Presentation on theme: "Fighting the Enemy Within! Immune / Lymphatic System"— Presentation transcript:
1 Fighting the Enemy Within! Immune / Lymphatic System phagocytic leukocyteFighting the Enemy Within!Immune / Lymphatic Systemlymphocytesattackingcancer celllymphsystem
2 Avenues of attack Points of entry Routes of attack digestive system respiratory systemurogenital tractbreak in skinRoutes of attackcirculatory systemlymph system
3 What’s in your lunchbox? Why an immune system?Attack from outsidelots of organisms want you for lunch!animals are a tasty nutrient- & vitamin-packed mealcells are packages of macromoleculesno cell walltraded mobility for susceptibilityanimals must defend themselves against invadersvirusesHIV, flu, cold, measles, chicken pox, SARSbacteriapneumonia, meningitis, tuberculosisfungiyeast (“Athlete’s foot”…)protistsamoeba, Lyme disease, malariaAttack from insidedefend against abnormal body cells = cancersMmmmm,What’s in your lunchbox?
4 Lymph system Production & transport of leukocytes Traps foreign invadersLymph systemlymph vessels(intertwined amongst blood vessels)lymph node
5 Development of Red & White blood cells Red blood cellsinflammatory responsefight parasitesdevelop into macrophagesshort-lived phagocytes60-70% WBC
12 Destroying cells gone bad! Natural Killer Cells perforate cellsrelease perforin proteininsert into membrane of target cellforms pore allowing fluid to flow into cellcell ruptures (lysis)apoptosisvesiclenatural killer cellperforincell membraneperforin punctures cell membranecell membranevirus-infected cell
13 Anti-microbial proteins Complement system~20 proteins circulating in blood plasmaattack bacterial & fungal cellsform a membrane attack complexperforate target cellapoptosiscell lysisextracellular fluidcomplement proteins form cellular lesionplasma membrane of invading microbecomplement proteinsbacterial cell
14 Inflammatory response Damage to tissue triggers local non-specific inflammatory responserelease histamines & prostaglandinscapillaries dilate, more permeable (leaky)increase blood supplydelivers WBC, RBC, platelets, clotting factorsfight pathogensclot formationaccounts for swelling, redness & heat of inflammation & infection
15 Inflammatory response Reaction to tissue damagePin or splinterBlood clotswellingBacteriaChemicalalarm signalsPhagocytesBlood vessel
16 Fever When a local response is not enough systemic response to infectionactivated macrophages release interleukin-1triggers hypothalamus in brain to readjust body thermostat to raise body temperaturehigher temperature helps defenseinhibits bacterial growthstimulates phagocytosisspeeds up repair of tissuescauses liver & spleen to store iron, reducing blood iron levelsbacteria need large amounts of iron to growCertain bacterial infections can induce an overwhelming systemic inflammatory response leading to a condition known as septic shock.Characterized by high fever and low blood pressure, septic shock is the most common cause of death in U.S. critical care units.Clearly, while local inflammation is an essential step toward healing, widespread inflammation can be devastating.
17 3rd line: Acquired (active) Immunity Specific defenselymphocytesB lymphocytes (B cells)T lymphocytes (T cells)antibodiesimmunoglobulinsResponds to…antigensspecific pathogensspecific toxinsabnormal body cells (cancer)
18 How are invaders recognized: antigens proteins that serve as cellular name tagsforeign antigens cause response from WBCsviruses, bacteria, protozoa, parasitic worms, fungi, toxinsnon-pathogens: pollen & transplanted tissueB cells & T cells respond to different antigensB cells recognize intact antigenspathogens in blood & lymphT cells recognize antigen fragmentspathogens which have already infected cells“self”“foreign”
19 Lymphocytes B cells T cells bone marrowLymphocytesB cellsmature in bone marrowhumoral response system“humors” = body fluidsproduce antibodiesT cellsmature in thymuscellular response systemLearn to distinguish “self” from “non-self” antigens during maturationif they react to “self” antigens, they are destroyed during maturationTens of millions of different T cells are produced, each one specializing in the recognition of oen particar antigen.
