8 - Immunity: Defence Against Disease


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8 - Immunity: Defence Against Disease

  1. 1. IMMUNITY: defence against disease
  2. 2. What is the Immune System? <ul><li>Immunity is all about the body’s ability to distinguish “self” from “non-self” </li></ul><ul><li>Can be broadly separated in to ‘specific’ and ‘non-specific’ immunity. </li></ul>
  3. 3. Non-Specific Immunity <ul><li>First line of defence </li></ul><ul><ul><li>Prevention: barriers to foreign particles </li></ul></ul><ul><ul><ul><li>Skin (physical barrier including fats and salts) </li></ul></ul></ul><ul><ul><ul><li>Mucous membranes (in throat / nose) </li></ul></ul></ul><ul><ul><ul><li>Natural secretions (sweat, tears, stomach acid, milk, semen – all contain antimicrobial agents) </li></ul></ul></ul><ul><ul><ul><li>Natural flora (good bacteria) </li></ul></ul></ul>
  4. 4. Second line of defence <ul><li>Phagocytes and Killer Cells </li></ul><ul><li>… are white blood cells </li></ul><ul><li>Phagocyctes are produced in the bone marrow and move to the point of entry of the foreign article and engulf / destroy </li></ul><ul><ul><li>Neutrophils (most common WBC) </li></ul></ul><ul><ul><li>Monocytes (largest WBC) </li></ul></ul><ul><ul><ul><li>When leaving the blood, mature in to macrophages </li></ul></ul></ul><ul><ul><ul><li>Can target free-floating microorganisms </li></ul></ul></ul><ul><ul><ul><li>Will ingest and use some parts, excrete the rest </li></ul></ul></ul>
  5. 5. Second line of defence <ul><li>Natural Killer (NK) cells </li></ul><ul><li>… are also white blood cells </li></ul><ul><li>Target and destroy body cells that have been infected by viruses </li></ul><ul><li>Other white blood cells </li></ul><ul><li>Attach to and destroy multi-cellular pathogens that are too large to be engulfed </li></ul>
  6. 6. Second line of defence <ul><li>Complement </li></ul><ul><li>20 different types made in liver and circulate in an inactive state </li></ul><ul><li>Once 1 activated, the rest follow in a cascade </li></ul><ul><ul><li>Stick to invading micro-org and make identifiable to phagocytes </li></ul></ul><ul><ul><li>Stimulate phagocytes </li></ul></ul><ul><ul><li>Attract phagocytes to site of infection </li></ul></ul><ul><ul><li>Destroy membrane of micro-org </li></ul></ul>Animation
  7. 7. Second line of defence <ul><li>Interferon </li></ul><ul><li>An infected cell will release interferon that will stimulate the release of viral resistant proteins by nearby cells </li></ul><ul><li>Cytokines </li></ul><ul><li>Hormone-like (receptor specific) chemical messengers used by cells of the immune system </li></ul>
  8. 8. Second line of defence <ul><li>INFLAMMATION </li></ul><ul><li>Release of seratonin causes arterioles around cut to dilate to increase blood flow and become more permeable to p’cytes </li></ul><ul><li>P’cytes release histamine to attract more p’cytes </li></ul><ul><li>Clot forms to contain infection </li></ul><ul><li>Pus forms (living & dead WBCs and debris) </li></ul><ul><ul><li>Eventually re-absorbed by cells, excreted vi blood or secreted through skin </li></ul></ul>
  9. 9. Inflammation
  10. 10. Inflammation
  11. 11. Specific Immunity <ul><li>Third line of defence </li></ul><ul><li>Initiated by foreign particle entering body </li></ul><ul><li>Adaptive & acquired </li></ul><ul><li>Long lasting – often for life </li></ul><ul><li>Recognises, reacts & remembers </li></ul><ul><li>Reacts faster in future occurrences </li></ul>
  12. 12. Cells of the 3 rd Line <ul><li>Lymphocytes (WBCs produced in bone marrow) </li></ul><ul><ul><li>B Cells (mature in bone marrow) </li></ul></ul><ul><ul><ul><li>Plasma cells </li></ul></ul></ul><ul><ul><ul><li>Memory B cells </li></ul></ul></ul><ul><ul><li>T Cells (mature in thymus) </li></ul></ul><ul><ul><ul><li>Cytoxic T cells </li></ul></ul></ul><ul><ul><ul><li>T helper cells </li></ul></ul></ul>
