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 macromoleculesanimals must defend themselves against invaders (pathogens)Viruses: HIV, flu, cold, measles, chicken poxBacteria: pneumonia, meningitis, tuberculosis Lyme diseaseFungi: yeast (“Athlete’s foot”…)Protist: amoeba, malariaAttack from insidecancers = abnormal body cellsMmmmm,What’s in your lunchbox?
4 Lymph system Production & transport of leukocytes Traps foreign invaderslymph vessels(intertwined amongst blood vessels)lymph node
5 Development of Red & White blood cells Red blood cellsinflammatory responsefight parasitesLeukocytesLymphocytesdevelop into macrophagesshort-lived phagocytes60-70% WBC
8 2nd line: Non-specific patrolling cells Patrolling cells & proteinsattack pathogens, but don’t “remember” for next timeleukocytesphagocytic white blood cellsmacrophages, neutrophils, natural killer cellscomplement systemproteins that destroy cellsinflammatory responseincrease in body temp.increase capillary permeabilityattract macrophagesbacteriamacrophageyeast
9 Leukocytes: Phagocytic WBCs Attracted by chemical signals released by damaged cellsingest pathogensdigest in lysosomesNeutrophilsmost abundant WBC (~70%)~ 3 day lifespanMacrophages“big eater”, long-livedNatural Killer Cellsdestroy virus-infected cells & cancer cells
10 Destroying cells gone bad! Natural Killer Cells perforate cellsrelease perforin proteininsert into membrane of target cellforms pore allowing fluid to flow in & out of cellcell ruptures (lysis)apoptosisvesiclenatural killer cellperforincell membraneperforin punctures cell membranecell membranevirus-infected cell
11 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
12 Inflammatory response Damage to tissue triggers local non-specific inflammatory responserelease chemical signalshistamines & prostaglandinscapillaries dilate, become more permeable (leaky)delivers macrophages, RBCs, platelets, clotting factorsfight pathogensclot formationincreases temperaturedecrease bacterial growthstimulates phagocytosisspeeds up repair of tissues
13 Fever When a local response is not enough system-wide 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.
14 3rd line: Acquired (active) Immunity Specific defense with memorylymphocytesB cellsT cellsantibodiesimmunoglobulinsResponds to…antigenscellular name tagsspecific pathogensspecific toxinsabnormal body cells (cancer)B cell
15 How are invaders recognized? Antigenscellular name tag proteins“self” antigensno response from WBCs“foreign” antigensresponse from WBCspathogens: viruses, bacteria, protozoa, parasitic worms, fungi, toxinsnon-pathogens: cancer cells, transplanted tissue, pollen“self”“foreign”
16 Lymphocytes B cells T cells mature in bone marrow humoral response systemattack pathogens still circulating in blood & lymphproduce antibodiesT cellsmature in thymuscellular response systemattack invaded cells“Maturation”learn to distinguish “self” from “non-self” antigensif react to “self” antigens, cells are destroyed during maturationTens of millions of different T cells are produced, each one specializing in the recognition of oen particar antigen.
17 B cellsAttack, learn & remember pathogens circulating in blood & lymphProduce specific antibodies against specific antigenTypes of B cellsplasma cellsimmediate production of antibodiesrapid response, short term releasememory cellscontinued circulation in bodylong term immunity
18 Antibodies Proteins that bind to a specific antigen Y Y Y Y Y Y Y Y multi-chain proteinsbinding region matches molecular shape of antigenseach antibody is unique & specificmillions of antibodies respond to millions of foreign antigenstagging “handcuffs”“this is foreign…gotcha!”YYYYYYantigen- binding site on antibodyantigenYYYvariable binding regionYYeach B cell has ~50,000 antibodies
19 Structure of antibodies YYantigen-binding siteYYYsYvariable regionYYYYlightchainYlightchainheavychainslight chainsantigen-bindingsiteheavy chainsB cellmembrane
20 What do antibodies do to invaders? neutralizecaptureprecipitateapoptosismacrophage eating tagged invadersinvading pathogens tagged with antibodiesY
21 Classes of antibodies Y Immunoglobulins IgM 1st immune response Weeks246IgMIgGExposuretoantigenAntibody levelsinvading pathogens tagged with antibodiesImmunoglobulinsIgM1st 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???Ymacrophage eating tagged invaders
22 B cell (aka “humoral”) immune response 10 to 17 days for full responseB cells + antibodiesYinvader (foreign antigen)tested by B cells(in blood & lymph)memory cells“reserves”YYrecognitionYcaptured invadersmacrophageYclones1000s of clone cellsplasma cellsrelease antibodiesYY
23 Vaccinations Immune system exposed to harmless version of pathogen stimulates B cell system to produce antibodies to pathogen“active immunity”rapid response on future exposurecreates immunity without getting disease!Most successful against viruses
24 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
25 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.
