1. Topic 11.1 (and 6.3)

2. Blood Clotting When blood vessels get broken, blood is able to escape from the closed circulatory system and pathogens have a way to enter the body. To prevent excessive blood loss and the entry of pathogens, a clot will form to seal the damaged blood vessels.

3. Blood Clotting There are a few components in your blood that are important for blood clotting: 1) Prothrombin and Fibrinogen These are plasma proteins Always present in blood but inactive unless you start to bleed

4. Blood Clotting 2. Platelets Small, irregularly shaped blood cells made in bone marrow They start as large cells, and then break into many smaller fragments No nucleus Live only 8-10 days

5. Blood Clot 1) A cut occurs damaging a small blood vessel 2) Blood (including rbc, wbc, plasma proteins and platelets) will ooze out of the cut. 3) The damaged tissues will release chemicals that will cause platelets to adhere to each other and the damaged area causing a plug.

6. Blood Clot 4) The platelets and damaged tissue will release clotting factors which include the enzyme thrombokinase. 5) Thrombokinase will catalyze the conversion of prothrombin (a plasma protein) into the enzyme thrombin 6) Thrombin will catalyze the conversion of soluble fibrinogen (a plasma protein) into insoluble fibrin

7. Blood Clot FIBRIN: A fibrous protein which forms a mesh-like network that helps to stabilize the platelet plug 7. More cellular debris will become trapped in the fibrin mesh and a stable clot will form preventing further blood loss or the entry of pathogens http://www.pennmedicine.org/encyclopedia/em_Display Animation.aspx?gcid=000011&ptid=17

8. Blood Clotting Summary thrombokinase (enzyme release from damaged platelets) prothrombin thrombin (plasma protein) thrombin fibrinogen fibrin (plasma protein)

10. Lymphatic System The lymphatic system transports a watery, clear fluid known called lymph The lymph distributes leucocytes (wbc) and other factors throughout the body. It also interacts with the circulatory system to drain fluid from cells and tissues and remove foreign invaders and microorganisms. It contains lymphocytes that protect the body against antigens by producing antibodies

11. Lymph nodes are small ball-shaped organs throughout the body, and part of the lymphatic system. They become enlarged when there is an infection because an increase in T and B lymphocytes. http://www.pennmedicine.org/encyclopedia/em_Disp layAnimation.aspx?gcid=000083&ptid=17 http://www.pennmedicine.org/encyclopedia/em_Disp layAnimation.aspx?gcid=000083&ptid=17

13. The Immune Response & Antibody Production When a pathogen enters your body, the immune system will try to get rid of it. Remember, your leukocytes recognize cell surface proteins (antigens) and can determine if a cell is “self” or “not self “self”= body cell “not-self” = a foreign cell

15. (Remember, there are lots of different types of leukocytes.) The first type of leukocyte that will encounter a pathogen is usually a macrophage. The macrophage will ingest the pathogen through phagocytosis and partially digests it. The macrophage will take the antigens of the pathogen and display on its own cell membrane This is known as antigen presentation The macrophage will then go to the lymph nodes

16. In the lymph node, the macrophage will present the antigens to various types of helper-T cells (T H ) Helper-T cells are a types of lymphocytes A helper-T cell with receptors on its membrane that are complementary to the antigen will be selected. (They basically take an imprint of the antigen) These helper-T cells will undergo mitosis to make clones of itself.

17. The helper-T cells will then go to a B lymphocyte (also called a B cell) B lymphocytes make antibodies The B cell will identify the blueprint of the antigen and make antibodies against the antigen that can be released and attach to the antigens of the pathogen When a B cell is activated, it will also undergo mitosis to make clones of itself It will make plasma cells and memory cells

18. Types of B Lymphocytes Plasma cells (Plasma B cells): these cells will make antibodies immediately to fight off the current infection Memory Cell (Memory B Cells): These cells do not secrete antibodies during the 1 st infection. They are long-lived cells which will remain circulating in the bloodstream If the individual becomes infected with the same pathogen, the memory B cells will be ready to release antibodies against the pathogen

21. Note When the macrophage displays the antigens on its cell membrane, the antigens are attached to MHC proteins (major histocompatibility complex proteins) Helper T-cells will only respond to antigens attached to MHC proteins Cytotoxic T-cells or Killer T-Cells are another type of lymphocyte They recognize cells that have been invaded by pathogens and will destroy these cells.

22. http://www.pennmedicine.org/encyclopedia/em_DisplayAnimation.aspx?gcid=000073& ptid=17 http://www.pennmedicine.org/encyclopedia/em_DisplayAnimation.aspx?gcid=000073& ptid=17 http://highered.mheducation.com/sites/0072943696/student_view0/chapter14/animati on__t-cell_dependent_antigens__quiz_1_.html http://highered.mheducation.com/sites/0072943696/student_view0/chapter14/animati on__t-cell_dependent_antigens__quiz_1_.html http://highered.mheducation.com/sites/0072943696/student_view0/chapter14/animati on__the_immune_response.html http://highered.mheducation.com/sites/0072943696/student_view0/chapter14/animati on__the_immune_response.html Antigen formation (advanced) http://highered.mheducation.com/sites/0072943696/student_view0/chapter14/animati on__antigen_processing.html http://highered.mheducation.com/sites/0072943696/student_view0/chapter14/animati on__antigen_processing.html

23. Immunity Immunity depends upon the persistence of memory cells or the presence of antibodies for the antigens of the disease. Immunity develops when the immune system is challenged by a specific antigen and produces antibodies and memory cells in response.

