Quiz 8, Chapters 14 & 15

How bacterial pathogens damage host cells

Damage: 1. By using host's nutrient 2. causing direct damage in vicinity of the invasion 3. By producing toxins, which are transported by blood and/or lymph. Toxins can damage cells/tissue/organs far removed for the original site of invasion 4. By inducing hypersensitive reactions

Protozoa: Virulence factors

Plasmodium: reproduces in host cells causing them to rupture. Taxoplasma: can grow in phagocytic vacuoles of macrophages. Giardia intestinalis: attaches to host cell with sucking disc and digests host's cells and tissue fluids. Antigenic variation: Trypanosoma: Giardia Trypanosoma: produces a specific antigen when it enters the human bloodstream; within two weeks Trypanosoma expresses different antigen.

Normal (resident) microbiota

do not cause disease under normal conditions (normal flora)

Parasitism

relationship in which one organisms benefits at the expense of the other

symbiosis

relationships between two organisms in which at least one organisms, depends on the other

Exceptions to Koch's Postulates

- Microbe cannot grow on synthetic medium (e.g., Treponema pallidum, syphilis) - Microbe cannot be isolated from host; tissues are transplanted. (legionellosis). Tissue incubated in alternative host (like embryonated eggs) - Pahtogens can cause several diseases

Koch's Postulates

- The same pathogen must be present in every case of the disease - The pathogen must be isolated from the diseased host and grown in pure culture - The pathogen from the pure culture must cause the disease when it is inoculated into a healthy, susceptible laboratory animal - The pathogen must be isolated from the inoculated animal an must be shown to be the original organism.

Severity/ Duration of Disease

-Acute disease: develops rapidly but lasts only a short time -Chronic disease: develops more slowly, continues for long periods -Subacute disease: intermediate between acute and chronic -Latent disease: causative agent remains inactive for a time but then becomes active to produce disease symptoms -Herd immunity: many people with immunity exists in population

Epidemiology

-Analytical epidemiology: analysis of a particular disease to determine its probable cause -Experimental epidemiology: begins with hypothesis about a specific disease; experiments are performed to test the hypothesis. Effectiveness of drug (e.g., people treated with placebo and or drug) -Case reporting: important to "measure" incidence of disease and to establish chain of transmission; report of specified disease to local state, and governmental agencies

Extent of Host Involvement

-Bacteremia: presence of bacteria in the blood -Toxemia: presence of toxins in the blood -Viremia: Virus in the blood -Primary infection: acute infection that causes the initial illness -secondary infections: caused by opportunistic pathogen after a primary infection Subclinical (inapparent) infection: infection does not cause any noticeable illness

Healthcare-associated infections (HAIs)

-Compromised host: resistance of disease impaired by disease (AIDS destroy T cells); burns, trauma -Chain of Transmission: person-to-person; fomites -Control of Healthcare-Associated Infections: hand washing, disinfecting

Transmission of Disease

-Contact transmission: spread of disease agent by direct contact, indirect contact, or droplet trasnmission (person-to-person transmission) -Indirect contact transmission: agent transmitted from reservoir to susceptible host by means of non-living object (fomite) such as towel drinking cup; syringes -Droplet transmission: microbes transmitted by droplet nuclei -Vehicle transmission: by food, water, air, blood, bodily fluids, drugs intraveneous fluids -Waterborne transmission -Foodborne transmission -Airborne transmission

Fungi; Virulence factors

-Fungi can cause disease; however a well-deined set of virulence factors does not exist. -Fungi grow inside or on host -Chronic fungal infections such as athletes foot can cause allergic response. -Trichothecenes: fungal toxins that inhibit protein synthesis in eukaryotic cells. Produced by Fusarium and Stachybotrys. Symptoms: headaches, chills, severe nausea, vomiting, and visual disturbances. Found an grains and wallboard. -Virulence factors: candida albicans and Trichophyton cause skin infections; produce proteases that modify host cell membrane and allow attachment of fungus. Cryptococcus neoformans: causes a type of meningitis; has capsule that protects fungus from phagocytosis. -Clavis purpurea (grows on grain) toxin contained in sclerotia: highly resistant protions of the mycelia of fungus that can detach. Toxin= ergot; natural source of LSD; produces hallucinations; constricts capillaries and can cause gangrene Alfatoxin: produced by Asperigillus flavus in human body, toxin might be altered into carcinogen Mycotoxins: phalloidin and amanitin (Amanita phalloides, deathcap).

