SC NATS 1670 Lecture Notes Fall/Winter 2023-2024 PDF

SC NATS 1670 LECTURE & WRITTEN NOTES CONCEPTS IN HUMAN HEALTH AND DISEASE FALL/WINTER 2023-2024 Thursday in LAS A Dr. Motti Anafi I A DIVERSITY Part OF LIFE A e INTRODUCTION TO CELL BIOLOGY h * smallest Is unit of Unity of Life life cell is the basic ↳ The unit of life the cell a feder...

SC NATS 1670 LECTURE & WRITTEN NOTES CONCEPTS IN HUMAN HEALTH AND DISEASE FALL/WINTER 2023-2024 Thursday in LAS A Dr. Motti Anafi I A DIVERSITY Part OF LIFE A e INTRODUCTION TO CELL BIOLOGY h * smallest Is unit of Unity of Life life cell is the basic ↳ The unit of life the cell a feder - resour Unicellular ↳Multicellular double always stranded DNA - DNA as genetic material ->Several RNAs ALL CELLULAR LIFE Transcription ↓ RNA HAS THE FOLLOWING Translation ↓ -> Living organisms are expressing DNA all the time CHARACTERISTICS Proteins -> Looking at ' a cell for the nucleic IN COMMON: ↓ acid, you will find both DNA and Phenotypes RNA -> several Enzymes expressed - - I *All cellular life is a result of reproduction &S cells divide into two , - Cell fromWA membrane > Reproduction -> Energy (ATP) e - C 2) CELL STRUCTURE: PROKARYOTES VS EUKARYOTES Nucleus RNA processing * EIE Organelles &E Eukaryotes ② • the most reliable feature distinguishing a eukaryotic cell from a prokaryotic cell is the presence of a nucleus Cell wall PE rx - e and " Prefer hot, high temperature to survive DIVERSITY OF PROKARYOTES ENVIRONMENTAL CONDITIONS - -> Temperature Grows best below 20°C ↳) Psychrophiles -> Grows best above 50° C Grows best bet ween 20 to 50° C Mesophiles =Some hyperthermophilic archaea live in hot springs 1Thermophiles Each environment will contain bacterial cells Dot some sort) -> Four categories of microbes based on temperature ranges for growth would no - be organisms able to survive s pH (acidic or basic environment) 3 Acidophiles Due to inflammation Grows well at pH of 1 or 2 (acidic) E Helicobacter pylori in the stomach ex _ ->Is the cause of peptic ulcer and gastric cancer - - Is inflammation which is a result of infection by helicobacter pylori ↳ can treat antibiotics (1) using -7 Grows best near neutral pH -> Neutrophile >Grows well at basic pH --Alkaliphile Result of long time infection helicobacter pylori -> Water ↳ Most cells require a minimum moisture content ↳ Some bacteria can make spores: cells that survive in the near absence of water - Salt - - ↳ Most cells require a moderate level of salt ↳Some cells can exist in very high salt concentrations (holophiles) > The habitat of halophiles: highly saline water - S Often contain red to orange pigments (protect them from intense solar energy) -> Oxygen availability -> ↳ Require energy for growth -> Aerobic ↳ Require lack of oxygen growth - - Important for metabolism Anaerobic -- Nutrient availability ↳Most microorganisms require organic and inorganic nutrients to grow and survive ↳ Cyanobacteria grow in the absence of key nutrients ↳ Inorganic compounds from the atmosphere THE EVOLUTION OF LIFE ON EARTH cells evolved to learn how to use the oxygen for ↳Bacterial their purposes cells to make it not toxic Take the characters from the oxygen to help develop energy Origin of life o discovering cill 3 what combines · cleus e 0 · O Prefer less aggressive environments I so - -1 Contain a chemical called peptidoglycan 3 > - Both have a outer cell membrane and a cell wall lacks -> Metabolisms are D very different - Archaea cells and bacteria are similar in the morphology archaea - Both are extremophiles Like to thrive in extremely salty cold or acidic environments Similar metabolisms (Archaea and Eukayrotes) -> All based on DNA sequencing of a ribosomal RNA ARCHAEA be found in extreme environments ↳ Can such as high salt rich with methane and also hot in acidic places • BASIC EVOLUTION PRINCIPLE - if you adapt to new environment, you are going to be the only one that will be able to live there,they take advantage that no one else would like to live there - archaea are prokaryotes • thermoacidophiles swamps, digestive • methanogens -> Wetlands, systems of women • Halophiles - Extremely high salt concentrations exivents When t wo levels of temperature are mixed together, organisms are going to live there -> Further away from the hot springs, the temperature is going to be reduced and other organisms will be able to live there YEAST • a fungi, eukaryotic unicellular organism E • most commonly used in the food industry - under aerobic conditions used as a baker's yeast - under anaerobic conditions used for alcohol production ↳ • involved in human diseases such as - yeast infections - opportunistic infections (e.g. AIDS) - - = - MOLDS • filamentous fungi with a mycellial structure ↳ - mycelium is a highly branched system of tubes that contain mobile cytoplasm with many nuclei • moles are used for production of citric acid and antibiotics • the mold Penicillium produces penicillins • involved is allergic reactions • aspergillosis is the group of diseases caused by the mold aspergillus - opportunistic infection - = PROTOZA S • unicellular eukaryotes lack a cell wall • they cause a number of human diseases e.g. malaria • have several roles - digestions - removing bacteria from wastewater E VIRUSES ⑤•• complexes of nuclei acids and proteins use functions of the host cells in which they are proteins • not cellular life • viral parasite causes changes in the cell • directing the host cell's metabolism to ↳ the production of new virus particles may cause cellular death E ->Lipid envelope in some viruses Part 1 CELL STRUCTURE AND FUNCTION mee INTRODUCTION TO CELLS THE CELL THEORY 27 Was developed in the 1600s E -the discovery microscopy E All living things are made of cells New cells are created by old cells dividing into t wo Van Leeuwenhoek was the first person to see and describe bacteria and yeast, cell sperm and, blood cells and witness the circulation of blood through capillaries ↳Cells are the basic building unit of life O- et have y different Viruses are not shape - (Human cell) Considered smallest cell is much larger compared to bacteria ⑧ m Bacteria cells, they are not cellular life, they are parasites of cellular life Viruses can enter a human cell and they can replicate in those cells THE CELL " Unicellular made up of one cell bacteria, yeast, etc Multicellular made up of several billions of cells most plants and animals these cells work together to help the organisms grow and survive E n CELLS: BIOLOGICAL MEMBRANES en e nee e FUNCTION OF CELL MEMBRANE - = to be protective Separate the inside of a cell from the outside environment Provide a surface on which chemical reactions occur Regulate the passage of materials into/out of cells Separate cells from one another, allows recognition and interactions The structure of the membrane must separate bet ween t wo watery compartments (bet ween the outside and the inside Az0-> ↓ 84 - H Water prefers to have the positive (-t) and negative interact with each other by forming hydrogen bonds It H ,+ (3 Polar molecules such as acetone will dissolve in water and be part of water Non-polar molecules like fatty acids are going to disrupt the hydrogen bonds that the water molecules want to make =D cannot hydrogen bond -Water + all be cannot mix HYDROPHOBIC MOLECULES ↳ The structure of phospholipids is responsible for basic function of membranes as barriers bet ween t wo (water) compartments If you add phosphate, you are making this hydrophilic head to he even more hydrophilic J o ↳Phospholipids are amphiphatic emphatic means they have t wo different chemical characters Hydrophilic Hydrophobic Y ↳ Phospholipids are amphiphatic in that they have hydrophilic phosphate containing head and very hydrophobic tall ↳They interact with water so they arrange themselves so that the polar head have a contact with water molecule and their hydrophobic tails move away from the water ↳The head have a contact with the water while the tail mingling themselves among each other which are interacting with each other by hydrophobic bones - Making the LIPID BILAYER ↳ Inside the cell the ↳ membrane can divide into subcellular compartments which are called organelles All the endoplasmic reticulum and all the other membranebound are using the same principle -Water can interact through the negative charge of the oxygen with the positive part of the head and wise versa -Hydrophilic because there is a lot water ↳Hydrophobic does not interact with water - + Gil Water will be repelled by ⑧ I I/ - 0 heads going bind to with water needam nitta is Why phospholipids form players spontaneously when they are dispersed in water - The "head" group is polar and hydrophilic attracted by water from both sides of the membrane - ↳ The long "tall" is non polar and hydrophobic - repelled by water -The hydrophobic portion of t wo molecules or more tend to associate with each other ↳ Lipohilic (lipid-lover) hydrophobic bonds -> three different powers to stabilize the phospholipid bilayer VESICLE 7 - all the movement of by vessicles proteins are - When using the vesicle from the outside, it can be fused with the ↳ plasma membrane and the drug inside can be moved inside the stool to the inside of the cell Naturally vesicles are formed in the cell all the time to help move chemicals outside or inside of the cell ↳ It is pocket made of membrane that is separated from the cytoplasm of the cell carrier of molecule in and out of the cell without crossing the ↳ Amembrane directly but the fusion actually puts whatever in the vesicle on the other side of the membrane THE PLASMA MEMBRANE A FLEXIBLE BARRIER ↳ Bilayers of the naturally occurring phospholipids are flexible jelly-like fluids, not solids ↳ ↳ fluidity of bottle lipid yellowish type is critical for its function of material TRANSMEMBRANE PROTEINS ↳ Transport proteins ↳) Signal transduction ↳) received react signals accordingly AEx: cancer cells know how to use these abilities, know how to take advantage of these cells and signals, phospholia ter Her2 receptor - - in ↳Scientists discover that they can