1. Unit 4 – Immunology and Public Health Specific cellular defences

2. Learning Intention: To learn about the immune system and specific cellular defences Success Criteria: By the end of the lesson I should be able to Describe the role of white blood cells in immune surveillance to include cytokine release and resulting accumulation of specific WBCs at infection sites/tissue damage. Explain clonal theory to include lymphocytes having a single type of membrane receptor specific for one antigen. State that antigen binding to these sites leads to repeated division of the lymphocyte, resulting in a clonal population of lymphocytes. State that lymphocytes are responsible for a specific response to foreign antigens and come in T and B forms.

3. Immune Surveillance A range of different types of white blood cells continuously circulate in the blood monitoring the state of the tissues If damage is detected some of these white blood cells release cytokines into the blood This attracts large numbers of phagocytes and T cells to the damaged or infected area Often white blood cells squeeze through the pores in the capillaries to gain access to the tissue Lymphocytes on patrol White blood cells, called lymphocytes, move through the bloodstream alongside red blood cells.

4. Release cytokines to attract WBC ( phagocytes and T lymphocytes ) to areaT lymphocytes WBC Damaged cells

5. Lymphocytes Lymphocytes are made in the bone marrow from stem cells. Some leave and mature in the thymus gland (T-lymphocytes) and others remain and mature in the bone marrow (B- lymphocytes)

6. Clonal selection theory Each lymphocyte produces only one type of antigen receptor. However, due to the huge number present, they are able to cover every possible antigen. Very quickly after being made, any lymphocytes with antigen receptors for self-antigens are destroyed. The remainder patrol the body until they are activated by binding to a non-self antigen, causing them to clone themselves many times making a large clonal population.

7. Clonal selection theory

8. Confusing self and non-self As we saw previously, our immune system should be able to read the surface antigens of a cell and tell if it is self or non-self. However, sometimes it can fail to recognise our own cells and attack them – autoimmunity e.g. Rheumatoid arthritisheumatoid arthritis Multiple Sclerosis.Multiple Sclerosis Type 1 diabetes Our immune system can also over react to harmless substances to give allergies.

9. Auto immunity When the immune system no longer tolerates it’s own antigens, the T-lymphocytes attack the cells. In rheumatoid arthritis, cytokines cause inflammation which will attack the bone and cartilage in joints, causing them to be replaced with fibrous tissue which leaves the joint less mobile than before.

10. Allergy B-lymphocytes sometimes over-react to harmless substances like dust, pollen and feathers etc. or even medicines such as penicillin. The B-lymphocytes release antibodies which cause mast cells to release histamine. Some allergies are so severe that they can trigger anaphylactic shock where the histamine causes such a huge drop in blood pressure it can be life threatening.

11. Questions 1)What are the two types of lymphocytes? 2)Where do T lymphocytes mature? 3)Why are cytokines released at the site of infection? 4)What is the name of the proteins found on cell surfaces that illicit an immune response? 5)Describe clonal selection. 6)a) What is autoimmunity? b) Give a condition linked to autoimmunity.

12. Answers Q1-6 1)What are the two types of lymphocytes? – B and T lymphocytes 2) Where do T lymphocytes mature? – Thymus gland 3) Why are cytokines released at the site of infection? - to summon other immune cells to the site of the infection 4) What is the name of the proteins found on cell surfaces that illicit an immune response? - Antigen 5) Describe clonal selection. – Immature lymphocytes with ‘self’ markers destroyed Remaining lymphocytes patrol body until activated by binding ‘non-self’ antigen Activated lymphocytes copied ( cloned) and mount attack 6) a) What is autoimmunity? - The immune system recognises ‘self’ as ‘non- self’ and attacks tissues b) Give a condition linked to autoimmunity. – MS, Rheumatoid arthritis, type 1 diabetes

13. Learning Intention: To learn about the immune system and specific cellular defences Success Criteria: By the end of the lesson I should be able to Explain the role of T lymphocytes in immunity to include their ability to identify cells as non-self, due to recognition of specific surface proteins. Describe the function of antigen presenting cells (APCs) to include capture of the pathogen and display of its antigens on the cell surface. State that B lymphocytes are activated by APCs and T lymphocytes to produce clones of B lymphocytes. State that these cloned B lymphocytes secrete antibodies into lymph and blood that make their way to the infected area. State that an allergy is a normally harmless hypersensitivity by B lymphocytes to an antigen. State that some B and T lymphocytes produced as a resut of clonal selection survive long term as memory cells. State that the presence of these memory cells result in a more rapid and greater secondary immune response.

14. Autoimmune Disease T lymphocytes have specific surface proteins that allow them to distinguish between the surface molecules of the body’s own cells and cells with foreign molecules on their surface. Failure in regulation of the immune system leads to a T lymphocyte immune response to self cells (auto immune disease).

15. Autoimmune Disease

16. True or False The next four slides each have a pair of statements on them about autoimmune disease. Decide which statement is true and which is false. Be prepared to explain your reasoning!

17. Chicken pox, CJD, legionnaires’ disease and meningitis are examples of autoimmune diseases. Crohns disease, type 1 diabetes, Graves disease, psoriasis and rheumatoid arthritis are examples of autoimmune diseases.

