11.1 Antibody Production and Vaccination Antigens in Blood Transfusion Every organism has unique molecules on the surface of their cells. Antigen: any foreign molecule that can trigger an immune response. Most common types: proteins and very large polysaccharides. Location: found on the surface of cancer cells, bacteria, and on the envelopes of viruses. Humans: surface of our own cells contains proteins and polypeptides. Immune systems function based on recognizing distinction between foreign antigens and self. Antigens on the surface of red blood cells stimulate antibody production in a person with a different blood group. Blood groups are based on the presence or absence of certain types of antigens on the surface of red blood cells. Blood groups ABO and Rhesus are the two most important antigen systems in blood transfusions. All three (ABO) involve a basic antigen sequence called antigen H. In blood types A and B, this antigen H is modified with the addition of a molecule. o Antigen A results with the additional molecule N-acetylgalactosamine o Antigen B results with the additional molecule galactose o Antigen AB results with the presence of both types of antigens o Transfusion: a medical procedure where a patient is given blood from a donor. A transfusion with wrong blood type results in 1. the immune response agglutination (clumping of recipient antibodies and donor red blood cells with incompatible surface antigens) followed by 2. hemolysis (destruction of red blood cells and potential coagulation of blood in the vessels). Blood typing involved mixing samples of blood with antibodies (blood types vs antibody serums) A can donate to A and AB, B can donate to B and AB, and AB cannot donate, and O can donate to A B or AB. The Specific Immune Response, Role of Plasma Cells, Clonal Selection & Memory Cell Formation B lymphocytes are activated by T lymphocytes in mammals Plasma cells secrete antibodies Activated B cells multiply to form a clone of plasma cells and memory cells. Principle of “Challenge and response” effectiveness/efficiency. Antigens on the surface of pathogens which have invaded the body are the “challenge”. “Response” involves the following: 1. Macrophage ingests pathogen and the pathogen antigens are displayed in the macrophage plasma membrane. 2. The Helper T cells specific to the antigen displayed by macrophage bind to the antigens (_) and are activated by the macrophage. 3. Select B cells are activated by 1. cytokine signaling proteins released by the helper T cells and 2. the binding of specific/fitting B cells 4. B cell divides repeatedly through mitosis to produce a clone of mostly antibodysecreting plasma cells (mature B cells) and smaller number of memory cells enforced by the rER. 5. Antibodies produced by the clone of plasma cells are specific to antigens on the pathogen and help to destroy it. The Role of Antibodies Antibodies aid the destruction of pathogens in a number of ways Opsonization: antibodies make a pathogen more recognizable to phagocytes so they more readily engulfed. Once bound, they can link the pathogen to phagocytes. Neutralization of viruses and bacteria: antibodies can prevent pathogens from docking and thereby entering host cells Neutralization of toxins: antibodies can bind to the toxins produced by pathogens, preventing them from affecting susceptible cells. Activation of Complement: ultimately creates a perforation in the membranes of pathogens. 1. antibodies activatine a complement cascade which 2. forms a membrane attack complex that 3. allows water and ions to enter the pathogen and cause it to burst Agglutination: antibodies can cause pathogens to stick together so they are prevent from entering cells and are easier for phagocytes to ingest Immunity Immunity depends upon the persistence of memory cells Antibodies + memory cells = immunity Immunity: either having antibodies against the antigen or memory cells that allow rapid production of the antibody Immunity develops once the immune system through “Challenge and response” principle and primary/secondary/etc. response Vaccines Lead to Immunity Vaccines contain antigens that trigger immunity but do not cause the disease Vaccines contain a live attenuated pathogen or some derivative of it with same antigens to stimulate a primary immune response and thereby develop immunity Zoonosis Pathogens can be species-specific although others can cross species barriers Zoonosis: a pathogen which can cross a species barrier. Example: Bubonic plague, bird