Cells 29 November 2011 14:20

Guide for use of these notes First of all thank you for choosing to download these notes to study from I hope you find them useful, please feel free to email me if you have any problems with the notes or if you notice any errors. I don't promise to respond to all emails but I'll do my best. I organise my notes so that you should read the learning objectives on the left then proceed down the right hand side for a few learning objectives and then cross back over to the left and continue like that. Anything in this highlighted green is a definition or explains basically something's function. Text highlighted in yellow or with a star is what I would deem important and key to your information. Italics and bold just help to make certain terms stand out. The notes are a bit quirky but I hope you like them and find some of the memory aides strange enough so that they stick in your head. I provide them to you in OneNote format as that is how I created them, they can be saved as PDF but the formatting is not as nice. The one caveat with this is that these notes are freely copy able and editable. I would prefer if you didn't copy and paste my notes into your own but used them as a reference or preferably instead embellished these already existing notes by adding to them.

Good luck with first year Stuart Taylor

Stuart's Cells Page 1

C1 Cells and Organelles 13 December 2011 21:26

Learning objectives Understand what constitutes a cell, and the scale of cells and molecules

Understand what constitutes a cell, and the scale of cells and molecules

Demonstrate the following on a suitable transmission electron micrograph: nucleus; nucleolus; nuclear envelope; mitochondrion; rough endoplasmic reticulum; smooth endoplasmic reticulum; ribosomes; Golgi apparatus; secretory granule; plasma membrane; cytoskeletal components.

Dimension of a Cell Size of a cell 10-100µm, typically 10 Volume of a cell ? (nanolitres ?) Weight of a cell : (density = 1.06) Dimension of a virus (nanometres, nm ?) Dimensions of a molecule (nm, Angstroms ?) Concentration of molecules (molarity); number of molecules in a given volume Number of molecules in one Mole= 6.03x 10 23

Describe the predominant types of molecules in a cell Identify the essential characteristics of prokaryotic and eukaryotic cells. Explain the relationship of individual cells to the organisation of the whole body.

Demonstrate the following on a suitable transmission electron micrograph: nucleus; nucleolus; nuclear envelope; mitochondrion; rough endoplasmic reticulum; smooth endoplasmic reticulum; ribosomes; Golgi apparatus; secretory granule; plasma membrane; cytoskeletal components.

Understand that movements of molecules and organelles in cells and that the movement of cells are essential processes Understand that cancer is a disorder of cell division

Describe the predominant types of molecules in a cell • • • • • • • • •

Soluble proteins ions (K+, Na+, Mg2+, Ca2+, PO42-, Cl-) sugars Nucleotides: e.g. ATP, cAMP, GTP amino acids mRNA tRNA Lipids, cholesterol Peptides

Understand that movements of molecules and organelles in cells and that the movement of cells are essential processes Molecules move spontaneously Diffusion, Brownian motion (temperature dependent, Robert Brown, 1827, and Einstein, 1905) Other forms of movement require energy Hydrolysis of ATP Transport of molecules against a concentration gradient Movement of organelles Adaptation of hair cells in the ear Movement of cell membranes, ruffling Growth and migration of cells. Nerve growth, development Cell division, movement of chromosomes Muscle contraction (skeletal and smooth), the heart beat All require specialised motor proteins

Understand that cancer is a disorder of cell division • Cancer is caused by uncontrolled cell division. • This means that a tumour is made up of a large amount of cells rather than cells that are particularly large. • In essence it is hyperplasia which is causing the cancer not hypertrophy.

Mutations that can lead to cancer: • switch on of “divide” signals • switch off of “don’t divide” signals

Explain the relationship of individual cells to the organisation of the whole body.

• loss of correction mechanism on DNA copying • loss of escape mechanism from cell division

• Individual cells of similar function are collectively known as a tissue. • Tissues are the functional units of organs. • Organs make up organ systems and organ systems make up organisms.

• loss of limit on number of times a cell can divide • loss of control keeping cell within tissue boundaries • ability to evade body defence mechanisms

Extra information

• • • •

Vesicles are transient organelles, fuse with cell membranes Phospholipid bilayer is 8nm Cytoplasm is everything apart from the nucleus including the organelles. Cytosol is just the liquid component of the cell excluding all the organelles.