block this receptor by an antibody, biological Drug, which is actually antibodies in this drug is called erceptine ↳Antibodies combined to the receptor specifically and when the ligand is there to interact with this receptor -the antibodies are going to block the ligand from interacting with a receptor and instead send a bad message to the cell replicate HYDROPHOBIC BONDS -cancer cells are going to be highly confused, and what cells are doing when they are highly confused you is kill themselves ↳cells that have this abnormity to kill themselves simply because the drugs make them confused ↳both proteins and lipids as well, able to diffuse laterally throughout the membrane again H CROSSING THE MEMBRANE * nee TRANSPORT OF SMALL MOLECULES ⑤ Plasma membrane is a physical boundary bet ween highly organized insides of the cell and the chaotic external environment exchange menallower enamt interplay surroundings an so where around free and the the jail exchange the the forms it , of like is that between the cell wall the locks cytoplasm the environment everything not barrier a molecules external ↳ membrane plasma locked is THE CELL MEMBRANE T ↳ the cell maintained because the is selective is ↳ specific passage the cell permeable small of molecules control the plasma membrane molecules small proteins transport to to carrier across mediate the selective the composition of membrane , Its allowing cytoplasm THE PLASMA MEMBRANE AS A STABLE MEMBRANE ↳>Plasma membrane forms a stable barrier bet ween t wo polar (watery) compartments - en ↳) because interior of the the phospholipids bilayer by hydrophobic fatty and water-soluble Impermeable occupied is to ↳ this of chemicals that the * are in molecules * barrier In Its the intracellular allow the cytosol call that to is maintain different extracellular fluids membrane enclosed from and each those of such generally molecules as can steroids cause is by hydrophobic are of the *** repelled compartments However , Hydrophobic molecules zhelp- concentrations is membrane chains , the the membrane , can the by / C er The,ell yet in without plasma membrane DIFFUSION the cell membrane, phospholipids are arranged in double layer or ↳ Inplayer with the polar hydrophilic heads immersed in water and the non-polar Hydrophobic hydrocarbon tails in the anterior of the membrane move away from water EFFECT IS ISOTONIC, HYPOTONIC AND HYPOTONIC SOLUTIONS ON CELLS -> Without control of the water burst proper water , will out PASSIVE DIFFUSION ↳ The simplest mechanism by which molecules can cross the plasma membrane The net flow of molecules is always down their concentration gradient ↳No energy is needed I E The direction of simply by molecule ↳ power the the transport inside/outside is the coming SIMPLE DIFUSSION ↳basic one way by place to which molecules determined Is concentration relative of the cell from [] gradient FACILITATED DIFFUSION can move from another ↳ requires some level permission channel proteins EsTransporters of (carriers) -> need a certain inducer to open up the channel cret direction of movement) -> molecules will cross the membrane to their 23 according gradient ↳ eventually equal concentration permet he and get in [] gradient according out to their FACILITATED DIFFUSION ->The difference bet ween the channels and the carrier transporters is the channel need to recognize the molecule to be entered inside the active transport so the active transport is mediated by transporters coupled to an energy source ->bind ACTIVE TRANSPORT eg -> to the cytoplasmic 3 binding - -> . Sodium-Potassium pump an side sites I binding sites first Sodium !↳ cons bind to their ↓ higher affinity sites , inside the I K Nat has to - - ↳ ability hydrolyze ATP the andsterto Ihe become phosphate phosphorylated) A sites binding to cytosol) I exposed cell Binding stimulates the hydro lysis of ATP and phosphorylation of the pump affinity induces d second tional -exposes sodium the -> sodium binding sites to the of the cell outside -reduce the exposed affinity -pump will change conformation is conforma range ↑ now outside of the cell ↳ bound sodium is L released whene here it stimulate of the the hydrolysis phosphate group bound Is sodium potassium pump is an active transport mechanism that is driven by the breakdown of ATP and works through a series of conformational changes in the transmembrane protein. Three sodium ions bond to the cytoplasmic side of the protein, causing the protein to change its confirmation and it’s new confirmation. The molecule because phosphorylated at the expense of a molecule of ATP the phosphorylation, and uses a second confirmational change that has located three sodium ions across a membrane. In this conformation, the protein has a little affinity for sodium ions and the three bound sodium ions dissociates from the protein and diffuse to the extra cellular fluid. The new conformation has a high affinity for potassium ions, t wo of which bind to the extracellular side of the protein, the bound phosphate now associates and the protein