flu, West Nile virus Cause: growth of contact through livestock contact or habitat disruption Histamines White cells release histamine in response to allergens Histamines cause allergic symptoms Histamines are released by basophils and mast cells. Mast cells: immune cells in connective tissue that secrete histamine in response to infection. Basophils: immune cells in blood that release histamine Effects: Dilation of small blood vessel in infected area causing vessels to become leaky. This 1. Increase flow of fluid containing immune components to infected area and 2. allows some immune components to leave the blood vessel Plays a role in bringing on symptoms of allergy such as in the nose, rashes, or swellings o To lessen the effects of allergic responses, anti-histamines can be taken Hybridoma Cells and Monoclonal Antibodies Fusion of a tumor cell with an anti0body producing plasma cell creates a hybridoma cell Monoclonal antibodies are produced by hybridoma cells Monoclonal Antibodies: purified antibodies that are produced by a clone of cells, derived from a single cell, which recognize only one antigen. Used both for treatment and diagnosis of diseases. Creation of Hybridoma Cell: Creation of cells for monoclonal antibody o Antigen recognized by the antibody injected in a mammal where plasma B cells which produce the desired antibody are made by the immune system o Plasma cells removed from the spleen of the mammal (only some correct) Fusion of B cells with cancerous myeloma cells. Resulting cells are called hybridoma cells Testing of Hybridoma Cells: As many types of B cells are extracted from a spleen and fused with myeloma cells, many types of hybridoma cells are created and tested to find the desired one Duplication of Hybridoma Cells: Desired hybridoma cell is allowed to divide and form a clone (example, in a fermenter) 11.2 Movement Bones and Exoskeletons Anchor Muscles Bones and exoskeletons provide anchorage for muscles and act as levers. Exoskeletons: external skeletons that surround and protect most of the body surface of animals Levers: size and direction of forces changes. Includes effort force, fulcrum, and resultant force First-class Lever: When F between E and R Second-class Lever: When R is between F and E Third-class Lever: When E is between F and R Skeletal Muscles are Antagonistic Movement of the body requires muscles to work in antagonistic pairs Antagonistic: when one contracts, the other relaxes. Produce opposite movements of muscles at a joint (triceps extend biceps flex forearm) Antagonistic pairs of muscles in an insect leg Grasshopper Femur, joint, tibia, joint, tarsus In massive muscles of femur, extensor muscle relaxes and flexor muscles contracts to flex/bring tibia, then opposite which produces a powerful propelling force The Human Elbow is an Example of a Synovial Joint Annotation of a diagram of the human elbow Different Joints Allow Different Ranges of Movement Synovial joints allow certain movements but not others. Flexion (Bending), Extension (Straigtening), Abduction (Sideways), Adduction (Sideways back), Structure of Muscle Fibers Skeletal muscle fibers are multinucleate and contain specialized endoplasmic reticulum Muscles used to move the body are called skeletal muscle and striated muscle. Two types: smooth and cardiac. Striated muscle is composed of bundles of muscle cells known as muscle fibers Embryonic muscle cells fuse together to form muscle fibers resulting in 1. Many nuclei present including single plasma membrane (sarcolemma) around each fiber and 2. Muscle fibers are much long than typical cells Sarcoplasmic reticulum: wrapped around every myofibril, it conveys the signal to contact to all parts of the muscle fiber at once using the ATP from mitochondria between myofibrils Myofibrils are plentiful parallel, elongated structures within each muscle fiber. These have alternating light and dark bands which give striated muscle stripes. Structure of Myofibrils Each myofibril is made up of contractile sarcomeres Z-line: a disc-shaped structure in the center of each myofibril light band Sarcomere: the part of a myofibril between one Z-line and the next Pattern is due to arrangment of two types of protein filament: thin actin & thick myosin Each myosin filament is surrounded by six actin filaments and forms cross-bridges with them during muscle contraction In the center of the sacromere, there is another line called the M-line (visible by EM) Mechanism of Skeletal Muscle Contraction The contraction of