  13. 13. Maturation of Lymphocytes
  14. 15. How B & T cells identify foreign material <ul><li>On the surface of every cell, genes code for the production of MHC (major histocompatibility proteins). </li></ul><ul><li>MHC distinguishes “self” from “non-self” </li></ul><ul><ul><li>MHC Class 1 (on all cells except RBCs) </li></ul></ul><ul><ul><li>MHC Class 2 (only on B & T cells and some macrophages) </li></ul></ul>
  15. 16. How B & T cells identify foreign material <ul><li>B & T cells display </li></ul><ul><ul><li>Their own antigens </li></ul></ul><ul><ul><li>Receptors for self </li></ul></ul><ul><ul><li>Receptors for non-self </li></ul></ul>
  16. 17. B cells and ‘Clonal Selection Theory’ <ul><li>B cells have immunoglobins (Ig) </li></ul><ul><li>on their surface </li></ul><ul><li>There are millions of different types of antigens and millions of different types of Igs. </li></ul><ul><li>When an Ig on a B cell interacts with an antigen it results in the proliferation of that type of B cell and its corresponding Ig </li></ul><ul><li>Effectively the antigen is determining what type of Ig becomes abundant in the body </li></ul>
  17. 18. Clonal Expansion <ul><li>After replicating some B cells mature in to antibody producing plasma cells and others mature in to memory B cells </li></ul>
  18. 19. How much antibody is produced? <ul><li>After the body has been exposed to a pathogen, on a subsequent exposure, memory B cells are able to produce large amounts of the specific antibody required, this is what we call immunity. </li></ul>There is no need for clonal expansion as a small amount of memory B cells are able to produce a large amount of antigen
  19. 20. Structure of an antibody <ul><li>4 polypeptide chains </li></ul><ul><li>Heavy chains joined to light by flexible hinges </li></ul><ul><li>Variable binding site </li></ul><ul><li>5 different types of antibodies (immunoglobins) </li></ul><ul><ul><li>IgG, IgD & IgE (1 molecule) </li></ul></ul><ul><ul><li>IgA (2 molecules) </li></ul></ul><ul><ul><li>IgM (5 molecules) </li></ul></ul>Heavy chains (long) Light chains (short) Hinge Antigen binding sites
  20. 21. Antibodies When faced with a virus each binding site can join to a different particle, thereby forming an antigen-antibody complex and deactivating the virus Bacteria are much larger than viruses, but a macrophage has a receptor site for the long-chain end of the antibody and can engulf the entire antibody-antigen complex
  21. 22. T cells <ul><li>B cells are produced in the bone marrow but mature in the thymus. </li></ul><ul><li>Similar to B cells, the body produces millions of varieties of T cells </li></ul><ul><li>When a pathogen is encountered, the T cells with the corresponding binding site will proliferate. </li></ul><ul><li>T cells do not produce antibodies – with phagocytes they form the body’s cellular immunity. </li></ul>
  22. 23. Helper T cells (Th) <ul><li>After ingesting a pathogen, a phagocyte will use an MHC class 2 to display the antigenic protein on its surface </li></ul><ul><li>A helper T cell will the appropriate receptor site will bind to the phagocyte and stimulate the proliferation of B cells </li></ul>
  23. 24. Cytotoxic T cells (Tc) <ul><li>Uses MHC class 1 & 2 molecules to identify whether a cell contains any ‘non-self’ proteins </li></ul><ul><li>Destroys cells via proteins that punch holes in the cell membrane </li></ul><ul><li>Will ideally destroy a cell before a the contained virus can replicate </li></ul><ul><li>Can’t kill free-floating virus particles (non-cellular agents) </li></ul>
