Immune System


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Immune System

  2. 2. The Immune System <ul><li>Recall the components of blood </li></ul><ul><li>Recall what is a pathogen </li></ul><ul><li>Recall the function of the skin </li></ul>
  3. 3. Two types of immune response <ul><li>Non-specific </li></ul><ul><ul><li>External </li></ul></ul><ul><ul><ul><li>E.g. Skin, mucus, tears </li></ul></ul></ul><ul><ul><li>Internal </li></ul></ul><ul><ul><ul><li>Phagocytic cells, antimicrobial proteins, inflammatory response </li></ul></ul></ul><ul><li>Specific </li></ul><ul><ul><li>E.g. lymphocytes, antibodies </li></ul></ul>
  4. 4. Innate immunity <ul><li>Plants and animals have mechanisms that target a wide range of pathogens </li></ul>
  5. 6. Skin and the mucus membrane as the first line of defense <ul><li>Imagine a body without a skin </li></ul><ul><ul><li>First, it is gross </li></ul></ul><ul><ul><li>Secondly, it is not protected against invading pathogens </li></ul></ul><ul><ul><li>Epithelial lining makes a good barrier against pathogens </li></ul></ul><ul><li>Mucus membrane lines the digestive, respiratory and genitourinary tracts </li></ul>
  6. 7. The skin <ul><li>Not only function as a barrier </li></ul><ul><li>Secretions from sebaceous(oil) and sweat glands make it acidic </li></ul><ul><ul><li>pH range of 3-5 </li></ul></ul><ul><ul><li>Most bacteria cannot live in an acidic environment </li></ul></ul><ul><ul><li>Normal flora are adapted to this kind of environment </li></ul></ul>
  7. 8. Mucus and other substances <ul><li>Mucus, saliva, tears- washes pathogens that might enter the body </li></ul><ul><ul><li>Antimicrobial proteins are also present </li></ul></ul><ul><li>Lysozyme- destroys cell wall of bacteria </li></ul><ul><ul><li>Destroys bacteria that might enter through the respiratory tract or around the eyes </li></ul></ul>
  8. 9. Mucus and other substances <ul><li>Mucus- traps some microbes </li></ul><ul><ul><li>Is moved by the beating cilia in the respiratory tract </li></ul></ul><ul><li>Bacteria in mucus that is swallowed is destroyed in the stomach </li></ul><ul><ul><li>Hepatitis A can live in acidic environment </li></ul></ul>
  9. 10. Cilia
  10. 11. Phagocytic cells, inflammation, antimicrobial proteins <ul><li>When an opening occurs in the skin through abrasion or wound the second line of defense is activated </li></ul><ul><li>Phagocytosis is the main mechanism employed by the body </li></ul><ul><li>Phagocytosis- synergistic with inflammation and antimicrobial protein response </li></ul>
  11. 12. Phagocytic cells and natural killer cells <ul><li>Mostly made up of neutrophils (60-70%) </li></ul><ul><ul><li>Damaged cells release chemical signals that attract neutrophils </li></ul></ul><ul><ul><li>Engulfs damaged cell (neutrophils are also destroyed) </li></ul></ul><ul><li>Monocytes 5% of WBC </li></ul><ul><ul><li>Become macrophages </li></ul></ul><ul><ul><li>Long-lived cells </li></ul></ul><ul><ul><li>Engulfs cell to form vacuoles that fuse with lysozymes (lysosomes) </li></ul></ul>
  12. 13. Macrophage engulfing two RBC <ul><li>Two actions of macrophage: </li></ul><ul><li>Through toxic forms of O2 </li></ul><ul><li>-superoxide anion </li></ul><ul><li>-nitric oxide </li></ul><ul><li>Use of lysozyme </li></ul>
  13. 14. Resistant bacteria towards lysosomal destruction <ul><li>Mycobacterium tuberculosis </li></ul><ul><ul><li>Resistant to lysosomal destruction </li></ul></ul><ul><ul><li>Can even proliferate inside the macrophage </li></ul></ul>