the skeletal muscle is achieved by the sliding of actin and myosin filaments from myosin pulling actin inwards towards the center of the sarcomere, shortening each sarcomere, ∴ shortening overall length of the muscle fiber Myosin causes the sliding with heads periodicall spaced which bind to special sites periodically spaced, creating cross-bridge, though which force is exterted using energy from ATP The Control of Skeletal Muscle Contraction Calcium ions and the proteins tropomyosin and troponon control muscle contractions Tropomyosin: a regulatory protein that blocks the binding sites on actin in a relaxed muscle. Troponin: a protein which causes tropomyosin to move 1. Signal from motor neuron to muscle fibre for contraction 2. Calcium ions released 3. Calcium ions bind to troponin 4. Troponin moves tropomyosins∴actin bind sites exposed 5. Myosin heads then bind and pull towards sarcomere center, moving actin filament The Role of ATP in the sliding of filaments ATP hydrolysis and cross-bridge formation are necessary for the filaments to slide 11.3 The Kidney and Osmoregulation Different responses to changes in osmolarity in the environment Animals are either osmoregulators or osmoconformers Osmolarity refers to the solute concentration of a solution. Osmoregulators: the maintenance of a constant internal solute concentration. All terrestrial animals, freshwater animals, and some marine organisms like bony fish o Typically 1/3 of seawater, 10 times that of fresh water Osmoconformers: animals whose internal solute concentration tends to be the same as the concentration of solutes in the environment. The Malpighian Tubule System The Malpighian tubule system in insects and the kidney carry out osmoregulation and removal of nitrogenous wastes Hemolymph: a circulating fluid that combines the characteristics of tissue fluid and blood. When animals break down amino acids, the nitrogenous waste product is toxic and needs to be excretes in the form of uric acid or urea. Malpighian Tubules: tubes that branch off from the intestinal tract. Cells lining the tubules are responsible for actively transporting ions and uric acid into the lumen of the tubules. Water the moves into the lumen by osmosis. All contents in the tubules are emptied into the gut. Contents then move to the hindgut where most of the water and salts are reabsorbed while the nitrogenous waste is excreted with the feces. Drawing the Human Kidney Comparing the Composition of Blood in the Renal Artery and the Renal Vein The composition of blood in the renal artery is different from that in the renal vein Why: 1. As kidney function in both osmoregulation and excretion 2. Way in which blood enters and leaves kidney are different How: 1/5 of blood plasma is filtered in the kidney (all substance in plasma besides large protein molecules). Specific substances are then actively reabsorbed and unwanted leave through urine Renal Artery Renal Vein Enters kidney Leaves kidney Higher concentration of toxins that have not been completely metabolized (drugs/pigments) and nitrogenous waste Oxygenated blood Higher amounts of CO2 as it is a waste product of metabolism Deoxygenated blood b/c metabolic activity in kidneys will require blood oxygen Blood will contain variable amount of water/salt Blood will have a fixed amount of water and salt as osmoregulation has occurred High concentrations of glucose Lower concentrations of glucose, as some would have been used by metabolism in the kidneys Plasma proteins are present in equal amounts The Ultrastructure of the Glomerulus The ultrastructure of the glomerulus and Bowman’s capsule facilitate ultrafiltration Glomerular filtrate is formed because: Blood pressure in capillaries is exceptionally high in the glomerulus. Capillary walls are particularly permeable, resulting in large amounts of tissue fluid forming. o Tissue fluid forms when blood plasma is pushed out of capillaries due to high internal pressure. Most solutes are filtered out freely alongside blood plasma, except large protein molecules. Ultrafiltration: the separation of molecules based on size (to become glomerular filtrate) Parts of Ultrafiltration System: 1. Fenestrations: gaps in the wall of the capillary about 100 nm in diameter. Allow fluid but no blood cells to escape 2. Basement Membrane: covers and supports the wall of the capillaries. Made of negatively charged glycoproteins which ∴ repel negatively charged proteins from being filtered out 3. Podocytes: form the inner wall of the Bowman’s