Immune System: Defense Against Disease Topics 6.3 and 11.1

1. Immune System: Defense Against Disease Topics 6.3 and 11.1 Maria Sarao Samantha Bryan Emily Waggoner

2. Vocabulary- It's important Pathogen- An organism or virus that causes a disease Antigen- Any foreign macromolecule (either proteins, polysaccharides or structures on the surface of bacteria) that triggers an immune response Antibody- Antibodies are proteins that bind to particular antigens and mark them for elimination from the body Antibiotics- Any substance that is able to kill or inhibit a microorganism such as bacteria

3. Vocabulary Parte 2 Virus- An infective agent consisting of a protein coat surrounding an RNA or DNA core Are not cells and do not possess membranes or organelles. They cannot manufacture their own proteins and must invade living cells to take over their protein production “machinery” Leucocytes- White blood cells Phagocytic leucocytes Specialized white blood cells that engulf foreign/invading pathogens and destroy them•

4. Different Types of Leucocytes

5. Helpful Video: https://www.khanacademy.org/science/biology/immunology/v/role-of-phagocytes-in-innate-or-nonspecific-immunity Note: What is a MHC? • Polypeptides from pathogen attach to proteins from the phagocyte (antigen presenting protein) • Polypeptide + antigen presenting protein = MHC II • MHC II's are recognized by helper-T cells • Helper-T cells have receptors that bind to MHC II's • This activates helper T-cells so that they can release cytokines and alert other immunological cells of the pathogen

6. 6.3.1: Define pathogen. Pathogen- An organism or virus that causes a disease • This includes bacteria, viruses, and other microorganisms that can cause disease. • Synonym: germ

7. 6.3.2: Explain why antibiotics are effective against bacteria but not against viruses. • Antibiotics are chemicals that take advantage of the differences between prokaryotic and eukaryotic cells. • One type of antibiotic can selectively block protein synthesis in bacteria. • Another may inhibit the production of a new cell wall by bacteria, thus blocking their ability to grow and divide. • In both cases, our body cells will remain unaffected by the medicine. • Viruses are not affected because they use our own body cells' metabolism to replicate. • Therefore, any chemical that would inhibit this would also be damaging our own cells.

8. 6.3.3: Outline the role of skin and mucous membranes in defense against pathogens. • Skin and mucous membranes serve as external forms of defense against pathogens • Skin is the physical barrier • Mucous membranes: mucous is lined in certain areas of the body. -Trachea -Urethra -Nasal passages -Vagina • When a pathogen enters the body, mucous surrounds the pathogen, the body senses the excess mucous, so coughing is induced to expel the pathogen.

10. 6.3.4: Outline how phagocytic leucocytes ingest pathogens in the blood and in body tissues. • A type of white blood cell • Float around the body in blood • Phagocyte surrounds the pathogen by endocytosis • A vacuole containing the pathogen travels to a lysosome • The membranes of the vacuole and lysosome fuse • Digestive enzymes in the lysosome destroy the pathogen • The pathogen “debris” is released by exocytosis

11. Phagocytic Leucocytes * QUICK REMINDER: a macrophage is a type of phagocyte

12. Quick Review Video http://www.youtube.com/watch?v=KhqXxn5ay1U

13. 6.3.5: Distinguish between antigens and antibodies. Antibodies Protein molecules produced in response to a specific pathogen Therefore, each antibody is different.... But all have are a "Y" shaped protein Antigens Foreign proteins embedded in the outer surface of the pathogen (i.e. the capsid of a virus) These trigger an immune response Most pathogens have several different types of antigen and so may trigger the production of several different types of antibody At the end of the forked end of the antibody, there is a binding site where the antibody attaches itself to the antigen, and thus the pathogen.

15. Explain Antibody Production 6.3.6/11.1.4 • Beta Cells produce antibodies in small amounts (in comparison to the infection). • Antibodies are produced in response to a specific type of pathogen. • Each antibody is y-shaped. At the end of each fork, there is a binding site, which is where the antibody attaches to the antigen.

