Three Lines of Defence

1. Three Lines of Defence Protecting the body against infection

2. http://www.elwoodstudio.com/key_pages/sub/skin.html First Line of Defence – Skin • The first line of defense provides physical barriers for the pathogen, such as our unbroken skin. • The skin provides a protective, mechanical barrier against infection due to its layer of keratin which microorganisms cannot penetrate. • It protects our internal organs and tissue from having direct contact with environmental pathogens. • The skin provides niche for non-harmful pathogens to live. These pathogens – mostly bacteria – can inhibit the growth of harmful bacteria. • The dryness of the skin also prevents growth of pathogens.

3. First Line of Defence – Fluids • Mucous membranes occur along the alimentary canal, urogenital canal, reproductive tract and respiratory surfaces. These membranes produce mucous which traps the pathogens. The mucous contains the antibody IgA which prevents viruses and bacteria from attaching. • Oils are secreted from oil glands in the skin. They can inhibit the growth of some bacteria and fungi. • Tears contain lysosomes that help destroy the cell wall of some organisms • Saliva can also destroy or inhibit pathogens with lysosomes. • Sperm contains compounds that act against bacteria. • Urine flushes the lower urinary tract as it is sterile and acidic.

4. http://www.clevelandclinic.org/health/wordofmouth/ http://pediatrics.med.unc.edu/div/infectdi/pcd/home.htm First Line of Defence - Cilia • Cilia are like tiny hairs that line the airways and trap pathogens. They sweep back and forth to help move pathogens trapped in mucous back up the airways so that they can be coughed up, sneezed out or swallowed. • Eye lashes are not cilia, but pathogens can also get caught in them and therefore not enter the eye.

5. First Line of Defence - Chemicals • Chemical barriers provide conditions that are not hospitable for microorganisms. • The pH of the skin, which is slightly acidic, can prevent the growth of some pathogens. • The skin secretes salt, which also inhibits bacterial growth. • The pH in the stomach can destroy many pathogens. • Acids in the vagina inhibit growth of fungi and bacteria in the female reproductive tract.

6. Second Line of Defence • If a pathogen makes it past the first line of defense, it enters into the body and initiates the immune response. • The second line of defense consists of an internal and non-specific type of defense. • The actual immune response is triggered by an antigen. • An antigen is a marker protein that is located on the surface of bacteria and viruses, or is part of a toxic molecule (such as venom). The body recognizes the foreign antigen as ‘non-self’. • Each pathogen has its own antigen.

7. http://www.mnsfld.edu/~mcb/ Second Line of Defence - Phagocytosis • Phagocytes are white blood cells (lymphocytes) that engulf and destroy foreign microorganisms. • Macrophages are typical phagocytes. They are large, mobile, long living and filled with lysosomes.

8. Second Line of Defence - Inflammation • When a pathogen enters our body an inflammation response is triggered by the damaged tissue. • Blood vessels dilate so that the blood flow is increased to the site of infection. This raises the temperature at the site of infection. • The increased blood flow brings an increased number of white blood cells and helps contain the infection.

9. http://www.sirinet.net/~jgjohnso/index.html Second Line of Defence – Lymph System • The lymph system consists of lymph nodes, lymph capillaries and fluid lymph. • The lymphatic system collects fluid from the blood vessels and tissues and filters it of foreign bodies. • The lymph nodes produce white blood cells that are added to the lymph as it flows towards the heart. The nodes act as filters. • Valves prevent the back flow of lymph and muscular contractions assist movement along the lymph capillaries where it reenters the circulatory system near the heart.

10. Second Line of Defence – Cell Death • Cells at the site of a wound start to die in order to seal off the area and help prevent further infection. • Programmed cell death is known as apoptosis.

11. Second Line of Defence – Other secretions • Virus infected cells have been found to produce chemicals called interferons that induce nearby non-infected cells to produce antiviral enzymes. • These antiviral enzymes block the translation of the viral messenger RNA into a polypeptide. The virus therefore cannot reproduce. • Interferons are most helpful when fighting short term viral infections such as colds and influenza. • Today, interferons are commercially available using DNA technology.

