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“Fighting the Enemy Within”

phagocytic leukocyte. “Fighting the Enemy Within”. Immune System. lymphocytes attacking cancer cell. lymph system. Avenues of attack. Points of entry digestive system respiratory system urogenital tract break in skin Routes of attack circulatory system lymph system.

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“Fighting the Enemy Within”

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  1. phagocytic leukocyte “Fighting the Enemy Within” Immune System lymphocytes attacking cancer cell lymph system

  2. Avenues of attack • Points of entry • digestive system • respiratory system • urogenital tract • break in skin • Routes of attack • circulatory system • lymph system

  3. Why an immune system? All in agood day’swork! • Attack from outside • lots of organisms want you for lunch! • animals must defend themselves against unwelcome invaders • viruses protists • bacteria  fungi • we are a tasty vitamin-packed meal • cells are packages of macromolecules • no cell wall • traded mobility for susceptibility • Attack from inside • defend against abnormal body cells = cancers

  4. Types of Immunity • Innate Immunity = non-specific protection against many different microbes • Acquired Immunity = specific protection against microbes

  5. Lines of defense Barriers Non-Specific • 1st line: • Nonbroad, external defense • “walls & moats” • skin & mucus membranes • 2nd line: • broad, internal defense • “patrolling soldiers” • leukocytes (phagocytic WBCs) • 3rd line: • specific, acquired immunity • “elite trained units” • lymphocytes & antibodies Non-specific patrol Immune system

  6. 1st: External defense • non-specific defense • external barrier • epithelial cells & mucus membranes • skin • respiratory system • digestive system • genito-urinary tract Lining of trachea: ciliated cells & mucus secreting cells

  7. 1st: Chemical barriers on epithelium • Skin & mucous membrane secretions • sweat • pH 3-5 • tears • washing action • mucus • traps microbes • saliva • anti-bacterial = “lick your wounds” • stomach acid • pH 2 • anti-microbial proteins • lysozyme • digests bacterial cell walls

  8. 2nd: Internal, broad range patrol leukocytes • innate defense • rapid response • Inflammatory response • Interferons • cells & proteins • attack invaders that penetrate body’s outer barriers • leukocytes • phagocytic white blood cells • anti-microbial proteins • inflammatory response

  9. Leukocytes: Phagocytic WBCs • Neutrophils • attracted by chemical signals released by damaged cells • enter infected tissue, engulf & ingest microbes • amoeba-like (fierce!) • digest via lysosomes • ~3 day life span • Macrophages • “big eater” • bigger, long-lived phagocytes

  10. Phagocytosis • phagocytes are white blood cells (leukocytes) that ingest microbes • neutrophils and macrophages are the most common

  11. Phagocytes macrophage yeast

  12. Nonspecific Defenses: Lymphatic System • “filters” interstitial fluid and blood continually • immune system cells in the lymph (in lymph nodes) take care of foreign particles and microbes

  13. Lymph system Production & transport of leukocytes Traps foreign invaders lymph vessels (intertwined amongst blood vessels) lymph node

  14. Development of Red & White blood cells inflammatory response Red blood cells fightparasites short-lived phagocytes 60-70% WBC develop into macrophages

  15. Inflammatory response • Damage to tissue triggers local inflammatory response • release histamines & prostaglandins • capillaries dilate, more permeable • increase blood supply • delivers WBC, RBC, platelets, clotting factors • lead to clot formation • swelling, redness & heat of inflammation & infection • Brings more phagocytes

  16. Inflammatory Response • Chemokines are small proteins that guide macrophages and signal them to increase lysosome contents

  17. Inflammatory response • Reaction to tissue damage Pin or splinter Blood clot swelling Bacteria Chemical alarm signals Phagocytes Blood vessel

  18. Signs of Inflammation • Redness • Due to the dilation of blood vessels • Swelling • Due to extra fluid in the area • Heat • Due to dilation of blood vessels (increased blood flow) • Pain • Extra fluid presses on nerves