  24. 25. Movement of B & T Cells <ul><li>Organs connected by lymphatic vessels </li></ul><ul><li>Memory B & T cells circulate in lymph </li></ul><ul><li>Antigens attacked on site of carried to lymph node </li></ul><ul><li>Swelling of lymph node caused by B Cell expansion </li></ul>
  25. 26. Acquiring Specific Immunity <ul><li>Active Immunity </li></ul><ul><ul><li>Natural (B & T cell proliferation in response to antigen) </li></ul></ul><ul><ul><li>Induced (Immune response triggered by induced antigen </li></ul></ul><ul><ul><ul><li>A dead microorganism </li></ul></ul></ul><ul><ul><ul><li>Attenuated (unable to reproduce) microorganism </li></ul></ul></ul><ul><ul><ul><li>Toxoid (artificial low-dose toxin) </li></ul></ul></ul><ul><ul><ul><ul><li>Booster shot on any of the above may be required to maintain immunity (maintain levels of B & T memory cells in lymph) </li></ul></ul></ul></ul><ul><li>Passive Immunity </li></ul><ul><ul><li>Natural (mother to foetus / breastfeeding baby) </li></ul></ul><ul><ul><li>Induced (administered antibiotic) </li></ul></ul>
  26. 27. Passive Immunity <ul><li>Called passive as the antibodies are not made by user </li></ul><ul><li>An advantage is that the user receives a lot of antibodies in a very short space of time </li></ul><ul><li>A disadvantage is that the immunity is temporary as no memory cells are created </li></ul>
  27. 28. Summary of Acquired Immunity
  28. 29. Monoclonal antibody production <ul><li>Snake antivenom is produced in rabbits </li></ul><ul><li>Rabbit is injected with very small dose of venom to produce immune response </li></ul><ul><li>Doses of venom gradually increased </li></ul><ul><li>Blood harvested, antibodies isolated </li></ul><ul><li>Rabbit makes more blood with more antibodies </li></ul>
  29. 30. Immunity – what can go wrong? <ul><li>Allergies </li></ul><ul><ul><li>Histamine is usually released by mast cells to attract more phagocytes to an infected area </li></ul></ul><ul><ul><li>If IgE is produced against an antigen it can bind to mast cells </li></ul></ul><ul><ul><li>Upon re-exposure to the allergen, large amounts of histamine can be released, resulting in: </li></ul></ul><ul><ul><ul><li>Capillary dilation </li></ul></ul></ul><ul><ul><ul><li>Airway constriction </li></ul></ul></ul><ul><ul><ul><li>Mucous secretion </li></ul></ul></ul><ul><ul><ul><li>Pain </li></ul></ul></ul><ul><ul><ul><li>Itching </li></ul></ul></ul>Facilitates movement of phagocytes in to area Symptoms of the above
  30. 31. Rh Incompatibility <ul><li>Human blood cells have certain marker proteins that belong to either the ABO or Rhesus (Rh) blood group </li></ul><ul><li>Rh is inherited as a dominant allele, so </li></ul><ul><ul><li>Rh + Rh + or Rh + Rh - = Rh positive </li></ul></ul><ul><ul><li>Rh - Rh - = Rh negative </li></ul></ul><ul><li>So an Rh - mother can still have an Rh + child due to the father’s genotype </li></ul>
  31. 32. Rh Incompatibility <ul><li>During the first pregnancy, at birth the placenta will detach from the uterine wall and the foetal blood will cause the mother to create Rh antibodies </li></ul><ul><li>During the second pregnancy the mother’s T helper cells will produce antibodies that will cross the placenta and attack the foetus’ RBCs and organs </li></ul><ul><ul><li>Resulting in haemolytic disease of the newborn </li></ul></ul><ul><ul><li>If untreated, effect will worsen with each subsequent pregnancy </li></ul></ul>
  32. 33. Rh Incompatibility <ul><li>Treatment </li></ul><ul><ul><li>If, after the first pregnancy the mother gets a large dose of Rh antibodies, she will not have an immune reaction </li></ul></ul><ul><ul><li>Therefore no memory B cells will be present to cause complications in subsequent preganancies </li></ul></ul><ul><li>Other mother-foetus incompatibilities </li></ul><ul><ul><li>Blocking factor in the maternal serum will inhibit production of antibodies against foetal antiges </li></ul></ul><ul><ul><li>Placental cells will absorb small amounts of antibody </li></ul></ul>