12. Third Line of Defence • Third line of defense consists of a specific immune response and is the bodies main immune response. • It helps the body to build up a resistance and fight long term infections. • This line of defense comprises of antibodies, T cells and B cells. • Antibodies are proteins produced in the lymph that bind to specific antigens and destroy them. • T cells and B cells are lymphocytes that are activated by the presence of antigens.

13. Third Line of Defence - Antibodies • Antibodies (also called immunoglobulins) are receptor proteins located in the blood plasma (and other body fluids) that combine and neutralise an antigen. • They are highly specific for the particular antigen that stimulated their synthesis and release. • The antigen-antibody complex activates a series of proteins that destroy the bacteria and release histamine (that attracts phagocytes) that causes an inflammatory response. Antibody Antigen Antigen/ antibody complex Bacterial cell

14. Third Line of Defence

15. http://www.nearingzero.net/index.html

16. Third Line of Defence - Antibodies • Antibodies can react in a number of ways: • They can combine with the antigen to cover it’s active site. • It may dissolve parts of the cell wall. • It can neutralize the toxins produced by the antigen. • IgA causes the bacteria to clump together and become less active so that it can be taken more easily to the lymph. • It can make the antigen more susceptible to phagocytosis.

17. Third Line of Defence – T Cells • T cells (or T lymphocytes) are types of non-phagocytitic white blood cells that produce a ‘cell mediated response’ and destroy antigens. • They derive from bone marrow stem cells that migrate to the thymus to become T cells. They circulate through the blood, lymph and spleen and are inactive until they come into contact with an antigen. • The antigen combines with the antibody and activates it to make copies of itself. • Once activated, some T cells secrete substances that can directly destroy antigens, others cause the bacteria to clump together so they can be taken more easily to the lymph, while others stimulate B cells and macrophages. • After an infection, some T cells remain in the body as memory cells ready incase a similar infection of the same pathogen occurs.

18. http://www.acm.uiuc.edu/sigbio/project/updated-lymphatic/lymph8.htmlhttp://www.acm.uiuc.edu/sigbio/project/updated-lymphatic/lymph8.html http://www.nearingzero.net/index.html Third Line of Defence – T Cells

19. Third Line of Defence – T Cells • Killer T Cells, or Cytotoxic T cells (Tc) secrete chemicals that destroy antigens directly or inhibit replication of viruses. They also enhance macrophage activity. Cytokines help co-ordinate B & T cells. Natural killer cells are a type of cytotoxic T cell that destroys abnormal host cells such as cancer cells or those infected by viruses. • Helper T Cells (Th) secrete interleukins (hormone like messenger chemicals between lympocytes) which enhance antibody production by B cells and helps regulate cytotoxic T cells . HIV infects T4 helper cells which reduces their number and function. They can also stimulate macrophages for phagocytosis. • Memory T Cells retain the ability to recognise the original invading antigen. Future infections can be dealt with much quicker and more effectively as they can produce large numbers of antibodies very quickly. • Suppressor T Cells help turn off the immune response once the antigen is destroyed and the infection is under control.

20. Third Line of Defence – B Cells • B cells are non-phagocytitic white blood cells and provide the ‘antibody mediated’ response. • They derive from bone marrow stem cells that stay and develop in the bone marrow and later accumulate in the spleen and lymph nodes. • The presence of antigens stimulates the lymphocytes to divide by mitosis to clone themselves. They then differentiate into plasma cells that send antibodies into the blood, or into memory cells. This usually occurs in the lymph node and causes it to swell when the body is fighting an infection. • The plasma cells secrete immunoglobulins/antibodies with a shape that is compatible with the antigen in order to form the antibody-antigen complex.

21. Third Line of Defence – B & T Cell Interaction • Once an antigen enters the body it is ingested and processed by a macrophage. When engulfing an antigen, macrophages display fragments of the antigen on their outer membrane which B & T cells recognize. • B & T cells can collaborate because they are in close proximity and often make contact with each other. • They are also both regulated by cytokines. Cytokines are proteins secreted by T cells and macrophages that signal to other cells to initiate the immune response (such as B cells transforming to plasma cells). • B cells cannot function without T cells that stimulate them to produce antibodies, and helper T cells induce B cells to divide and produce large numbers of clones.

