Lymphatic System, Viruses, and Immunity

1. Lymphatic System, Viruses, and Immunity

2. Body has 3 lines of defense • Skin • WBC • Acquired defenses

3. Lymphatic System • In animals is part of the immune system, made up of a network of conduits that carry a clear fluid called lymph • It also includes the lymphoid tissue and lymphatic vessels through which the lymph travels in a one-way system in which lymph flows only toward the heart. • Lymphoid tissue is found in many organs, particularly the lymph nodes, and in the lymphoid follicles associated with the digestive system such as the tonsils. • The system also includes all the structures dedicated to the circulation and production of lymphocytes, which includes the spleen, thymus, bone marrow and the lymphoid tissue associated with the digestive system

4. Function of the lymphatic • The lymphatic system has multiple interrelated functions: • it is responsible for the removal of interstitial fluid from tissues • it absorbs and transports fatty acids and fats as chyle to the circulatory system • it transports immune cells to and from the lymph nodes in to the bone • The lymph transports antigen-presenting cells (APCs), such as dendritic cells, to the lymph nodes where an immune response is stimulated. • The lymph also carries lymphocytes from the efferent lymphatics exiting the lymph nodes.

5. Primary lymphoid organs • The thymus and the bone marrow constitute the primary lymphoid tissues involved in the production and early selection of lymphocytes. • The thymus has 2 funtions: • Thymus gland produces thymic hormones to aid in maturation of T lymphocytes • Immature I lymphocytes migrate from the bone marrow through the bloodstream to the thymus to mature…without mature T cells, the body’s response to specific pathogens is weak

6. Secondary lymphoid organs • Maintain mature naive lymphocytes and initiate an adaptive immune response. The peripheral lymphoid organs are the sites of lymphocyte activation by antigen. • Activation leads to clonal expansion and affinity maturaton • Provides the environment for the foreign or altered native molecules (antigens) to interact with the lymphocytes. • It is exemplified by the lymph nodes, and the lymphoid follicles in tonsils, Peyer's patches, spleen, adenoids, skin, etc. that are associated with the mucosa-associated lymphoid tissue (MALT)

7. Bacteria • Single celled prokaryotes that don’t have a nucleus. • They lack membrane-bound organelles, and can function and reproduce as individual cells, but often aggregate in multicellular colonies • Their genome is usually a single loop of DNA, although they can also harbor small pieces of DNA called plasmids. • Bacteria are surrounded by a cell wall, which provides strength and rigidity to their cells. • They reproduce by binary fission or sometimes by budding, but do not undergo sexual reproduction.

8. Growth of E. coli

9. Bacteria can be good • Microorganisms are used in brewing, winemaking, baking, pickling, cultured dairy products yogurt and chesses. • Specially-cultured microbes are used in the biological treatment of sewage and industrial waste effluent, a process known as bioaugmentation • Microbes can be harnessed for uses such as creating steroids and treating skin diseases • The bacteria that live within the human digestive system contribute to gut immunity, synthesise vitamins such as folic acid and biotin, and ferment complex indigestible carbohydrates

11. Treating a bacteria infection • Bacterial infections may be treated with antibiotics, which are classified as bacteriocidal if they kill bacteria, or bacteriostatic if they just prevent bacterial growth • Antibiotics are used both in treating human disease and in intensive farming to promote animal growth, where they may be contributing to the rapid development of antibiotic resistance in bacterial populations (Khachatourians, 1998) • Disinfectants such as bleach are used to kill bacteria or other pathogens on surfaces to prevent contamination and further reduce the risk of infection.

12. What is a virus? • A virus particle, or virion, consists of the following: • Nucleic acid - Set of genetic instructions, either DNA or RNA, either single-stranded or double-stranded • Coat of protein - Surrounds the DNA or RNA to protect it • Lipid membrane - Surrounds the protein coat (found only in some viruses, including influenza; these types of viruses are called enveloped viruses as opposed to naked viruses)

13. What is a virus? • They cannot reproduce on their own, and for this reason they are not considered alive by some biologist. • They can reproduce within cells with disastrous results to the host organism

14. Lytic cycle • A virus particle attaches to a host cell. • The particle releases its genetic instructions into the host cell. • The injected genetic material recruits the host cell's enzymes. • The enzymes make parts for more new virus particles. • The new particles assemble the parts into new viruses. • The new particles break free from the host cell.