capsule. Wrap around glomerulus capillaries with foot processes whose gaps prevent certain small molecules from being filtered out of blood in the glomerulus. The foot processes make a fibrous mesh. The Role of the Proximal Convoluted Tubule The proximal convoluted tubule selectively reabsorbs useful substances by active transport Selectively reabsorbs useful substances by active transport. Glomerular fluid contains 1.5 kg of salt and 5.5 kg of glucose and is around 180 dm-3 in volume. Volume of urine is only 1.5 dm-3, hence almost all of the filtrate is selectively reabsorbed in the PCT into blood. PCT reabsorbs all glucose, amino acids and 80% of water, sodium, and mineral ions Sodium Ions Actively transported from filtrate to space outside tubule by pump proteins located on the outer membrane of the tubule. Ions are then passed on to peritubular capillaries. Chloride Ions Active transport of sodium ions sets up a charge gradient that causes chloride ions to simply move down this charge gradient from filtrate to space outside the tubule. Glucose Ions Glucose is co-transported using specific proteins. Movement of Sodium ions down concentration gradient from outside tubule to inside provides energy to proteins for glucose to move to space outside tubule. Water Pumping of solutes to space outside the solute sets up a solute concentration gradient. Therefore, reabsorption of water occurs through osmosis. Annotation of Diagrams of the Nephron Bowman’s capsule: Collects the fluid filtered from the blood. PCT: Has many mitochondria to provide ATP for active transport of ions. Loop of Henlé: Descending limb carries filtrate into medulla and ascending limb brings it back out to cortex. Distal convoluted tubule (DCT): Fewer microvilli and fewer mitochondria (than PCT). Collecting duct: Carries filtrate back through cortex and medulla to renal pelvis. Blood flows through vessels in this order: • Afferent arteriole (blood from renal artery into kidney); • Glomerulus (high pressure capillary bed during which ultrafiltration occurs); • Efferent arteriole (Narrow vessel which generates high pressure in glomerulus); • Peritubular capillaries (low pressure capillary bed which absorbs fluid from convoluted tubules; • Vasa recta (unbranched capillaries with a descending limb and ascending limb); • Venules (carry blood to the renal vein) The Role of the Loop of Henlé The loop of Henlé maintains hypertonic conditions in the medulla Overall Effect: create a gradient of solute concentration in the medulla (hypertonic conditions) by pumping Na ions out of the filtrate of fluid in the medulla (interstitial fluid) in ascending limb Wall of ascending limb is impermeable to water, so water is retained in the filtrate. Interstitial concentration of 500 mOsm is achieved. Cells in the wall of the descending limb are permeable to water, the highly hypertonic interstitial fluid in the medulla causes water to be drawn out of filtrate in the descending limb until the volume of water = volume of interstitial fluid. This results in the ascending limb being able to pump out more sodium ions into interstitial fluid raising concentration to 700 mOsm. This process can continue until the interstitial fluid reaches a concentration of around 1200 mOsm (in humans). This is an example of a countercurrent multiplier system. Counter current because the fluid flows in opposite direction and a multiplier because it allows a steeper concentration gradient to develop than would develop with a concurrent system. Some Animals Have Relatively Long Loops of Henlé The length of the loop of Henlé is positively correlated with the need for water conservation in animals Loops of Henlé are found within the medulla, and in order to accommodate longer ones, the medulla must become relatively thicker Functions of ADH ADH controls reabsorption of water in the collecting duct Solute concentration is hypotonic in DCT, because proportionately more solutes than water passed out of filtrate in the loop of Henlé. If solute concentration low, relatively little water is reabsorbed passing through DCT and CD. Thus large volume of urine produced with low concentration returning blood normal If solute concentration high, ADH released by pituitary gland causing walls of DCT and CD to become more permeable to water, causing more water reabsorption. Filtrate passing down CD deep into medulla where solute concentration of interstitial fluid is high creates concentration gradient for water to be continually to reabsorbed into