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  1. 1. Immunology Basics Dr.T.V.Rao MD Dr.T.V.Rao MD 1
  2. 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) Dr.T.V.Rao MD 2
  3. 3. Dr.T.V.Rao MD 3
  4. 4. 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 4
  5. 5. 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 Dr.T.V.Rao MD 5 and molecules of the immune system
  6. 6. Role of the immune system• Defense against microbes• Defense against the growth of tumor cells – kills the growth of tumor cells• Homeostasis – destruction of abnormal or dead cells (e.g. dead red or white blood cells, antigen-antibody complex)
  7. 7. Viruses Role of the immune systemParasitesInfluenza is to protect from: TapewormsPolio mellitus Malaria Helminths Fungi Bacteria Candida albicans Tubercule bacillus Dr.T.V.Rao MD Staphylococci7
  8. 8. March towards modern times… War on smallpox… 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)Lady Mary WortleyMontague 1989- WHO announced (1689-1762) smallpox was eradicated from the world Dr.T.V.Rao MD 8
  9. 9. 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”) Dr.T.V.Rao MD 9
  10. 10. First insights into mechanics of immunity…Emil von Behring 1880’s- Metchnikoff discovered phagocytic cells that ingest S. Kitasato 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? Dr.T.V.Rao MD 10Elie Metchnikoff
  11. 11. 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 11
  12. 12. What is Response to Infection• Immunity can be Innate ( Nonadapative )• Adaptive - Acquired. Dr.T.V.Rao MD 12
  13. 13. Immunology is a Complex Subject Dr.T.V.Rao MD 13
  14. 14. Two types of immunity1. Innate (non-adaptive) – first line of immune response – relies on mechanisms that exist before infection2. Acquired (adaptive) – Second line of response (if innate fails) – relies on mechanisms that adapt after infection – handled by T- and B- lymphocytes Dr.T.V.Rao MD 14 – one cell determines one antigenic determinant
  15. 15. 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)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. The immune system Immune systemInnate (non-specific) immunity Adaptive (specific) immunity•Anatomic barriers (Skin, mucous •Antigen specificitymembranes) •Diversity•Physiological barriers •Immunological memory(temperature, pH) •Self/nonself recognition•Phagocytic Barriers (cells that eatinvaders)•Inflammatory barriers (redness,swelling, heat and pain) Dr.T.V.Rao MD 17
  18. 18. Dr.T.V.Rao MD 18
  19. 19. Different types of ImmunityA - Non specific 1 Species 2 Racial 3 IndividualB Specific 1.Species 2 Racial 3 Individual Dr.T.V.Rao MD 19
  20. 20. Types of Immunity Acquired ImmunityA Active Natural ArtificialB Passive Natural Artificial Dr.T.V.Rao MD 20
  21. 21. Resistance to Infectious Disease• Innate immunity (nonspecific resistance) protects us against all pathogens: “over-the-counter defenses”• Adaptive immunity (specific resistance) is defenses against specific pathogens: “prescription defenses”
  22. 22. Innate ImmunityInnate Immunity is resistance that ispreexisting and is not acquiredthrough contact with a foreignsubstance known as antigenIndividual has innate Immunity bygenetic or constitutional Make UpNon related to prior contact withMicroorganisms or Immunization Dr.T.V.Rao MD 22
  23. 23. Physical and Chemical Barriers • Skin, mucus membranes • Cilia, mucus, reflexes • pH, lysozyme, fatty acids, defensins • Normal flora • Genetic resistance – species differences – individual differences
  24. 24. 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 24
  25. 25. Race - Immunity• Genetic resistance Plasmodium falciparum malaria resistance in Africa• In sickle cell anemia immune to malaria Dr.T.V.Rao MD 25
  26. 26. Individual - Immunity• Twins homozygous twins exhibit similar resistance• Susceptibility similar in Leprosy• Tuberculosis similar resistance Dr.T.V.Rao MD 26
