MMG 301 Week 10 - Dr. Delekta PDF

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Week 10 Sunday, November 7, 2021

3:18 PM

Mi crobi a l G Grrowth C Coontrol: R Ra a d i a ti on a annd N Noon-Chemotherapeutic Antimicrobials Usin ing gH Heeat to R Reeduce oorr K Kiil l Mi Miccrobes: • The autoclave will kill all microbes and spores encountered by humans if 121 degrees C at 15 lb/in2 is maintained ○ Larger objects of larger volume require longer autoclave time

• Pasteurization is a heating method that is intended to reduce numbers, but not kill all microbes ○ Mainly used on heat-sensitive liquids, such as milk ○ Increases storage life ○ Most pathogenic bacteria can be killed during pasteurization • Pasteurization is performed by either batch or continuous flow processing ○ Pasteurization is performed two different ways: tch Meethod od:: heated for certain period of time hM § Batc ntiinuous F Fll ow: heated for a brief time period followed by cooling § C ont C ont ntrrol ooff Mi Miccrobial G Grrowth U Ussing U UV Va annd I Iooniz iziing R Ra adi dia ati on: • Radiation exposure results in time-dependent accumulated damage that eventually kills cells and viruses Radiation

S ter eriil izing E Efffect

Uses

UV lilig ght

DNA Damage RNA Damage

Disinfecting surfaces, air, and water

G amm mma aR Ra ay s ( ion oniizing ra raddiation on))

Damage to DNA, RNA, and proteins

Sterilizing medical devices, foods, and pharmaceuticals

cim ducction: 10-fold reduction in viable organisms mal rreedu • Deci ○ Dependent on: § Genome size § Size of nucleoid § Size of the organism S ter eriil izati tioon ooff G Gas as assses a annd L Liiquids T Th hro ugh F Fiil trati tioon: • Filtration can be used to remove bacteria and eukaryotic cells from liquids or gasses ○ Filters of different porosities are used, depending on the purpose (what is been filtered out, viscosity, etc.) ○ Many different types of devices are available for small or large volumes High Ef artic ul ate Ai Effficienc ncyy P Pa icu Airr) F Fiil te terrs: filters 0.3 § HEPA ((H micron particles with 99.98% efficiency mbrr ane F Filililt t ers: uniform sized holes are present, typically used § Memb in sterilizing solutions

• The filtration principle is used for personal protection masks and respirators in healthcare settings ro tective eeqquipme PPE) include filters to prevent rsoonal p pro rot mennt ((P ○ Pers exchange or pathogen-containing droplets between patients and healthcare workers § Spread of germs can be prevented by facemasks and respirators that filter out aerosol droplets that may contain pathogens • In research settings or in hospitals, isolation of pathogens from contact with humans is done using a combination of methods ○ In hospitals, filtration and airflow is controlled so that pathogens do not escape contaminated areas ○ Biosafety levels are defined for any situation where pathogens are involved Biosafe ty L fet Leev el elss) are implemented - the higher the level the ○ BS L ((B higher levels or risk and containment needed

○ Biosafety levels are defined for any situation where pathogens are involved fet Leev el elss) are implemented - the higher the level Biosafe ty L ○ BS L ((B the higher levels or risk and containment needed Non Non--C he hem mothera rap p euti c A Anntimicr croobial Ag Ageents: • Chemotherapeutic and non-chemotherapeutic agents are classified according to the effect that they have or growing microorganisms "-static": static": ○ "§ Stops growth § Often reversible cidal": "-cidal": ○ "§ Kills organism § Reduces viable cell count, but not total cell count ○ ""-lytic": lytic": § Kills organism, and bursts cell wall of dead cells § Reduces total cell count and viable cell count * * Al Alll ooff tth hes esee m meethod odss ddeepend oonn tth he 1) ccooncent ntrration ooff a ag gent 2 2)) expo possure ttim im imee a annd 3 3)) tteemperat atu ure

• Chemical antimicrobial agents can be classified according to where they are and what they are intended to do Chemical Agent

Purpose

Use

Sterilizers

Kill all microbes; kill spores; very toxic to animals

Hospital labs/lab equipment; medical devices

Disinfectants

Used on non-living surfaces; may kill spores

Homes; Hospitals

Antiseptics

Non-toxic to living tissues and skin

Wounds; surgical sites; directly on body

Sanitizers

Reduce number of microbes

Food preparation

but may not kill all

• Many factors influence the effectiveness of an antimicrobial agent microbi al a gent ffa actors tim bia ag rs:: ○ Anti § Concentration § Exposure time § Addition of others ingredients (e.g. detergents) croobial Fa Facctors: ○ Micr § Level of resistance § Population size § Biofilms

