Cellular Respiration Overview - F24 PDF

Cellular Respiration - Overview DISP Biology Cellular respiration is a metabolic pathway Enzyme Enzyme Enzyme Reaction Reaction Reaction Starting Product(s) molecule(s) 1) Anabolic –...

Cellular Respiration - Overview DISP Biology Cellular respiration is a metabolic pathway Enzyme Enzyme Enzyme Reaction Reaction Reaction Starting Product(s) molecule(s) 1) Anabolic – Build complex molecules from simple ones + + + energy 2) Catabolic – Break down complex molecules into simple ones + + + energy Anabolic Requires energy Build complex molecules from simple ones Catabolic Releases energy Break down complex molecules to simple ones Cellular Respiration - an Oxidation Reduction Reaction Oxidation= Loss electrons (lose e-, H+) Reduction= Gain electrons (gain e-, H+) glucose Loses H+, e- Gains H+, e- and becomes CO2 becomes water Glucose (organic compound) oxidized to CO2 by removing H+ and e- H+ and e- removed from glucose are transferred to O2 to form H2O Cellular respiration - stepwise oxidation of glucose C6H12O6 + 6O2 6H2O + 6CO2 + ENERGY Energy released because electrons relocated to electronegative oxygen Cellular respiration moves electrons in stepwise fashion so that released energy can be harnessed H+ and e- ← Free energy (G) → O2 Energy released in cellular respiration used to make ATP ATP = Adenosine triphosphate is the energy currency of cells Mutual repulsion among the 3 phosphate groups Higher energy (“storing potential to Analogous to a react with water” compressed spring Energy can be released by hydrolyzing ATP to remove a phosphate group  Energy released by ATP hydrolysis can be used for work Higher energy (“storing potential to react with water”) Lower energy products ATP Powers Cellular Work Chemical Building polymers from monomers Transport Pumping substances across membranes Mechanical Muscle cell contraction, transport of vesicles on axons Mechanism: ATP or P binding causes molecule shape change Cellular respiration takes place in mitochondria Cellular respiration stages 1. Glycolysis (in cytosol) Glucose (6C) → 2 pyruvate (3C) Some ATP 2. Pyruvate oxidation (mitochondrial matrix) pyruvate (3C) → 2C + CO2 3. Citric Acid Cycle (mitochondrial matrix) 2C → CO2 + CO2 4. Oxidative phosphorylation: electron transport and chemiosmosis (inner mitochondrial membrane) H+ and e- that were removed from sugar transferred stepwise to O2. Most ATP produced Electron carriers mediate electron transfer to O2 NAD+ → NADH + H+ FAD → FADH2 e- e- e- NAD+ and FAD are molecules that ‘carry’ H+ and e- to the electron transport chain so that they can ultimately reach oxygen.  Cellular Respiration – Glycolysis and Fermentation DISP Biology Cellular Respiration - Overview glucose ATP Loses H+, e- Gains H+, e- and becomes CO2 becomes water Glucose (organic compound) oxidized to CO2 by removing H+ and e- H+ and e- removed from glucose are transferred to O2 to form H2O Electron carriers NAD+ and FAD shuttle H+ and e- Cellular respiration stages Glucose (6C) Oxidative Pyruvate Citric acid Glycolysis phosphoryl oxidation cycle ation CYTOSOL MITOCHONDRIAL MATRIX INNER MITOCHONDRIAL 2 Pyruvate (3C) MEMBRANE 2 ATP 2 NADH Glucose (6C) split to 2 x 3C sugars, rearranged to 2 pyruvate (3C) Energy investment phase 2ATP used Energy payoff phase 4ATP formed e-, H+ removed from glucose transferred to NAD+ forming 2NADH  Energy investment phase – spend 2 ATP Phosphorylated ATP ATP sugar easier to split ADP ADP Glucose 3 carbon sugar Energy payoff phase x 2: 2NADH, 4ATP 2 ATP 2 H2O 2 ATP 2 NADH 2 ADP 2 NAD+ 2 ADP 3 carbon sugar 2 Pyruvate x2 H+ & e- removed from each 3C sugar transferred to electron carrier Next step depends on whether O2 present or not Lactic acid fermentation (in bacteria, yeast, muscle) Products? 