occurance of disease

-Incidence: number or people in a population, who develop the disease during a particular time period -Prevalence: number of people in a population that develop the disease at a specific time, regardless of when the disease started -sporadic disease: disease occurs occasionally -endemic disease: disease constantly present in population -epidemic disease: many people acquire disease in relatively short period -Pandemic disease: disease occurs world-wide (influenza)

Extent of Host Involvement

-Local infection: microbe infects small area of body -Systemic (generalized) infection: microorganisms or their products spread through entire body -Focal infection: agents enters through blood or lymph and enter specific parts of body where they are confined to specific areas -Sepsis: toxic inflammatory condition resulting from bacteria and/or their toxins -Septimica: blood poisoning, systemic infection arising from multiplication of pathogens in blood

Portals of Exit

-Pathogens exit via specific routes (e.g., secretions, excretions, discharges, or tissues. -Portals of exit relate to the infected part of the body. -Exit lets pathogen spread through populations. -Most important; repiratory and gastrointestinal tract. -Respiratory route: tuberculosis, whooping cough, pneumonia, mumps, measles, chicken pox, influenza. -Genitourinary tract: sexually transmitted diseases; present in secretions from penis and vagina. Urine: typhoid fever. -Skin/wound infections: ringworm, herpes simplex, warts. -needles/syringes: AIDS and hepatitis B

Helminths

-Presence of helminths in host cause disease symptoms. -Can cause cellular damage: some worm species use host tissues for their own growth. -Other worms produce large parasitic masses. -Deplete host's nutrients -Cysts damage organs (e.g., brain). -Elephantiasis: roundworm Wuchereria bancrofti: parasite block lymphatic circulation, leading to accumulation of lymph and extreme swelling of legs and other body parts. In addition, waste products by the parasite contribute to the symptoms of the disease.

Patterns of Diseases

-Required: reservoir of infection; source of pathogens -Steps: transmission, invasion pathogenesis -Predisposing factors: make body more susceptible to disease and may alter the course of the disease (e.g., gender, genetics)

Numbers of Invading Microbes

-Virulence is often expressed as ID50. -ID50: Infectious dose for 50% of a sample population. -Bacillus anthracis: -ID50 skin: 10-50 endospores. -ID50: inhalation: 10,000 - 20,000 endospores.

Classifying Infectious Diseases

-disease: changes in body structure and function -sign: objective changes that be observed and measured -symptoms: changed in body function -syndrome: group of symptoms or signs -communicable disease: infectious agent is transmitted directly or indirectly from infected person to another person -contagious disease: very communicable disease (chicken pox) -noncommunicable disease: disease is not spread from one host to the next host

Reservoirs of infection

-source of pathogens -Human reservoirs: human body (carriers: people with pathogen, e.g., HIV, hepatitis) -Animal reservoirs: zoonoses; disease that occur primarily in the wild and domestic animals that are transferred to humans (rabies, Lyme disease) -Nonliving reservoirs: soil and water

Vectors

-vector: animals that carry pathogens arthropods largest group -Mechanical Transmission: passive transport (e.g., on insect) -Biologiccal transmission: active process (e.g., insect bite)

Koch's Postulates

1. Microorganisms are isolated from a diseased or dead animal 2. the microorganisms are grown in pure culture 2b. microorganisms are identified 3. Microorganisms are inoculated into a healthy laboratory animal 4. Disease is reproduced in a laboratory animal 5a. The microorganisms are isolated from this animal and frown in a pure culture. 5b. microorganisms are identified

pathogen

A microorganism that causes disease (one or multiple)

how bacterial pathogens penetrate host defenses

Antigenic Variation -adaptive immune response; produces anitbodies that recognize specific markers (antigens) on pathogen. Binding of antibody labels the pathogen for destruction. -Microbes can vary the structure of molecules and therefore antigens; antibodies do not recognize the pathogen. Host has to produce new antibodies. Ex: N. gonorrhoeae- several variants of Opa protein Influenza virus- variants of coat proteins Trypanosoma brucei gambiense (sleeping sickness)