Summary: • Heat can be used to kill all microorganisms and spores by the application of high temperatures or to reduce the number of viable microorganisms through short-term heating at moderate temperatures (pasteurization) • Radiation can be used to kill microorganisms on the surface and in liquids or air (UV light), or in any radiation-permeable container (ionizing radiation) ○ Sensitivity of microorganisms to heat or radiation can be measured experimentally to determine a value known as the decimal reduction time • Filtration can remove microorganisms from liquids and gasses and reduce the transmission of many human-human pathogens • Non-therapeutic antimicrobial chemical agents can stop growth, kill but leave cells intact, or kill by lysis • Sterilizers, antiseptics, disinfectants, and sanitizers are solutions of chemical antimicrobial agents that kill or reduce viable cell numbers of microorganisms. Generally, the safer the microbial agent is for human contact, the less effective it is for killing microorganisms

Immunology I ntr trooductio ionn ttoo I Im mmu munnity: • Humans and animals have physical and chemical mechanisms for resisting pathogens that does not depend on previous exposure te rreesis tance is protection from pathogens that does not nat ist ○ Inna rely on previous exposure to the pathogen § Physical barriers § Chemical barriers § Normal microflora ○ Other factors can affect risk for infections: § Age, stress, overall health mprromised h hoost is one in which mechanisms of resisting § A comp pathogens is weakened by: □ Injury □ Illness from a pathogen or from another disease □ A weakened immune system (immunocompromised) I nna nat te v vss. Ad Ada ap ti v e I Im mmunity ty:: • Innate immunity (non-specific immunity) involves mechanisms that work against ALL potential microbial pathogens; does not rely on previous exposure to a pathogen ○ Innate immunity is a preexisting ability to recognize pathogens or their toxins and destroy or inactivate them: § Innate immunity is carried out by cells known as phagocytes □ Specialized white blood cells - engulf and kill most pathogens

• Adaptive immunity (or acquired immunity) is the ability to recognize and destroy SPECIFIC pathogens or their toxic products that results from PRIOR exposure to that pathogen ○ Adaptive immunity relies on previous exposure to a pathogen Th i f t

§ Three main factors: 1. Recognize a pathogen and their toxins 2. Discriminate between a pathogen and normal body cells 3. Eliminate the pathogen and/or toxin § Specialized cells called lymphocytes are responsible for adaptive immunity - are activated and programmed to digest and present an antigen □ Antigen: any molecule or portion of a molecule that stimulates an immune response; examples include proteins and polysaccharides • Phagocytes are amoeba-like cells that ingest and destroy pathogens, alerting other immune cells ○ There are several types of phagocyte cells, but macrophages are usually the first line of defense against pathogens pathogen-- ass ssoo ciated m moo l ecul ula ar § Phagocytes recognize pathogen patt PA MP's) - structures that are part of the cell tteerns ((PA PAM of many commonly encountered pathogens tteern rreeco cog gnition § This recognition occurs through patt receptors on the surface of phagocytes □ After contact with PAMP, phagocyte becomes activated to ingest and destroy the pathogen □ Molecular pieces of the pathogen are then attached to protein complexes and presented on the cell surface • T-cells interact with antigen-presenting phagocytes during the immune response ○ Adaptive immunity consists of: § Antibody mediated components § Cell mediated components ○ Certain phagocytes take up pathogens, digest to break down, and present antigens (digested proteins) to T cells § Each T cell recognizes a single specific antigen, which binds cell l rreecep ept tor to a T-ce

Majo jorr H Hiistoc ocoompatib ibiil ity Pr Prooteins: • Progression of adaptive immunity and the importance of the major hist M HC ) pr stoo compat atii bil ity ((M proo teins: ○ T-cells (TH1 and TH2) interact with the MHC I II lexx on I ccoomple the surface of phagocytes (macrophage) § TH1 then releases cytokines and induces an inflammatory response § TH2 expresses different cytokines that activate B-cells (another form of white blood cells)

• MHC I is expressed on every cell type of the body, as opposed to MHC II ○ This is because every cell in your body is susceptible to pathogens ○ If the pathogen is infecting a cell, MHC 1 will be loaded with tor ((T TCR cell l R Reecep ept CR)) antigens and recognized by a T-ce toxic Tcells , not TH1 or TH2, are involved in this tot T-cells § C yto process - released perforin and granzyme , which kills the pathogen