2 lactate (ionized form of lactic acid) 2 NAD+ (Lactic acid) Fermentation regenerates NAD+ by transferring H+ & e- to pyruvate Why is this important? Allows glycolysis to continue; continue making ATP when O2 is scarce (i.e. in muscle cells in intense exercise) Alcohol fermentation (in bacteria, yeast) Products 2 NAD+ 2 CO2 2 ethanol Applications? CO2: bubbles (i.e. in carbonated beverages, bread) Ethanol: alcoholic beverages, biofuel If O2 present aerobic cellular respiration proceeds Cellular respiration stages  Cellular Respiration Pyruvate Oxidation and Citric Acid Cycle DISP Biology Cellular Respiration - Overview glucose ATP Loses H+, e- Gains H+, e- and becomes CO2 becomes water Glucose broken down to CO2 by transferring H+ and e- to O2 Electron carriers NAD+ and FAD shuttle H+ and e- Cellular respiration stages Glucose (6C) Oxidative Pyruvate Citric acid Glycolysis phosphoryl oxidation cycle ation CYTOSOL MITOCHONDRIAL MATRIX INNER MITOCHONDRIAL 2 Pyruvate (3C) MEMBRANE 2 ATP 2 NADH Cellular respiration stages Pyruvate (3C) Oxidative Pyruvate Citric acid Glycolysis phosphoryl oxidation cycle ation CYTOSOL MITOCHONDRIAL MATRIX INNER MITOCHONDRIAL CO2 (1C) MEMBRANE Acetyl-CoA (2C) NADH Pyruvate oxidation in mitochondrial matrix 1. Carboxyl (-COO) group released as CO2 2. 2C compound oxidized by transferring e- to NAD+ 3. 2C compound binds to coenzyme A = Acetyl-CoA Products? CO2 NADH (electron carrier) Acetyl-CoA (2C, high energy) Cellular respiration stages Acetyl-CoA (2C) Oxidative Pyruvate Citric acid Glycolysis phosphoryl oxidation cycle ation CYTOSOL MITOCHONDRIAL MATRIX INNER MITOCHONDRIAL 2 CO2 (1C) MEMBRANE 3 NADH 1 FADH2 ATP Citric acid cycle completes oxidation to CO2 CoA Acetyl-CoA  Acetyl-CoA (2C) Coenzyme A comes off Oxaloacetate (4C) Citrate (6C) NADH CO2 Regenerate oxaloacetate by: Transferring e- and H+ to e- carriers FADH2 CO2 Removing 2C as CO2 NADH PRODUCTS: CO2 NADH, FADH2 ATP ATP Cellular respiration stages  Cellular Respiration – Oxidative Phosphorylation DISP Biology Cellular respiration stages NADH FADH2 O2 Pyruvate Citric acid Oxidative Glycolysis oxidation cycle phosphorylation CYTOSOL MITOCHONDRIAL MATRIX INNER MITOCHONDRIAL MEMBRANE H2O ATP Cellular respiration stages  ATP is produced by phosphorylation of ADP During cellular respiration ATP formed by: 1) Substrate level phosphorylation: Phosphate transferred from substrate (organic) molecule to ADP P + + ADP ATP enzyme Glycolysis: 2ATP Citric Acid Cycle: 2ATP 2) Oxidative Phosphorylation: 26-28 ATP Electron transport chain Chemiosmosis Electron transport chain: Stepwise transfer of electrons from carriers to O2 Energy released as electrons relocated to electronegative oxygen Electrons moved in stepwise fashion so released energy can be harnessed Electron transport chain includes a series of multiprotein complexes with each complex more electronegative than the previous e- ← Free energy (G) → O2 Electron carriers bring hydrogen ions and electrons to the electron transport chain NAD+ → NADH + H+ FAD → FADH2 e- e- e- NAD+ and FAD shuttle H+ and e- to the electron transport chain Electron transport chain NADH FADH 2 I II III IV O2 Electrons pass through multiprotein complexes in the electron transport chain NADH is oxidized when it transfers an electron to complex I FADH2 is oxidized when it transfers an electron to complex II I III IV e- II e- NAD+ FAD Electrons pass through multiprotein complexes in the electron transport chain Ubiquinone (Q) picks up electrons from complexes I and II and ‘shuttles’ them to complex III I Q III IV e - e - II NAD+ FAD Electrons pass through multiprotein complexes in the electron transport chain Cytochrome c (cyt c) like ubiquinone, is a shuttle. It moves electrons between complex III and complex IV Cyt c e- I Q III IV II NAD+ FAD Electron transport chain We’ve moved electrons from high to low ‘free’ energy. They’ve ended up combined with oxygen. Oxygen also picks up H+ from the surroundings to make water. What does this have to do with our ultimate goal of making ATP? Cyt c I Q III IV II Electron Transport Chain + Chemiosmosis Electron transport chain: Energy released by “downhill fall of electrons” to oxygen used to pump H+ across inner mitochondrial membrane (into intermembrane space)  Electron Transport Chain + Chemiosmosis Chemiosmosis H+ gradient drives synthesis of ATP. H+ diffuses down concentration gradient causing rotation of ATP synthase – catalyzes