18. Autoimmune diseases can be caught from close contact with infected people. An autoimmune disease is caused by an overactive immune response in which the body’s own cells are destroyed.

19. Autoimmune diseases can be easily cured with a combination of antibiotics and anti-viral drugs. Treatment of autoimmune disease only serves to alleviate the symptoms, it does not cure the disease.

20. Children can be vaccinated against autoimmune diseases – this prevents them from getting ill in later life. There is no known prevention for autoimmune disease.

21. Lymphocytes White blood cells called lymphocytes are responsible for recognising particles that do not belong to the host as foreign and eliminating them.White blood cells called lymphocytes are responsible for recognising particles that do not belong to the host as foreign and eliminating them. 'foreign' particles can include antigens, cells infected by pathogens, toxins released by pathogens, transplanted tissue and, sometimes, cancer cells.'foreign' particles can include antigens, cells infected by pathogens, toxins released by pathogens, transplanted tissue and, sometimes, cancer cells. There are two main types of lymphocytes:There are two main types of lymphocytes: B lymphocytes (B cells);B lymphocytes (B cells); T lymphocytes (T cells).T lymphocytes (T cells).

23. T-lymphocytes There are two different types of T- lymphocytes or T-cells. - helper T cells (T H cells) - cytotoxic T cells (T C cells) Helper T cells become activated when they have come into contact with a foreign antigen. Cytotoxic T cells cause apoptosis of an infected cell.

24. T H Cells Antigen presenting cell

25. T H Cells As seen before, there is a vast pool of different T H cells with different forms of antigen receptors. One of them will be specific to the antigen. When the phagocyte has engulfed the foreign cell and has presented the foreign antigen, one of the T H cells will be able to bind with it.

26. T H Cells Once one version of the T H cell is activated, it goes on to multiply to give either; - further clones of activated T H cells - clones of memory T H cells The activated T H cells release cytokines which will stimulate cytotoxic T cells (T c cells) and also stimulate B cells

27. Animation http://www.youtube.com/watch?v=Hc3t bNBSR5Yhttp://www.youtube.com/watch?v=Hc3t bNBSR5Y

28. T C cells Cytotoxic T cells are also activated in a similar way, where the specific antigen receptor binds to the antigen on the presenting cell. They go on to multiply to give either; - clones of the activated T C cells - clones of memory T C cells The activated T C cells go on, under the action of cytokines from T H cells, to destroy infected cells

29. Destruction of infected cells Apoptosis is where cells are programmed to self destruct. The T C cells bind to an infected cell as they have copies of the foreign antigen on their surface. The T C cells release chemicals which perforate the cell membrane allowing further chemicals access to the cell causing the DNA and proteins to be broken down. The cell now slowly shrinks and dies, allowing a phagocyte to engulf and digest it. This means the cell remains whole so the foreign pathogen is not released to infect more cells.

30. T C cells and cancer T C cells are also able to recognise antigens found on the surface of cancer cells. They are then able to bring about the lysis of large cancer cells.

31. Allergy B lymphocytes becoming hypersensitive to a normally harmless antigen triggering an immune response. This sensitises the body to the allergen. secretion of histamine when it next enters the body. Histamine = inflammation

32. B-lymphocytes B lymphocytes are able to recognise foreign antigens and engulf them. Some will become clone antibody-producing B cells, others become cloned memory B cells They then display the antigens on their surface waiting for a T H cell to release cytokines and activate it.

33. Activated B lymphocytes Activated lymphocytes can produce a protein specific to the antigen called antibodies. The antibodies are able to bind to the antigen creating an antigen-antibody complex.

34. Antibody action The binding of the antibodies causes the inactivation of the pathogen (or the toxin it produces) and pathogen to become more susceptible to phagocytosis

35. Immunological memory When a pathogen infects the body, it takes time to raise an immune response and select the correct T and B cells (clonal selection) and produce antibodies. This is called the primary response, and very often it is too slow to prevent the pathogen causing illness. However, if the person survives, and they come across the pathogen a second time they have memory T C, T H and B cells.

36. Memory Cells When the foreign antigen is recognised by these memory cells, they very quickly proliferate and form many clones of both T cells and antibody-producing B cells. This means that their are more antibodies produced faster and for a longer duration. This is the secondary response.

38. Antigen engulfed and presented on its surface Formatio n of clone memory T C cell Formatio n of cloned activated T C cells Formatio n of clone memory T H cell Formatio n of cloned activated T H cell Formatio n of clone memory B cells Formatio n of cloned antibody producing B cells T C cell activatedT H cell activatedB cell activated Produce cytokines to stimulate Infected cell destroyed Antibodies produced

39. Summary Specific defences Damaged cellscytokines T lymphocyteautoimmune B lymphocyte allergy T lymphocyte cytotoxic- apoptosis. helper-secrete cytokines that activate B lymphocytes and phagocytes. B lymphocytes Antigen-antibody complexes- inactivate /phagocytosis/cell lysis

40. Questions 1.How does a T C cell lead to the destruction of an infected cell? 2.a) What does an activated B cell produce? b) How do these molecules bring about destruction of a pathogen? 3.What term is used to describe the first infection of the body by a pathogen? 4.If the body is re-infected at a later date, what is this known as?

41. Questions 5.Which cells are central to being able to fight off re-infection? 6.How does the immune response to the second infection compare to the first?