I mmu munne C Ceel ls a annd A Annti tib bodies: • T-cells: ○ Only recognize antigens on the surface of host cells that are jorr h hiistoc ocoompatib ibiil ity "presented" on a protein complex; the majo mpll ex ((M HC)) comp MHC ○ T cell subtypes: § Tc cytotoxic cells: kill host cells that have been infected by a virus § Th Helper cells - two types: □ TH1: release cytokines that induce inflammation □ TH2: stimulate antigen-reactive B-cells to proliferate and produce antibodies

• B cells are responsible for antibody mediated immunity: elll s: el ○ B ccel § Antibody production is stimulated by a series of events: 1. Antigen-recognizing B-cells ingest and degrade antigen 2. Antigen is presented to a TH2 cell 3. If TH2 cell recognizes the same antigen, the B cell is then stimulated to produce antibodies a) Some types of antibodies serve as receptors on B cell surface b) Some antibodies are released (produced by plasma cells) to target pathogen for destruction morry B B-- cells; long term ○ Some B cells differentiate into memo production • Antibodies are complex proteins that inactivate and target antigencontaining viruses and cells for destruction ○ Anti bodies ((iimmunog tib ogll obul in inss) : § Composed of five major classes based on physical and Ig IgM gM,, gG , I gM immunological properties and distribution - IgA, I annd I Ig I gD, a gE □ IgG is composed of: ® 2 light chains ® 2 heavy chains § T-cell receptors or antibodies do not recognize whole molecules, but small regions of large molecules called epit al al le itoopes ((al alsso cca ledd a anntige gennic ddeete terrminate tess)

Natu turral v vss. A Arrtifici cia al A Addapt ptiiv e I Im mmu munnity: • Immunity can occur naturally or be induced by artificial human intervention m mu turr al I Im munn ity: • Natu ○ Natural active immunity: after an infection, immunity to a pathogen develops

pathogen develops ○ Natural passive immunity: newborns receive IgG antibodies across the placenta prior to birth - provide short-term disease protection after birth tiff icial I Im ty:: m munity • Arti ○ Artificial active immunity: uses vaccination to produce response that provides immunity § In some cases, additional subsequent booster vaccinations provide for longer immunity ○ Artificial passive immunity: no response of the immune system is involved - individual receives antibodies § Example: injection of antiserum (serum containing antibodies against the specific pathogen or toxin) into a person recently infected or exposed to a toxin • Vaccination is production of artificial active immunity that is induced by an antigen or mixture of antigens ○ These antigens are called vaccines and can be made from: § Toxoid: exotoxins that have been chemically inactivated but are still antigenic act pa genn: pathogens (bacteria or virus) are tiv ated p athoge § Inac killed by reaction with chemical compounds or heat ttenua ted p ath at uat pa thoogen: a mutated variant of a § Live a pathogen is used □ Mutant can not cause significant disease but will stimulate immune response Summary: • Innate resistance are physical, chemical, or microbiological factors that prevent pathogens from colonizing or growing • Innate immunity requires part of the immune system that is preprogrammed from birth to recognize certain pathogen molecules; adaptive immunity requires exposure to a pathogen in order to mount an immune response • Phagocytes engulf pathogens, destroy them, and present pieces on

• • • •

their cell surface to be recognized by other immune system cells, including: ○ Cytotoxic T cells that kill host cells that have been infected ○ Helper T cells that initiate inflammation and stimulate B cells Antibodies are immune system proteins that bind to specific regions (epitopes) of molecules (antigens) Super antigens are pathogen produced proteins that cause an extreme immune response that can result in tissue damage A variety of molecules and pathogens can be used to create immunity through vaccination An example is the annual influenza vaccine, which are manufactured based on predicted strains for the upcoming year

V i rul e n c e a annd P Pa a t h og e n e si s Pathogenesis: thogene croobial pa pat nessis is the process by which microorganisms cause • Micr disease ○ The process is initiated by exposure of a host to a pathogen § Pathogenicity is the ability of a microorganism to cause disease porrtunist stiic p pa hog atho gen can cause disease because the § An oppo normal resistance mechanism of a host are weakened § Invasion is entry of a pathogen through a protective epithelium layer § An infection is growth of a pathogen at an anatomical site § To invade and infect an anatomical site pathogens express v iru rull ence fa facctors