16. Production of Antibodies Cont.d 1. Before antibody production, a neutrophil releases chemicals to kill the pathogen. If this isn’t successful, macrophages arrive. 2. The macrophage attempts to ingest the pathogen. 3. A protein floating in the blood (C3B) senses the pathogen and attaches to the surface of the pathogen. 4. If these methods don’t work and the pathogen invades a cell, the cell sends out a stress signal. 5. This signal brings a natural killer (NK) cell to kill the entire cell, in hopes of stopping the pathogen. 6. The other method is to prevent the pathogen from entering the cell in the beginning, which is when antibodies are used. 7. A specific B-lymphocyte is identified that can produce an antibody to bind to the antigen.

17. Antibody Production Cont.d 8. The B-lymphocytes are cloned (divide repeatedly through mitosis) to rapidly increase the number of antibodies being produced. 9. Antibody production begins. 10. The antibodies are released in the bloodstream, searching for the correct antigen to bind to. 11. This binding leads to the presence of T-helper cells to produce chemicals to kill the pathogen. 12 T-helper cells (another type of leucocyte that is specific to that antigen) bind to the antigen presented by the macrophages and are activated/stimulated.

18. Antibody Production Cont.d Basic Overview http://www.youtube.com/watch?v=KpNFAEbLcvk http://www.youtube.com/watch?v=Nw27_jMWw10 http://www.youtube.com/watch?v=Non4MkYQpY Detailed http://www.youtube.com/watch?v=AmAa2g3fiI4

19. Review of HIV/AIDS: • HIV stands for human immunodeficiency virus • AIDS stands for acquired immunodeficiency syndrome. • HIV is the virus that causes AIDS • Directly attacks T helper cells (T lymphocytes) • Piggybacks onto one of the T helper cells and then uses that access into the cell to overtake the host cell and replicate. • Once enough of the viruses have been replicated, the cell bursts and the virus infects other T cells.

20. 6.3.7: Outline the effects of HIV on the immune system. • HIV virus kills Helper T-cells • Helper T-Cells tell B-cells there is a pathogen • no T cells, no recognition of other pathogens • Immune system cannot mount an effective defense against invading pathogens • Patients then succumb to secondary infections

21. 6.3.8: Discuss the cause, transmission, and social implications of AIDS. • AIDS = Acquired immunodeficiency syndrome • HIV = Human immunodeficiency virus Cause - HIV infects helper-T cells, but can lie dormant in the host cell for many years until a chemical signal activates it - Helper-T cells communicate which cells need to replicate and produce antibodies - When Helper-Tcells die, communication is lost and antibodies are not produced - Therefore, the individual cannot fight off pathogens and develops AIDS - Since HIV mutates quickly it is hard to develop medication

22. 6.3.8 continued Transmission - HIV transmitted through bodily fluids (i.e. during sex, by reusing unsterile needles, or breastmilk) - In the past blood for transfusions was not tested for HIV and other blood-borne illnesses Social Implications - AIDS used to be associated with homosexuals and drug abusers - Was called GRID (Gay-related immune deficiency) - Individuals with HIV are often discriminated against for things like employment, access to insurance and education, etc. - Not all countries/areas have the education and medical technology to treat prevent/treat HIV/AIDS - Infection rates can be increased if patients are grouped together in large wards The best way of prevention is to educated people on how to decrease their risk of exposure to HIV.

23. http://www.youtube.com/watch?v=hzQQiCPWSYA

24. 11.1.1: Describe the process of blood clotting Plasma Proteins and platelets circulate in blood plasma. Two Clotting Proteins: Remain inactive until receive a signal. -prothrombin -fibrinogen 1. Damaged cells release chemicals which stimulate platelets to adhere to the area. 2. Other platelets begin adhering, eventually forming a barrier or plug. 3. A signal is sent to bring prothrombin to the area. 3. The damaging tissue and platelets also release clotting factors which convert prothrombin into thrombin. -Thrombin is produced to lead to the production of fibrinogen and eventually fibrin which makes up the clot.