addition of Pi to ADP → ATP Overall energy flow in cellular respiration Glucose NADH (and to lesser extent FADH2) Electron transport chain Proton motive force (H+ gradient) ATP Anaerobic cellular respiration – FYI, not tested Instead of transferring H+ and e- to O2… …Transfer to another electronegative molecule. i.e. SO42- in sulfate reducing marine bacteria (H2S produced as a by product instead of H2O) https://phys.org/news/2014-03-reveals- insights-sulfate-reducing-bacteria.html Video: Cellular Respiration – a useful review Osmoregulation DISP Biology  Form How things work Anatomy and physiology function to maintain homeostasis Homeostasis: Maintaining a steady state (internal balance) by balancing losses and gains (i.e. nutrients, heat, waste, solutes) Allows constant condition despite changes in environment Temperature Nutrient availability O2 availability Osmolarity (concentration of solutes) Osmoregulation: balance uptake/ loss of water & solutes Osmolarity: total concentration of solutes (dissolved substances ) in solution Units: Milliosmoles/litre (mOsm/L) 300 mOsm/L body fluids of mammals; 1000 mOsm/L seawater Challenges when external osmolarity differs: Envision two compartments separated by membrane that allows water to cross Direction of water flow by osmosis: Low to high solute High to low free water Water balance in animal cells Predict the net direction of water flow 100mM 75mM 50mM sucrose 50mM sucrose 75mM sucrose 100mM sucrose sucrose sucrose Osmolarity higher in cell No net water movement Osmolarity lower in cell Cell gains water Cell loses water Hypotonic solution Cells gain water Some marine organisms match body fluids to surroundings Most marine invertebrates are osmoconformers: allow internal osmolarity to change to match surroundings, even if surroundings change Example habitats with changing osmolarity: Tide pool: Increase osmolarity with evaporation Decrease osmolarity with rain Estuary: Mixing of ocean and river water (intermediate osmolarity) Osmoconformers stay isotonic with surroundings Inorganic ion Organic solute cell Increasing osmolarity of surroundings ↑ organic solutes (not inorganic ions) with ↑ osmolarity of surroundings Green crabs found in habitats with differing osmolarities Open ocean, estuaries, lakes Mostly osmoconforming (matching body fluids to surroundings) but some osmoregulating (controlling internal osmolarity) Osmoregulators control internal osmolarity by countering passive losses or gains Passive losses/gains Freshwater (i.e. fish and invertebrates in lakes): Body fluids higher osmolarity than surroundings ions Body fluids gain water & lose solutes passively H2O Marine (i.e. fish and marine birds in ocean): ions Body fluids lower osmolarity than surroundings H2O Body fluids lose water and gain salt passively Terrestrial Body fluids lose water H2O  Example osmoregulator: fish balance passive losses or gains Freshwater fish Marine fish (in seawater) Ions (and some water) ions Water & ions in food ions in food Drink No drinking Ions and water Ions and water in Active ion water in water ions feces uptake at gills feces Ions and water in Ions and water concentrated urine in dilute urine (small volume) (large volume) Active (requires ATP for active transport of solutes) passive Active transport of Cl- across gills is mediated by chloride cells. Na+ follows Cl- Fish That Move Between Freshwater and Seawater (Diadromous fish) Salmon (adult life in seawater; spawn in FW rivers) Eels (spawn in seawater; juveniles go to rivers) Migrations require reorganization of osmoregulatory systems Marine birds and reptiles drink seawater??? Salt glands help expel excess salt Ions actively pumped from blood into tubes carrying salt water  flickr.com/photos/mrandrewmurray/500062539 http://www.sligobirding.com/PetrelHead120807A.jpg Land animals lose water to surroundings Mechanisms to reduce water loss: 1. Behavioral adaptations – i.e. active at night to reduce evaporative water loss 2. Body coverings 3. Regulating excretion Photo by Stanley Hillyard Underside of toad Bufo punctatus. Extra blood flow to “pelvic seat” aids rapid water uptake. 