1. The Immune System Chapter 10

2. Invaders all around Right now, as you sit in class, there are billions of viruses, bacteria, dust mites, dust particles – you name it – floating around this room The vast majority of it won’t get into your system since your skin is a natural barrier to anything that tries to infiltrate your body But what about all those openings in your head?

3. Keeping invaders out If the interiors of our bodies didn’t need to communicate with the outside world, we would probably get sick far less often However, because we need to ingest food, breathe, and hear – openings in our bodies are required to allow these functions to happen

4. The greatest army of all Your body has an amazing ability to fight off potential invaders Although we hate getting sick – it is a sign that we are healthy – our immune system is at work, destroying invaders and learning how to keep them out, if they ever invade again

5. ANTIGENS

6. Know your enemy Any material that is foreign to our body are known as ANTIGENS They can be biological, like bacteria They can also be inorganic: like pollen that illicits allergic reactions They can be organic: like viruses and prions

7. What’s alive and what’s not? The most common anitgens that we fear are usually bacteria and viruses However it is important to note the differences in how they infect us

8. Bacteria Bacteria are living organisms, and when they invade the human body, they live outside of the cells of the body, using substances around the cells to metabolize for energy

9. Localized infections For this reason, bacterial infections are usually localized – they affect the specific areas that they invade Not all bacteria are harmful; only some cause problems and a few form symbiotic relationships with us – such as E.coli that live inside our intestines and help us digest certain types of molecules

10. Bacterial infections Examples of bacterial infections include

11. Organic antigens Viruses, and an up and coming invader, prions, are antigens that are often described as being “alive” but they are technically not

12. Viruses Viruses are essentially a protein capsule that house DNA or RNA This means that viruses are harder to fight than bacteria because they are often hidden inside cells – and they can mutate by incorporating DNA from their hosts into newly reproduced viruses

14. Viral infections

15. Prions A recent infectious agent, prions, are gathering attention because of the dangerous nature of their infections Prions are essentially short infectious proteins

16. Accumulation As more and more prions form, they aggregate (group together) and form plaques in normal tissue

17. Prion diseases Mad Cow Disease or Bovine Spongiform Encephalopathy (BSE) Scrapie is seen in sheep – and is named so because the brain disruption causes sheep to scrape themselves against trees – forgoing all other activities like eating or sleeping – until they die

18. Death outside the body Viruses and bacteria can be killed by heat– some are more resilient than others Prions are more notorious – they are very resistant to heat

19. The attack This is the equivalent of a cell’s “face” – just as we can recognize someone foreign that we have never seen before, the unique nature of glycoproteins is the method by which cells recognize each other

20. Your body knows you That means that your immune system – your security force – can recognize “self” cells by the unique glycoproteins that are found on the surface of your cells

21. Friendly fire Rheumatoid arthritis, Lupus, and Grey’s disease are examples of autoimmune diseases

22. Hurts so good Do you ever wonder why certain similar symptoms: runny, stuffed up nose and fever, for example, can show up in completely different conditions? Someone with allergies and a cold can develop congestion Fevers can be a common symptom in the flu, and severe food poisoning

23. You do it to yourself You might be surprised to find out that a lot of the pain you experience when you are sick is not the mechanism of action of the invader In fact, most of the time it is your body’s immune response that creates the terrible symptoms that you experience

24. Similar actions This explains why similar symptoms appear in various illnesses Since your immune system battles all of these different invaders, the spectrum of symptoms is similar since the mechanism of attack for all invaders is similar

25. THE IMMUNE SYSTEM

26. Meet your personal army Your immune system is divided up into two basic groups INNATE IMMUNE SYSTEM: this is your unspecialized infantry – ACQUIRED IMMUNE SYSTEM: this is your special forces –

27. Recruitment Immune cells originate from the bone marrow Stem cells from the bone marrow differentiate and specialize into cells that will either become part of the innate or acquired immune system Since they travel in the circulatory system, they will make up a

28. Basic Training Innate immune system cells will then roam the body or set up shop at specific “base camps” – areas where there is a high concentration of immune cells These areas in the body are where fluid tends to be stagnant – usually associated with the lymphatic system that recycles plasma back into the circulatory system

29. Roll Call Innate Immune System CellFunction Platelets-formed from a larger cell called a MEGOKARYOCYTE -helps to stop bleeding by plugging up openings in tissue Macrophage ”foot patrol” -derived from monocytes -Macro=big, phage = eater -these cells patrol your body, engulfing antigens and then presenting evidence of infection to T-cells (acquired immune cells) Eosinophil “communications” -help to release a large number of chemicals known as CYTOKINES that help signal immune cells and start up inflammatory responses in the immune system -also secrete RNAses to help battle viruses Basophil “communications” -secrete histamine and help initiate inflammatory responses -also secrete cytokines Neutrophil “light infantry” -highly mobile -can move towards sites of infection when signalled by cytokines -can phagocytose anitgens and digest them with a variety of enzymes and chemicals