reverts to its original confirmation exposing the t wo potassium ions to the cytoplasm on the inside of the cell. This confirmation has a little affinity for potassium ions so the t wo bound potassium ions dissociate from the protein and diffuse into the interior of the cell. LINK BETWEEN ACTIVE AND PASSIVE TRANSPORT -> associated with mitochondria -> ->High glycolysis concentration of hydrogens is mediating by active transport and then the high concentration of hydrogen is going to drive a motor and this is by passive transport ↳ making ATP ENDOCYTOSIS AND EXOCYTOSIS ↳The substances taken in by single-celled organisms are often particles or large polar molecules that cannot cross the hydrophobic plasma membrane - Many single-celled eukaryotes employ endocytosis to ingest such food particles. ↳ In this process the plasma membrane extends out ward and surrounds the food particle. ↳Cells use three major types of endocytosis ↳phagocytosis, pinocytosis, and receptor-mediated endocytosis. ↳ If the material the cell takes in is particulate such as a bacterium or a fragment of organic matter the process is called phagocytosis If the material of the cell takes in is liquid it is called pinocytosis. Specific molecules such as low density lipoproteins ldl are often transported into eukaryotic cells through receptor-mediated endocytosis ↳ Molecules to be transported first bind to specific receptors on the plasma membrane ↳The interior portion of the receptor protein is embedded in the membrane. The protein clathrin coats the inside of the membrane in the area of the pit. -When an appropriate collection of molecules gathers in the coated pit the pit deepens and seals off to form a coated vesicle which carries the molecules into the cell. Exocytosis is the reverse of endocytosis. This process results in the discharge of material from vesicles at the cell surface to the outside of the cell E E -> receptors on the Specific molecules surface of the cell bind to E The uptake of bacteria by phageocytes is an active process which requires the triggering of specific receptors on the phagocyte FC receptors which bind antibody-coated bacteria are one of the receptors capable of triggering phagocytosis Binding of the aggregated antibody molecules to fc receptors on the phagocyte causes the cell to engulf the bacterium the phagocyte First produces pseudopods or ruffles that surround the bacterium and then fuse trapping the bacterium within what is now an intracellular vesicle The phagosome within the phagocyte lysosomes fuse with the phagosome delivering their enzymatic contents to degrade the engulfed bacterium. ORGANELLES AND PROTEINS SORTING mean ORGANELLES ↳] Eukaryotic cells are highly organized with many functional units THE ORIGIN OF MITOCHONDRIA S All bacteria that was able to enter the cell like billion years ago ( ↳ ↳ (I are cell bacterial organelles originated have that from energy-conversion mechanisms chloroplasts -> Is an organelle and genome ↳circular -> every its to own genome similar similar with size the its own ribosome ribosome bacterial ribosome ↳ Used for translation mitochondrial -> of products They are the descendants of some bacteria which was endocytosed by larger cell but not digested - Have many similarities to bacterial cell: • similar size/shape to prokaryotic cells • double membrane • circular DNA • genes without introns antibiotics • small ribosomes ↳ Generally, likely to be a bacterial cell that enter the Iarge cell before nucleus or after nucleus -> Is -> symblotic effect In 1981, Len margulis proposed that current eukaryotic cells evolved from a grouping of cells a large anaerobic prokaryotic predatory cell likely engulfed an aerobic bacterium. The bacterium becomes surrounded by a vacuole made of the predator cell membrane. The predatory cell is unable to digest the bacterium which persists in the cytoplasm of its host. The combination was mutually beneficial to both organisms over time the t wo cells became dependent on each other and the engulfed aerobic bacteria evolved into mitochondria. The predatory cell may also have met and engulfed a photosynthetic bacterium the photosynthetic bacterium also becomes surrounded by a vacuole made of the predator cell membrane and the predatory cell is unable to digest the bacterium. Over time the t wo cells became dependent on each other and the engulfed aerobic bacteria evolved into chloroplasts. ↳ cell's to does DNA code proteins needed to is and the genes the for ↳ This have not create new necessary mitochondria chloroplasts -> Involved with: ⑧ ATP production - cellular respiration ⑤ Apoptosis programmed cell death THE FUNCTION OF MITOCHONDRIA IN ATP PRODUCTION ↳ Involved with releasing the energy of food molecules This energy is expressed as a proton gradient EThe inner membrane contains a complex of enzymes which are transforming the energy in the proton gradient into chemical energy stored in ATP RNA for -> usuy used 17 generated the At inner membrane of - released for oxidative by energy mtochondria