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• ability to recruit blood vessels to growing tumour • ability to migrate into blood stream or lymph vessels • ability to establish tumours in the “wrong” tissue Cancer is a disorder of cell division resulting in excess cellular proliferation where the balance between cell production and cell death is lost. All options limit cell production except "switching on of 'divide' signals" which up-regulates cell proliferation.

Organelles 27 March 2012 10:57

My learning Objectives

Nucleus

Understand the role, size and location of many of the organelles within the human cell including Nucleus Ribosomes Rough Endoplasmic Reticulum Smooth Endoplasmic Reticulum Golgi Apparatus Endosomes Mitochondria Lysosomes Peroxisomes Cytoskeleton

Ribosomes • Ribosomes are the protein factories of the cell. • Ribosomes are large particles about 20nm in diameter are composed of about 70-80 proteins. • Eukaryotic ribosomes are 80s composed of two subunits, the 60s and the 40s. • Prokaryotic ribosomes are 70s composed of a 50s and a 30s. • Note that the two fragment numbers do not add up, this is because the Svedberg Unit is a measurement of sedimentation upon centrifugation, rather than size or volume. • The two subunits combine during protein synthesis and are free floating at other times. • A typical cell may contain as many as 10million ribosomes. • The proteins synthesised on the RER pass into its lumen and is eventually transported to the Golgi Apparatus.

• The nucleus is the largest of the membrane bound organelles and is the most prominent. • Skeletal muscle cells are multi-nucleated. • Function of the nucleus is to contain the genetic information for transmission to the next generation of cells or for protein synthesis.

• Surrounding the nucleus is the nuclear envelope, composed of two membranes, which contains nuclear pores. These pores form when the two membranes join each other resulting in circular rims. • RNA molecules used in protein synthesis pass through these pores. • The nucleolus is the most prominent structure within the nucleus. • The nucleolus is a densely staining filamentous region without a membrane. • In this region are genes associated with the production of rRNA.

Rough Endoplasmic Reticulum Smooth Endoplasmic Reticulum • A reticulum is an extensive network of membranes which enclose a space which is continuous throughout the network. • The RER is granular and has ribosomes attached to its cytosolic surface and has a flattened-sac like appearance. • The RER is involved in packaging proteins that will eventually be sent to the Golgi. • The SER has no ribosomal particles on its surface and has a branched, tubular structure. • It is the site at which certain lipid molecules are synthesized, it also has a role to play in detoxification of certain hydrophobic molecules, and it also stores and releases calcium ions which can act as a intracellular messenger.

Golgi Apparatus • The Golgi Apparatus is a series of closely apposed, flattened membranous sacs, which are slightly curved and form a cup like structure. • Associated with this organelle, particularly near its concave surface, are a number of roughly spherical, membrane enclosed vesicles. • Proteins that come from the RER undergo modification (post-translational modification?) as they pass through each Golgi compartment. • For example carbohydrates can be linked to proteins to form glycoproteins and the polypeptide can be shortened by the removal of the terminal part of the chain. • The Golgi also sorts the proteins for transportation in the aforementioned vesicles, either to the plasma membrane for exocytosis or to other cellular organelles. • Vesicles are 50nm or larger.

Endosomes • These are a number of membrane bound tubular and vesicular structures that lie between the Golgi and the plasma membrane.

• Certain types of vesicles that pinch off of the plasma membrane travel to and fuse with the endosomes.

• Like the Golgi endosomes are involved in sorting, modifying and directing vesicular traffic in cells.

• May be taken advantage of/modified in intracellular bacterial infections such as Salmonella and Listeria.

Mitochondria

Lysosomes • These are spherical or oval organelles surrounded by a single membrane and are typically 0.1–1.2 μm.

• A typical cell may contain several hundred lysosomes. • The fluid within a lysosome is acidic (pH 4.8) and contains a variety of digestive enzymes.

• Lysosomes act to break down bacteria and the debris from dead cells, in addition to organelles that have been damaged.