26 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
27 What if the attacker gets past the B cells in the blood & actually infects (hides in) some of your cells?You need trained assassins to recognize & kill off these infected cells!Attack of the Killer T cells!TBut how do T cells know someone is hiding in there?
28 How is any cell tagged with antigens? Major histocompatibility (MHC) proteinsproteins which 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”MHC proteinWho goes there?self or foreign?T or B cellMHC proteinsdisplaying self-antigens
29 How do T cells know a cell is infected? Infected cells digest some pathogensMHC proteins carry pieces to cell surfaceforeign antigens now on cell membranecalled Antigen Presenting Cell (APC)macrophages can also serve as APCtested by Helper T cellsMHC proteins displaying foreign antigensinfected cellTH cellWANTEDT cell with antigen receptors
30 T cells Attack, learn & remember pathogens hiding in infected cells recognize antigen fragmentsalso defend against “non-self” body cellscancer & transplant cellsTypes of T cellshelper T cellsalerts rest of immune systemkiller (cytotoxic) T cellsattack infected body cellsmemory T cellslong term immunityT cell attacking cancer cell
31 T cell (aka “Cell mediated”) response killer T cellactivate killer T cellsAPC: infected cellrecognitionhelper T cellinterleukin 2helper T cellinterleukin 1stimulate B cells & antibodiesYorAPC: activatedmacrophageinterleukin 2cloneshelper T cellYrecognition
32 Attack of the Killer T cells Destroys infected body cellsbinds to target cellsecretes perforin proteinpunctures cell membrane of infected cellapoptosisvesicleKiller T cellKiller T cell binds to infected cellcell membraneperforin punctures cell membranecell membraneinfected celldestroyedtarget cell
33 Immune system & Blood type antigen on RBCantibodies in blooddonationstatusAtype 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
34 pathogen invasion antigen exposure antigens on infected cells Immune responsepathogen invasion antigen exposureskinskinfree antigens in bloodantigens on infected cellsmacrophages(APC)humoral responsecellular responseB cellsalerthelper T cellsalertT cellsplasma B cellsmemory B cellsmemory T cellscytotoxic T cellsYantibodiesYantibodies
35 HIV & AIDS Human Immunodeficiency Virus virus infects helper T cellshelper T cells don’t activate rest of immune system: killer T cells & B cellsalso destroys helper T cellsAIDS: Acquired ImmunoDeficiency Syndromeinfections by opportunistic diseasesdeath usually from“opportunistic” infectionspneumonia, cancersHIV infected T cell
37 Immune system malfunctions Auto-immune diseasesimmune system attacks own molecules & cellsLupus: antibodies against many molecules released by normal breakdown of cellsrheumatoid arthritis: antibodies causing damage to cartilage & boneDiabetes: beta-islet cells of pancreas attacked & destroyedmultiple sclerosis: T cells attack myelin sheath of brain & spinal cord nervesAllergiesover-reaction to environmental antigensallergens = proteins on pollen, dust mites, in animal salivastimulates release of histamine
39 Make sure you can do the following: Explain the interplay between the humoral and cell-mediated responses.Demonstrate how the HIV virus leads to a breakdown of the immune system.Explain why a vaccine works.Explain the causes of immune system disruptions and how disruptions of the immune system can lead to disruptions of homeostasis.