  14. 15. Specific Macrophages <ul><li>Lung- alveolar macrophage </li></ul><ul><li>Liver- Kupffer’s cells </li></ul><ul><li>Kidney- mesengial cells </li></ul><ul><li>Brain-microglial cells </li></ul><ul><li>Connective tissue-histiocytes </li></ul>
  15. 16. Still on the types of leukocytes..... <ul><li>Eosinophil- make up 1.5 % of all WBC </li></ul><ul><ul><li>Action is on parasites (e.g. vermiform such as Schistosoma mansoni) </li></ul></ul><ul><ul><li>discharge destructive enzyme from their cytoplasmic granules on the external wall of parasites </li></ul></ul><ul><ul><li>Other non-specific defense </li></ul></ul><ul><li>Natural killers cells (NK cells)- do not attact pathogens directly </li></ul><ul><ul><li>Destroy infected cell as well as abnormal body cells </li></ul></ul><ul><ul><li>do not engulf cells, rather lyse infected cells </li></ul></ul>
  16. 17. Schistosoma mansoni
  17. 19. The lymphatic system
  18. 20. The inflammatory response <ul><li>Injured area: precapillary arteriole dilates; postcapillary venule constrict- WHY? </li></ul>
  19. 21. The inflammatory response <ul><li>To increase blood supply- so what? </li></ul><ul><li>This in turn will lead to edema </li></ul>
  20. 22. The inflammatory response <ul><li>Inflammatory response may be caused by the following: </li></ul><ul><ul><li>From the pathogen itself </li></ul></ul><ul><ul><li>Histamines released by the body (from basophils and mast cells) </li></ul></ul><ul><ul><li>Prostaglandins (dilate/constrict BV or aggregate/disaggregate clotting factors) </li></ul></ul>
  21. 23. Phagocytosis during inflammatory response <ul><li>Phagocytosis begins an hour after an injury occurred </li></ul><ul><li>Phagocytic cells move in the area through the increased permeability of the BV </li></ul><ul><li>Attracted to chemotactic factors released by the pathogens </li></ul><ul><li>Chemokines released by endothelial cells, monocytes can also attract phagocytic cells </li></ul>
  22. 24. Chemokines <ul><li>Bind to receptors of different leukocytes </li></ul><ul><ul><li>E.g. Induce toxic form of oxygen in lysosome </li></ul></ul><ul><ul><li>Release of histamine from basophil </li></ul></ul>
  23. 25. Sequence of events.... <ul><li>After inflammation, phagocytic cells arrive on the scene </li></ul><ul><ul><li>Neutrophils arrive first, followed by macrophages </li></ul></ul><ul><ul><li>Macrophage- engulfs pathogens and other debris </li></ul></ul><ul><ul><li>Pus- made up of dead phagocytic cells, fluid and proteins that leaked from the BV </li></ul></ul>
  24. 26. Severe infection <ul><li>Fever is an immune response to severe infection </li></ul><ul><ul><li>Can be caused by the pathogens </li></ul></ul><ul><ul><li>May be due to pyrogens released by some leukocytes </li></ul></ul><ul><ul><li>Can facilitate phagocytosis </li></ul></ul><ul><ul><li>Septic shock- high fever, hypotension </li></ul></ul>
  25. 27. Antimicrobial proteins <ul><li>Proteins that attack microbes or stall reproduction of microbes </li></ul><ul><li>Lysozyme is an example </li></ul><ul><li>Also, presence of the complement system </li></ul><ul><ul><li>Made up of 20 serum proteins </li></ul></ul><ul><ul><li>Action: lysis or attraction of phagocytic cells </li></ul></ul><ul><ul><li>Is also part of specific immune response </li></ul></ul>
  26. 28. Antimicrobial proteins <ul><li>Interferons </li></ul><ul><ul><li>Secreted by virus-infected cells </li></ul></ul><ul><ul><li>Neighboring cells are stimulated to produce chemicals that can inhibit viral infection </li></ul></ul><ul><ul><li>Not virus-specific </li></ul></ul><ul><ul><li>A specific type of interferon activates phagocytes </li></ul></ul>