• They contain hydrolase enzymes. Stuart's Cells Page 3

• Very important in ATP synthesis. • Mitochondria are spherical or elongated, rodlike structures surrounded by an inner and outer membrane. • This outer membrane is continuous whereas the inner is highly folded into sheets or tubules called cristae, which extend into the inner mitochondrial space known as the matrix. • As many as 1000 may be found in highly metabolically active cells such as those with secretory functions i.e. endocrine cells. • Mitochondrion have been found to exist in an extended network (reticulum) which is thought to be important in the distribution of fatty acids and oxygen throughout a cell. • Mitochondria are also the site of lipid beta oxidation and synthesis of certain lipids such as oestrogen and testosterone. • Red blood cells lack organelles, including mitochondria, and can neither

• The fluid within a lysosome is acidic (pH 4.8) and contains a variety of digestive enzymes.

• Lysosomes act to break down bacteria and the debris from dead cells, in addition to organelles that have been damaged.

• They contain hydrolase enzymes.

Peroxisomes • Moderately dense single membrane oval structures. • They consume molecular oxygen which is used to remove hydrogen from organic molecules including lipids, alcohol and potentially toxic ingested substances. • One of the reaction products is H2O2 (hydrogen peroxide) hence their name. Although this is toxic to cells peroxisomes are able to break it down to reduce its concentration. • Peroxisomes are also necessary for lipolysis of fatty acids into two-carbon fragments that can be used in generating ATP.

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• Mitochondrion have been found to exist in an extended network (reticulum) which is thought to be important in the distribution of fatty acids and oxygen throughout a cell. • Mitochondria are also the site of lipid beta oxidation and synthesis of certain lipids such as oestrogen and testosterone. • Red blood cells lack organelles, including mitochondria, and can neither reproduce nor carry out extensive metabolic activities.

Cytoskeleton • Network of protein filaments that is explored in depth here T1 Epithelial Organisation.

C2 Infectious Diseases 13 December 2011 11:00

Type of Disease Causing Agent

Distinguishing features and methods of replication

Virus

Obligate parasites take over host SARS, HIV, influenza nuclear synthetic machinery in order to replicate. Divides by budding out of cell. Can congregate in liver then spontaneously released causing fever spike.

""

Bacteria

Prokaryotes that replicate by binary fission. Three main types Bacillus which are rod shaped, Coccus disc shaped, Spirillus spiral shaped. Chromosome of DNA but no nucleus.

Shigellosis, dysentary. Tuberculosis Meningococcal meningitis.

Fungi

Single celled Eukaroytes that can Candida albicans and Aspergillus either exist as yeasts or molds. fumigatus. Molds grow as long filaments called hyphae.

Learning Objectives Name the main types of infectious agents causing disease in humans List the key differences between prokaryotes and eukaryotes Give examples of each type of infectious agent and the disease it causes Name the distinguishing features of the different types of infectious agent and explain how they replicate

Shigella mechanism-> Cell entry- vacuole lysis- intracellular replicationcell to cell spread using host actin/ cytoskeleton.

Key Differences Between Pro and Eukaryotes

Prokaryotes

Also single celled Eukaryotes about Plasmodium spp, and Leishmania Leishmaniasis - sand 30 types are human parasites. spp fly vector and malaria Trophozoites- process whereby parasite absorbs nutrients from host. May have complex life cycles involving multiple hosts e.g. malaria and mosquitos.

Helminthes

Have a single chromosome- Haploid

Have two copies of a chromosome. Haploid or diploid

Poorly defined cytoskeleton

Cytoskeleton is better (actin, microtubules?)

RFT

Cell walls contain peptido-glycan

Cell walls of fungi contain chitin, plants cellulose, mammals do not.

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Candidasis, Aspergillosis

Protozoa

Multicellular organisms which contain Flatworms (flukes), roundworms and tapeworms. Life cycles outside of host and are transmitted by vectors.

• Eukaryotes have developed by integrating prokaryotes. • Eukaryotes are better organised.

Shigella spp, Mycobacterium tuberculosis, Neisseria meningitidis and Bacillus anthracis.

Diseases Caused

Systemic infection from these can affect immunocompromised people.