30. macrophage eosinophil basophil neutrophil

31. Black Ops Cells that are members of the acquired immune system will undergo further training T-CELLS Within the thymus, T-cells will mature, and “learn” to fight off specific antigens B-CELLS,

32. Roll call Acquired Immune System: T-cells CellFunction Cytotoxic T-Cell ”black ops” -destroy infected self cells and tumour cells Helper T-Cells ”the general” -activates T-cells and B-cells -shuts down immune response -shuts down autoimmune reactive T-cells Memory T-Cell ”operations experts” -to “remember” former infections by storing information regarding protein markers about an antigen -reactivates acquired immune response in case of re-infection Killer T-Cell ”field commanders” -communicates with macrophages and other IIS cells to identify antigens -helps to activate Helper T-Cells to start immune responses and can also kill tumour and infected cells

33. Killer T-cell

34. Roll Call Acquired Immune System: B-Cells Cell Function Plasma B-Cell “munitions experts” -to create antibodies to target specific antigens -these antibodies attack antigens that are free floating outside cells Memory B-Cell “munitions archive” -long living cells that remember specific antigens – these cells know how to produce antibodies that can attack specific antigens -will quickly reproduce antibodies to prevent re-infection of cells Antibodies (Ab) “ordinance” (fancy word to refer to ammunition) AKA: Immunoglobulins (Ig) -Y-shaped proteins produced by Plasma B-cells -these proteins attach themselves to antigens -antibodies can cause antigens to cluster into large groups preventing mobility -also marks antigens so they can be easily recognized by macrophages or neutrophils -some Ab can activate pathways on bacteria that punch holes in their cellular membranes causing them to burst

35. B-cell

36. A word on ordinance Antibodies have two main sections: The arms of the “Y” The stalk of the “Y” Once the arms of the antibody attaches to a virus, the stalk of the antibody is recognized by macrophages/neutrophils and this helps to mediate endocytosis

38. THE IMMUNE RESPONSE

39. Rules of Engagement Let’s start the immune response with a basic infection scenario – someone has sneezed near you and have inhaled some of the ejected droplets These droplets contain a species of rhinovirus – a species of virus that causes the common cold

40. Foot patrol A macrophage that roams around your upper respiratory tract, comes across one of these viruses and engulfs it when it realizes it is foreign Meanwhile, the virus has attached itself to some cells at the back of your throat – and has began to infect the cells near your tonsils

41. Report The macrophage swallows the virus and digests it Some of the protein from the virus’ protein coat is attached to a large complex molecule called a MHC = Major Histocompatability Complex

44. Initial invasion As the macrophage tries to give it’s report, the lymphocytes in the tonsils have noticed that a foreign invader is around Basophils and Eosinophils secrete cytokines – these cytokines signal to other macrophages and neutrophils that there is an invader

45. Front line attack As a larger number of WBC reach your tonsils, you notice a “tickle” in the back of your throat, and perhaps on day 2, your throat is sore This is the result of the inflammatory response

46. Localized response You will notice, therefore, that the innate immune system produces localized immune responses This is the reason why, after getting a cut, your skin will swell and become red and sensitive if not cleaned properly; your innate immune system is sending in the troops to fight antigens

47. A good response The pain is not a bad thing; along with incoming macrophages and neutrophils are T- cells that are attracted to the cytokines Our heroic macrophage continues to find T- cells to report to; presenting the viral protein over and over again until finally – he comes across the right Helper T-Cell that has the right receptor to fit to the antigenic protein in the MHC

48. Feeling miserable http://highered.mcgraw- hill.com/sites/0072507470/student_view0/chapter22/animation__an tigen_processing.html http://highered.mcgraw- hill.com/sites/0072507470/student_view0/chapter22/animation__an tigen_processing.html By now, day 3 or 4, you are noticing more and more effects of the immune response; your nose is getting stuffed up

49. Help is on the way The Helper T-Cell springs into action; it begins to activate Cytotoxic T-cells, Killer T-Cells and Plasma B- Cells that recognize the same proteins These cells begin to multiply in number to increase their forces

50. Everyone join the fray Your throat looks like a war zone now Roaming Killer and Cytotoxic T’s are destroying infected throat cells All the while cells that are infected are trying to desperately release more and more viruses – but now that your immune system is on the look out, they aren’t getting to infect very many cells

51. Meanwhile Day 4-6: you are helping the system along By now you are drinking lots of tea, water, and soup to help the production of mucous Each time you blow your nose, thousands of viral particles are being ejected out

52. The battle is won Eventually, the viral threat is banished Helper T-cells call off the Killer and Cytotoxic T- cells; their numbers start to drop