  27. 29. Self vs Non-self <ul><li>Self recognition is important in an immune response </li></ul><ul><li>Presence of receptors/markers in pathogens that enter the body </li></ul><ul><li>Very efficient, even undigested proteins are considered as antigens </li></ul>
  28. 30. Self vs Non-self <ul><li>Lymphocytes react on special surface glycoproteins encoded by genes called Major Histocompatibilty Complex (MHC) </li></ul><ul><li>In Humans, Human Leukocyte Antigens (HLA) </li></ul><ul><li>Class I MHC- Almost all nucleated cells </li></ul><ul><li>Class II MHC- macrophages, B cells, activated T cells, cell in the interior of the thymus </li></ul><ul><li>Varies from one person to another </li></ul>
  29. 31. Invertebrate immunity <ul><li>Self and non-self is also exhibited by invertebrates starting from sponges </li></ul><ul><li>Cells of different sponge species if mixed sort themselves and reaggregate </li></ul><ul><li>Coelomocytes- phagocytic cells in sea stars </li></ul><ul><li>Cytokines are also present </li></ul><ul><ul><li>E.g. Coelomocytes produce interleukin-1 that enables proliferation of coelomocytes </li></ul></ul>
  30. 32. coelomocytes Sea urchin coelomocyte Coelomocytes from Placobdella
  31. 33. More on invertebrate immunity <ul><li>Makes use of innate, non-specific rather than active </li></ul><ul><li>Exception is the hemolin protein in the hemolymph of insects </li></ul><ul><li>Hemolin acts like vertebrate lymphocyte </li></ul><ul><li>Hemolin belongs to the immunoglobulin superfamily </li></ul>
  32. 34. Absence of immunological memory <ul><li>Memory cells of vertebrates increase the immunological response of the body towards a pathogen </li></ul><ul><li>Coelomocytes do not possess this trait </li></ul><ul><li>Another exception: the earthworms </li></ul><ul><ul><li>First graft is rejected for two weeks </li></ul></ul><ul><ul><li>Second graft is rejected in about a week </li></ul></ul>
  33. 35. Active immunity vs Passive immunity <ul><li>Active immunity- immunity through recovery from a disease </li></ul><ul><ul><li>Natural or artificial </li></ul></ul><ul><li>Passive immunity- immunity passed by another individual </li></ul><ul><ul><li>short-lived </li></ul></ul>
  34. 36. Specific immunity: the third line of defense <ul><li>Lymphocytes- cells responsible for the specific immune response </li></ul><ul><li>There are two types: B cells and T cells </li></ul><ul><li>Antigen- molecules that elicit specific response from lymphocyte </li></ul><ul><ul><li>E.g. Molecules from bacteria, fungi, virus, parasitic worms </li></ul></ul><ul><li>Antigens activate B cell in producing antibodies </li></ul>
  35. 38. Recognition of antigens by B cells and T cells <ul><li>Specificity is possible because membrane-bound antigen receptor </li></ul><ul><li>B cell antigen receptor- transmembrane version of antibodies </li></ul><ul><ul><li>Also called membrane antibodies </li></ul></ul><ul><li>T cell antigen receptor- called T cell receptor </li></ul><ul><ul><li>Structurally related to membrane antibodies </li></ul></ul><ul><ul><li>T cell receptor never released in secreted form </li></ul></ul>
  36. 39. Clonal selection <ul><li>Antigen binds to a specific antigen receptor (B cell) </li></ul><ul><li>B cell produce its clone </li></ul><ul><li>Some B cells become plasma cells (short-lived) that can secrete antibodies to the specific antigen </li></ul><ul><ul><li>Plasma cells- also called effector cells </li></ul></ul><ul><li>Some B cells become memory cells (long-lived) for re-exposure to the antigen </li></ul>