• Adherence is the ability of a microorganism to attach to tissue surfaces and cells ○ Adherence is the attachment of microorganisms to host tissues herrence fa facctors § Adherence is aided by adhe ssu pissm ue ttrropi § Adherence is usually specific: tiss Gl c c l x l ( ll l h id )

□ Glycocalyx: polymers (usually polysaccharides) surrounding some bacterial cells that aid in attachment and biofilm formation ® Often called slime layers or capsules herrence pr prooteins that are often □ Pathogens use Adhe found on fimbriae and pili to stick to host cells mbrriae a and nd//or p piili nd ® Proteins or glycoproteins on fimb bind to specific proteins and glycoproteins on surfaces of host tissues

V iru rull ence Fa Facctors: rull ence fa facctors that enhance • Most pathogens have multiple v iru pathogenesis and invasiveness ○ A virulence factor is a pathogen-produced substance that promotes the establishment and pathogenesis of an infectious disease ○ Examples of enzyme virulence factors that modify the host environment: § Hyaluronidase: breaks down hyaluronic acid polymer that glues host cells together § Collagenase: breaks down collagen in connective tissue § Streptokinase: destroys fibrin of blood clots § Coagulase: found on the exterior of S. aureus cells - created a fibrin layer around the cell that prevents immune system from detecting bacteria Exotoxins: • There are three types of exotoxins - proteins or enzymes that are exported from pathogenic bacteria and are toxic to host cells • Exotoxins are proteins that are excreted by bacteria and are toxic ○ Toxicity to the host can come from bacteria: § Growing at an infection site § Colonizing a site without invasion § Direct ingestion of pre-formed toxin through contaminated

food ○ Exotoxins that affect the small intestine are known as enterotoxins 1. Cytotoxins: cause damage to host cell membranes, can cause host cell lysis and death toxxins: consist of two subunits; B subunit binds to 2. AB to surface of specific host cells and A subunit enters host cell where it acts as an enzyme to produce host cell damage 3. Superantigens: proteins that cause a hyper stimulated immune response resulting in excessive inflammation and tissue damage • Cytolytic exotoxins damage the membrane of host cells by several mechanisms toll ytic ex exootoxins are often called hemolysins, a broad term ○ C yto derived from their ability to lyse red blood cells § Some hemolysins are phospholipases - cleaves phosphate group from phospholipids § Another type can cause holes in host cell membranes - an aph occcal a all ph pha hyl ococ a-toxin example is S tap • Hemolysin production by bacteria are easily observed using blood agar plates ○ Nutrient agar growth medium is sterilized, cooled to 45 degrees, and mixed with defibrinated sheep blood pht theria ttooxin is an AB exotoxin that kills host cells by blocking • Diph protein translation ○ Diphtheria toxin: § Extremely cytotoxic - only one toxin molecule kills one host cell ip htheria rynnebacte terrium ddip iph iaee - a bacterial § Produced by C ory pathogen of the upper respiratory tract § An AB toxin: □ B component binds to host cell receptors A ti th t t ll d bl k

□ A component is an enzyme that enters cells and blocks tRNA from entering the ribosome by catalyzing modification of elongation factor • Tetanus and botulism toxins are AB toxins that affect muscle/nerve interaction ○ Similar toxins that elicit opposite affects on animal host muscles ○ Both toxins are AB toxins ○ Block neurotransmitter release from nerve cells that signal muscles ○ Produced by species of the spore-forming anaerobe Clostridium, normally found in soils ox tull ism ttox oxiin: Stimulates muscle relaxation • Botu tridium b um ost bootul in inu ○ Produced by C l os ○ There are 7 types of botulism toxin § Type A has medical uses ○ Botulism usually results from improper food preservation, where bacteria grow and produce toxins ○ Toxin spreads throughout the body, eventually affecting many muscles ara acccid p pa rall ysis ○ Results in fl ac tannus T Tooxi xinn: Stimulates muscle contraction • Teta ○ Produced by Clostridium tetani ○ Bacterium colonizes and grows in deep, anoxic wounds ○ Exotoxin spreads throughout body § Toxin binds to inhibitory interneurons, preventing their function § As a result, muscles are constantly stimulated to be contracted tic p ara ast pa rall ysis ○ Results in spas ○ Vaccination using a chemically inactivated, purified version of the toxin can prevent tetanus • Enterotoxins are exotoxins that affect the small intestine briio cch lerrae hole ○ Cholera is caused by V ibr...