6- 10g water/hour ventrally through aquaporins Reduce water loss with body coverings Vertebrate skin layers Insects have waxy exoskeletons Land snails have shells Reptiles, birds, mammals stratum corneum: dead cells Layers of dead, keratinized skin cells lipids/keratin in and between cells in terrestrial vertebrates Sehgal, J Dermatitis 2018, 3:1 Regulating Excretion Excretory systems control body fluid solute concentrations and dispose of metabolic wastes Nitrogenous bases (subunits of nucleic acids) Nitrogenous waste – from breakdown of proteins and nucleic acids Contain N Amino acid (subunit of a protein) Animals excrete nitrogenous wastes in different forms: ammonia 1)_____________ urea 2)___________ uric acid 3)________________ These differ in toxicity and the energy costs of producing them Forms of Nitrogenous Wastes NH3 (ammonia) Inexpensive but toxic, good in aquatic environments: diffuses across gills, dilute with lots of water Urea (ammonia + CO2) More expensive than ammonia, less toxic don’t need to dilute in as much water (conserve) Uric acid Most expensive, non-toxic least water needed (not water soluble)  Mammalian excretory system: kidney Filter body fluids to produce a fluid waste called urine, which empties into the renal pelvis  Nephron = functional unit of kidney Bundle of capillaries (glomerulus) Reclaim nutrients Dump everything else Reclaim H2O, Bowman’s capsule: ions as Sieve liquid from needed blood through here Leave big things behind in capillaries (i.e. blood cells, proteins, other big molecules) Regulation of fluid retention in the kidney by antidiuretic hormone (ADH) ADH increases aquaporins (water channels) in the collecting duct Increase H2O reabsorption through aquaporins decreases blood osmolarity ↑ ____urine volume ↑ urine osmolarity ____ Diuretics (i.e. alcohol) inhibit ADH Renin-angiotensin system (RAS) regulates blood volume, independent of osmolarity Respond to drop in blood volume, pressure by increasing Na+ and water reabsorption and constricting blood vessels Circulation DISP Biology Circulation Transport throughout organism and/or between organism and environment: O2, CO2 Nutrients/Waste Hormones Immune factors Heat Circulation – 2 transport mechanisms 1. Diffusion over short distances (~1mm) –if cells in close contact with environment In flatworms, diffusion is sufficient 2. Convection Bulk flow of body fluids over longer distances (driven by a pump) In most organisms there is a combination of diffusion and convection General design of circulatory systems 1. Pump (muscular heart, or cilia) – to move circulatory fluid (i.e. blood) 2. Distribution system – tubes for circulatory fluid Closed circulatory systems: blood vessels (arteries, capillaries, veins) Open circulatory systems: body sinuses 3. Exchange areas (i.e. capillaries) – diffusion in and out of circulatory fluid, tissues Capillaries are small blood vessels 1-2 cell layers thick – allows substances to diffuse between blood and tissues. Open vs closed circulatory systems Open circulation Closed circulation Fluid is not confined to blood vessels Fluid confined to blood vessels Fluid in body sinuses (spaces in tissue) Fluid bathes cells and organs directly Create more pressure in closed system, for more efficient delivery to tissues Examples: annelids, vertebrates Examples: arthropods  Closed circulatory system aka cardiovascular system Blood vessels are specialized for different functions Arteries – blood from heart to capillaries Branch to arterioles which branch to capillaries Capillaries – exchange surface for diffusion between blood and tissue cells Blood flow ~200 x slower in capillaries Converge into venules which converge into veins Veins – blood from capillaries to heart Blood vessel structure matches function Arteries and veins have 3 layers: 1. Endothelium – cells that line vessel 2. Smooth muscle – contractions help pump blood 3. Connective tissue – elastic fibres allow stretch/recoil Arteries thicker walled (experience high pressure blood from heart) Artery Thick connective tissue allows artery to resist stretching, Vein return