  27. 27. 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 27
  28. 28. Hormonal Influence on Immunity• Diabetes mellitus• Hypothyroidism in adults• Adrenal dysfunction• Stress increases steroids predisposes to Infection Dr.T.V.Rao MD 28
  29. 29. 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 29
  30. 30. Mucous Membranes• Respiratory tract Shape of Nose, Nasal orifice Dr.T.V.Rao MD 30
  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 31 pyogenic infections MD Dr.T.V.Rao
  32. 32. Respiratory tract barrier to prevent Infections• Cilia in Respiratory tract• Propel the foreign particles• Respiratory secretion contain Dr.T .V.Rao MD 32
  33. 33. Oral Cavity• Saliva• Stomach HCl• Large intestine large number of bacteria Dr.T.V.Rao MD 33
  34. 34. Conjunctiva• Contain lachrymal secretions• Tears contains antibacterial substances• Lysozyme present except in CSF, Sweat, Urine Dr.T.V.Rao MD 34
  35. 35. Other Mechanisms• Flushing action of urination drives out Microbes in the Urethra• Spermine in Semen Dr.T.V.Rao MD 35
  36. 36. Antibacterial Substances• May be present Blood as Complement• Antibacterial substances in Blood Betalysin, Leukin Lacto peroxidase in Milk Dr.T.V.Rao MD 36
  37. 37. 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 tumor cells. Interferons belong to the large class of glycoproteins known as cytokines• Interferons are more useful than Antibodies Dr.T.V.Rao MD 37
  38. 38. Microbial Antagonists Normal flora Help us• Normal Microbial flora Dr.T.V.Rao MD 38
  39. 39. Normal flora Helps 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 Bactericides make up a large percentage of the inhabitants. These organisms contribute to our existence in several ways’ Dr.T.V.Rao MD 39
  40. 40. Other Normal Flora• Streptococcus and Bactericides make up a large percentage of the inhabitants. These organisms contribute to our existence in several ways’• Help us by competing with pathogens such as Salmonella• Help us by providing vitamins or eliminating toxins (e.g. Bactericides)• Harm us by promoting disease (e.g. dental caries)• Cause neither help nor harm (e.g. "commensals"). Dr.T.V.Rao MD 40
  41. 41. Normal Bacterial Flora of Conjunctiva Dr.T.V.Rao MD 41
  42. 42. Cellular Factors in Innate Immunity• Metichinkoff 1883• Cells called as Phagocytic cells Microphages, MacrophagesMicrophages Polymorph nuclear neutrophilsMacrophages Histiocytes wandering Amoeboid cellsMonocytes in BloodCells in Reticuloendothelial SystemThese cells remove foreign particles Dr.T.V.Rao MD 42
  43. 43. Phagocytes• Phagocytes = eating cells –Neutrophils (PMNs) are present in the highest numbers in blood –Macrophages (“big eaters”) in the tissues encounter the pathogen first • Secrete cytokines ---> inflammation, systemic responses
  44. 44. How Phagocytes act• Phagocytic cells reach the site o Inflammation• Attracted by Chemo tactic substances• Ingest particle material Dr.T.V.Rao MD 44
  45. 45. Cellular and Inflammatory Components of Innate Immunity• Cellular –Phagocytic cells• Inflammatory –Vasodilation –Capillary permeability Dr.T.V.Rao MD 45
  46. 46. Dr.T.V.Rao MD 46
  47. 47. Phagocytosis
  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. Mechanism of Phagocytosis• Bacteria are phagocycosed into vacuole (Phagosome)• Forms phagolysosome• Lytic enzymes destroy the Bacteria• Brucella and Leprosy Dr.T.V.Rao MD 49
  50. 50. Natural Killer cells NK cells Dr.T.V.Rao MD 50
  51. 51. Mediators of inflammationVasodilation, smooth muscle contractionIncreased vascular permeabilityEdema, extravasation (histamines, prostaglandins, kinins)ExtravasationChemo taxis (cytokines, chemokines, complement)Systemic response- fever, acute-phaseproteins C-reactive protein
  52. 52. Interferon  and  Function