called also Phosphorylation as a synthesis deoxyribose mitochondria -> * to make ATP , environments) ↳ outer ↳ system Inner + high ↳ pumps energ protons is (two needed chemical membrane concentration using -> NAD H-> - organelle an from gradient electrons/ nutrients from matrix to Inter [] +04[] membrane space First stage- make gradients of motions of hydrogens ->Second stage - use this gradient in order to make ATP ↳ Mitochondria using energy from food gives the energy for active transport of hydrogen ions proteins by hydrogen pumps Y gradient drive the rotation activity of the ATP -> ATP production synthetase -> -> uses the high concentration of my drogen ↳ remains Inside ↳s ↳ membrane activating ATP inner ADP+ P1 = ATP -> transmitted by egys THE HUMAN MITOCHONDRIAL DNA (m+DNA) (HON) -> Leber's Hereditary Optic Neuropathy NUCLEUS bound uner men brane of -7 -The largest organelle nucleus ->DNA is packed into chromosomes ->The nucleus membrane allows gene expression to be regulated by postranscriptional mechanisms , such as splicing SORTING AND TARGETING OF PROTEINS ↳Pores in the nuclear envelope allow the import of particles containing mrna and proteins into the cytosol free ribosomes translate the mrna molecules into protein some of these proteins will reside in the cytosol others will associate with specialized cytosolic proteins and be imported into mitochondria or other organelles the synthesis of cell secreted and integral membrane proteins is initiated by free ribosomes which then duct to protein translocators ↳at the surface of the endoplasmic reticulum nascent proteins pass through an aqueous pore in the translocator ↳cell secreted proteins accumulate in the lumen of the endoplasmic reticulum while integral membrane proteins become embedded in the endoplasmic reticulum membrane -proteins are transported from the endoplasmic reticulum to the golgi apparatus by vesicles traveling along the microtubules so ribosomes found in t wo locations in the cell ↳ FROM THE ENDOPLASMIC RETICULUM TO THE GOLGI APPARATUS -> vessicles from : carriers the ER to of molecules the 6016I in the cells APPARATUS e . y . THE GOLGI APPARATUS STRUCTURE E Each golf, body consists of flattened membrane sacs Those sacs contain enzymes ready to modify proteins for shipment to specific locations source IS ~golgs apparatus -single membrane ↳lysosomes are membrane-bound vesicles that contain hydrolytic enzymes these enzymes digest particles or cells taken into the cell by phagocytosis ↳they also digest old organelles such as mitochondria, the hydrolytic enzymes that degrade proteins nucleic acids lipids and carbohydrates are formed in the endoplasmic reticulum and then transported to the golgi apparatus by transport vesicles ↳the lysosomes arise from the golgi apparatus when particles such as viruses or bacteria are ingested by phagocytosis ↳]the lysosome fuses with the particle-containing vesicle called a phagosome and delivers the hydrolytic enzymes lysosomes also fuse with organelles such as defective or worn out mitochondria this results in the destruction and recycling of these structure ↳ rich enzymes (n50 low plt hydrolytic activated by enzymes) FUNCTION OF LYSOSOMES -> housekeeping -> -> heterophagy Programmed fingers -> in function : Ingest cell an unprogrammed ↳ cardiac cells lack of : remove and worn organelles Cartophagy digest things death remodeling : embryo cell (ex death associated oxygen : : outside the cell as the froy) damage/death myocardial to with infarction part 1 EMERGING INFECTIOUS DISEASES en Proportion of deaths due to infectious diseases => -> due to Cancer bacterial infection disease/alzheimers are older for age Enkovzwitwaor a or rent cause ene few ↳ no drugs significant people threat birth my high 25 % as -> able to reduce today infectious disease , compared to back then >trends demonstrate increasing expectancy in -> World population ↳ 2040 will 1960 IS be I sing up trippled compared ~ ↑ ABS life to Huge gan bet ween life expectancy in rich countries compare to poor countries Suffered a lot of HIV, AIDS, -> pandemics like went down ne levels the 50s in I -> Influenza of 1918 ↳ Southern Africa 1 > I I HIV AIDS mainly - DRUGS ↳ the Isub-Saharan with calculated treatment Africa) additional by pathogen by -not always treatment that 6 dollars billion a bacteria TUBERCULOSIS can provide a full Fe founder for billions of dollars became 2) WARREN BUFFETT I S = available -> Bill and Melinda gates foundation (2000-2009) -> -> E main HIV AIDS : diseases - suffers most) (Malaria)(- south Africa--> affected help can and 3 medical of microsoft available n e e ↳ ->> and ↳ provides wealth $60m pledges Cameron Gates 85 % of his gave for additional $100 polic vaccination Microbes have caused the most devastating epidemics in recent human history Beneficial roles of microbes -> responsible for ↳body -> first time c-section more micro consists health 30 trillion of 39 frillion delivery babies have blotical diseases , Is transfers keep pathogens away from our to the