to original shape (like a reinforced garden house) Veins thinner walled (experience low pressure) Smooth muscle contractions assist blood return to heart Valves prevent back flow  Blood vessel structure matches function endothelium Capillaries have thin walls to facilitate exchange of materials between blood and interstitial fluid (fluid bathing tissues) basal lamina Narrow diameter slows flow for effective exchange Note that ~4-8L fluid is lost from capillaries to surrounding fluid daily. Lost fluid becomes “lymph”. It is returned to blood vessels via the lymphatic system. Capillaries only slightly wider than a red blood cell Modeling fluid flow in blood vessels Laminar flow in blood vessels Layers (laminae) of fluid move past each other, overcoming friction Arrow lengths proportional to velocity Layers in center are fast but layers next to vessel wall don’t move Poiseulle’s law Change in radius has biggest effect on flow rate Blood flow can be regulated by adjustive vessel diameter 1) Vasoconstriction - contract smooth muscle in arteriole walls 2) Vasodilation - relax smooth muscles in the arteriole walls 3) Contract precapillary sphincters smooth muscle rings at entrance to capillaries Modify blood flow to organs as needed: i.e. skin, digestive tract, skeletal muscles Only 5-10% capillaries have blood flowing through at a given time  Plaques (fatty deposits) narrow blood vessels Coronary artery supplies oxygenated blood to heart cells https://learning-center.homesciencetools.com/article/heart-dissection-project/ ↓ ____radius ↓ flow rate → ___ → ____ ↓ O2 to heart cells (heart attack if damaged)  Closed circulation: Single vs double circulation Deoxygenated blood Oxygenated blood Fish Mammals Potential problems Benefits 1. Heart supplied with low O2 blood 1. Blood supplied to tissues and heart is freshly oxygenated 2. No pump to give fresh energy to oxygenated blood leaving gills 2. Pumping blood from left side of the heart imparts fresh energy en route to tissues Can place an upper limit on performance Mammalian Heart – structure and function 2 Atria – left and right relatively thin walls collection chambers for returning blood 2 Ventricles – left and right thicker walls contract forcefully Valves prevent backflow atrioventricular valves AND semilunar valves Mammalian cardiovascular system Body tissues Blood leaving _________________________ (systemic tissues) (tissues) is low ________ in O2. vena cavae Blood returns to heart via the_____________ right atrium In heart blood goes into ___________________, then right ventricle ______________________ low Blood ________ in O2 is pumped out by contraction of right ventricle ______________________. Blood leaves through the Pulmonary artery __________________________ lungs and and travels to the _______ O2 picks up _______. lungs Blood leaving the _________________________ high in is _______ O2. Blood returns to heart via the __________________________________ pulmonary vein left atrium In the heart blood goes into the _______________, then left ventricle __________________________. high Blood _________ in O2 is pumped out by contraction of the ____________________________________. left ventricle Spread of depolarization across heart allows coordinated contraction Cardiac action potential ~100-500ms. Allows heart to contract long enough to pump blood Gap junctions (protein-lined channels between adjacent cells) allow spread of depolarization Areas with concentrated gap junctions are “intercalated disks” Gap Junctions: protein channels connect neighbor cell cytoplasm Animation: Gap Junctions Right-click slide / select “Play”  Pacemaker cells in Sinoatrial node in right atrium set rate of heart contraction by having most frequent action potentials Depolarization spreads over heart chambers via gap junctions and depolarized muscle cells contract. Purkinje fibres are specialized muscle cell bundles penetrate fibrous layers to send electric impulse to other chambers Electrocardiogram (EKG) detects electric currents as they spread across the heart.  