53. You start to feel better By day 6-8 you notice that your throat hurts less and you are less stuffed up Your mucous is running clear and watery now that there are no dead WBC or viruses to clog it up as much

54. Other possible symptoms Certain viruses and bacteria (like the influenza virus) have glycoproteins that can signal the immune system to secrete a specific set of cytokines (rhinoviruses do not initiate a fever – hence no fever usually equals a cold not flu)

55. Cold vs. flu Influenza differs slightly to the rhinovirus in how it affects us; the immune response is much stronger leading to a large amount of circulating cytokines leading to aches and pains as well There is thought that some of the tissue damage caused by the flu may also be a reason for this

56. Never again The memory cells retain the DNA blueprint of the antigen If you are exposed to the same antigen, then your body will rise up quickly to kill it

57. Vaccination This is the basis of ACTIVE IMMUNIZATION Your body will mount an immune response – but you will not be at threat of an actual infection After the immunization your body will have the memory cells capable of recognizing the antigen PASSIVE IMMUNITY Active immunizations last longer than passive

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59. Where does the variety come from? One thing you should notice is the amazing SPECIFICITY of the immune system This specificity is good and bad about the immune system It’s good because it allows the immune system to streamline attacks and to ensure that they aren’t attacking the wrong thing

60. The face of the enemy The only negative thing is that a small change in the antigen means that an entire new immune response must be initiated since each acquired immune cell is so specific This is why virus and bacteria continue to plague us; especially viruses

61. Mutations Since bacteria and viruses have short lifespans, multiple generations mean multiple opportunities for changing around genes

62. Retroviruses Viruses that contain RNA are known as RETROVIRUSES

63. Our gene shuffling That is part of the purpose of training T-cells in the thymus and B-cells in the spleen One of the things that occur is a re-shuffling of DNA in these cells to produce surface molecules that can recognize different proteins That means that each T-cell exiting the thymus or B-cell exiting the spleen has a unique section of DNA that codes for surface proteins capable of binding with specific MHC + antigen protein complexes

64. Systemic vs. Local immune responses The immune response is so powerful that if it gets out of control, it can kill us In fact, infection by the H1N1 or SARS virus causes death because the viral infection occurs in the lungs, causing such a massive localized inflammatory response that patients quite literally drown to death – they develop such bad pneumonia (fluid accumulation in the lungs) that it can’t be removed fast enough

65. Systemic immune response The cytokines released by the revved up immune system become so wide spread that they start affecting other body systems Since the immune response affects fluid control in our body this can affect our cardiovascular system and ultimately our organs, causing death

66. Other triggers The immune response can also be triggered by autoimmune responses or allergic responses Whether or not the immune response remains localized or goes systemic will depend on the nature of the antigen or cause, and ofcourse, the genetic profile of the person Some individuals have a tendency to have stronger immune responses than others

67. HIV: HUMAN IMMUNODEFICIENCY VIRUS

68. Man down So what happens if you come across a virus that cripples your immune system? Remember that viruses are specific; they can only attack certain types of cells The HIV virus is designed to attack T-cells They specifically target T-cells through a cell marker on T-cells called a CD4 molecule

70. Infection route HIV is transmitted through bodily fluids: vaginal fluids, pre-seminal fluid, semen, breast milk and blood It is a relatively large virus The most common forms of infection come from sexual intercourse, infected needles in drug paraphanelia, and mother-child infection

71. Evolution HIV is related to SIV = Simian Immunodeficiency Virus that infects primates but doesn’t produce the same symptoms in primates The virus is believed to have arisen in African primate populations This contact allowed the virus to evolve and mutate – eventually producing a version that was able to affect humans adversely

72. Immunity There is a very, VERY, VERY small percentage of the population that is immune to the HIV virus due to a specific mutation in the CD4 molecule that prevents it from binding to HIV

73. Changing face HIV is a retrovirus Once it gains access to a T-cell, it uses an enzyme known as a REVERSE TRANSCRIPTASE to turn RNA into DNA This DNA is then implanted into the T-cell DNA to turn it into a viral producing factory

75. AIDS When an HIV infection becomes widespread, compromising the T-cell count, the individual is immuno-compromised

76. Dangers? Based on what you know, what are the risks of HIV infection, and ultimately, how does someone “die” of AIDS?

77. Opportunistic invaders With the immune system down – especially the T-cells, the immune system becomes unable to fight off viruses and cancers

78. Common invaders Karposi’s Sarcoma: Pneumocytosis pneumonia: Chronic GI tract infections:

79. The rich and poor divide HIV infections can be controlled with good medications Those infected with HIV can have comfortable lives for many years Untreated HIV infections tend to progress to AIDS within 10 years However, the medication is expensive, and the divide between first and third world countries is very apparent in the availability of these drugs to individuals suffering from it