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Human Cell Biology and Physiology Timothy Billington PhD CLOUD OF KNOWLEDGE 4th Formative test 1. In bone, there are which 4 types of cells? What are each of their functions? 2. Where would you find the linear proteins Myosin and Actin? 3. We know that muscle cells produce large amounts of ATP, even at rest. The energy in ATP is then stored in the phosphate bond of another compound. What is this compound? Explain energy transfer using simple equations 4. What name is given to the voltage across a muscle cell sarcolemma? 5. Inside a muscle cell there are long structures running the length of the cell. Name them. 6. Which filamentous structures do you find in a sarcomere? Explain what happens in a sarcomere when a muscle contracts 7. What event initiates a contraction in a leg muscle? 8. What is the neuromuscular junction? What sequence of events happens in an NMJ? 9. What is a cholinergic synapse? Name the 4 events which occur at such a synapse. 4th Formative test continues 10. What is an Axon? What is the Myelin sheath and what does it do? 11. What is a Synapse? 12. Describe the distinctive structural features of a Neuron 13. What is an Action Potential? 14. Which ionic movements are occurring during a Depolarisation? 15. What happens when the peak transmembrane voltage is reached? 16. Which ionic events are occurring during Repolarisation? 17. Bone structure is continuously broken down and then replaced as growth occurs. This process is a balance of the activities of 2 types of bone cells. Which are they? 18. The matrix of bone consists of a metal salt. Name the salt. QUICK REMINDER OF WHAT WE WERE LOOKING AT LAST WEEK Cells in the Immune System LYMPHOCYTES CLASSES of LYMPHOCYTE CELLS in the IMMUNE SYSTEM T - CELLS CYTOTOXIC T-CELLS B - CELLS NK CELLS Differentiate into ‘PLASMA’ CELLS NATURAL KILLER CELLS Attack foreign cells infected by viruses MEMORY T-CELLS Respond to previously encountered Antigens Make & secrete Antibodies in response to antigenic compounds Perform immune surveillance Attack cancer cells in normal tissues Week 6 (Nov 10) begins here ACTION OF NK CELLS IN THE IMMUNE SYSTEM Target NK NK cell detects a foreign cell and adheres to it. NK cell has detected that the foreign cell (Target) has unusual components in its cell membrane Golgi Apparatus [ )))) ] in NK is re-aligned to face the target cell. GA produces a flood of enzymes (perforins, ) which move toward the target cell’s membrane. )))) (((( Week 6 begins here ACTION OF NK CELLS IN THE IMMUNE SYSTEM Perforins are (exocytosed) released by the NK, and perforate the Target cell membrane. The enzymes then destroy Target cell membrane proteins and kill the Target cell Debris from Target cell. EXOCYTOSIS: process by which materials are actively moved out of a cell vesicle cytoplasm Material to be moved out of cell, is packaged in a membrane-bound vesicle in the cytoplasm Vesicle moves to the cell membrane, combines with it and then releases its contents In the NK story above, the vesicle contained enzymes called perforins ENDOCYTOSIS: process by which materials are moved into a cell 1 2 3 1. Cell detects a substance in the extracellular fluid 2. Cell membrane envelops the substance, forming a membrane bound vesicle 3. Vesicle buds off and enters the cytoplasm WHAT IS AN ANTIGEN? An antigen is a substance ( protein, carbohydrate, nucleic acid or lipid) that is produced by a foreign body. Pollen grains are examples of antigens. Our immune system cells ( B-CELLS ) detect that the substance is foreign B-cells make an Antibody specific to the Antigen WHAT is the STRUCTURE of an ANTIBODY MOLECULE? Antigen binding sites Pale shading indicates the structures common to all antibody molecules. They are invariant. Heavy shading indicates Antigen binding sites have variable protein structure. In this way they can be made specific for a given antigen. Light protein chain Heavy protein chain TWO most important & frequent processes in the immune system manufacture of Antibody molecules Ab formation of Antigen-Antibody complexes AgAb B-CELLS RESPOND to ANTIGENS by MANUFACTURING SPECIFIC ANTIBODY PROTEINS Antigen – Antibody complex Antigenic Determinants ‘Key and lock’ analogy Antigen-Antibody complex is then destroyed by proteinases ( hydrolytic enzymes ) ANTIGEN-ANTIBODY BINDING Antigen shapes are called EPITOPES Corresponding binding site shapes on Antibodies are called PARATOPES 3 Antigens 3 different antibodies MEMORY B- CELL Retains information about the shape and type of antigens it comes into contact with Memory cells: remain in the tissue recognize an antigen that they have ‘seen’ previously [ “IMMUNE MEMORY”] produce the required antibody which is specific for that antigen antigen-antibody complex is formed the complex is then destroyed by proteinase enzymes Nett result ANTIGEN IS DESTROYED Let’s return to GASEOUS EXCHANGE We have seen that Oxygen diffuses from the blood stream to the cells AND THAT Carbon Dioxide diffuses from cells to the blood stream Capillary CELL DIFFUSION of GASES ALWAYS DOWN THEIR CONCENTRATION GRADIENT IN LUNGS Oxygen diffuses from AIR to BLOOD Carbon Dioxide diffuses from BLOOD to AIR IN TISSUES Oxygen diffuses from BLOOD to CELL Carbon Dioxide diffuses from CELL to BLOOD Concentration gradients for gaseous diffusion For any gas, the concentration is measured as Partial ppO2 in Air in the lung alveoli is > Pressure (pp) in mm Hg ppO2 in blood in the lung capillaries oxygen will diffuse from Air to Blood AIR IN / OUT Blood In Respiratory membrane De-oxygenated blood Oxygenated blood ALVEOLUS Blood Out Concentration gradients for gaseous diffusion ppCO2 in the Cell Question: > ppCO2 in Blood In which direction will Carbon Dioxide diffuse?? Now let’s look at some actual partial pressure examples For all gases, the greater the difference in pp between two environments, the faster will be the diffusion. The ALVEOLI are the smallest air spaces in the lung. Exchange of gases with Air only takes place there. In the lung ALVEOLUS Alveolar Air ppO2 = 100 ppCO2 = 40 ppO2 = 40 ppCO2 = 45 Lung capillary blood Respiratory membrane [ 1 cell thick ] Question: Which arrow represents Carbon Dioxide diffusion? Now let’s move to a tissue in the body, perfused by capillaries, and look at a typical cell: Body tissue capillary pp O2 = 95 pp CO2 = 40 Respiratory membrane Question: Which arrow indicates diffusion of Oxygen? CELL pp O2 = 40 pp CO2 = 45 HOW is CARBON DIOXIDE TRANSPORTED in the BLOODSTREAM? CO2 diffuses into the capillary blood stream from aerobically metabolising cells in peripheral tissues For every 100 molecules of diffused CO2 7 diffuse into the plasma and dissolve 93 diffuse into red blood cells 23 bind to Hb and form carbamino-haemoglobin Hb.CO2 70 react chemically with water to form carbonic acid (hydrogen carbonate) H2 O + CO2 Hydrogen carbonate carbonic anhydrase Question: What do we mean by aerobic? Question: What do we mean by anaerobic? Example: interior of muscles. [Lactic acid is an end product] Let’s review briefly the material on CHEMORECEPTORS CHEMORECEPTORS = Neurons which are sensitive to minute CHANGES in the concentration of specific chemicals in body fluids eg carbon dioxide levels in blood, acidity (hydrogen ion levels) in blood Neurons are in the walls of the Carotid arteries and monitor blood going to the brain Also in the wall of the Aorta, where they monitor blood going to the periphery We are not consciously aware of the action of chemoreceptors because they do not send action potentials to the sensory cortex of the brain CHEMORECEPTORS continue when the chemoreceptors for Carbon Dioxide register a CHANGE to an abnormally high pp of this gas in blood cells in the respiratory control centres in the base of the brain send an action potential to the diaphragm and thoracic cavity muscles which leads to deeper inhalation and fuller exhalation by exhaling more fully, CO2 is blown off in the alveoli and so the normal CO2 pp in the blood is re-established . Question: As the depth of inhalation is increased, which dissolved gas would you expect to increase its pp in capillary blood? HOMEOSTASIS: A VERY IMPORTANT CONCEPT Maintenance of a constant internal environment in the body The pp Carbon Dioxide control mechanism is a good example of a homeostatic regulation Think of homeostasis in terms of a familiar analogy Maintenance of a constant room temperature ROOM TEMPERATURE CONTROL RECEPTOR = GETTING TOO HOT INFORMATION IS SENT THERMOMETER CONTROL CENTRE = THERMOSTAT HOMEOSTASIS NORMAL ROOM TEMPERATURE SET POINT 20C EFFECTOR = TEMP FALLS AIR CONDITIONER TURNS ON