20 B cells Humoral response = “in fluid” Specific response defense against attackers circulating freely in blood & lymphSpecific responseproduce specific antibodies against specific antigenTypes of B cellsplasma cellsimmediate production of antibodiesrapid response, short term releasememory cellslong term immunity
21 Antibodies Proteins that bind to a specific antigen Y Y Y Y Y Y Y Y Y multi-chain proteins produced by B cellsbinding region matches molecular shape of antigenseach antibody is unique & specificmillions of antibodies respond to millions of foreign antigenstagging “handcuffs”“this is foreign…gotcha!”YYYantigen- binding site on antibodyantigenYYYYvariable binding regionYYeach B cell has ~100,000 antigen receptors
22 Structure of antibodies YStructure of antibodiesYantigen-binding siteYYYsYvariable regionYYYYYlightchainlightchainlight chainsantigen-bindingsiteheavy chainsheavychainsB cellmembrane
23 How antibodies work Y invading pathogens tagged with antibodies macrophage eating tagged invadersinvading pathogens tagged with antibodiesY
24 Classes of antibodies Y Immunoglobulins IgM IgG IgA IgE IgD Weeks246IgMIgGExposuretoantigenAntibody levelsinvading pathogens tagged with antibodiesClasses of antibodiesYmacrophage eating tagged invadersImmunoglobulinsIgM1st immune responseactivate complement proteinsIgG2nd response, major antibody circulating in plasmapromote phagocytosis by macrophagesIgAin external secretions, sweat & mother’s milkIgEpromote release of histamine & lots of bodily fluidsevolved as reaction to parasitestriggers allergic reactionIgDreceptors of B cells???
25 invader (foreign antigen) 10 to 17 days for full responseB cell immune responseB cells + antibodiesYinvader (foreign antigen)tested by B cells(in blood & lymph)memory cells“reserves”YYrecognitionYcaptured invadersYclone1000s of clone cellsplasma cellsrelease antibodiesYY
26 1° vs 2° response to disease Memory B cells allow a rapid, amplified response with future exposure to pathogen
27 How do vertebrates produce millions of antibody proteins, if they only have a few hundred genes coding for those proteins?antibodyBy DNA rearrangement & somatic mutation vertebrates can produce millions of B & T cellsTranslation of mRNArearrangementof DNAmRNAVTranscription of geneDDNA of differentiated B cellJCCB cellchromosome of undifferentiated B cell
28 Vaccinations Immune system exposed to harmless version of pathogen triggers active immunitystimulates immune system to produce antibodies to invaderrapid response if future exposureMost successful against viral diseases
29 Jonas Salk 1914 – 1995 Developed first vaccine against polio April 12, 1955Developed first vaccineagainst polioattacks motor neuronsAlbert Sabin1962oral vaccinePoliomyelitis (polio) is caused by a virus that enters the body through the mouth. The virus multiplies in the intestine and invades the nervous system. It can cause total paralysis in a matter of hours.One in 200 infections leads to irreversible paralysis. Among those paralyzed, 5-10 percent die when their breathing muscles are immobilized.Polio mainly affects children under age 5.Salk vaccine = inactivated poliovirus vaccine (IPV), based on poliovirus grown in a type of monkey kidney tissue culture, which is chemically inactivated with formalinSabin vaccine = oral polio vaccine (OPV) using live but weakened (attenuated) virus, produced by the repeated passage of the virus through non-human cells at sub-physiological temperatures
30 Polio epidemics 1994: Americas polio free 1916 The first major polio epidemic strikes in the United States; 27,000 people suffer paralysis and 6,000 die. Increasing numbers of outbreaks occur each year.1921 Franklin D. Roosevelt is diagnosed with polio.1928 Iron lungs are introduced to help patients with acute polio breathe.1932 Franklin D. Roosevelt is elected President of the United States1949 Dr. John Enders, Dr. Frederick Robbins and Dr. Thomas Weller develop a way to grow poliovirus in tissue culture, a breakthrough that aided in the creation of the polio vaccine. Their work earned the three scientists the Nobel Prize in physiology and medicine in 1954.1952 The United States reports 57,628 polio cases -- the worst U.S. epidemic on record.1979 The last U.S. case of polio caused by wild poliovirus is reported.1988 Worldwide, polio continues to affect some 350,000 people in 125 countries.1994 The Americas are certified polio-free.2000 The Western Pacific region is certified polio-free.2002 Europe is certified polio-free.