15. Once the new viruses are made, they leave the host cell in one of two ways: • They break the host cell open (lysis) and destroy the host cell. • They pinch out from the cell membrane and break away (budding) with a piece of the cell membrane surrounding them. This is how enveloped viruses leave the cell. In this way, the host cell is not destroyed.

16. How a virus works… • An infected person sneezes near you. • You inhale the virus particle, and it attaches to cells lining the sinuses in your nose. • The virus attacks the cells lining the sinuses and rapidly reproduces new viruses. • The host cells break, and new viruses spread into your bloodstream and also into your lungs. Because you have lost cells lining your sinuses, fluid can flow into your nasal passages and give you a runny nose. • Viruses in the fluid that drips down your throat attack the cells lining your throat and give you a sore throat. • Viruses in your bloodstream can attack muscle cells and cause you to have muscle aches.

17. What are some examples of viruses? • Common cold • Influenza and Avian Influenza • Chickenpox • Ebola • AIDS • HPV • SARS • Shingles • Smallpox • Human Immunodeficiency Virus (HIV) • bovine spongiform encephalopathy ("mad cow" disease) • Viruses that have an association to cause human cancers include some genotypes: • human papillomavirus (HPV) • hepatitis B • hepatitis C • Epstein-Barr virus • Kaposi's sarcoma-associated herpesvirus and human T-lymphotropic virus

18. How are viruses classified? They are classified by: • Shape • Nucleic acid they contain (DNA or RNA) • The kind of organism they infect

19. What do viruses need? • A virus is a type of parasite—it depends on a host organism for survival and reproduction

20. How do viruses behave? • A virus may be active • A virus can be dormant or latent

21. Active Virus • ATTACHMENT: A specific virus attaches to the surface of a specific cell • INVADE: The nucleic acid (DNA or RNA) of the virus is injected into the cell. • COPY: The viral nucleic acid takes control of the cell an begins to make new virus particles. • RELEASE: The cell bursts open, hundreds of new virus particles are released from the cell. These virus particles go on to infect other cells.

22. How does our body respond to viruses? Immunobiology, 5th ed. Janeway

23. Reduction of the spread… • Carrier organisms - mosquitoes, fleas • The air • Direct transfer of body fluids from one person to another - saliva, sweat, nasal mucus, blood, semen, vaginal secretions • Surfaces on which body fluids have dried

24. What are vaccines? • A vaccine is a substance that stimulates the body’s immune response. • The goal of vaccination is to prevent or control an infection.

25. Immunity • Immunity • The ability of the body to fight infection and/or foreign invaders by producing antibodies or killing infected cells. • Immune System • The system in the body responsible for maintaining homeostasis by recognizing harmful from nonharmful organisms and produces an appropriate response.

26. How acquired defense works • Our bodies detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own healthy cells and tissues in order to function properly. • Detection is complicated as pathogens can evolve rapidly, producing adaptations that avoid the immune system and allow the pathogens to successfully infect their hosts. • The human immune system adapts over time to recognize specific pathogens more efficiently. This defense system responds to antigens, molecules the immune system recognizes as foreign to the body. This adaptation process is referred to as "adaptive immunity" or "acquired immunity" and creates immunological memory • Immunological memory created from a primary response to a specific pathogen, provides an enhanced response to secondary encounters with that same, specific pathogen.

27. Antibodies • Y-shaped protein molecule. • Made up of variable and constant regions. • Made up of Heavy and Light chains. • Produced by B-Lymphocytes • Function: Recognize antigens, bind to and deactivate them. • Note: Variable region recognizes the anitgens.

28. How an antibody operates/works? Deactivation of a bacterium by an antibody.

29. Foreign Invaders • Called Pathogens • Viruses, bacteria or other living thing that causes disease/immune response. • Antigens • Toxins that pathogens produce that cause harm to an organism.