  19. Fever • When a local response is not enough • systemic response to infection • activated macrophages release interleukin-1 • triggers hypothalamus in brain to readjust body thermostat to raise body temperature • higher temperature helps defense • inhibits bacterial growth • stimulates phagocytosis • speeds up repair of tissues • causes liver & spleen to store iron reducing blood iron levels • bacteria need large amounts of iron to grow

  20. 3rd: Acquired Immunity • Specific defense • lymphocytes • B lymphocytes (B cells) • T lymphocytes (T cells) • antibodies • immunoglobulins • Responds to… • antigens • specific microorganisms • specific toxins • abnormal body cells

  21. Antigens • Proteins that serve as cellular name tags • foreign antigens cause response from WBCs • proteins belonging to: • viruses, bacteria, protozoa, parasitic worms, fungi, toxins • non-pathogens: pollen & transplanted tissue • B cells & T cells respond to different antigens • B cells recognize intact antigens • invaders in blood & lymph • T cells recognize antigen fragments • invaders which have infected cells “self” “foreign”

  22. Lymphocytes • B cells • mature in bone marrow • humoral response system • “humors” = body fluids • produce antibodies (2000 over a 4-5 day life span) • T cells • mature in thymus • cellular response system • Learn to distinguish “self” from “non-self” antigens during maturation

  23. B cells • Humoral response = “in fluid” • defense against attackers circulating freely in blood & lymph • Specific response • produces antibodies against specific antigen • tagging protein = immunogloblin • millions of different B cells, each produces different antibodies,each recognizes a different antigen • types of B cells • plasma cells • immediate production of antibodies • short term release • memory cells • long term immunity

  24. Antibodies Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y • Proteins that bind to a specific antigen • multi-chain proteins produced by B cells • antibodies match molecular shape of antigens • immune system has antibodies to respond to millions of antigens (invaders) • tagging system • “this is foreign!” Y Y Y Y variable binding region Y Y Y Y each B cell has ~100,000 antigen receptors

  25. How antibodies work

  26. B cell immune response Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y invader(foreign antigen) B cells + antibodies memory cells “reserves” recognition Y capturedinvaders Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y clone 1000s of clone cells plasma cells release antibodies 10 to 17 days for full response tested by B cells (in blood & lymph)

  27. Primary versus Secondary Response • Primary Response = initial immune response to antigen • Secondary Response = immune response when exposed the same antigen a second time (carried out by Memory cells)

  28. 1° vs 2° response to disease • Memory B cells allow a rapid, amplified response with future exposure to pathogen

  29. How can we have so many antibody proteins & so few genes? Variable region Antibody Constant region Light chain B cell Heavy chain Variable DNA combinations: • 1M different B cells • 10M different T cells Rearrangement of DNA Translation of mRNA Transcription of gene V mRNA 40 genes for Variable region DNA of differentiated B cell D J C C Chromosome of undifferentiated B cell

  30. T cells • Immune response to infected cells • defense against invaders inside infected cells • viruses & bacteria within infected cells, fungi, protozoa & parasitic worms • defense against “non-self” cells • cancer & transplant cells • Kinds of T cells • helper T cells • stimulate immune system • killer T cells (Cytotoxic cells) • attack infected body cells

  31. How are cells tagged with antigens T cell MHC proteins displaying self-antigens • Glycoproteins on surface of cells have unique “fingerprint” • major histocompatibility proteins (MHC) • human leukocyte antigens (HLA) • MHC proteins constantly export bits of cellular protein to cell surface • “snapshot” of what is going on inside cell

  32. How do T cells know a cell is infected MHC proteins displaying foreign antigens T cell • Infected cells digest some pathogens & export pieces to MHC proteins on cell surface • antigen presenting cells (APC) invading pathogen T cell antigen receptors

  33. T cell response Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y infected cell killerT cell activatekiller T cells stimulateB cells &antibodies activated macrophage helperT cell helperT cell helperT cell helperT cell helperT cell Y Y Y Y Y Y Y Y interleukin 2 interleukin 1 or interleukin 2