22. http://www.livestockconcepts.com/LA200.html Antibiotics • The first antibiotic – penicillin - was discovered by Howard Florey and Alexander Fleming who won the Nobel Prize in 1945 for their work. • Penicillin is derived from the Penicillium mould and after becoming commercially available in 1941 saved the lives of many people with serious bacterial infection. • There is now a wide range of antibiotics available and they all inhibit or kill bacteria in a variety of ways. Some destroy cell walls, others destroy cell membranes, while others interfere with cellular processes such as protein synthesis. • Some antibiotics are ‘broad-spectrum’ and act on a wide range of bacteria, while others are narrow-spectrum and only act on one or two bacteria.

23. Second Line of Defence – The Immune Reponse • The immune response is the reaction of an organism to either prevent or overcome an infection caused by an invading pathogen. • The body recognises the foreigners (by their antigens) and tries to destroy them. • Organisms can be born with a natural immunity to a pathogen and therefore will not be affected by it. • Humans can acquire immunity passively by being given the antibodies via a vaccine. This type of immunity only lasts a few weeks as the person does not make their own antibodies. Babies can acquire natural passive immunity via the mothers placenta. • Acquired immunity can also be active via exposure to antigens. This type of immunity can occur naturally if the person is exposed to the pathogen and produces their own antibodies, or through vaccinations where the antigen is introduced to the persons immune system artificially.

24. Vaccination • Vaccination is the introduction (orally or intravenously) of an attenuated (less virile) or dead pathogen that induces an immune response. B cells produce the antibody to destroy the antigen, and T memory cells develop to prepare the body for future infections. • If memory cells decrease in numbers over time, booster vaccinations can be given. • Vaccines do not cause the disease as the pathogens are not alive. • Before 1700s the smallpox virus killed in pandemic (worldwide) proportions. In 1797 Edward Jenner noticed that milkmaids did not contract the disease. He injected a young boy with cow pox and then with smallpox and noted that he did not contract the disease. The first innoculation (developed from the sore of a milkmaid with cowpox) against a deadly disease had been discovered. The WHO introduced this vaccine worldwide in the1960s and has now eradicated smallpox. • Today we vaccinate children against bacterial diptheria and viral polio.

25. Organ Transplant • Organ transplant is being used more and more to treat patients whose own tissues no longer function sufficiently. Organs that can be transplanted include the kidney, liver, heart, lung and bone marrow. • The introduced organ contains antigen proteins that are recognised as foreign to the host body which leads to the stimulation of an immune response that could attack the new tissue. • Tissue transplant should be carried out between individuals who are genetically similar for the tissue proteins – that is, they have a high MHC (major histocompatibility). Identical twins for example are completely compatible. • Drugs that suppress the immune response are necessary so that the host does not reject the new organ. • The obvious problem with this is that, with a suppressed immune system, the host is prone to the dangers of any infection. The use of suppressive drugs must be balanced with the risk of life threatening infection.

26. References • American Lung Association of Ohio and Cleveland Clinic Health System (2000) Youth Tobacco Protection Program Retrieved from site http://www.clevelandclinic.org/health/wordofmouth/ May 2004. • Aubusson, P. and Kennedy, E. (2000) Biology in Context. The Spectrum of Life Oxford University Press, Melbourne, Australia. • Board of Studies (2002) STAGE 6 SYLLABUS Biology Board of Studies, NSW, Australia. • Carson, J. (2000) University of North Carolina Paediatrics Department. Retrieved from site http://pediatrics.med.unc.edu/div/infectdi/pcd/home.htm May 2004. • Humphreys, Kerri (2002) The Search for Better Health. Science Press, Australia. • Johnson, J. (2004) The World of Biology Retrieved from site http://www.sirinet.net/~jgjohnso/index.html May 2004. • Kinnear, J and Martin, M (2001) Biology 2 HSC Course: Jacaranda HSC Science John Wiley & Sons, Australia, Ltd.

27. References • Kim, Nick [no date] Nearing Zero retrieved from website http://www.nearingzero.net/index.html January 2004. • Mudie, K. et.al. (2000) Heinemann Biology Malcom Parsons, National Library of Australia, Australia. • Sternik, J. (2002) Cell and Molecular Biology. Mansfeild University. Retrieved from site http://www.mnsfld.edu/~mcb/ May 2004.