you do when you~Saliva~ finger? cut your- Saliva contains many chemicals that break down bacteria- Thousands of different types of bacteria can survive these chemicals, however
  37. 37. Other Mechanisms• Flushing action of urination drives out Microbes in the Urethra• Spermine in Semen Dr.T.V.Rao MD 37
  38. 38. Antibacterial Substances• May be present Blood as Complement• Antibacterial substances in Blood Betalysin, Leukin Lacto peroxidase in Milk Dr.T.V.Rao MD 38
  39. 39. Interferons in Immunity• Interferons (IFNs) are natural proteins produced by the cells of the immune system of most vertebrates in response to challenges by foreign agents such as viruses, parasites and tumour cells. Interferons belong to the large class of glycoproteins known as cytokines• Interferons are more useful than Antibodies Dr.T.V.Rao MD 39
  40. 40. Microbial Antagonists Normal flora Help us• Normal Microbial flora Dr.T.V.Rao MD 40
  41. 41. Normal Flora Help Us• We harbour near 1014 bacteria. This group of organisms, traditionally referred to as "normal flora" (although they are not plants) is composed of a fairly stable set of genera, mostly anaerobes. While each person has a relatively unique set of normal flora, members of the Streptococcus and Bacteroides make up a large percentage of the inhabitants. These organisms contribute to our existence in several ways’ Dr.T.V.Rao MD 41
  42. 42. Normal Flora Help Us• Help us by competing with pathogens such as Salmonella• Help us by providing vitamins or eliminating toxins (e.g. Bacteroides)• Harm us by promoting disease (e.g. dental caries)• Cause neither help nor harm (e.g. "commensals"). Dr.T.V.Rao MD 42
  43. 43. Normal Bacterial Flora of Conjunctiva Dr.T.V.Rao MD 43
  44. 44. Cellular Factors in Innate Immunity• Metichinkoff 1883• Cells called as Phagocytic cells Microphages, MacrtophagesMicrophages Polymorphonuclear neutrophilsMacrophages Histiocytes wandering Amoeboid cellsMonocytes in BloodCells in Reticuloendothelial SystemThese cells remove foreign particles Dr.T.V.Rao MD 44
  45. 45. Role of phagocytes• Phagocytes are several types of white blood cells (including macrophages and neutrophils) that seek and destroy invaders. Some also destroy damaged body cells.• Phagocytes are attracted by an inflammatory response of damaged cells.
  46. 46. How Phagocytes act• Phagocytic cells reach the site o Inflammation• Attracted by Chemo tactic substances• Ingest particle material Dr.T.V.Rao MD 46
  47. 47. Dr.T.V.Rao MD 47
  48. 48. Capsule In Innate immunity• Some bacteria have capsules• Streptococcus pneumonia• Klebsiella pneumonia• Bacteria with capsules are not ingested by Phagocytes unless in the presence of opsonins• Bacteria are fixed against fixed surface such as alveoli Dr.T.V.Rao MD 48
  49. 49. Innate Host Defenses Against Infection• Anatomical barriers – Mechanical factors – Chemical factors – Biological factors• Humoral components – Complement – Coagulation system – Cytokines• Cellular components – Neutrophils – Monocytes and macrophages – NK cells – Eosinophils
  50. 50. Anatomical Barriers - Mechanical Factors System or Organ Cell type MechanismSkin Squamous epithelium Physical barrier DesquamationMucous Membranes Non-ciliated epithelium Peristalsis (e.g. GI tract) Ciliated epithelium (e.g. Mucociliary elevator respiratory tract) Epithelium (e.g. Flushing action of nasopharynx) tears, saliva, mucus, urine
  51. 51. Anatomical Barriers - Chemical Factors System or Organ Component MechanismSkin Sweat Anti-microbial fatty acidsMucous Membranes HCl (parietal cells) Low pH Tears and saliva Lysozyme and phospholipase A Defensins (respiratory & GI Antimicrobial tract) Sufactants (lung) Opsonin