24. Immunity ACTIVE IMMUNITY: Due to the production of antibodies by the organism itself after the introduction of antigens PASSIVE IMMUNITY: Due to the acquisition of antibodies from another organisms in which active immunity has be stimulated Ex: from mother to fetus via the placenta or breast milk Ex: the injection of antibodies (often used as treatment after a snake or spider bite)

25. Active Immunity can be….. NATURAL IMMUNITY: Antibodies are present because the individual naturally came into contact with the pathogen ARTIFICIAL IMMUNITY Antibodies are present because the individual was given a vaccine and introduced to a weak or dead form of the virus

26. Vaccination Vaccines can trigger immunity The secondary response to an antigen is must faster than the first response Vaccinations deliberately expose an individual to a weakened/dead/similar pathogen In this way, the individual can create memory B cells against the antigens of the pathogen and be prepared for an infection If the individual comes into contact with the pathogen after vaccination, they will have a faster immune response and will likely avoid illness

27. http://www.pennmedicine.org/encyclopedia/em_Disp layAnimation.aspx?gcid=000137&ptid=17 http://www.pennmedicine.org/encyclopedia/em_Disp layAnimation.aspx?gcid=000137&ptid=17

28. Benefits of Vaccinations Eradication of some diseases (e.g. small pox – which was the first infections disease of humans to have been eradicated by vaccination) Fewer people get the diseases (because already have the antibodies) Prevents disability and other effects of the pathogen Ex: polio can cause paralysis (no polio, no polio related paralysis) Herd immunity If many people in the population are vaccinated, the disease will not spread and there will be a decreased chance that someone who did not get the vaccine will contract it anyway

29. Dangers of Vaccination Overloading the immune system with antigens will reduce the ability to handle other infections Other pathogens could grow in the solution with the vaccine The vaccine could have other harmful substances (often added to increase shelf life of vaccine)

30. Artificial immunity is less effective Diseases avoided as a child are more serious as an adult Ex: chicken pox in adults can result in shingles Side Affects Can lead to allergic reactions and autoimmune responses

31. Monoclonal Antibody Production The primary immune response of an organism is called a polyclonal response. This is because the pathogen will have many type of antigens on its cells surface, not just one. So several kinds of plasma B cells will go under clonal selection to produce several kinds of antibodies After a polyclonal immune response, it is difficult to separate the different kinds of antibodies

32. Monoclonal Antibody Production How are monoclonal antibodies obtained? 1) A mammal (i.e. a mouse) is injected with a particular antigen 2) The mouse’s plasma B cells will produce antibodies against the antigen 3) The plasma B cells are extracted and fused with a B- cell tumour cell (a rapidly dividing B-Cell) to create a hybrid called “hybridoma cells” 4) Hybridoma cells grow in culture producing identical antibodies that can be collected

34. Uses of This Technology Blood Type Tests Pregnancy Tests Tests for diseases and infections

35. Ex: Pregnancy Tests Remember, when a woman is pregnant she secretes the (protein) hormone HCG (human chorionic gonadotropin) in her urine The antibodies for HCG can be fixed to a testing strip and attached to a dye.

36. Ex Pregnancy Tests The Test Strips Contain: (B) free moving antibodies for HCG which are attached to a dye. (C) immobilized antibodies that will bind to HCG (D) immobilized antibodies that will bind to dye bearing antibodies.

37. Ex: Pregnancy Tests If a woman is pregnant: She urinates on test strip. HCG in her urine attaches to the HCG antibodies (with dye) in test strip. The complex of “HCG- antibodies-dye” attach at both C and D, causing 2 lines to appear on the pregnancy test. (a positive result)

38. If the woman is not pregnant: There will be no HCG in her urine. So nothing will attach to the antibodies (with the dye) The antibodies will not attach to point C, but will attach at point D, creating 1 line to appear (a negative result)

39. Monoclonal Antibodies as Treatments When body cells become cancerous, they begin to produce specific antigens on their cell membrane A possible treatment for cancer is to produce monoclonal antibodies that target the cancer-cell antigens The antibodies could be modified to carry a toxin to those cells or a radioisotope to mark the cells for radiation therapy

40. Zoonosis Pathogens are usually specific to their hosts (remember they need the appropriate antigens to enter the host cells) There are viruses that are specific to birds, pigs, bacteria, humans. Ex: Tobacco Mosaic Virus, only affects tobacco plants.

41. Zoonosis Humans are the only known organism susceptible to pathogens such as syphilis, polio, and measles. A zoonosis is a pathogen which can cross a species barrier. Ex: west Nile virus, bird flu A major factor in the increased appearance of zoonotic disease is increased contact between humans and animals (particularly livestock)

42. Zoonosis Why is zoonosis troubling? Leads to an increase in the number of pathogens that could infect us (and other species) Leads to more biodiversity in pathogens which can make them harder to develop an immunity to.

43. Histamines Some white blood cells release the molecule histamine in response to an infection. Histamine causes the dilation of small blood vessels in the infected area. This will increase the flow of fluid containing immune components to the area. It also causes the blood vessels to become leaky

44. Histamines Histamine contributes to a number of symptoms of allergic reactions. Many cells have histamine receptors. Histamine plays a role in causing the symptoms of allergy in the nose (itching, fluid build up, sneezing, mucous secretion, inflammation)

46. Histamine also plays a role in the formation of allergic rashes Histamines can cause the dangerous swelling known as anaphylaxis Anti-histamines can lessen the affects of allergic responses.