Imicrobiota) raginal microbes (lactobacillus) ↳ less ↳ ↳> cells microbial cells microbes durin every exposed Vaginal -> our tissues and organs baby -> -> -> energy received are from the byproduct microbes of plants supply 50 % of oxygen we breathe ↳ ↳ rely microorganisms food production such as milk products on -> the -> natural microbial flora provides protection microbes against more virulent digestion -> Vitamin K like - -> make Vitamins MICROBES AND DISEASES -> natural on -> -> ability to cause many infectious host microbes have caused , evolution , favours diseases the operates on it spreading capacity NOT disease a natural selection its microbes of microbial to -> its evolution most can be less used devastating as or a epidemics non-virulent failure in recent of microbes the human microbe history to adapt I the Reducing -> restoration - of vaginal diseases : microbiota baby immediately the - exposing - microbiota wrong agriculture ↳ microorganisms help I -human body ↳ bacteria Vitamins in our allowing large them to Intestine be down break help I absorbed waste synthesize into the bloodstream ↳A very tiny minority of mircobes act as pathogens or disease-causing agents, representing a natural threat, not only to human life, but to all life forms ↳ Microorganisms maintain balance in environment by recycling, vital, nutrients such as nitrogen, sulfur, phosphorus, carbon, and oxygen ↳Microorganisms results in plants supplying 50% of the oxygen we breathe IMPORTANT ROLES OF MICROBES ↳ responsible ↳ organic Waste things for O2 and compounds (ex breakdown ↳ recycle ↳ responsible dead : organic nucleic , molecules amino acids) from dead animals , material to create new turning plants trees , into , living forms of life Yeast-wine for bread) ↳ Natural microbial flora provides protection against more virulent microbes Drug preparation killed about 40 % population Making vitamins eg. vitamin K ↳Digestion for food /ex: E >ebola of African - MICROBES HOST EQUILIBRIUM Diseases can be severe But Large majority of microbes do not cause aggressive diseases, which kill their host quickly ⑮ TUBERCULOSIS VS EBOLA -> -> both both are pathogens can kill acute - disease - Lely die -II Ho shortly zox affected -> har >rids to the infect spread B natural evolution capacity microbial , ↳ not on natural non-virulent of its a microbe ability selection , to he from netDigitates host for a of / operates cause evolution , a on its years spreading disease favours less or microbes ↳ Any severe infectious diseases are a failure of the microbeto adapt to its host ↳ unfortunately , ↳ improvements WVACLINES ' can kill both include better good/bad sanitation cells -> 1969 Us surgeon General to Congress : Its time to close the book on infectious diseases" ↳> thought to wrongly over was microbes think the EMERGING INFECTIOUS DISEASES => ↳ Infectious diseases as a ↓ , MRSA ↳ ↳ no treatment strains IS available (umited) Viruskept ~ : W t-no with Tuberculosis ↳ Drug-restraint group will not disappear ↳ New disease-causing -> agents -> ex HHVS war , AIDS idea SARS , MERS , COVID 19 EBOLA ↳ moving Outbreaks of existing diseases ↳ West Nile Virus ↳ North America 1999 mos quitOS ↳ Pandemic -> Influenza monkey ↓ similar - to pox -s > smallpox hum affect monkey ->praine Spread from pet store, 7 a pathogen made a move rapidly -> - -> -> - 1918 Spanish Flu Pandemic -> -> - -> -> pox rodents dog Diseases transmission within population: today vs old days -> 4000 - -> 2000 years ago years ago I-boats many animals now got the today -> ↳ natives OLD 9 travelling virus/diseases ex: months TODAY 9 hours arplanes (from water) DAYS Cory 19 ↳Air net works in 2005 were much more busier compared to 1933 ↳ Less viruses being moved by the airline industry back then ↳ Today it is worst by airline industry 9th floor of the metropole hotel > SARS CASE TRANSMISSION No available drugs for the outbreak ⑧ ↑ ↓ A ↳ -> no vaccines * Public health took measures to stop people travelling BIOTERRORISM ↳ Intentional release of bacteria, viruses, or toxins for the purpose of harming or killing civilians 9/1) -> caused so that SPORES ANTHRAX by envelope were THREE WAYS ANTRAX ENTERS THE X Throughout the skin (CUTANEOUS ANTHRAX) - Inhaled opening it dispersed the powder by people Rare disease in North America, typically among farmers that take care of cows spores BODY * Throughout digestive tract (GASTROINTESTINAL ANTHRAX) * Respiratory (INHALATION ANTHRAX) to the air ↳Cutaneous is the most common type of infection when it is taking place, the spores are going to land on the skin and bacteria are going to be germinated ↳ treatment - Gastrointestinal anthrax is extremely rare -> : antibiotics uncooked ↳]Inhalation anthrax -> brings occurred the most in 2001 lymph , cyprofloxacin meat not , spores notes deep and cooked into the dissolve properly lungs cause , into the very severe disease) CINHALATION) ex : - pneumonia ↳Biological agents are not easy to detect, making it difficult to trace back the illness -severe/deadly disease Potential