micro final

scientists trying to develop

antiviral chemicals that interfere with viral replication •Current options effective only against specific type of virus; none eliminate latent infections

autoimmune disease

targets body issues

inactivated vaccines

unable to replicate advantage: cannot cause infection or revert pathogenic forms disadvantage: no replication, so no amplification in vivo; immune response is limited severe booster doses usually needed example flu shot

MHC II Deficiency (Bare Lymphocyte Syndrome)

•Rare disease caused by lack of MHC II expression on APCs •Caused by genetic mutation •Regulators of MHC II gene •Results in lack of cell-mediated immunity •T cells cannot be properly activated.

viruses difficult to target selectively

•Rely on host cell's metabolic machinery (can't target host!!); lack cell walls, ribosomes, other structures targeted by antibiotics •Many encode their own polymerases; represent potential targets

respiratory systems

•Replenishes O2 •Releases CO2 •Vocal cords: sounds •Nose detects odors •Eyes and ears not part of system, but serve as major portals of entry to body

tetracyclines are bacteriostatic

•Reversibly bind to 30S subunit -Block tRNA attachment; prevent translation

autoimmunity

•Self tolerance •B and T cells learn not to react with self antigens •T cells •Deleted in the thymus •B cells •Undergo apoptosis in bone marrow •Loss of self tolerance •Autoimmune disease •Results in tissue damage •Infection can trigger the formation of autoimmune reactions •Example: M protein of S. pyogenes

t-cell disorders

•Severe combined immunodeficiencies (SCIDs) •No T cells are made. •By 6 months of age, most SCID infants develop recurrent infections. •Treatment is bone marrow transplant or IVIG.

Which of the following is target for an antiviral drug? a.cell wall synthesis b.protein synthesis by ribosomes c.an enzyme in a biochemical pathway d.DNA or RNA synthesis

d

Which of the following statements about rashes is NOT true? a.A change in color and texture of the skin is usually referred to as a rash. b.An exanthem is a widespread skin rash accompanied by systemic symptoms. c.An enanthem is a rash on mucous membranes. d.Exanthems are usually caused by infectious agents, and enanthems are usually caused by allergic reactions.

d

allergen

foreign antigen; similar structure or shape to host

therapeutic dose

minimum dose per kg of body weight that stops growth

septicemia

pathogen replicates to high numbers, overcomes the innate immune system

requirements of an effective vaccine

1.It should not harm the person being vaccinated. 2.It should stimulate B-cell and T-cell responses. 3.It should result in long-term memory. 4.It should not require many boosters. 5.It should protect against the natural pathogen.

Mechanisms of Acquired Resistance

1.Antibiotic-Inactivating Enzymes •Penicillinase -destroys penicillin 2.Alteration in Target Molecule •Minor structural changes can prevent binding of antibiotic 3. Decreased Uptake of the Medication •Changes in porin (PORES) proteins of outer membrane of Gram-negatives 4. Increase elimination-pump it out

steps of pathogenesis

1.Entry (via portal) 2.Tissue attachment and colonization 3.Immune avoidance 4.Host damage 5.Pathogen exit (via portal)

steps in establishing an infection

1.Adherence •Adhesins attach to host cell receptor •Often located at tips of pili •Binding highly specific; exploits host cell receptor 2.Colonization •Grow/Multiply •Growth in biofilms •Avoidance of secretory IgA 3.Delivering Effector Proteins to Host Cells •Secretion systems in Gram-negatives •Several types discovered; some can inject molecules other than proteins •Effector proteins induce changes -Can induce uptake of bacterial cells -Can lead to the cells death

four basic types of vaccines

1.Killed whole cells or inactivated viruses •Use inactivated (dead) organism •Antigenicity remains •Ex: cholera and rabies 2.Live, attenuated (weakened) bacteria or viruses •Mutated for growth in host only •Mimic infection, generated stronger immunity •Ex: MMR 3.Antigen molecules purified from the pathogen •Toxoid, subunit, conjugated 4.DNA vaccines (not commercially available) •Attenuated: elicits stronger immune response, but can sometimes cause disease •Inactivated: elicits weaker immune response, but cannot cause infections

antiviral agents

1.Prevent Viral Entry •New group of chemicals prevent viral entry into host cell -Enfuvirtide binds to an HIV protein that promotes fusion of viral envelope with cell membrane 2.Interfere with Viral Uncoating •Nucleic acid must separate from protein coat •Two chemicals target this step—amantadine, rimantadine -Block influenza A viruses, prevent or reduce severity -Viral strains easily develop resistance; usefulness limited 3.Interfere with Nucleic Acid Synthesis •Nucleoside Analogs: structure similar to nucleosides -Incorporation into nucleotide chain can stop nucleotides from being added or alter base-pairing properties •Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) inhibit reverse transcriptase by binding to site other than nucleotide-binding site 4.Prevent Genome Integration -Inhibit HIV-encoded enzyme integrase; prevent virus from inserting DNA copy of genome into host cell -Raltegravir is first approved chemical of this class 5.Prevent Assembly and Release of Viral Particles •Virally encoded enzymes required for assembly, release •Protease inhibitors are virus specific

different types of rashes

A.Macular: Flat and red, less than 1 cm in diameter B.Vesicular: Small blisters are formed C.Papular: Small, solid, and elevated (dermis layer) D.Pustular: A papule filled with pus

periodontal disease

Advanced inflammation causing the gums to bleed and pull away from the teeth •Gingivitis: swelling and redness of the gums •Chronic periodontitis: destructive response that damages structures that support teeth •Signs and Symptoms •Gingivitis marked by gums that are tender, bleed easily •Chronic periodontitis characterized by bad breath, red shiny gums that bleed easily, loosening of teeth -Base of teeth becomes discolored, gums recede •Causative Agent •Dental plaque at point where gum joins tooth •Mostly Gram-negative anaerobes •Epidemiology •Almost 90% at 65; smokers, impaired immunity are factors •Treatment and Prevention •Cleaning, minor surgery to remove; flossing and brushing

