phagocytic leukocyte “Fighting the Enemy Within” Immune System Chapter 51 AP Biology lymphocytes attacking cancer cell lymph system 2006-2007 Avenues of attack Points of entry digestive system respiratory system urogenital tract break in skin Routes of attack circulatory system lymph system AP Biology Why an immune system? Attack from outside lots of organisms want you for lunch! animals must defend themselves against unwelcome invaders viruses bacteria All in a good day’s work! protists fungi we are a tasty vitamin-packed meal cells are packages of macromolecules no cell wall traded mobility for susceptibility Attack from inside AP Biology defend against abnormal body cells = cancers Lines of defense 1st line: Barriers broad, external defense “walls & moats” skin & mucus membranes 2nd line: Non-specific patrol broad, internal defense “patrolling soldiers” leukocytes (phagocytic WBCs) 3rd line: Immune system specific, acquired immunity “elite trained units” AP Biology lymphocytes & antibodies 1st: External defense non-specific defense external barrier epithelial cells & mucus membranes skin respiratory system digestive system genito-urinary tract Lining of trachea: AP Biology ciliated cells & mucus secreting cells 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 AP Biology anti-microbial proteins lysozyme digests bacterial cell walls 2nd: Internal, broad range patrol leukocytes innate defense rapid response cells & proteins attack invaders that penetrate body’s outer barriers leukocytes phagocytic white blood cells anti-microbial proteins inflammatory response AP Biology 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 AP Biology Phagocytes macrophage AP Biology yeast Lymph system Production & transport of leukocytes Traps foreign invaders lymph vessels (intertwined amongst blood vessels) AP Biology lymph node Development of Red & White blood cells inflammatory response Red blood cells fight parasites AP Biology develop into macrophages short-lived phagocytes 60-70% WBC 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 AP Biology Inflammatory response Reaction to tissue damage Pin or splinter Blood clot swelling Bacteria Chemical alarm signals Phagocytes Blood vessel AP Biology 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 AP Biology of iron to grow 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 AP Biology 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” AP Biology “foreign” Lymphocytes B cells mature in bone marrow humoral response system “humors” = body fluids produce antibodies T cells mature in thymus cellular response system Learn to distinguish “self” from “non-self” antigens during maturation AP Biology 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 AP Biology types of B cells plasma cells immediate production of antibodies short term release memory cells long term immunity Y “this is foreign!” variable binding region Y Y Y Y Y Y Y Y Y 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 Y Y Y Proteins that bind to a specific antigen Y Y Antibodies Y Y Y Y Y AP Biology Y Y each B cell has ~100,000 antigen receptors How antibodies work AP Biology 10 to 17 days for full 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 release antibodies Y Y plasma cells AP Biology recognition Y Y Y Y Y Y Y Y Y Y Y Y Y captured invaders Y memory cells Y B cells + antibodies Y Y Y Y Y tested by B cells (in blood & lymph) invader (foreign antigen) “reserves” Y Y B cell immune response clone 1000s of clone cells 1° vs 2° response to disease Memory B cells allow a rapid, amplified response with future exposure to pathogen AP Biology 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: Transcription of gene • 1M different B cells • 10M different T cells mRNA DNA of differentiated B cell C AP Biology Rearrangement of DNA V 40 genes for Variable region D C J Chromosome of undifferentiated B cell 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 AP Biology 1914 – 1995 Jonas Salk Developed first vaccine against polio April 12, 1955 AP Biology Polio epidemics 1994: Americas polio free AP Biology 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 AP Biology 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 AP Biology killer T cells attack infected body cells How are cells tagged with antigens Glycoproteins on surface of cells have unique “fingerprint” major histocompatibility proteins (MHC) MHC proteins constantly export bits of cellular protein to cell surface “snapshot” of what is going on inside cell T cell MHC proteins displaying self-antigens AP Biology How do T cells know a cell is infected Infected cells digest some pathogens & export pieces to MHC proteins on cell surface invading pathogen antigen presenting cells (APC) MHC proteins displaying foreign antigens T cell AP Biology T cell antigen receptors T cell response infected cell helper T cell Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y helper T cell AP Biology stimulate B cells & antibodies Y activated macrophage Y or helper T cell helper T cell Y interleukin 1 activate killer T cells Y helper T cell killer T cell Attack of the Killer T cells Destroys infected body cells binds to target cell secretes perforin protein punctures cell membrane of infected cell Killer T cell Killer T cell binds to infected cell Vesicle Cell membrane Perforin punctures cell membrane Cell membrane AP Biology Infected cell destroyed Target cell Immune response pathogen invasion antigen exposure free antigens in blood humoral response macrophages cellular response B cells helper T cells T cells Y Y Y Y Y Y Y Y Y antibodies AP Biology memory B cells Y plasma B cells Y antigens on infected cells memory T cells cytotoxic T cells 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 -IgE AP Biology 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 AP Biology Any Questions?? AP Biology 2006-2007