Center for Disease Control and Prevention (CDC)

Collects information about notifiable infectious diseases -Publishes: morbidity and mortality weekly report: contains data on morbidity and mortality -Morbidity rate: number of people affected by a notifiable disease in a given period of time -Mortality rate: number of deaths resulting from a notifiable disease in a given time period

Cytopathic effects of viruses

Cytopathic effects: visible effects of viral infection -cytocidal effects: resulting in cell death -Noncytocidal effects: cytopathic effects that do not result in cell death

How bacterial pathogens penetrate host defenses

Cytoskeleton of host aids in invasion: -Sytoskeletoon consists of microfilaments, microtubles, and intermediate filaments -Salmonella strains can produce surface proteins (invasins) that rearrangs nearby actin filaments -S. typhimurium causes membrane ruffling; microbe sinks into the ruffle and is engulfed by the host cell -listeria species use actin to propel themselves though cells and from one cell to another. Attach to cadherin in gap junctions to move from cell to cell

Pathogenic properties of viruses

Depend on: -gaining access to host -evasion of host's defenses -capability to cause damage to or death of host cell while replicating

How bacterial pathogens damage host cells: endotoxins

Detection of endotoxin in e.g., drugs. Tests: Limulus amebocyte lysate (LAL) -horseshoe crab (Limulus polyphemus) contains white blood cells (amebocytes_ with large amount of a protein that causes clotting. In the presence of endotoxin, amebocyte lyse, release protein that forms a gel-clot (precipitate). Positive test for the presence of endotoxin.

Algae

Dinoflagellates Alexandrium: neurotoxin, saxotoxins; cause paralytic shellfish poisoning.

How bacterial pathogens damage host cells: Direct damage

Direct damage Destroy destruction; when pathogens metabolize and multiply in cells, the cells usually rupture Some bacteria (E. coli, shigella, salmonella) encourage host epithelial cells to take them up by phagocytosis; once inside the cell, the bacteria pass through and are Excreted by reverse phagocytosis. This process can disrupt host cells. Some bacteria enter host cell via enzymes, which can damage cells.

How bacterial pathogens damage host cells: Endotoxins

Endotoxins: -Loacted within the bacteria: e.g. cell-wall -Example: Lipid A present in outer membrane of gram-negative bacteria. -Endotoxins are released during multiplication or when gram-negative bacteria die and cell walls lyse. -Endotoxins stimulate macrophages to release cytokines in high doses. Conditions improve when endotoxins is broken down. -All endotoxins produce the same symptoms: chills, fever, weakness, generalized aches, in some cases shock (septic shock) and death. -Activation of blood clotting enzymes: obstruct capillaries resulting in reduced blood supply and death of tissue (disseminated intravasular coagulation (DIC)). Shock: life-threatening decrease in blood pressure. Septic shock: shock caused by bacteria -caused by release of cytokines from machrophages. -Phagocytosis of gram-negative bacteria by macrophages causes secretion of tumor-necrosis factor (TNF). -TNF damages blood vessels and increases permeability of blood vessels. -blood vessels lose large amounts of fluid, resulting in drop in blood pressure and shock -Dramatic drop damages kidneys, lungs, and gastrointestinal tract

How bacterial pathogens damage host cells: endotoxins

Endotoxins: -presence of gram-negative bacgeria such as Haemiphilus influenzae in cerebrospinal fluid causes the release of TNF and IL-1. -Result: weakened breain-blood barrier; more bacteria can enter central nervous system -Septic shock: 3 out of 1000 people develop septic shock; nearly half die within 6 months Representative disease: Salmonella typhi- typhoid fever Proteus- urinary tract infections Neisseria meningitidis- meningococcal meningitis

