1. Unit 4 - Immunology and Public Health CfE Higher Human Biology 22. 22. Specific Cellular Defences

2. Learning Intentions I can describe clonal selection theory. I can state that lymphocytes have a single type of membrane receptor specific for one antigen. Antigen binding leads to repeated lymphocyte division resulting in a clonal population of lymphocytes I can describe the structure of T- and B-lymphocytes I can state that Lymphocytes respond specifically to antigens on foreign cells, cells infected by pathogens and toxins released by pathogens. I can state that 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. I can state that immune system regulation failure leads to T-lymphocyte immune response to self- antigens (auto immune disease). I can state that allergy is a hypersensitive B- lymphocyte response to an antigen that is normally harmless. I can state that one group of T-lymphocytes destroy infected cells by inducing apoptosis. Another group of T-lymphocytes secrete cytokines that activate B lymphocytes and phagocytes. When pathogens infect tissue, some phagocytes capture the pathogen and display fragments of its antigens on their surface. These antigen presenting cells activate the production of a clone of T-lymphocytes that move to the site of infection under the direction of cytokines. I can state that each B-lymphocyte clone produces a specific antibody molecule that will recognise a specific antigen surface molecule on a pathogen or a toxin. Antigen-antibody complexes may inactivate a pathogen or toxin or render it more susceptible to phagocytosis. In other cases the antigen- antibody complex stimulates a response which results in cell lysis. B-lymphocytes activated by antigen presenting cells and T-lymphocytes produce a clone of B-lymphocytes that secrete antibodies into the lymph and blood where they make their way to the infected area. I can describe immunological memory. I can state that some T- and B-lymphocytes produced in response to antigens by clonal selection survive long-term as memory cells. A secondary exposure to the same antigen rapidly gives rise to a new clone of lymphocytes producing a rapid and greater immunological response

3. Immune surveillance the Third Line of Defence There are a wide range of different immune cells (white blood cells) which are constantly patrolling the body, looking for signs of infection or damage. They can summon other immune cells by releasing cytokines and they may also carry out a response themselves. this results in large numbers of phagocytes(non-specific) and T cells(specific) collecting at the damaged/infected site. White blood cells can also squeeze through the capillary wall to get access to surrounding tissues.

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

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. A non-self antigen could include viruses, bacteria, bacterial toxins, cancer cells and molecules on the surface of transplanted cells.

7. Clonal Selection Theory

9. Confusing self and non-self Antigens are protein molecules (in plasma membrane) present on the surface of all cells. 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 arthritis - the immune system attacks and erodes the cartilage at a joint-the cartilage is replaced by fibrous tissue which joins the two bones together making the joint immovableheumatoid arthritis Multiple Sclerosis - the immune system attacks the myelin sheath around the nerve cells so that they can no longer transmit nerve impulses efficiently and the person suffers major disabilities. Multiple Sclerosis Type 1 diabetes Any lymphocyte ( during maturation of B cells and T cells) with an antigen receptor that would fit a body cell surface protein is weeded out and destroyed by apoptosis. Our immune system can also over react to harmless substances to give allergies.

10. ABO blood group system Four types of blood group exist in humans and they are A,B, AB and O. The surface antigens on the red blood cells (RBCs)of an individual determine their blood group. There are 2 antigens, A and B. When Individuals possess one antigen they are either group A (has A antigens) or B (has B antigens); with both antigens they are group AB; and with neither they are group O. The antibodies in the blood plasma of an individual are determined by their blood group and are the ones opposite to their blood group. Individuals with group A have anti-B antibodies; those with group B have anti-A antibodies; those with group AB have neither anti-A nor anti-B; and those with group O have both anti-A and anti-B antibodies.

11. Blood Groups Knowledge of an individuals blood group is essential for blood transfusions. Antibodies in the plasma of the recipient would attack foreign antigens of an unsuitable donor. If a person with group A blood (with A antigens on the surface of blood cells) were to be given a transfusion of group B blood (with B antigens) then anti-B antibodies( from group A person) would combine with the B antigens on the surface of the donated red blood cells and this would result in clumping (agglutination) of the blood which gets all lumpy. This can block small blood vessels and lead to major problems, maybe even death. Certain combinations of blood groups are compatible. For example a person with blood group B can receive blood of type O without risk of agglutination because group B blood has anti A antibodies and O has no antigens on the surface Blood group B person can also receive blood from group B.