Heart contracts and relaxes in rhythmic cardiac cycle Systole = contraction phase Diastole = relaxation/filling phase Valves ensure directionality of blood flow Atrioventricular valves - separate atrium/ventricle Closed by – ventricle contraction Open when – ventricle relaxed, blood flows from atrium to ventricle Sound – “lub” from blood recoil against closed AV valve during ventricle contraction Semilunar valves - control flow to aorta/pulmonary artery Opened by – ventricle contraction Closed when – ventricle relaxed Sound – “dub” from vibrations caused by closing semilunar valves Gas Exchange DISP Biology Gas exchange – O2 uptake from and CO2 discharge to environment 1. Convection (bulk fluid flow) Breathing brings O2 to gas exchange surface (alveoli in lungs) 2. Diffusion Across gas exchange surface (alveoli) into blood (capillaries) 3. Convection Oxygen transport in blood vessels (i.e. arteries) 4. Diffusion From blood vessels (capillaries) into mitochondria in cells In diffusion steps gases must diffuse down partial pressure gradients 1. Convection (bulk fluid flow) Breathing brings O2 to gas exchange surface (alveoli in lungs) 2. Diffusion Across gas exchange surface (alveoli) into blood (capillaries) 3. Convection Oxygen transport in blood vessels (i.e. arteries) 4. Diffusion From blood vessels (capillaries) into mitochondria in cells  Partial pressure: individual pressure exerted by a gas in a mixture of gases At sea level atmosphere exerts pressure that causes column of mercury to rise 760 mm Atmospheric pressure = 760 mmHg Atmosphere is 21% O2 Partial pressure O2 = 0.21 x 760 mm Hg = 160 mmHg https://saylordotorg.github.io/text_general-chemistry-principles-patterns-and-applications-v1.0/s14-gases.html Gases (i.e. O2) diffuse down partial pressure gradients 2) At gas exchange surface (alveoli): O2 combines with respiratory pigment hemoglobin (Hb) after diffusing into blood in capillaries O2 + Hb → HbO2 Only free gas molecules contribute to partial pressure 4) At tissues O2 is consumed in cellular respiration, CO2 produced Respiratory surfaces have extensive surface area for diffusion Lungs are infoldings of the body wall Alveoli are the gas exchange surface ~100 m2 surface area Rate of oxygen diffusion is fast when surface area is large, and distance is short Oxygen diffuses in moist film lining alveoli, then into capillaries that surround alveoli Section 42.5 in text describes different types of respiratory surfaces: for example: gills, tracheal systems, skin O2 diffuses into red blood cells in capillaries and binds to Hemoglobin Only 4.5 ml O2/L dissolves in blood plasma Mammals transport 200ml O2/L in blood Hemoglobin: respiratory pigment in red blood cells, increases O2 carrying capacity of blood ~50x 4 protein subunits (2α, 2β) 4 iron containing ‘heme’ groups that can each reversibly bind O2  Pulse oximeters measure blood oxygen saturation level Oxygen percent saturation Light beams pass through the blood in finger Measure changes in light absorption in oxygenated or deoxygenated blood. ToronTek Pulse Oximeter - Finger tip- Blood oxygen monitor and pulse rate monitor | Best Buy Canada Cooperativity in O2 binding and release by hemoglobin subunits Hemoglobin with more O2 bound has shape that causes it to bind O2 tighter At high PO2 Hemoglobin binds more O2. Promotes O2 loading into blood at alveoli where PO2 is high Hemoglobin with less O2 bound has shape that causes it to bind O2 more loosely At low PO2 Hemoglobin binds less O2. Promotes O2 unloading at tissues where needed CO2 promotes O2 unloading by hemoglobin (Hb) O2 loading onto hemoglobin at lungs; high PO2 O2 unloading from hemoglobin at tissues Low PO2 (caused by exercise or active metabolism) CO2 also promotes O2 unloading at tissues. CO2 + H2O H2CO3 HCO3- + H+ ↑ +, ___ ↑ CO2, ___H ___ ↓ affinity for oxygen ↓ pH, ___Hb Hb with H+ bound has lower affinity for/releases O2 Bohr shift - decrease in hemoglobin affinity for O2 at low pH During exercise ↑ CO2, ↑ H+, ↓ pH, ↓ hemoglobin affinity for oxygen Because hemoglobin with H+ bound has a shape that holds O2 less tightly Compare PO2 40 mmHg at pH 7.4 and 7.2 pH 7.4: hemoglobin 70% loaded with O2 