  34. Attack of the Killer T cells • Destroys infected body cells • binds to target cell • secretes perforin protein • punctures cell membrane of infected cell (causes death) Vesicle Killer T cell Killer T cellbinds toinfected cell Perforinpuncturescell membrane Cell membrane Cell membrane Infected cell destroyed Target cell

  35. Immune response Y Y Y Y Y Y Y antibodies Y Y Y Y pathogen invasionantigenexposure free antigens in blood antigens on infected cells macrophages humoral response cellular response helperT cells B cells T cells plasmaB cells memoryB cells memoryT cells cytotoxicT cells

  36. Immunizations • Active immunity = immunity due to exposure to an antigen (produces memory cells) • Immunizations (vaccinations) allow an individual to develop active immunity to an antigen without actually getting “sick” during initial exposure • Vaccines are usually made up of weakened viruses or microbes

  37. Vaccinations • Active immunity • immune system exposed to harmless version of pathogen • Stimulates immune system to produce antibodies to invader • rapid response if future exposure • Most successful against viral diseases

  38. Jonas Salk 1914 – 1995 • Developed first vaccine • against polio April 12, 1955

  39. Polio epidemics 1994: Americas polio free

  40. Passive immunity • Maternal immunity • antibodies pass from mother to baby across placenta or in breast milk • critical role of breastfeeding in infant health • mother is creating antibodies against pathogens baby is being exposed to • Injection • injection of antibodies • short-term immunity

  41. Immune Responses to Donor Tissue • There are 3 kinds of antigens associated with blood: A, B, and Rh • Antibodies are produced that react to the wrong blood type (Anti A and Anti B) • This causes agglutination (clumping of RBCs) and lysis (bursting) of RBCs which can lead to serious conditions

  42. Blood Donors and Recipients • What blood type is the Universal donor? • Type O  does not have any surface antigens (A or B) so the donor’s body will not attack it • What is the blood type of the Universal recipient? • Type AB  no anti A or B, so it won’t attack any of the other blood cells

  43. Rh factor • The Rh factor is another surface protein that is found on the surface of red blood cells • An individual either has the Rh factor on RBC (+) or doesn’t (-) – genetically determined • Individuals who are Rh- will produce antibodies that attack Rh+ cells • This is particularly dangerous if a mother is Rh- and her fetus is Rh+ (she produces antibodies against Rh)

  44. Tissue Donors • In tissues, the body looks at MHC molecules to identify self from non-self. • What is the best host of tissue you might need for a transplant? • Yourself  or someone very closely related to you (identical twin would be ideal)

  45. HIV & AIDS • Human Immunodeficiency Virus • virus infects helper T cells • helper T cells don’t activate rest of immune system: T cells & B cells • also destroy T cells • Acquired ImmunoDeficiency Syndrome • infections by opportunistic diseases • death usually from other infections • pneumonia or cancer

  46. Immune system malfunctions • Auto-immune diseases • immune system attacks own molecules & cells • lupus • antibodies against many molecules released by normal breakdown of cells • rheumatoid arthritis • antibodies causing damage to cartilage & bone • diabetes • beta-islet cells of pancreas attacked & destroyed • multiple sclerosis • T cells attack myelin sheath of brain & spinal cord nerves • Allergies • over-reaction to environmental antigens • allergens = proteins on pollen, from dust mites, in animal saliva

  47. Allergies • When the immune system “overreacts” or becomes hypersensitive to certain antigens • Most allergies involve the actions of IgE antibodies • This causes mast cells to release histamine

  48. Allergies • Histamine triggers inflammatory responses  leads to allergy symptoms such as runny nose, tearing eyes, etc. • Many allergy medicines are antihistamines to block the receptors for histamine

  49. Key attributes of immune system • 4 attributes that characterize the immune system as a whole • specificity • antigen-antibody specificity • diversity • react to millions of antigens • memory • rapid 2° response • ability to distinguish self vs. non-self • maturation & training process to reduce auto-immune disease

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