the blood. The filtrate, as a result, becomes a small volume of concentrated urine. Animals Vary in Terms of the Type of Nitrogenous Waste They Produce The type of nitrogenous waste in animals is correlated with evolutionary history and habitat. Ammonia is produced due to the breakdown of amino acids and nucleic acids. Highly basic and alters pH balance. Highly reactive chemical (hence toxic) In freshwater habitats, organisms can release waste as ammonia as it can be diluted in environment. Amphibians release waste as ammonia during larval form then switch to urea to save energy expenditure. Terrestrial organisms expend energy convert ammonia to less toxic forms (urea/uric acid o Birds and insects release waste as uric acid (require most energy to create) but does not require water to be released. For birds less water saves flight energy o Uric acid is released as it is not soluble and crystallizes rather than building up to toxic concentrations within the egg Dehydration and Overhydration Dehydration Effects: Darker urine Lethargy due to no water for metabolic waste removal and ∴ exposure to muscles Blood pressures falls resulting in increased heart rate Body temperature regulation affected due to inability to sweat Overhydration Effects (hypotonic): Swelling of cells: Headache and nerve function disruption Treatment Options for Kidney Failure Blood in tubing flows through dialysis fluid. Tubing is partially permeable and allows small molecules to pass through into dialysis fluid but not blood cells and protein molecules. Purified blood is returned to patient via a vein. Kidney transplant is also a viable option. Donors can be deceased or alive. Only one kidney needed to survive. Urinalysis Blood cells, glucose, proteins and drugs are detected in urinary tests 11.4 Sexual Reproduction Similarities Between Oogenesis and Spermatogenesis Spermatogenesis and oogenesis both involve mitosis, cell growth, two divisions of meiosis and differentiation Oogenesis: the production of egg cells in the ovaries Germinal epithelium cells in the fetal ovary divide by mitosis and distribute themselves through the cortex of the ovary. At 4/5 months (fetus), the cells grow and start to divide by meiosis. By 7 months they are in the first division of meiosis and follicle cells form around them. Primary Follicle: the combined group of cell at this point; 400,000 in ovaris at birth. No more primary follicles are produced, but at start of each menstrual cycle small batch stimulated to develop and one becomes a mature follicle containing a secondary oocyte. Spermatogenesis: the production of sperm in the testes Testes are composed of narrow tubes (seminiferous tubules) with groups of cells filling the gaps between the tubules (interstices). The cells are called interstitial cells. Out layer of cells called the germinal epithelium, where sperm production begins. Outer layer of cells in the seminiferous tubules are called the germinal epithelium, where sperm production begins. Spermatogonium are at the outermost part of the germinal epithelium. Spermatozoa are cells that have developed tails (flagella). Sertoli cells are nurse cells and exist in the walls of the seminiferous tubule. Spermatogenesis follows the following sequence of events: o Germinal epithelium cells (2n) divide by mitosis. o Diploid cells grow larger to become primary spermatocytes (2n). o Each primary spermatocyte carries out first division of meiosis to produce two secondary spermatocytes (n). o Each secondary spermatocyte carries out the second division of meiosis to produce two spermatids (n). o Spermatids associate with Sertoli cells to develop flagellum and become spermatozoa. o Sperm detach from Sertoli cells and are carried out by the fluid in the seminiferous tubule. Diagrams of Sperm and Egg Differences in the Outcome of Spermatogenesis and Oogenesis Spermatogenesis and oogenesis processes result in different numbers of gametes & cytoplasm amounts Each mature sperm consists of different parts to a mature egg. Each meiotic division results in four spermatids. Sperm differentiation eliminates most of the cytoplasm, whereas the egg increases its cytoplasm. First meiotic division in eggs produces one large egg cell and one polar body and the second meiotic division produces a similar result, therefore only one egg is produced per meiotic division. Egg is much larger than sperm. Sperm are produced continuously whilst only a few hundred mature eggs are produced during the lifetime of a female. Preventing