pH 7.2: hemoglobin 60% loaded with O2 Unload O2 where most needed, where already consumed by cellular respiration ↑ temperature also reduces Hb affinity for O2 – promotes O2 unloading at active tissues Hemoglobin facilitates both O2, CO2 transport 4. CO2 exhaled away by breathing (convection) 3. CO2 unloaded from blood to alveoli (diffusion) 2. CO2 transport in blood (convection) 1. CO2 loaded from tissues into blood (diffusion) Most CO2 transported in blood plasma as HCO3- (more soluble) CO2 diffuses from tissues to blood. Most then combines with water CO2 + H2O H2CO3 (carbonic acid) Carbonic acid not stable. It dissociates to form bicarbonate and H+ H2CO3 HCO3- and H+ H+ binding to hemoglobin leads to: More CO2 dissolved in blood If ↓ free H+ - Need to ↑ HCO3- to maintain chemical equilibrium CO2 diffuses out of blood at capillaries at alveoli Free CO2 diffuses out of blood ↓CO2 in blood causes reaction below to shift left to maintain equilibrium CO2 + H2O H2CO3 HCO3- + H+ Overall, HCO3- converted to CO2 at the alveoli CO2 diffuses into alveoli and is exhaled away Breathing control coordinates gas exchange, circulation, metabolic demand Normal blood pH 7.4 Exercise ↓ CO2, ↑ pH ↑ CO2, ↓ pH Medulla oblongata receives signals about low blood pH ↓ pH cerebrospinal ↓ pH detected by fluid Medulla signals rib chemosensory cells in muscles to increase blood vessels ventilation rate and depth Immunology DISP Biology Innate vs. adaptive immunity? Innate immunity (all animals) Barrier defences -first line of defense Mechanical Body coverings (i.e. skin, exoskeleton) Ciliated cells on the Mucous protects mucous membranes surface of the trachea Ciliated cells line mucous membranes and clear mucous Chemical Photo by Gabrielle Tompkins Lysozyme in tears, saliva, mucous Stomach acid Low pH (3-5) secretions from oil/sweat glands Innate immunity Pathogens which breech barriers are detected Receptors bind fragments of molecules found in pathogens, not animal cells Example pathogen molecules Flagellin (bacteria) Lipopolysaccharide (bacteria) dsRNA (viruses) Receptors detect molecules common to pathogen group, not specific pathogen “Toll-like receptors (vertebrates) Innate immunity Internal responses to pathogens Once detected, pathogens targeted by: pathogen 1. Phagocytosis – immune cells ingest (engulf) and break down pathogen Macrophages (“big eaters”) Neutrophils (circulate in blood) Dendritic cells (vertebrates, in skin layer) 2. Antimicrobial peptides or proteins 3. Natural killer cells (vertebrates) Secrete chemicals that trigger cell death  Innate immunity Internal responses to pathogens Inflammatory response 5. Neutrophils 6. Neutrophils 1. Mast cells (phagocytic cells) phagocytose release migrate out of invading histamine capillaries bacteria 2. Macrophages release cytokines 3. Histamine and cytokine 4. Dilation and increased release at injury site leads to… permeability of capillaries ↑ fluid to site ↑ neutrophils to site Neutrophils crawl toward chemical cues Adaptive immunity (vertebrates) AKA Acquired immunity Remember pathogen; recognize it; mount a larger immune response on second exposure Respond to specific pathogens Involves T cells and B cells (white blood cells called lymphocytes) Large diversity of T and B cell receptors  B-cell and T-cell receptors T and B cells have surface receptors that recognize and bind antigens: Any substance that triggers immune response by B or T cell (i.e. bacterial or viral proteins or polysaccharides) 2 identical antigen 1 antigen binding binding sites per receptor site per receptor B-cell T-cell ~100,000 identical receptors on each B or T-cell Receptor diversity by combining different subunits ~1 million different B cell antigen receptors ~10 million different T cell antigen receptors Diversity arises from only 20,000 genes Variable (1 of 40) Joining (1 of 5) Constant Antigen receptors form during differentiation of B and T cells Lymphocytes maturing in thymus become T cells Lymphocytes maturing in bone marrow become B cells T-cells and B cells with self-reactive antigen receptors are marked for apoptosis How is adaptive