Bioterrorism Agents CDC Category A >organisms (bacteria Es ↳ Antrax and Virusus Bubonic Plaque (X Pestis) . ↳ Tularaemia ↳ smallpox ↳ Viral haemorrhagic fevers (eg ↳sent to . Ebola Africa ↳ Botulinum toxin All are easily disseminated or transmitted person to person High mortality rate of some (smallpox, Ebola) Public panic and social disruption Cost of coping with bioterrorism resources of the health care system ↳ research and development (R&D) * - TREATMENTS > give Cyprofloxacin high antibiotics circulation concentration but a e BIOTERRORISM: WHAT CAN BE DONE BY FIRST RESPONDERS ↳ Nurse performing triage often will be the firstresponder which is E the most important Awareness Reporting -> SMALLPOX ( VARIOLA MAJOR) ↳ ⑧ 0 EPIDEMIC 1977 - last L we pathogen only organism that was erradicated Why was the eradication of smallpox so successful? 70s • Eradicated for medical reasons a , • 1980, declared that smallpox is not around any longer - smallpox - Smallpox is a disease that we have a really good vaccine - first maximum developed (200 years ago) C time had is -> -> having good a good eradicating polic properly affect only people * SKIN # used POLIO most in US host for and measles DIRECTLY ON still only numpr only smallpox VALINE have -> infecting viruses cabinerradae) symptoms -> In - for vaccine always E factors Important most = of no symptoms time army ↳ Smallpox was infecting people highly contagious but the equilibrium that these vials have with people is not so strong - Polio and measles aged good equilibrium do not and have easy to a strong kick host virus equilibrium with us /TOO AGRESSIVE) out • Old vaccine had side effects, people stopped getting them - Out since 1980 manypeople • immunity helped out a lot • 1519 AD, transferred from Europe to the Americas into non-immunized, un exposed population e - -> people born 1980 after ↳ no not are exposed or vaccine immunity Many soviet doctors were sending smallpox samples back to the Russian military -> If no smallpox, nobody gets vaccinated ->If no one is vaccinated,biological weapon based on smallpox would be most powerful weapon to eliminate human life => ! -> poor they were stockpiled security Developed a secret biological weapon, program using selected strain of smallpox The soviets produced dead diseases on industrial scale in these labs E Knowing DNA sequence of a microbe can make microbes from chemicals from the nucleoticles - -> horse-pox makes virus Oligonucleotides infected DNA into a cell and creates a virus I Sequences can turn into biological weapon and used in the wrong way -> as we stop to vaccinate against camelpox , smallpox-> monkey pod viruses other - 95% similar to go upy smallpox Smallpox evolved from camel pox about 3000 years ago -> I ↳ can be mutations evolved into humanpox • 2002, more than 60 millions people killed by smallpox • 24 hours to confirm diagnosis -Monkey pox becoming more humanized virus ↳ transmitted more easily When back to life, affect amoeba cells (ice melt can bring back viruses from the dead) • some viruses can be presented in frozen land (UNFREEZE THEM) SMALLPOX (FILM NOTES) • symptoms : - Begins with a high fever • highly contagious - must quarantine • “Active terrorist attack” • Hospitals were struggling with the daily routine to treat those with smallpox • Created smallpox hospitals FACTORS THAT AFFECT THE EMERGENCE OF DISEASES " Microbial adaptation drug resistance Human behaviour international travel sexual activity >Human susceptibility to infection poverty, malnutrition, poor sanitation ↳Changing ecosystems global warming Iclimate and weather ↳Wars (Polio in Afghanistan and Syria) - ANTIMICROBIAL DRUG RESISTANCE -Mycobacterium tuberculosis ↳ antibiotics ↳ helped -> Acinetobacter pathogen ↳ spread > Pseudomonas - -> ↳ through aeruginosa Staphylococcus aureus 40 % almost all is resistant to resistant hospitals antib 10+ (C) against eliminate bacteria Klebsiella pneumoniae -> => to a lot of He antibiotics SURGICAL TREATMENT FOR INFECTIOUS DISEASE: Back to pre antibiotics time -> infected remove parts of the lung in tuberculosis AMicrobes are outsmarting antibiotics Disease-causing bacteria colonized living tissue Penicillin kills bacteria (weakening walls) ->When walls collapse, bacteria die -> -> ->microbes reproduce by dividing into t wo replicating themselves each time random genetic changes in all livings are seen more frequently in microbes (reproduce rapidly as every 12 minutes) ->when enables a microbe to fend off an antibiotic -attack, there is a new stronger microbe ->resistant microbes can multiply quickly without competition ->Mutations, THE DEVELOPMENT OF T RESISTANT ORGANISM POPULATIONS - -> most cases , leave Slow evolution -> take ↳ -> If years When used 124 any -> for the Improve inappropriately hours later sanitation antibiotics antibiotics results is , resistance available resistant In alone bacteria drug for to be treatment strains resistant take , over strength developed takes a during in your while one night flow WHO SHOULD BE BLAMED FOR