  53. 53. Anti-Viral Interferons• IFN and IFN made by virus- infected cells• Not virus-specific• Bind neighboring host cells and induce synthesis of anti- viral proteins to block virus replication
  54. 54. Natural Killer Cells• All nucleated cells in body have membrane MHC = tissue typing antigens• In virus-infected cells, MHC is reduced in amount or contains virus peptides• NK cells recognize this ‘altered’ MHC and kill virus-infected cells (also tumor cells)
  55. 55. 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 55
  56. 56. 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 56
  57. 57. Dr.T.V.Rao MD 57
  58. 58. Inflammation• Outpour plasma, and dilute the toxic material• Produce fibrin barrier and localized the infection Dr.T.V.Rao MD 58
  59. 59. Fever• Natural defense Mechanisms• Destroy infectious agents• Therapeutic – Trepanoma palladium• Production of Interferons Dr.T.V.Rao MD 59
  60. 60. Antibacterial substances in Blood and Tissues• The complement system possess bacterial activity and plays role in the bactericidal activity and destroys the pathogenic bacteria• Betalysin – anthrax• Leukins and Plakins• Lactic acid found in muscles• Lacto peroxidase in milk Dr.T.V.Rao MD 60
  61. 61. 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. Dr.T.V.Rao MD 61
  62. 62. 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 62
  63. 63. 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 Dr.T.V.Rao MD 63
  64. 64. 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, Dr.T.V.Rao MD produces antibodies) 64
  65. 65. Cell-mediated immune response1.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-self2. T-cell goes into effectors cells stage that is able to Dr.T.V.Rao MD 65 kill infected cells
  66. 66. Cell mediated immune responsePrimary response – production of specific clones of effector T cells and memory clones – develops in several days – does not limit the infectionSecondary response – more pronounced, faster – more effective at limiting the infectionExample - cytotoxic reactions against intracellular parasites, delayed hypersensitivity (e.g., Tuberculin test) and allograft rejection Dr.T.V.Rao MD 66
  67. 67. Humoral immune response1. B lymphocytes recognize specific antigens – proliferate and differentiate into antibody-secreting plasma cells2. Antibodies bind to specific antigens on microbes; destroy microbes via specific mechanisms3. Some B lymphocytes evolve into the resting state - memory cells Dr.T.V.Rao MD 67
  68. 68. Antibodies (immunoglobulins)•Belong to the gamma-globulinfraction of serum proteins•Y-shaped or T-shaped polypeptides – 2 identical heavy chains – 2 identical light chains• All immunoglobulins are notantibodies•Five kinds of antibodies – IgG, IgM, IgA, IgD, IgE
  69. 69. Measurement of Immunity• It is not possible to measure the immunity accurately• Detection of antibodies• Detected by agglutination tests, Precipitation tests, complement fixation HI ELISA• Skin Tests, Schick test , Dick Tests• Tuberculin Test – Delayed Hypersentivity tests in Tuberculosis MD Dr.T.V.Rao 69
  70. 70. Local Immunity• Can be produced by Oral Vaccines• Sabins vaccine for polio given orally X Salk will not protect Local Immunity but produces systemic Immunity• Locally produced Antibodies IgA protect the gut from entry of pathogens• Local immunity antigen protects the individuals Dr.T.V.Rao MD 70
  71. 71. Herd Immunity• This indicates the overall level in the community and important in control of infections in the community (HERD )• When Herd immunity is low epidemics occur.• Eradication of communicable diseases depends on the development of high level of herd immunity rather than high level of Individual Immunity Dr.T.V.Rao MD 71
  72. 72. • Programme Created byDr.T.V.Rao MD for Medical and Paramedical Students in the Developing World • Email • Dr.T.V.Rao MD 72