immune response generated? Pathogen must contact matching lymphocyte receptor Only small number receptors will match a given antigen Lymph vessel Pathogens to lymph nodes Capillary via lymph vessels Pathogen exposed to lymphocytes until antigen is matched to receptor Antigen receptor match triggers cell division and Lymph node packed with downstream events lymphocytes (B and T cells) B cells are activated “directly” by binding antigen Binding of antigen to B cell receptor triggers clonal selection: Stimulates cell to divide to make clone of cells with matching receptors Many B cells with Clone of cells differentiate to: receptor matching the antigen Memory cells (long lived) Population of cells that could recognize, respond to same antigen in the future Effector cells (short lived) Act on antigen (pathogen) Plasma cells with B cells Cytotoxic T cells with T cells Immunological memory Prior exposure to an antigen alters the speed, strength and duration of the immune response Primary immune response peak – 10-17 days Secondary immune response peak – 2-7 days Reservoir of long-lived T and B memory cells (can last decades) give rise to many more effector cells if pathogen is encountered again Immunological Memory Animation: Role of B Cells Copyright © 2025 Pearson Canada, Inc. 43 - 15 Immunological memory Use information on previous 2 slides to explain the biological basis for the differences in primary and secondary immune responses to antigen A. Note that antibodies are released by effector cells called plasma cells. Effector cells fight infections Plasma cells are effector cells produced from B cells Produce and secrete antibodies Antibodies travel in body fluids (blood and lymph) where they neutralize or destroy pathogens/toxins - humoral response Cytotoxic T cells are effector cells produced by T cells Secrete granzymes to poke holes in infected cells (kill infected cells)  Antibodies from plasma cells fight infections Neutralization Neutralization Opsonization Activation of complement Pathogen with Antibodies mark proteins and pore antibody bound is pathogen for phagocytosis and formation “blocked” Targets a “membrane attack can aggregate pathogens complex” to pathogen cell membrane Effector cells from T cells are Cytotoxic T cells Cytotoxic T cells activation by activated Helper T cells How are Helper T cells activated? Helper T cells activated after binding to an antigen presenting cell Phagocytic cell like dendritic cell or macrophage displays antigen on surface Activated helper T cells divide to make more T cells 1) Activated helper T cells 2) Memory helper T cells 3) Cytotoxic T cells Activated helper T cells release cytokines which stimulate: B cells Cytotoxic T cells  B cells also present antigens to Helper T cells In addition to antigens binding to B cell receptors, B cells can present the antigen to a helper T cell. Cytokines released from activated helper T cells stimulate division of B cells with matching antigens.  Cytotoxic T cells – two step activation 1) Activated by cytokines (from Activated helper T cells ) 2) AND attaching to antigen presenting cell displaying matching antigen Destroy infected cells by poking holes with proteins including perforin and Granzymes Vaccines trigger primary immune response and immunological memory Preparations of antigen with dead/deactivated pathogen or genes that encode proteins. Examples: inactivated toxins virus capsule proteins genes for microbial proteins mRNA vaccines – mRNA is converted to protein by host cells If pathogen with antigen encountered there will be a strong and rapid secondary immune response "Syringe and Vaccine" by NIAID is licensed under CC BY 2.0 Immunization programs reduce disease incidence  COVID-19 Vaccines Moderna US trial: 30,000 participants Placebo 185/15,000 developed COVID 19 symptoms (30 severe) Vaccine 11/15,000 developed COVID 19 symptoms (0 severe) https://www.sciencemag.org/news/2020/11/absolutely-remarkable- no-one-who-got-modernas-vaccine-trial-developed-severe-covid-19 Moderna and Pfizer vaccine: COVID 19 mRNA sequence Lyme Disease Vaccine | Lyme Disease | CDC