ANTIBIOTICS RESISTANCE? Earn financial alds extra ↓ • Misuse/abuse of antibiotics - farmers ( 80% of all antibiotics are used on factory farm animals) ⑤ - used as growth promoters, chicken farms used this antibiotics to gain weight (faster growth) - How antibiotics concentration ③health workers -> they = problem) main to chance Increase the come with resistance - antibiotics are recommended immediately and given right away ex: streptococcus obtains m protein and when developed immunity to this pathogen, once it is gone the, the immune system will turn against your heart rheumatic fever ↳ ↳> diseases auto immune - ↳ -> can that disease get , affecting treatment heart right away , joints , skin , brain mean develop antibiotic are meant - patients -hospitals 0 ↳ to avoid mutagens used be used like drugs making = resistance for drugs as att periods bacterial hospital - /drugs A inflammatory the metal for cancer COaX mutations + antibiotics ANSENE (bacterial ceins) • Antibiotics policy in third world countries ↳ some countries ↳s treated ↳ greater for give it one exposure over the counter day (temporally f(x) to antibiotics resistance - -> agrie rete twate • Antibiotics were developed from "natural product" ↳bacteria are exposed to antibiotics for billions of years part * of the Alexander evolution of microbe and other organisms flaming ↳selective pressure (induced evolution) -microbial “genetic internet” ↳ exchange of plasmid that often contain resistance genes for multiple drugs plasmids expressing genes -> these to used are for can find their pathogenic bacteria genes way from antibiotic non-pathogenic resistance and bacteria only necessary- when THE DEVELOPMENT OF RESISTANT ORGANISMS IN POPULATIONS ↳Resistance by bacteria acquired 2 ways New mutations if chromosomal genes - - slow process multiple steps Gene transfer - aacquisition of - fastest A-plasmids transformation , transduction conjugation , via and * cells whest bacterial sense Kill can IS going 76 them ⑤ -> batter cellslike gramnegative are to going pick up by mutations e ANTIBIOTIC DRUG RESISTANCE MECHANISM INACTIVATION OF ANTIBIOTICS ↳ Enzymes that alter th antibiotic to inactivate its function 2x : MODIFICATION ↳ modify ADATION - : Chloramphenicol a : acetyl drug by adding beta-lactamase ↳ enzymes that know a transferase certain chemical (penicillinase) how to destroy the beta lactam ring • Gram positive bacteria release the beta-lactanese enzyme from the cell into the extracellular environment where it inactivates the drug before it enter the bacteria cell • in contrast, gram-negative bacteria retain the beta-lactamese within the periplasmic space resulting in a more efficient mechanism than grampositive bacteria • the destruction of the betalactam ring of the antibiotic renders incapable of binding penicillin, binding protein • Becomes resistant to that drug Clavulinic acid rescues the effect of the beta lactamases ↳ Binds strongly to beta lactamases -inhibits their activity ↳Synergistic effect with penicillin and cephalosporins > beta-lactamase -> clavulinc and can can ALTERED TARGET SITES destroy Inhibit penicillin-> enzymes beta-lactamase -> work enzymes stop again working The bacterial cell can alters or eliminate the target the sit for the antibiotics ->ex. Penicillin binding protein (transpeptidase) -> bacterial cells are trying to escape Ex. Production of altered penicillin binding proteins can still cross link the peptidoglycan layers of the cell wall but have a reduced affinity for beta-lactamase antibiotics thus rendering the bacteria resistant to the effects. Glen Collin and other beta-lactam agents -> -> If an organism gains resistant to an antibiotic that acts on the ribosome the target site of binding for the drug is caned and the drug no longer bunds another mechanism need five drugs Deta-lactam all -> to -> -> a destruction penicillin that beta are => by the lactam are NDM the are - 1 to going most be subjected important antibiotics around colistin ↳ a antibiotics -> polymylin / In high toxicity antibiotics * baserlaphage better than drug regular RETARDING RESISTANCE Limit use of antimicrobials to necessary cases High concentration of drug and long treatment Use antimicrobial agents in combination E > Combination ↳ Developing therapy , sulfer drog new variations if existing drugs -> novel side chains added to original molecules ↳ Developing of drugs for new targets ↳ Better diagnostic tools (DNA based) when drugs their have constant are structure ouhear own in bacteriophage survive evoluti bacterial , cell to Some key notes: • child mortality in the 1900s was quite high • as vaccines and other antibiotics come into play, the life expectancy in the USA from 1900 - 1928 had gone up approximately 25% • world population from 1950 - 20150 have also increased by billions; from 3 billion to about 6 billion • when AIDS was introduced, life expectancy went down to the age of 50 • from the 30 million people infected with HIV, less than 1 million of those people receive the drugs to cure them