30. Origin of Viral Diseases • Viruses that originate in one organism pass to another, causing a disease in the new host • New pathogens, emerging viruses, pass in animals to animals spreading throughout the world

31. Influenza: • Most lethal virus in human history • The reservoir of influenza virus is in ducks, chicken, and pigs in Central Asia

32. 20th Century Flu Statistics

33. AIDS (HIV, Human immunodeficiency virus) • This virus first entered humans from chimpanzees somewhere in Central Africa probably around the early of the 20th century • Chimpanzee virus is called simian immunodeficiency virus (SIV) • SIV mutates at a rate about 1% per year • Studies have suggested that the nucleotide sequence of monkeys that carry SIV are closely related to other species

34. AIDS in the US from 1977-2006

36. Ebola Virus • Most lethal of emerging viruses from Central Africa • Attacks the human connective tissue with lethality rates up to 50% • One strand of this virus has a lethality rate in excess of 90% • Transferred through bodily fluids • Victims die too fast to spread the disease very far

37. Hantavirus • Highly fatal hemorrhagic infection “Sin Nombre” virus in the southwest United States in 1993 • RNA virus associated with rodents • Transmitted to humans through fecal contamination in areas of human habitation • Deer mouse (1993) was the source

38. SARS (Severe acute respiratory syndrome) • In 2003, a strain of coronavirus emerged to a worldwide outbreak • Respiratory infection with pneumonia-like symptoms that in over 8% of cases were fatal • This outbreak took 2 years to identify and virologist identified the Chinese horseshoe bat as the natural host. • They were carriers but not sickened by the virus

39. West Nile Virus • Mosquito borne virus • First detected in humans in Uganda, Africa, in 1937 • First infected people in North America in 1999 • Carried by infected crows and other birds

40. Chicken Pox - Shingles • Highly contagious illness caused by primary infection with varicella zoster virus • Chicken pox is spread easily through coughs or sneezes of ill individuals or through direct contact with secretions from the rash. Following primary infection there is usually lifelong immunity from further episodes of chickenpox. • After a chickenpox infection, the virus remains dormant in the body's nerve tissues. The immune system keeps the virus at bay, but later in life, usually as an adult, it can be reactivated and cause a different form of the virus called shingles.

41. How does the body fight infection/foreign invaders? The Body’s THREE lines of Defense First Line of Defense – The Skin • Provides Physical and Chemical barriers • Physical – hard to penetrate, made of indigestible keratin • Chemical – tears, sweat

42. Second Line of Defense – Nonspecific Immune Response These are defenses the body uses no matter what the invader may be. These defenses include: • Phagocytosis – (WBC) done by Macrophages • Natural Cell Killers • Inflammation - caused by release of Histamine from leukocytes • Fever – caused by histamines. The fever (high temp) kills invaders by denaturing their proteins.

44. Third Line of Defense –Specific Immune Response This is a specific response to a specific pathogen/antigen. • The response involves the creation of Antibodies.

45. The Pathway of Specific Immune Response Step 1 Pathogens eaten by Macrophage Step 2 Displays portion of Pathogen on surface Step 3 Pathogens Helper-T cell recognizes Pathogen

46. Activates B- Cell Activates Cytotoxic T- Cell Memory B-Cell Memory T-Cell Antibodies Kills Infected Cells

47. Cellular Immunity .vs. Antibody Immunity Cellular Immunity Antibody or Humoral Immunity • Carried out by T-Cells • Infected cells are killed by Cytotoxic T –Cells. • Carried out by B-cells • Antibodies are produced and dumped into blood stream. • Antibodies bind to antigens and deactivate them.

48. Immune Response Explained • Antigen infects cells. • Macrophage ingests antigen and displays portion on its surface. • Helper T- Cell recognizes antigen on the surface of the macrophage and becomes active. • Active Helper T-Cell activates Cytotoxic T-Cells and B-Cells. • Cytotoxic T-Cells divide into Active Cytotoxic T-cells and Memory T – Cells. • Active Cytotoxic T-Cells kill infected cells. • At the same time, B-Cells divide into Plasma Cells and Memory B- Cells. • Plasma cells produce antibodies that deactivate pathogen. • Memory T and Memory B cells remain in the body to speed up the response if the same antigen reappears. • Supressor T-Cells stop the immune response when all antigens have been destroyed.

49. Primary .vs. Secondary Immune Response • Primary Immune Response • This is a response to an invader the First time the invader infects the body. • No measurable immune response for first few days. • Next 10 – 15 days antibody production grows steadily • Secondary Immune Response • A more rapid response to an invader the 2nd time it invades the body. • Antibody production increases dramatically and in a much shorter time period..

50. Primary .vs. Secondary Immune Response