31 Passive immunity Obtaining antibodies from another individual Maternal immunityantibodies pass from mother to baby across placenta or in mother’s milkcritical role of breastfeeding in infant healthmother is creating antibodies against pathogens baby is being exposed toInjectioninjection of antibodiesshort-term immunity
32 You need trained assassins to kill off these infected cells! What if the attacker gets past the B cells in the blood & actually infects some of your cells?You need trained assassins to kill off these infected cells!TAttack of the Killer T cells!
33 T cells Cell-mediated response Types of T cells immune response to infected cellsviruses, bacteria & parasites (pathogens) within cellsdefense against “non-self” cellscancer & transplant cellsTypes of T cellshelper T cellsalerts immune systemkiller (cytotoxic) T cellsattack infected body cells
34 How are cells tagged with antigens Major histocompatibility (MHC) proteinsantigen glycoproteinsMHC proteins constantly carry bits of cellular material from the cytosol to the cell surface“snapshot” of what is going on inside cellgive the surface of cells a unique label or “fingerprint”T cellMHC proteinsdisplaying self-antigens
35 How do T cells know a cell is infected Infected cells digest pathogens & MHC proteins bind & carry pieces to cell surfaceantigen presenting cells (APC)alerts Helper T cellsinfected cellMHC proteins displaying foreign antigensT cellWANTEDT cell antigen receptors
36 activate killer T cells stimulate B cells & antibodies T cell responsekiller T cellactivate killer T cellsinfected cellhelper T cellinterleukin 2helper T cellinterleukin 1orstimulate B cells & antibodiesYactivatedmacrophageinterleukin 2helper T cellY
37 Attack of the Killer T cells Destroys infected body cellsbinds to target cellsecretes perforin proteinpunctures cell membrane of infected cellvesicleKiller T cellKiller T cell binds to infected cellcell membraneperforin punctures cell membranecell membraneinfected celldestroyedtarget cell
38 Blood type A B AB O blood type antigen on RBC antibodies in blood donationstatusAtype A antigens on surface of RBCanti-B antibodies__Btype B antigens on surface of RBCanti-A antibodiesABboth type A & type B antigens on surface of RBCno antibodiesuniversal recipientOno antigens on surface of RBCanti-A & anti-B antibodiesuniversal donorMatching compatible blood groups is critical for blood transfusionsA person produces antibodies against foreign blood antigens
40 pathogen invasion antigen exposure antigens on infected cells Immune responsepathogen invasion antigen exposureskinskinfree antigens in bloodantigens on infected cellsmacrophages(APC)humoral responsecellular responseB cellshelper T cellsT cellsplasma B cellsmemory B cellsmemory T cellscytotoxic T cellsYantibodies
41 HIV & AIDS Human Immunodeficiency Virus virus infects helper T cellshelper T cells don’t activate rest of immune system: T cells & B cellsalso destroy T cellsAcquired ImmunoDeficiency Syndromeinfections by opportunistic diseasesdeath usually from other infectionspneumonia, cancer
43 Immune system malfunctions Auto-immune diseasesimmune system attacks own molecules & cellslupusantibodies against many molecules released by normal breakdown of cellsrheumatoid arthritisantibodies causing damage to cartilage & bonediabetesbeta-islet cells of pancreas attacked & destroyedmultiple sclerosisT cells attack myelin sheath of brain & spinal cord nervesAllergiesover-reaction to environmental antigensallergens = proteins on pollen, dust mites, in animal salivastimulates release of histamine
44 Key attributes of immune system 4 attributes that characterize the immune system as a wholespecificityantigen-antibody specificitydiversityreact to millions of antigensmemoryrapid 2° responseability to distinguish self vs. non-selfmaturation & training process to reduce auto-immune disease
46 Blood type A B AB O blood type antigen on RBC antibodies in blood donationstatusA___________ antigens on surface of RBC___________ antibodies__BAB___________________ antigens on surface of RBC______ antibodies_____________ _____________O________________ on surface of RBC________________ antibodiesMatching compatible blood groups is critical for blood transfusionsA person produces antibodies against foreign blood antigens