Polyspermy Polyspermy: the event in which multiple sperm enter an egg Fertilization: the union of a sperm and egg to form a zygote. Acrosome Reaction: The zona pellucida is a coat of glycoproteins that surrounds the egg. The acrosome is a large membrane-bound sac of enzymes in the head of the sperm. Sperm binds to egg and enzymes from acrosome digest the zona pellucida. Penetration of the Egg Membrane: Sperm and egg fuse together and sperm nucleus enters the egg cell (fertilization). Cortical Reaction: Cortical granules are vesicles located near the egg membrane. The contents of these are released by exocytosis when egg is activated, with the enzyme digesting binding proteins and hardening zona pellucida so no further sperm can bind or permeate Internal and External Fertilization Fertilization in animals can be internal or external Aquatic animals often release gametes directly into water and have behaviors that bring eggs into proximity with sperm. Risky as it is prone to predation and environmental fluctuation. Terrestrial animals generally display internal fertilization as 1. gametes may dry out and 2. ensures sperm and ova are placed in close proximity to each other. Marine mammals still use internal fertilization. Developing embryos protected inside the female. Implantation of the Blastocyst Implantation of the blastocyst in the endometrium is essential for the continuation of pregnancy. Blastocyst forms after pregnancy. Upon fertilization, mitotic division occurs to form a 2-cell embryo. Occurs again to form a four cell embryo by 48 hrs. This continues slowly, alongside the migration of other cells, which gives the embryo the shape of a hollow ball (blastocyst). By 7 days the blastocyst is 125 cells and has reached the uterus after being brushed down the oviduct by the cilia of cells in the oviduct wall. Zona pellucida then breaks down and blastocyst sinks into the endometrium (implantation). Finger like projections on blastocyst allows it to penetrate uterus lining. Exchanges materials with mother’s blood (food and oxygen). By 8 weeks, begins to develop bone tissue and is considered a fetus. Role of hCG in Early Pregnancy HCG (Human chorionic gonadotropin) stimulates the ovary to secrete progesterone during early pregnancy. This helps maintain the uterus lining, which supplies the embryo everything it needs HCG stimulates the corpus luteum to continue to secrete progesterone and estrogen. Materials Exchange by the Placenta The placenta facilitates the exchange of materials between the mother and embryo. Humans are placental mammals. o Placenta is needed because the body surface area to volume ratio becomes smaller as the fetus grows. Two other groups of mammals: Monotremes(egg laying), Marsupials (pouch developed) Fetal tissues with contact to maternal tissues in the uterus wall. Fetus develops membranes that form the amniotic sac, which includes the amniotic fluid for the support and protection of fetus. Placental villus # increase during pregnancy and assist in exchange of materials with the mother Blood o Maternal blood flows in the inter-villous spaces around the villi (not confined to blood vessels). o Fetal blood circulates in capillaries close to the surface of each villus. Distance between fetal and maternal blood is small, and separation cells form the placental barrier which is selectively permeable. Release of Hormones by the Placenta Estrogen and progesterone are secreted by the placenta once it has formed, negating the role of the corpus luteum. Hence, switch over from corpus luteum to placenta occurs. The Role of Hormones in Parturition Progesterone inhibits secretion of oxytocin by the pituitary gland and myometrium contraction. The fetus (at the end of pregnancy) produces hormones that cause the placenta to stop secreting progesterone, therefore oxytocin secreted which stimulates myometrium contraction Stretch receptors detect contractions, which signal for greater oxytocin secretion, and more vigorous contractions as a consequence. Birth mediated by positive feedback involving estrogen & oxytocin for myometrium contractions Relaxation of muscle fibers cause cervix to dilate and uterine contractions then burst the amniotic sac. Further uterine contractions then push the baby out. Gestation Times, Mass And Growth, And Development Strategies: Altricial species (born weak and defenceless and immobile). Short gestation period. Precocial: born open eyed, hair, mobile, and often able to defend themselves. Long gestation period.