Eukaryotes

No internal membranes apart from a Membranes that define organelles few photosynthetic bacteria including nucleus, ER, (chloroplasts)? mitochondria. NO MEMBRANE BOUND ORGANELLES

Examples

Schistosoma Spp.

Schistosomiasis (Bilhaziasis)

C3 Cell Membranes 13 December 2011 11:00

Explain the formation of phospholipid bilayers in an aqueous environment. Draw the structure of phosphatidylcholine and identify the component parts. Describe the permeability properties of a phospholipid bilayer with respect to macromolecules, ions, water and organic compounds (including drugs).

Distinguish simple diffusion, facilitated diffusion and active transport of ions and molecules across cell membranes. NEW for 2011: Understand the picket and fence model of membrane proteins Categorise the functions of membrane proteins. Explain the movement of Na+ and K+ ions across the cell membrane against a concentration gradient and the consequences of failure of such a movement.

Explain the formation of phospholipid bilayers in an aqueous environment. • Hydrophilic head and hydrophobic tail causes specific arrangements as either micelles (droplets) or bilayers.

Draw the structure of phosphatidylcholine and identify the component parts. • Choline, phosphate and glycerol make up the polar (hydrophilic) fatty acid head. • Phosphatidylcholine has two tails made up of fatty acids, one that is straight and one that is kinked by a cis-double bond. Collectively these are known as the non-polar (hydrophobic) tails. • Cholesterol increases membrane stiffness packing between hydrophobic tails reducing membrane fluidity and thus increases stiffness

Explain how the entry of glucose and amino acids into the cell against a concentration gradient is coupled to ATP dependent Na+ transport. Explain how external chemical signals can be sensed at the interior of a cell. Be able to calculate the membrane potential from the Nernst equation Understand the role of membranes in synaptic transmission, using the neuromuscular junction as an example Describe the permeability properties of a phospholipid bilayer with respect to macromolecules, ions, water and organic compounds (including drugs). • • • •

Impermeable to macromolecules such as proteins and RNA. Are permeable to neutral molecules such as O2 and CO2 Impermeable to cations- Na,K, Ca Impermeable to anions- Cl, HCO3-

• Permeability can be mediated by proteins channels. • Two important coupled transporter types- symporters and antiporters. • Symporters bring material into a cell by facilitated diffusion. An example is bringing in sugars and amino acids with Na. Antiporters combine facilitated diffusion of one chemical i.e. Na down its concentration gradient with the active transport of another molecule out e.g. H+.

Distinguish simple diffusion, facilitated diffusion and active transport of ions and molecules across cell membranes. • Diffusion- Movement of a particle down a concentration gradient • Facilitated Diffusion- The movement of hydrophilic particles through pore proteins/ gated ion channels down a concentration gradient. These may be gated and they work by "hiding" charge from the hydrophobic core of the lipid bilayer. • Active transport- The movement of a particle against its concentration gradient using energy derived from the hydrolysis of ATP's phosphoanhydride bond. • Pinocytosis: engulfment by the membrane of extracellular solute and small molecules which end up in small intracellular membrane-bound vesicles • Phagocytosis: engulfment by the membrane of extracellular objects such as bacteria, cell debris, other cells. Again these end up in intracellular membrane-bound vesicles- macrophage, neutrophil

NEW for 2011: Understand the picket and fence model of membrane proteins • Membrane proteins are not stationary they are free to move within small compartments and also can occasionally hop between these compartments. • Membrane is scaffolded by the Membrane Skeleton MSK- which creates the compartments and is made up of the actin cytoskeleton. Ensures that proteins remain in the correct place. • Some proteins however are anchored to the membrane which is the picket anagram and ensures they are in the correct place- possibly signalling receptors.

• Exocytosis: Movement of proteins and other molecules (e.g. hormones, blood clotting factors) from intracellular vesicles towards the extracellular space by fusion with the cell membrane.

Categorise the functions of membrane proteins. • • • •

TREC Transport (Na+-Glucose transporter) Receptor- for hormones and growth factors Electron carrier (cellular respiration and photosynthesis in mitochondria and chloroplasts) • Cell recognition and adhesion- MHC

Explain how the entry of glucose and amino acids into the cell against a concentration gradient is coupled to ATP dependent Na+ transport.