How bacterial pathogens invade host

Enzymes: Extracellular enzymes (exoenzymes)- digest blood clots; junctions between cells; or connective tissue Coagulase (some staphhylococci)- coagulates fibrinogen in blood. Fibrinogen is converted to fibrin, forms blood clot that protects microbe Kinases (some streptococci)- fibrinolysin; breaks down fibrin in blood clots, allows bacterium to spread Hyaluronidase (e.g., some streptococci)- hydrolyzes hylauronic acid in connective tissues. Therapeutically used to spread drug in body Collegenase (some clostridium sec.)- breaks down collagen in connective tissues (e.g., muscles). Facilitates spread of as gangrene IgA proteases- digest antibodies that bind bacterium and target them for destruction

How bacterial pathogens damage host cells: exotoxins

Exotoxins Produces by bacteria and released into surrounding media following lysis or secreted into surrounding media. Exotoxins are proteins and many are enzymes. Genes for majority of exotoxins are carried by plasmids or phages. Exotoxins destroy certain parts of host's cells or inhibit certain metabolic functions. Exotoxins among the most lethal substances known: 1 mg botulinum exotoxin can kill 1 million guinea pigs. Exotoxin \causes botulism not the bacterial infection with C. botulinum. Toxoids: inactivated exotoxins used for vaccination (diphtheria, tetanus). Names: type of cell which they attack (cardiotoxin) or species (botulinum toxin).

(HAIs)

Infections that patients acquire when they are treated for another condition at health care facility (aka: nosocomial infections). Study on slides

How bacterial pathogens damage host cells: Nutrients

Iron Pathogens produce siderophores: iron-transporting proteins, which remove iron from host. Uptake by siderophore receptors on pathogen's surface. Other bacteria directly take up host's iron transport proteins or hemoglobin

Plasmids, lysogeny and pathogenicity

R plasmids- carry gene that determine microbe's pathogenicity Examples: tetanus neurotoxins; heat-labule enterotoxin; staapnylococcal enterotoxin D; adhesions and coagulase; special type of fimbria on pathogenic E. coli Lysogenic prophages: can carry gene that determine microbe's pathogenicity. Lysogenic conversion: change of characteristics of microbe due to prophage Examples: diphtheria toxin; erythrogenic toxins; staphylococcus enterotoxin A; botulinum neurotoxin; cholera toxin

CDC

Study on Slides

portals of entry

Study on Slides

reservoirs of infection

Study on Slides

Development of Disease

Study on slides

Epidemiology: Incidence

Study on slides

Microbial Mechanisms of Pathogenicity

Study on slides

Principal Sites of Healthcare-Associated Infections

Study on slides

Relative virulence of some microbial pathogens

Study on slides

Vectors

Study on slides

adherence

Study on slides

some virulence factors

Study on slides

Transient microbiota

transient microbiota; present for days, weeks and months and then dissapear

How bacterial pathogens damage host cells: Toxins

Toxins: Poisonous substances produced by microorganisms Toxigenicity: capacity of micrboes to produce toxins Toxemia: presence of toxins in the blood Intoxications: caused by presence of toxin not by microbial growth Toxins transported by blood and/or lymph can cause serious, even fatal, effects. Of the roughly 220 bacterial toxins, 40% cause disease by damaging the eukaryotic cell membrane

How bacterial pathogens damage host cells: exotoxins

Types of Exotoxins 1. A-B toxins 2. membrane-disrupting toxins 3. superantigen

How bacterial pathogens damage host cells: Exotoxins

Types of Exotoxins 1. A-B toxins consists of two polypeptides: A and B A: enzyme component B: binding component

How bacterial pathogens damage host cells: Toxins

Types of Exotoxins: Superantigens -antigens that provoke a very intense immune response. -Stimulate the proliferation of T cells -T cells release cytokines causing fever, nausea, vomitting, diarrhea. Staphylococcus toxins: food poisoning and toxic shock syndrome. Genotoxins (gram-negative bacteria e.g., Haemophilus, heliobacter) toxins that damage DNA. Cause mutations, disrupt cell division, cancer.

