1. THE IMMUNE SYSTEM Topic 6.3, 11.1

2. Specific & non-specific immunity Non-specific = general response to pathogens Specific = production of specific antibodies in response to a specific antigen PATHOGEN: living organism or virus that invades the body and causes disease (bacteria, viruses, protozoa, parasites, fungi)

3. First Stages in fighting infection First line of defense: Skin, Mucous Membranes (enzymes in mucous) Blood Clotting – if skin cut, skin is quickly sealed by blood clots Platelets release clotting factors Prothrombin  thrombin  fibrinogen  fibrin Why inactive until skin is cut?

4. Blood Cells

5. 2 nd Line of Defense: Phagocytes Produced throughout life by the bone marrow. Scavengers – remove dead cells and microorganisms. Non-Specific Immune Response – phagocytes respond the same way no matter what type of pathogen

6. Macrophages 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.

7. Macrophages

8. Phagocytosis

9. Lymphocytes Produce antibodies B-cells mature in bone marrow then concentrate in lymph nodes and spleen T-cells mature in thymus B and T cells mature then circulate in the blood and lymph Circulation ensures they come into contact with pathogens and each other

10. 3 rd line of defense: Specific Immunity & Antibody Production Antigen: Protein found in membrane or cell wall of a pathogen that enables the body to recognize the pathogen Antibody: Protein molecule produced by lymphocytes in response to antigens

11. B -Lymphocytes There are 10 million different B- lymphocytes, each of which make a different antibody. The huge variety is caused by genes coding for abs changing slightly during development. There are a small group of clones of each type of B-lymphocyte

12. B -Lymphocytes At the clone stage antibodies do not leave the B- cells. The abs are embedded in the plasma membrane of the cell and are called antibody receptors. When the receptors in the membrane recognise an antigen on the surface of the pathogen the B- cell divides rapidly. The antigens are presented to the B-cells by macrophages

13. B -Lymphocytes

14. Some activated B cells  PLASMA CELLSthese produce lots of antibodies, < 1000/sec The antibodies travel to the blood, lymph, lining of gut and lungs. The number of plasma cells goes down after a few weeks Antibodies stay in the blood longer but eventually their numbers go down too.

15. B -Lymphocytes Some activated B cells  MEMORY CELLS. Memory cells divide rapidly as soon as the antigen is reintroduced. There are many more memory cells than there were clone cells. When the pathogen/infection infects again it is destroyed before any symptoms show.

17. Antibodies Also known as immunoglobulins Globular glycoproteins The heavy and light chains are polypeptides The chains are held together by disulphide bridges Each ab has 2 identical ag binding sites – variable regions. The order of amino acids in the variable region determines the shape of the binding site

18. How Abs work Some act as labels to identify antigens for phagocytes Some work as antitoxins i.e. they block toxins for e.g. those causing diphtheria and tetanus Some attach to bacterial flagella making them less active and easier for phagocytes to engulf Some cause agglutination (clumping together) of bacteria making them less likely to spread

19. T-Lymphocytes Mature T-cells have T cell receptors which have a very similar structure to antibodies and are specific to 1 antigen. They are activated when the receptor comes into contact with the Ag with another host cell (e.g. on a macrophage membrane or an invaded body cell)

20. T-Lymphocytes After activation the cell divides to form: T-helper cells – secrete CYTOKINES  help B cells divide  stimulate macrophages Cytotoxic T cells (killer T cells)  Kill body cells displaying antigen Memory T cells  remain in body

23. Lymphocyte coordination Pathogens consumed by phagocytes which display antigen proteins Helper T Cells are activated – receptors that match the antigens bind to the macrophage Activated Helper T cells bind B cells with matching protein B Cell Clonal Expansion – produce and secrete antibodies (some memory cells) Antibodies destroy pathogen; memory cells remain in circulation for future exposure

24. Hybridomas Fusion of tumor cell with an antibody producing cell Immortality of a tumor cell but produces useful antibodies for therapy and diagnosis Grown in a fermenter and release large amounts of monoclonal antibodies –For disease diagnosis – ELISA test for HIV –In pregnancy tests – HCG binding –New cancer treatments – cytotoxic drug delivery

25. Active and Passive Immunity Active immunity Lymphocytes are activated by antigens on the surface of pathogens Natural active immunity - acquired due to infection Artificial active immunity – vaccination Takes time for enough B and T cells to be produced to mount an effective response.

26. Active and Passive Immunity Passive immunity B and T cells are not activated and plasma cells have not produced antibodies. The antigen doesn’t have to be encountered for the body to make the antibodies. Antibodies appear immediately in blood but protection is only temporary.

27. Active and Passive Immunity Artificial passive immunity Used when a very rapid immune response is needed e.g. after infection with tetanus. Human antibodies are injected. In the case of tetanus these are antitoxin antibodies. Antibodies come from blood donors who have recently had the tetanus vaccination. Only provides short term protection as abs destroyed by phagocytes in spleen and liver.

28. Active and Passive Immunity Natural passive immunity A mother’s antibodies pass across the placenta to the foetus and remain for several months. Colostrum (the first breast milk) contains lots of IgA which remain on surface of the baby’s gut wall and pass into blood

29. HIV & AIDS Human immunodeficiency virus = retrovirus that infects Helper T cells Uses RNA transcriptase to convert RNA to DNA and insert its genes into helper T cells so that even if all the virus is stopped in the body, infected helper T cells continue making new copies.

30. HIV & AIDS Acquired Immune Deficiency Syndrome = Helper T cells not functioning, then not making antibodies so can’t fight off infection Secondary infections (opportunistic pathogens) results in failure of the immune system – syndrome known as AIDS

31. HIV & AIDS Transmission: person to person in blood, vaginal secretions, semen, breast milk Most common through sexual contact and non-sterile syringe needles used to administer legal or illegal drugs

32. Antibiotics Kill or block the growth of BACTERIA –Block protein synthesis in bacteria –Prevent bacteria from producing a cell wall when they divide –Rupture bacteria cell membranes –Inhibit bacterial enzymes Penicillin – 1928 WHY WON’T THEY KILL VIRUSES?

33. Antibiotic Resistance Resistant forms survive and pass on resistance to other bacteria through plasmids when reproducing Increased risk with increased antibiotic use Over-prescribed antibiotics HOW CAN ANTIBIOTIC RESISTANCE BE PREVENTED?

34. Histamines Nitrogen containing molecule released in response to infection Causes dilation of blood vessels that become leaky so plasma escapes into surrounding tissue, causes swelling Itching or pain, fever common Allergic reactions – histamine can lead to excessive immune responses – sneezing, increased secretion of mucous, inflammation (asthma, hay fever, eczema)

35. Vaccination Contains antigen such as dead or Weakened pathogens or their toxins

36. Vaccination Injection into vein or muscle Oral

37. Vaccination Memory cells allow large amounts of antibodies to be produced very quickly if pathogen enters body again Vaccines used to raise the level of antibodies and memory cells so a person develops immunity and is protected from the disease without having to suffer from it