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Explain the movement of Na+ and K+ ions across the cell membrane against a concentration gradient and the consequences of failure of such a movement. Background- Proteins are anions which cannot diffuse out of the cell, the anions and their accompanying cations cause a high salt concentration which is remedied by water being pulled into the cell. But Na is quite happy to move down its

such a movement. Background- Proteins are anions which cannot diffuse out of the cell, the anions and their accompanying cations cause a high salt concentration which is remedied by water being pulled into the cell. But Na is quite happy to move down its concentration gradient into the cell.

Explain how the entry of glucose and amino acids into the cell against a concentration gradient is coupled to ATP dependent Na+ transport. • Glucose as a hydrophilic molecule is membrane impermeable. • There are higher levels of glucose outside the cell as it is being constantly metabolised in the cell. • Sodium is actively transported out (High conc of sodium outside) and glucose moves down its concentration gradient into the cell. • Then glucose binds to a specific glucose transporter and enters the cell (Glut-4) • This is a type of facilitated diffusion and involves many different proteins some of which are insulin sensitive.

The Na+-K+ ATPase • The Na+-K+ ATPase maintains the osmotic balance and stabilises the cell volume by exporting Na+. • The Na+ gradient is thus maintained. • The Na+ gradient is also used to drive the transport of sugars and amino acids- i.e. is an antiporter • Alpha chain- 1000 amino acids long this spans the membrane ten times and creates a hydrophobic pore. • Beta chain- 300 amino acids long.

Be able to calculate the membrane potential from the Nernst equation

Process of how it works

The electrochemical potential

The Na+-K+ pump exchanges 3 Na+ ions from inside the cell for two K+ ions on the outside. There are two consequences: Ionic gradients are created: less Na+ and more K+ inside the cell than outside. A charge gradient is created, as more positive charges are pushed out than are coming in. This results in the inside of the cell being at a more negative potential than the outside.

E x (V )=

Nernst Equation:

• Import of 2K+ • Export of 3Na+ 1. Driven by phosphorylation of aspartyl residue 2. Then hydrolysis of aspartyl phosphate. 3. Results in change of the "Conformational energy state" of the protein pump. • The consequence of a failure of the Na-K-ATPase transporter would be that sodium would not be exported and would just flow down its concentration gradient into the cell, established by the negative protein molecules. As a result of this it would create an osmotic potential whereby water would follow it. This would result in excessive water levels within the cell and could possibly cause the cell to burst.

RT [ X ]o ln zF [ X ]i

Where E is the membrane potential in V (A-level physics ?) R = Gas constant, 8.135 J K -1-1 mol-1-1 F = Faraday’s constant, 9.684 x 10 4 C mol-1-1 T = absolute temperature; –273.15 °C is absolute zero. At 25°C, T= -273 °C z = valence of the ion, 1 for Na ++ or K++ What is the membrane potential at 25 °C for: [K+]i = 166 mM and [K+]o = 5 mM

Explain how external chemical signals can be sensed at the interior of a cell. • Signals can be sent (exocytosis of hormones) or lipid soluble molecules, other rely on trans membrane receptors

• Potassium's was -87.68- nearly -90v.

Membrane

Lipid

Protein

Myelin Sheath

80%

20%

Plasma membrane

50%

50%

Mitochondrial inner membrane

25%

75%

• External messenger allows ion entry - allows the influx of calcium ions through a channel. • Another method is receptor mediated signalling

Action potentials

• Cell membranes have to: ○ Be selectively permeable ○ Permeable to waste and nutrients ○ Impermeable to macromolecules • Dihydropyridine is located in t tubule membrane • Ryanodine is located on sarcoplasmic membrane • Cell membrane is 6nm thick • Phosphatidylcholine is also called lecithin. • SYMPORTER BOTH IN • UNIPORTER ONE IN • ANTIPORTER ONE IN ONE OUT

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Action potentials

Extra Information

Action potentials occur in elongated cells (nerves, muscle) when the membrane potential is disrupted by a brief pulse of current which briefly opens voltage-gated Na+ channels. Na+ ions enter the cell and cause depolarisation, from – 70 mV to about +50 mV. Na+ channels become inactivated locally, preventing further Na + entry. Voltage-gated K+ channels open, resulting in K + efflux and help to restore the resting membrane potential. The process propagates down the nerve/muscle