COMMAND IS SENT HOW IS BODY TEMPERATURE REGULATED? RECEPTORS = GETTING TOO HOT TEMPERATURE SENSOR NEURONS IN SKIN and BRAIN HOMEOSTASIS INFORMATION IS SENT via action potentials CONTROL CENTRE = BRAIN Thermoregulation in hypothalamus (set point 37 C) NORMAL BODY TEMPERATURE EFFECTORS = SWEAT GLANDS IN SKIN INCREASED SECRETION TEMP FALLS BLOOD VESSELS IN SKIN DILATE COMMAND IS SENT via action potentials Question: To alter the set point on a room thermostat you simply choose a point on the dial How would you alter the set point of the sensitive cells in the hypothalamus? BLOOD: FUNCTIONS and PHYSICAL PROPERTIES FUNCTIONS include: Transport nutrients, dissolved gases, hormones, wastes Regulation acidity and ionic composition Fluid Loss restriction clotting @ sites of injury Defence against toxins, antigens & pathogens white cells & antibodies Body temperature regulation Question: absorbs & redistributes heat generated by active skeletal muscles Which 2 dissolved gases are of particular clinical interest? Which 4 ions? BLOOD continues PROPERTIES Physical Composed of Plasma and Formed Elements (Cells) Temperature @ ~ 38 C < 0 .1% Centrifuged whole blood Viscosity About 5x water, [ 5x as sticky, 5x as cohesive and 5x as resistant to flow ] Chemical Slightly alkaline, p H range: 7.35 - 7.45 ANTIGENS on the OUTER SURFACE of ERYTHROCYTES DETERMINE BLOOD GROUPS ABO blood types are genetically-determined Cells: A antigen Type A Plasma: B antibody B antigen Type B A antibody Both antigens Type AB No antibodies No antigen Type O B and A antibodies TRANSFUSIONS of BLOOD: GIVEN FACT: Antigen F AS YOU ALREADY KNOW: + Antibody to F Ag + Antigen F-Antibody F complex (ppt) Ab Observation: Type A person is transfused with Type B blood AgAb complex (precipitate) pptn of whole blood system and patient is then deceased Exercise: Explain what events happened in the above Question: Type B person is transfused with Type B blood. What happens? Type AB person is transfused with Type O blood. What do you predict? (NEW) TERMINOLOGY and DEFINITIONS Mitochondrion: often called the powerhouse of the cell. Energy is made here. Pl. Mitochondria. Cells usually have thousands of these, depending on their energy needs. Nucleus: houses the Deoxyribo Nucleic Acid (DNA) Nuclear membrane: encloses the nucleus and has pores for ingress and egress Nucleolus: Pl nucleoli. Nucleoli are transient organelles within the nucleus, which synthesise ribosomal RNA. Nucleoli are most prominent in cells which need to synthesise large amounts of protein. Rough Endoplasmic Reticulum: stacked membrane complex, studded with ribosomes, site of protein synthesis Smooth Endoplasmic Reticulum: stacked membrane complex, lacks ribosomes, site of lipid/fat synthesis Centrioles: cylindrical structures, composed of short microtubules. During cell division, the centrioles form the spindle apparatus which is used in the movement of DNA strands. Cells without centrioles cannot divide. (NEW) TERMINOLOGY and DEFINITIONS Plasma Membrane: semi-permeable, bi-layered phospholipid structure, enclosing the contents of each cell Cytoplasm: fluid interior of each cell. Composed of salts and water. Cytoskeleton: Literally the cell’s skeleton, an internal protein framework, gives the cytoplasm its strength and flexibility. Other details of this network are poorly understood. Organelle: any macromolecular structure suspended in the cytoplasm Ribosome: site of protein synthesis. Where m RNA is deciphered and amino acids are joined together to form proteins Protein: chain of amino acids in a particular sequence Golgi Apparatus: series of stacked membranes where newly-made proteins can be modified (NEW) TERMINOLOGY and DEFINITIONS Lysosome: vesicle containing digestive enzymes Secretory vesicle: contains products for export from the cell Cilium: finger-like structure extending from the cell and continuous with the plasma membrane. Pl. Cilia Microvilli: secondary folds in the cilia. Messenger RNA (m RNA) (mRiboNucleic Acid): linear chain structure, composed of nucleotides, which carries information from DNA to ribosomes for protein synthesis DNA: double-helical structure, composed of nucleotides, the basis of genes. Specifies inherited characteristics Chromosome: macro structure composed of very long DNA segments complexed with specific proteins