12. ABO Blood Group System If a person of group A was given a transfusion of group B then anti B antibodies (from group A person) would combine with he B antigens on the donated blood and clumping would result. People with blood group O can donate blood to people with blood groups A, B, AB and O i.e. O is the universal donator (O has neither antigen A nor antigen B present and clumping will not happen). People with group AB can receive blood from A, B, AB and O because neither anti A nor anti B antibodies are present It is the incompatibility between the donor’s cells and the recipients plasma which results in agglutination.

14. ABO blood group system

15. Agglutination of red blood cells

16. Rhesus D-antigen Humans have the ABO system of antigens on their red blood cells. most people have a further antigen on the surface of their red blood cells called antigen D and those who possess it are said to be Rhesus positive (Rh+). Those who lack antigen D and who react to its presence by forming anti-D antibodies are said to be Rhesus negative (Rh-).

17. Transfusion of Rh+ red blood cells to a Rh- person must be avoided because the recipient’s immune system would respond and produce anti- D antibodies which would remain leaving the person sensitised. Any subsequent transfusion of Rh+ red blood cells would be liable to cause the sensitised Rh- person to suffer severe agglutination which could be fatal. Antigen D is genetically determined by a dominant allele (D); lack of antigen D by a recessive allele (d). So Rh+ individuals have genotype DD or Dd; Rh- individuals have genotype dd

18. If a Rh- woman (dd) marries a Rh+ man (DD) each child will be Rh+ (Dd). If a Rh- woman (dd) marries a Rh+ man (Dd) there is a 50% chance that each of their children will be Rh+ (Dd). Inheritance of Rhesus D antigen Woman x man woman x man dd DD dd Dd Rh- Rh+ all Dd (Rh+) Dd and dd Rh+ and Rh-

19. If a Rh- mother has a Rh+ foetus (with antigen D) then the baby has antigen D on its blood cells which are foreign to the mothers immune system. Mothers and baby’s blood are not in direct contact and the immune system is unaware of this in the first pregnancy and nothing happens. During birth a small amount of foetal blood can mix with the mothers blood and the mothers immune system responds by producing anti-D antibodies (sensitised) and in subsequent pregnancies if the foetus is Rh+ antibodies against antigen D cross the placenta and attack and destroy foetal red blood cells (haemolytic disease of the new born). It can be treated by giving the baby blood transfusions and it can be prevented by injecting the mother with anti-D immunoglobulins soon after the birth of each Rh+ baby- these antibodies destroy any antigens from the foetus before the mothers immune system can respond to them.

20. 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.

21. Allergy An allergy is an exaggerated response by the body to environmental antigens that normally would be considered to be harmless. 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. Histamine produces the symptoms typical of hay fever like a blocked, runny nose to try and get rid of the foreign body. Symptoms are reduced by taking antihistamine drugs. 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.

22. 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.

23. 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

24. Rheumatoid Arthritis 1.What is rheumatoid arthritis? Describe in detail. 2.Who is more likely to suffer from this condition and in which age group does onset most frequently occur. 3.Which chemical messengers are thought to play a key role in the progression of this condition? 4.Explain this. 5.What treatment is available? 6.Draw a diagram from page 318 to illustrate the effect of this condition on a joint-colour.

25. Hay fever. 1.Which particle causes hay fever? 2.Why does this reaction take place? 3.Describe the process involved to result in hay fever-draw out figure 22.9 to answer this question. 4.What are the symptoms? 5.What is the treatment?

26. Allergic Asthma. 1.What is anaphylactic shock? 2.Give an example of something that may cause this. 3.Name the cells that release large amounts of histamine. 4.What effect does histamine have? 5.What should people do who are hypersensitive to these allergens? 6.Give another name for epinephrine.

27. Allergic Asthma. 1.What is asthma? 2.What are its effects? Draw figure 22.11 to help explain your answer. 3.Give examples of things that can cause an attack of this kind. 4.Who are more likely to be affected in the UK? 5.What can sufferers do to try to control their condition? 6.Do you know any asthmatics?