Understand the role of membranes in synaptic transmission, using the neuromuscular junction as an example • Depolarisation of the muscular post-synaptic membrane results in a propagated action potential. • The wave of depolarization extends into the t-tubules (invaginations of the cell membrane) to transmit the activation signal into the core of each muscle cell in the motor unit. • Close contact with the sarcoplasmic membrane via triadic junctions involving the dihydropyridine (t-tubule membrane) and ryanodine receptors (sarcoplasmic reticulum membrane) results in calcium release from the sarcoplasmic reticulum. A triadic junction is formed by one t-tubule and 2 sarcoplasmic reticulum terminal cisterna (one on either side of the t-tubule). • Calcium diffusion into the myofilaments lattice and calcium binding the troponin on the thin filaments (actin) in skeletal and cardiac muscle result in activation of the contractile machinery and contraction.

The protein regions in the core of the lipid bilayer have a predominantly –helical conformation. (Secondary structures of proteins ?). The protein cores are very stable in the protein

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C4 Blood and Blood Cells 13 December 2011 21:26

Learning Objectives

Main functions of blood

Main functions of blood Major components of blood Erythrocytes features and functions Haemoglobin importance, basic structure and role Anaemia definition and major causes Explain simply functions of leukocytes and platelets Major functions of plasma

• • • • • • •

Connective Tissue Haemostasis Maintain Homeostasis Support of genitalia Heat Distribution Immune response Transport CHMSHIT

Haemoglobin importance, basic structure and role

Major components of blood

• Haemoglobin is a protein made up of 4 subunits each with a Fe 2+ iron core (metalloprotein) • Oxygen binds to the iron forming oxyhaemoglobin. • Another type of haemoglobin is methaemoglobin which is an oxidised form whereby the Fe2+ core is replaced by Fe3+. This is unable to carry oxygen. • Broken down into bilirubin which is yellow and is a component of bile salts. • Carbon monoxide has 200x the affinity with comparison to oxygen so reduces ability to transport oxygen.

Methaemoglobin Common causes • Reduced cellular defence mechanisms ○ Children younger than 4 months exposed to various environmental agents ○ Cytochrome b5 reductase deficiency ○ G6PD deficiency ○ Hemoglobin M disease ○ Pyruvate kinase deficiency • Various pharmaceutical compounds ○ Local anesthetic agents, especially prilocaine as used in the Bier block ○ Amyl nitrite, chloroquine, dapsone, nitrates, nitrites, nitroglycerin, nitroprusside, phenacetin, phenazopyridine, primaquine, quinones and sulfonamides • Environmental agents ○ Aromatic amines (e.g. p-nitroaniline , patient case) ○ Arsine ○ Chlorobenzene ○ Chromates ○ Nitrates/nitrites • Inherited disorders ○ Some family members of the Fughate family in Kentucky, due to a recessive gene, had blue skin from an excess of methaemoglobin. • In cats ○ Ingestion of Paracetamol (i.e. acetaminophen, tylenol) Oxygen binding: • Haemoglobin has a low affinity for oxygen due to conformational shape of globin molecules • Oxygen binding breaks conformation and opens up structure. • Second oxygen molecule binds more easily and so on in a process known as cooperative binding.

Haemoglobin

Haem

• • • •

Erythrocytes- transport oxygen via haemoglobin Platelets- Enucleated cell required for clotting process Plasma- Serum containing hormones, dissolved substances Leukocytes- White blood cells that illicit an immune response.

Erythrocytes features and functions Features • Bi-concave disk, no nucleus, or organelles. • Molecules on surface convey blood group type. • 7.5µm in diameter • Dependent on dietary iron and has a 120 day lifespan broken by macrophages in the liver known as Kupffer cells) • Erythropoietin is the hormone which causes stem cells to differentiate into erythrocytes. Functions • Transports oxygen on haemoglobin. • Transports CO2 as carbonic anhydrase Life Cycle • Immature erythrocytes contain ribosomes: reticulocytes. • High circulating reticulocytes diagnostic (e.g. anaemia, chemotherapy) • Removed through reticulo-endothelial system (phagocytic macrophages in spleen).