  37. 40. Immunological memory <ul><li>Primary immune response- selective proliferation and differentiation of lymphocytes upon first exposure </li></ul><ul><ul><li>10-17 days to develop maximum effector cells </li></ul></ul><ul><ul><li>Selected B cells and T cells produce their respective effector cells </li></ul></ul>
  38. 41. Immunological memory <ul><li>Secondary immune response- re-exposure to the same antigen </li></ul><ul><ul><li>response is faster, greater magnitude, more prolonged </li></ul></ul><ul><ul><li>Also, more antibodies are produced </li></ul></ul><ul><ul><li>Antibodies have greater affinity to the antigens </li></ul></ul><ul><ul><li>Secondary response is called immunological memory </li></ul></ul>
  39. 42. Graph showing immunological memory
  40. 43. Lymphocyte development <ul><li>All blood cells develop from pluripotent cells </li></ul><ul><li>Lymphocytes also develop from pluripotent cells </li></ul><ul><li>T cells- mature in the thymus </li></ul><ul><li>B cells- mature in the bone marrow </li></ul>
  41. 44. Immune tolerance for self <ul><li>Maturing lymphocytes’ antigen receptors are rendered non-functional </li></ul><ul><li>If antigen receptors cannot be switched off, lymphocytes undergo apoptosis </li></ul>
  42. 45. The other cells.... <ul><li>Cytotoxic T cells- kills cells through lysis </li></ul><ul><li>Helper T cells- bind to antigen cell and secretes cytokine </li></ul><ul><li>Antigen-presenting cells (APCs)- engulfs bacteria (virus) and presents fragment of these pathogens to other lymphocytes </li></ul>
  43. 46. Humoral response and cell-mediated response <ul><li>Humoral immunity- involves B cell activation, production of antibodies in blood plasma and lymph called humor </li></ul><ul><li>Cell-mediated immunity- action of T cells </li></ul>
  44. 47. Overview of humoral response <ul><li>Macrophage engulfs the pathogen </li></ul><ul><li>Class II MHC binds to fragment of pathogen </li></ul><ul><li>MHC-antigen complex is presented by the phagocytic cell </li></ul><ul><li>A helper T cell with specific receptor for the antigen makes contact with the macrophage and releases cytokines </li></ul>
  45. 48. Overview of humoral response <ul><li>Activated T cell presents the antigen to a B cell </li></ul><ul><li>Cytokines activates the B cell </li></ul><ul><li>Activated B cells differentiate into plasma and memory cells </li></ul><ul><li>Plasma cells will produce the specific antibodies </li></ul>
  46. 49. Cell-mediated immune response <ul><li>Occurs when antigen displayed by APC activates Cytotoxic T cell </li></ul><ul><li>Cytotoxic cell can differentiate to Memory T cells or active cytotoxic T cells </li></ul><ul><li>Active against cancer cells and pathogens </li></ul><ul><li>Kills these cell through lysis </li></ul>
  47. 50. Antibodies <ul><li>Do not destroy antigens directly </li></ul><ul><li>Rather, neutralizes it or present it as a target for opsonization, agglutination, precipitation, or complement fixation, neutralization </li></ul>
  48. 51. Antibodies <ul><li>Opsonization- coating of antigens by antibodies to facilitate phagocytos </li></ul><ul><li>Neutralization- binds to the antigen and inactivates it </li></ul><ul><li>Agglutination- clumping of bacteria or virus to effectively neutralize or opsonize it </li></ul><ul><li>Complement fixation or precipitation- immune adherence occurs </li></ul><ul><ul><li>Microbes coated with antibodies and complement proteins adhere to BV walls </li></ul></ul>