How bacterial pathogens damage host cells: toxins

Types of exotoxins Membrane-disrupting toxins: cause cell lysis by disrupting cell membrane of host's cells. Membrane-disrupting toxins lyse cells by forming protein channels in the plasma membrane (S. auerus), or by disrupting the phospholipid structure (C. perfringens). Membrane-disrupting channels in the plasma membrane (S. aureus), or by disrupting toxins help bacteria to escape phagosomes by destroying the phagosome membrane. Leukocidins: destroy phagocytic white cells (staphylococci and streptococci). Hemolysins: destroy red blood cells by forming protein channels (streptolysins when produced by streptococci; destroy white and red blood cells).

Nature of infectious disease

Virulence factors of infectious agents -extracellular enzymes -secreted by the pathogen -dissolve structural chemicals in the body -Help pathogen maintain infection, invade, and avoid body defenses -important to virulence of the pathogen -mutant species that do not secrete the enzymes are often avirulent

Damage to cells caused by viruses

Virus usually kills the host cell. Death can be cause by accumulation of large numbers of multiplying viruses; damages to the host's cell membrane; inhibition of host's DNA, RNA and/or protein synthesis/

Viral mechanisms for evading host defenses

Viruses penetrate and grow inside cells, where the immune system cannot reach them. Attachment: viruses have attachment sites (ligands) for receptros present on targer cells. Attachment site for rabies virus mimics neurotransmitter acetylcholine. HIV has attachment site that binds the CD4 protein in T lymphocytes. Attachment sites located in valleys on HIV surface; CD4 but not antibodies can reach the attachment sites.

Development of Disease

_incubation period: interval between initial; infection and the first appearance of disease symptoms -Prodromal period: relatively short period that follows the period of incubation in some illnesses (early, mils symptoms) -Period of illness: period during which illness is most severer; person exhibits overt signs and symptoms of the disease -Period of decline: signs and symptoms of disease decline -Period of convalescence: body returns to pre-disease state

Pathogenicity

ability of a microbe to cause disease and overcome host defense system(s)

How microorganisms enter host: adherence

adherence or adhesion is a necessary step in pathogenicity -adherence often involves adhesins (ligands) on the surface of pathogen and complementary receptors on host cells -adhesins are often located in glycocalyx or on pili, fimbriae, and flagella -adhesins are often glycoproteins and/or lipoproteins -receptors are often sugars(e.g., mannose) -biogilms attach well to moist surfaces, which contain organic matter, in hosts

human Microbiome Project

analysis of microbial communities, microbiomes, that live in an on human body

portals of entry

avenues through which pathogens can enter hosts

how bacterial pathogens evade host defenses

capsules -capsule protects microbe from phagocytosis -streptococcus pneumoniae: avirulent without capsule, virulent with capsule

how bacterial pathogens evade host defenses

cell wall components -cell wall can contain chemical substance that contribute to virulence -s. Pyrogens: M protein: present in cell surfact and fimbriae. M protein mediated adhesion and protects microbe from phagocytosis -N. gonorrhoeae: uses fimbriae and ouer protein called Opa to attach to host -Mycobacteria: mycolic acid and acid fast membrane protect microbes from phagocytosis

infection

colonization of the body by pathogenic microbes

virulence

degree of pathogenicity

cause

etiology of disease

infection

growth of microorganisms in the body

disease

infection results in change of health

Pathogenisis

manner of development of disease

Emerging infectious diseases (EIDs)

new or changing and show an increase in incidence in the recent past Study on slides

Microbial antagonism (competitive exclusion)

normal microbiota benefit the host by preventing the outgrowth of harmful microorganisms. When the balance between normal microbiota and pathogen is upset, the pathogens can overgrowth normal microbiota

Parenteral routes

pahtogens enter through injured barriers (e.g., skin, mucous membranes)

How bacterial pathogens penetrate host defenses

penetration into Host Cell Cytoskeleton: adhesion of pathogen can trigger signals in the host cell that facilitate entrance of pathogen

Commensalism

symbiosis in which one organism benefits and the other remains unaffected

Mutualism

symbiosis that benefits both organisms

Epidemiology

the science that studies when and where diseases occur and how they are transmitted in populations Descriptive - Epidemiology: entails collection of all data that describe the occurrence of the disease under study - retrospective: backtracks the cause and the source of the disease -prospective: disease free population is selected and subsequent disease experiences are recorded

Pathology

the scientific study of disease