Anaemia definition and major causes Anaemia is defined as a low blood haemoglobin concentration. With reference to Mean Cell Volume (size of cell) there are 3 types of anaemia Microcytic- Failure of haemoglobin synthesis caused by iron deficiency. Causes -Fe deficiency resulting from ○ Parasitic infection ○ GI lesion ○ Menstruation (1/2 mg Fe lost) Normocytic- Acute blood loss Macrocytic- Hypertrophy of cells is caused by lack of mitoses (DNA synthesis and replication issues) which results in fewer but larger cells. Causes○ Folic acid- Vit B9 (required for thymine synthesis) deficiency : pregnancy ○ Vit B12 (needed for folic acids actions) deficiency: autoimmune disease, destroys B12 uptake in gut: pernicious anaemia; vegetarians, vegans • Sickle Cell anaemia is caused by a haemoglobin mutation

Explain simply functions of leukocytes and platelets • Leukocytes circulate in blood and lymphoid organs. Job is to fight infection sometimes by invading tissue.

B lymphocytes • Mature in bone marrow • Humoral (antibody-mediated) immunity • Foreign antigen → immunoglobulin (antibody) production

• Immunoglobulins: IgM; IgA; IgG; IgE; IgD • I think GAMED is an acronym for the decreasing amounts of the respective antibody in the body. Not just the blood or else IgM would be the highest. • Antibody-antigen reactions: assist phagocytosis by precipitation; agglutination (clumping) or coating in antibody (opsonisation) or prevent attachment of micro-organism to tissues (neutralisation) • Primary immune response: first exposure, antibodies appear after latent period, peak then fall • Secondary response: greater, quicker, longer response due to memory cells (long lived B-lymphocytes) • Passive immunity: inject immunoglobulins (vaccine) or cross placenta (colostrum in some species)

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• Neutrophils and monocytes are phagocytic. • Eosinophils are involved in allergic response • Basophils produce histamine and heparin- these are lowest leukocyte number in blood. Polymorphonuclear granulocytes

(colostrum in some species)

• Segmented nucleus • Full of cytoplasmic granules

T lymphocytes • Thymus dependent (derived in bone marrow, migrate to thymus, acquire surface antigenic molecules and become immunologically competent) • Cellular immunity (i.e. not antibodies)

• First on scene • Adhere to blood vessels in infected area and migrate to tissue • Engulf, kill and digest microorganisms • Release inflammatory mediators: toxic oxygen products, digestive enzymes, vasodilators, chemotaxins.

• Circulate → foreign antigen → blast transformation → progeny with receptors for antigen • Activated T-lymphocytes → chemotaxins (attract macrophages); lymphotoxin (kills cells); interferon (kills viruses) Subgroups: • Cytotoxic T cells (CD8+, “attack cells”) • Helper T cells (CD4+, secrete cytokines to help B and T cells, essential, HIV infects) • Suppressor cells (modify lymphocytes responses)

Platelets • No nuclei, produced from megakaryocytes. • Have cell receptors for platelet activators such as thrombin in coagulation cascade or for collagen within blood vessels. • Adheres to exposed collagen in wounds or atheromas • Release granules that causes activation and aggregation of more platelets. • Diameter of 2-3μm. • Lifespan of 8-10 days.

Major functions of plasma Fluid component of blood which acts as a carrier for cells and key components • Nutrients- Amino acids, glucose, lipids • Hormones- Thyroxin, erythropoietin, aldosterone • Proteins- Exert osmotic balance to maintain blood volume -Fibrinogen, albumin, globulins • Inorganic ions- Na, K, PO4, HCO3 • Products of metabolism- Lactic acid, urea.

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Monocytes • • • •

Large single horseshoe nucleus Precursors of macrophages, which means big eaters develop into macrophages in tissues. Arrive after granulocytes. Phagocytosis of debris, dead tissue and pathogens. Phagolysosome is fusion of lysosome with whatever has been ingested.

• Secrete inflammatory mediators and stimulate angiogenesis (vessel growth = repair) • Ingest and store antigens, present modifies antigen to lymphocytes