  52. 52. Anatomical Barriers - Biological Factors System or Organ Component MechanismSkin and mucous Normal flora Antimicrobialmembranes substances Competition for nutrients and colonization
  53. 53. Humoral ComponentsComponent MechanismComplement Lysis of bacteria and some viruses Opsonin Increase in vascular permeability Recruitment and activation of phagocytic cellsCoagulation system Increase vascular permeability Recruitment of phagocytic cells Β-lysin from platelets – a cationic detergentLactoferrin and Compete with bacteria for irontransferrinLysozyme Breaks down bacterial cell wallsCytokines Various effects
  54. 54. Cellular ComponentsCell FunctionsNeutrophils Phagocytosis and intracellular killing Inflammation and tissue damageMacrophages Phagocytosis and intracellular killing Extracellular killing of infected or altered self targets Tissue repair Antigen presentation for specific immune responseNK and LAK cells Killing of virus-infected and altered self targetsEosinophils Killing of certain parasites
  55. 55. LeucocytesInnate immunity is mediated largely by GRANULOCYTESAdaptive immunity mediated by LYMPHOCYTESThe growth, development and activities of granulocytes andlymphocytes are interconnected and often co-operative.
  56. 56. Neutrophils• 60% of WBCs• ‘Patrol tissues’ as they squeeze out of the capillaries.• Large numbers are released during infections• Short lived – die after digesting bacteria• Dead neutrophils make up a large proportion of puss. Dr.T.V.Rao MD 57
  57. 57. Macrophages• Larger than neutrophils.• Found in the organs, not the blood.• Made in bone marrow as monocytes, called macrophages once they reach organs.• Long lived• Initiate immune responses as they display antigens from the pathogens to the lymphocytes. Dr.T.V.Rao MD 58
  58. 58. Mechanism of Phagocytosis• Bacteria are phagocycosed into vacuole (Phagosome)• Forms phagolysosome• Lytic enzymes destroy the Bacteria• Brucella and Leprosy Dr.T.V.Rao MD 59
  59. 59. Lymphocyte subsets*DC, *NK CLP T CELLS B CELLS Common lymphoid T precursor B Th CTL PC Activate B cells Kill virus- Produce antibodies and macrophages infected cells PLASMA CELLS T HELPER CELLS CYTOTOXIC T LYMPHOCYTES
  60. 60. Natural Killer cells NK cells Dr.T.V.Rao MD 61
  61. 61. Dr.T.V.Rao MD 62
  62. 62. 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 Dr.T.V.Rao MD 63
  63. 63. Role of inflammation• Inflammation is signaled by mast cells, which release histamine.• Histamine causes fluids to collect around an injury to dilute toxins. This causes swelling.• The temperature of the tissues may rise, which can kill temperature-sensitive microbes.
  64. 64. Inflammation• Tissue Injury• Irritation• Arterioles constrict initially and then dilate• Slow the Blood flow and Margi nation of Leucocytes• Escape into tissues by diapedesis and accumulate in large numbers Dr.T.V.Rao MD 66
  65. 65. Dr.T.V.Rao MD 67
  66. 66. Inflammation• Outpour plasma, and dilute the toxic material• Produce fibrin barrier and localized the infection Dr.T.V.Rao MD 68
  67. 67. Fever• Natural defense Mechanisms• Destroy infectious agents• Therapeutic – Trepanoma pallidum• Production of Interferons Dr.T.V.Rao MD 69
  68. 68. Acute Phase proteins• 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. Dr.T.V.Rao MD 70
  69. 69. Do not Forget to Immunise Your Child Dr.T.V.Rao MD 71
  70. 70. • Programme Created by Dr.T.V.Rao MD for Medical and Paramedical Students in the Developing World • Email • doctortvrao@gmail.com Dr.T.V.Rao MD 72

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