  33. 34. Auto-immune diseases <ul><li>Breakdown of ability to distinguish ‘self ‘from ‘non-self’ </li></ul><ul><li>B & T cells attack and destroy own body cells </li></ul><ul><li>eg. Multiple sclerosis (MS), approx 1:1000 </li></ul><ul><ul><li>Immune system attacks own myelin sheath </li></ul></ul><ul><ul><li>Results in short-circuits in the CNS and impaired communication between CNS and PNS </li></ul></ul><ul><ul><li>Sites of damage can vary so symptoms differ </li></ul></ul><ul><ul><li>Damage from initial attack/s can be repaired </li></ul></ul><ul><ul><li>As more attacks occur scarring (plaques) build up </li></ul></ul><ul><ul><li>Once this occurs damage can’t be reversed </li></ul></ul><ul><ul><li>Disease is progressive in nature </li></ul></ul>
  34. 35. Multiple Sclerosis <ul><li>Diagnosis </li></ul><ul><ul><li>Originally had to be done via observations </li></ul></ul><ul><ul><li>Now an MRI can be used to find areas of brain with higher water content (plaques) </li></ul></ul><ul><li>Cause </li></ul><ul><ul><li>Unknown but possibly linked to a viruses which have proteins very simillar to our myelin proteins. Once the immune system disposes if it,, it continues to attack myelin sheath </li></ul></ul><ul><ul><li>Strong linkage with people living in colder climates </li></ul></ul><ul><li>Treatment </li></ul><ul><ul><li>Nothing very effective </li></ul></ul><ul><ul><li>Cortisone & B interferon can cause mild temporary improvement </li></ul></ul>
  35. 36. Rejection of Organ Transplant <ul><li>Only identical twins can be a perfect match </li></ul><ul><li>Recipient and donor typed to match as closely as possible </li></ul><ul><li>Helper T cells are the main immune cell responsible for transplant rejection </li></ul><ul><li>Recipient must take cyclosporin (a helper T cell inhibitor) for the rest of their lives to prevent rejection </li></ul>
  36. 37. Immune Deficiency Disease (IDD) <ul><li>Immune system is immature at birth </li></ul><ul><li>Once maternal antibodies from placenta and breast milk wear off, baby is exposed </li></ul><ul><li>If immune system dysfunctional, death will occur not long afterwards </li></ul><ul><li>People can be sustained through the donation of bone marrow (where immune cells are produced) </li></ul><ul><li>Donor and recipient must be typed on ABO, Rh and a number of other MHCs </li></ul>
  37. 38. Acquired Immune Deficiency Syndrome (AIDS) <ul><li>Caused by the Human Immunodeficiency Virus (HIV) </li></ul><ul><li>Infects only Helper T Cells and macrophages </li></ul><ul><li>Victims will usually die of a disease or infection that their body could not fight off </li></ul><ul><li>HIV can lay dormant for years </li></ul><ul><li>Death will usually follow onset of “full-blown” AIDS </li></ul><ul><li>Drugs that affect the membrane lipid bilayer of the virus can delay death </li></ul>
  38. 39. HIV / AIDS Virus Disruption of HIV-1 lipid surface
  39. 40. Plants <ul><li>Plants have no true immune system </li></ul><ul><li>Resistance to infectious agents has evolved through natural selection </li></ul><ul><li>Plants have mechanical barriers to infection </li></ul><ul><ul><li>Cuticle and epidermal cells form barrier </li></ul></ul><ul><ul><li>Infection will often enter through stomata </li></ul></ul><ul><li>Plants have chemical barriers to infection </li></ul><ul><ul><li>Citrus and mint plants produce oils </li></ul></ul><ul><ul><li>Stone fruit plants seal off infection site with “gum’ </li></ul></ul><ul><ul><li>Other plants have resins, tanins and phenolic substances </li></ul></ul>