26. 11.1.2: Outline the principle of challenge and response, clonal selection and memory cells as the basis of immunity. Challenge and Response • When the body is challenged by a foreign pathogen it will respond with both a non-specific and specific immune reaction • The body is capable of recognising invaders as they do not possess the molecular markers that designated all body cells as 'self' (MHC class I) • Non-specific immune cells (macrophages) present the foreign antigens to lymphocytes as examples of 'non-self' (on MHC class II) • These lymphocytes can then respond with the production of antibodies to destroy the foreign invaders Clonal Selection • Each B lymphocyte has a specific antibody on its surface that is capable of recognising a specific antigen • When antigens are presented to B cells (and TH cells) by macrophages, only the B cell with the appropriate antibody will become activated and clone • The majority of B cell clones will differentiate into antibody-producing plasma cells, a minority will become memory B cells (BM cells) • Because pathogens may contain several antigenic determinants, several B cell clones may become activated (polyclonal activation)

27. 11.1.2 Continued Memory Cells • a specific cell that is part of the immune system- obviously • starts in the bone marrow where lymphocytes are made • can be either a T cell or a B cell • function of these cells is characterized by the memory present in acquired immunity • once a memory cell has been exposed to a pathogen, it will recognize it much quicker in the event that it encounters the same pathogen again • There is a delay between initial exposure and the production of antibodies • When a B cell does divide and differentiate, a small proportion of clones will differentiate into memory cells • Memory cells remain in the body for years (or even a lifetime) • Because the individual no longer presents with the symptoms of infection upon exposure, the individual is therefore immune

28. 11.1.2- Continued Clonal Selection-

29. 11.1.3: Define active and passive immunity. Active Always leads to the production of memory cells and thus provides for long-term immunity to a pathogen. Memory cells are produced whenever the immune system is presented with an antigen and there is a full immune response. Passive When an organism acquires antibodies from another Only a short-term benefit to the receiver of antibodies because no memory cells Examples- transfer of antibodies from mother to placenta, acquisition of antibodies from mother's colostrum, and injection of antibodies in antisera (i.e. antivenoms for treatment of poisonous snake or spider bites)

30. 11.1.5: Describe the production of monoclonal antibodies and their use in diagnosis and treatment. Definition- Monoclonal antibodies are monospecific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cell, in contrast to polyclonal antibodies which are made from several different immune cells. Production- 1. Antigens that correspond to a desired antibody are injected into an animal 2. B-cells producing the desired antibody are harvested 3. Tumor cells are obtained from another source (tumor cells grow and divide endlessly) 4. B-cells are fused with tumor cells, producing hybridoma cells that divide endlessly, providing the desired antibodies 5. The hybridoma cells are cultured and the antibodies they produce are extracted and purified

31. 11.1.5 Continued Use in Diagnosis- Malaria 1. Monoclonal antibodies are made to bind to antigens in malarial parasites 2. A test plate is covered with antibodies 3. The sample is left on the plate long enough for malaria antigens (if present) to bind to antibodies 4. The sample is rinsed off -Any bound antigens are detected using more monoclonal antibodies with attached color-changing enzyme Use in Treatment- Rabies • Rabies usually causes death in humans before the immune system can control it. • Injecting monoclonal antibodies when a person gets infected will control the virus • At the same time, the person's body begins making its own antibodies • Triggers two-fold immune response • Passive through injection • Active through body’s production

32. 11.1.6: Explain the principle of vaccination. • You cannot be immune to a pathogen unless you're exposed to it at least once. • Vaccines act as the first exposure to a pathogen. • A vaccine is developed by weakening a pathogen an injecting it into the body. • A "weak" strain can be selected, or the pathogen can be heated or treated chemically. • Pathogen would still be recognized as foreign so a primary immune response would take place. • Memory cells would produce antibodies quickly if ever infected with strong pathogen. • Therefore, a vaccination doesn't prevent infection but the secondary immune response is quicker and more intense than the primary one. • Very mild or no obvious symptoms as a result

33. 11.1.7 Discuss the benefits and dangers of vaccination. Benefits: -Possible total elimination of a disease. Ex. Smallpox, hoping for polio and measles -Decrease in the spread of epidemics -Costs are minimal in comparison to treatment- preventative medicine is typically the most cost-effective approach -Each vaccinated person doesn’t have to experience the symptoms at all Dangers: -Before 1999, many vaccines contained thimerosal, containing mercury which poisoned infants -The perception exists that multiple vaccines given to children in a short period of time may overload their systems -Anecdotal evidence suggests that MMR vaccine may link to autism -Development of allergies