1. Defense Against Infectious Diseases Topic 11.1

2. Assessment Statements 11.1.1Describe the process of blood clotting. 11.1.2 Outline the principle of challenge and response, clonal selection and memory cells as the basis of immunity. 11.1.3Define active and passive immunity. 11.1.4Explain antibody production. 11.1.5 Describe the production of monoclonal antibodies and their use in diagnosis and in treatment. 11.1.6Explain the principle of vaccination. 11.1.7Discuss the benefits and dangers of vaccination.

3. Blood Clotting 0 Bruising 0 Braking small blood vessels (capillaries, arterioles, venules) allowing blood to escape the closed circulatory system 0 Allows entry point for pathogens 0 Clots 0 Seals damaged blood vessels 0 Prevents excessive blood loss and entering pathogens

4. Blood Clotting 0 Within blood, 0 Plasma proteins 0 Prothrombin and fibrinogen 0 Always present in blood plasma, remain inactive unless needed 0 Platelets 0 Form in bone marrow, one large cell breaks into many fragments

5. Blood Clotting 0 Damaged blood vessel 0 Release chemicals which stimulate platelets to adhere to damaged area 0 Other platelets adhere to those platelets  forming a ‘plug’ 0 Damaged tissue and platelets release chemicals to convert prothrombin  thrombin 0 Thrombin (active enzyme) catalyzes conversion of soluble fibrinogen into insoluble fibrin 0 Fibrin (fibrous protein) forms a mesh-like network that stablizes the platelet plug

6. Blood Clotting Damaged blood vessel Chemicals released Platelets adhere to damaged area Chemicals which convert Prothrombin Thrombin (enzyme) Fibrinogen Fibrin (forms mesh)

7. Immune Response 0 Body recognition of foreign cells 0 ‘self’: normal body cells 0 All body cells have common set of cell membrane proteins 0 ‘not-self’ (aka antigens): pathogens, transplanted organs, etc. 0 Different cell membrane proteins

8. Antibody Production 0 Leucocytes 0 B lymphocytes (B cell) 0 Synthesizes and secretes a specific antibody which binds to a specific antigen 0 Represent roughly 1% of all cells in bloodstream 0 No one type of B cell is found in high numbers 0 Cloning occurs to make enough antibodies to combat antigens

9. Antibody Production 1. Macrophage (phagocytic cell) – first to encounter an antigen 2. Macrophage engulfs ‘not-self’ antigen by phagocytosis and only partially digests it 3. Molecular pieces of antigen are displayed on cell membrane of macrophage (antigen presentation) 4. Helper T-cells chemically recognize antigen and become activated 5. Helper T-cells turn immune response from non-specific (‘not-self’) to antigen-specific (identity of pathogen) 6. Helper T-cells chemically communicate with (activate) specific B cell type (able to produce the antibody needed)

10. Cell Cloning 0 Activated B cell begins cell divisions (aka cell cloning) 0 Antibody-secreting plasma cells 0 Secrete antibodies immediately 0 Help fight off the first (primary) infection 0 Memory cells 0 Do not secrete antibodies during primary infection 0 Long-lived cells, remain circulating in bloodstream awaiting secondary infection

11. Fundamental Principles of True Immunity 0 Challenge and Response 0 Immune system must be challenged by antigen (primary infections) in order to develop immunity 0 All cellular events (macrophages, helper T-cells, B cells) are part of response 0 Clonal Selection 0 Identification of leucocytes (particular plasma B cell) help with specific pathogen 0 Multiple cell divisions which occur to build up numbers of that cell type 0 Memory Cells 0 Provide long-term immunity 0 Must experience a pathogen in order to produce these cells 0 Have true immunity to that specific pathogen

12. Antibody Production Production of more antibodies in less time

13. Active and Passive Immunity 0 Active 0 Always leads to the production of memory cells  long- term immunity 0 Passive 0 One organism acquires antibodies which were produced in another organism 0 Only short-term benefits 0 Examples: 0 Mother to fetus: placenta, colostrum 0 Injection of antibodies in antisera (antivenoms)

14. Polyclonal and Monoclonal Antibodies 0 Polyclonal Response 0 Primary immune response by an organism 0 Pathogen is recognized as many antigens (not just one) 0 Ex: capsid (protein coat) of a virus will have several types of protiens 0 Each protein/antigen can cause an immune response  causing several types of B cells to be made 0 Monoclonal 0 Production of the same type of antibodies

15. Production of Monoclonal Antibodies 1. Inject an antigen into a laboratory mouse 0 Choice of antigen extremely important 2. Animal goes through primary immune response 0 Polyclonal response 3. Spleen of animal is ‘harvested’ – gain access to many blood cells 4. Some of those cells will be leucocytes from recent immune response 0 Problems: 0 Keeping B cells alive for extended period of time 0 Identification of B cells that produces the desired antibody

16. Production of Monoclonal Antibodies 5. B cells are fused with myeloma (cancerous) cells  hybridoma 6. Hybrid cells have characteristics of both cells 0 Produce antibodies 0 Long lived (as are all cancer cells 7. Entire mix is transferred to environment to where the hydridoma cells are sole survivors 8. Hybridomas are cultured in separate containers 9. ELISA (enzyme-linked immunosorbent assay) test is performed to identify which B cells are producing desired antibodies 10. Antibody is purified from cell culture when needed

18. Uses of Monoclonal Antibodies 0 Diagnosis 0 Pregnancy testing 0 Embryo produces hormone HCG (human chronic gonadotropin) 0 Small amounts will be present in mothers bloodstream and urine 0 Hybridomas can be produced by injecting animal with HCG 0 B cells produce antibodies that recognize HCG as an antigen 0 Antibodies bind to HCG causing a color change  pregnant!

19. Uses of Monoclonal Antibodies 0 Treatment 0 Cancer 0 Cancerous body cells produce specific antigens on their membranes 0 One possible treatment is to produce monoclonal antibodies that target the cancer cell antigens 0 Monoclonal antibody could be modified to carry a toxin specific for that cancer cell, or 0 Attach radioisotope for pin-point radiation therapy 0 Advantage: direct target to cancer cells

20. Vaccinations 0 Reminder: you CANNOT be immune to a pathogen prior to being exposed to it 0 Vaccines 0 Act as the first exposure to pathogen 0 Developed by weakening pathogen, then injecting the pathogen into the body 0 Methods of production: 0 Selecting a particularly ‘weak’ strain 0 Heating the pathogen 0 Chemical treatment

21. Vaccinations 0 Immune response 0 Leucocytes recognize the weakened pathogen as ‘not- self’ and primary immune response ensues 0 Formation of memory B cells  which means long-term immunity 0 Vaccine DOES NOT prevent infection, but allows secondary immune response to occur 0 Much quicker and more intense

22. Vaccinations BenefitsDangers Possible total elimination of disease Small pox, polio, measles Prior to 1999, many vaccines contained thimerosal, a Hg-based preservative. Hg shown to be a neurotoxin Decrease in spread of epidemics and pandemics Perception exists that multiple vaccines given to children over short period will ‘overload’ their immune system Preventative medicine is typically the most cost-effective approach to healthcare Anecdotal evidence suggested that MMR vaccine may have a link to autism Each vaccinated individual benefits because the full symptoms of the disease are not experienced Cases have been reported of vaccines leading to allergic reactions and autoimmune responses