A patient developed a rash within 15 minutes of eating tomatoes. This is most likely a.type I hypersensitivity. b.type II hypersensitivity. c.type III hypersensitivity. d.type IV hypersensitivity. e.an autoimmune disease.

a

What is the primary method of treatment for diarrhea caused by a virus? a.rehydration therapy b.antibiotic therapy c.antitoxin therapy d.vitamins e.There is no effective therapy.

a

Which of the following diseases is caused by a bacterial pathogen? a.Plague b.mononucleosis c.Ebola hemorrhagic fever

a

Which of the following is a bacterial virulence factor? a.Capsule b.ribosome c.peptidoglycan d.DNA

a

Which of the following organisms can produce necrotizing fasciitis? a.Streptococcus pyogenes b.Neisseria gonorrheae c.Staphylococcus aureus d.Propionibacterium acnes e.Staphylococcus epidermidis

a

Peritonsillar abscess

abscess in the pharynx

Secondary immunodeficiencies

acquired at any age and caused by infection (HIV), immunosuppressive drugs, and radiation therapy

Immunodeficiency diseases (IDDs) are

are disorders where part of the immune system is missing or defective.

Oseltamivir (Tamiflu) and Zanamivir (Relenza)

are neuraminidase inhibitors that prevent influenza virus particles from leaving the cell.

Which antibiotic blocks the synthesis of peptidoglycan in a bacterial cell wall? a.erythromycin b.Penicillin c.tetracycline d.Ciprofloxacin

b

Which of the following bacterial infections causes an intoxication? a. listeriosis b. staphylococcal food poisoning c. salmonellosis d. Helicobacter pylori infection e. Streptococcus mutans

b

Which of the following sequelae can occur as a result of a streptococcal infection? a.formation of a pseudomembrane ● b.rheumatic fever ● c.encephalitis ● d.legionellosis ● e.whooping cough

b

bacteremia

bacteria in the bloodstream

Which of the following diseases is caused by Borrelia burgdorferi, is transmitted by the deer tick, and causes a bull's-eye rash? a.Rocky Mountain spotted fever b.typhoid fever c.Lyme disease d.malaria e.leishmaniasis

c

Which of the following is a property of a bacterial exotoxin? a.a type of lipid associated with cell membranes b.only released when the bacterial cells dies c.made of protein d.found only in Gram-negative bacteria

c

pathogens are

characterized by the presence of virulence factors. molecules produced by microbes that add in their ability to: 1) colonization host (this includes attachment to cells) 2) entry into and exit out of cells (if the pathogen is an intracellular one)

A benefit of vaccination is that a child will a.generate antibodies to a pathogen without getting sick. b.develop antibodies through natural immunity. c.develop more infections than necessary. d.protect other children who cannot be vaccinated. e.Both A and D.

e

Type A influenza is the cause of the majority of flu pandemics because a. there is no vaccine for type A influenza. ● b. it is the most common form of influenza. ● c. it can undergo antigenic drift. ● d. it can infect only humans. ● e. it infects a variety of animals where antigenic shift can then take place.

e

hair follicle infections

generally mild •Signs and Symptoms •Folliculitis is inflammation, causes red bumps (pimples) •If infection extends to adjacent tissues, yields furuncle -Localized redness, swelling, tenderness, pain -Pus may drain from the boil •May worsen to form carbuncle •usually forms when multiple boils are close together -Large area of redness, swelling, pain, draining pus -Fever often present •Causative Agent •Commonly caused by Staphylococcus aureus •Pathogenesis 1.S. aureus attaches to cells of hair follicle, multiplies, spreads to sebaceous glands 2.Infection produces inflammatory response -Neutrophils recruited -Plug forms from inflammatory cells, dead tissue 3.If infection enters bloodstream, can spread, reach heart, bones, brain •Epidemiology •S. aureus found in nostrils of nearly everyone (some have more than others) -20% of healthy adults carry continuously for year or more; 60% will be colonized during a given year -Transmission usually by hands •People with boils, other infections shed large numbers -Should not work with food or near patients with surgical wounds or chronic illnesses •Staphylococci survive well in environment -Fomites easily transmit -Since common, sources difficult to identify precisely •Treatment and Prevention •Boils, carbuncles may require minor surgery to drain pus •Patients usually given antibiotics afterward •Many strains resistant to multiple antibacterial medications

Primary immunodeficiencies

genetic and present in early childhood

sepsis

infection of the bloodstream

endocarditis

inflammation of the endocardium

gingivitis

inflammation of the gums

laryngitis

inflammation of the larynx

myocarditis

inflammation of the myocardium

pericarditis

inflammation of the pericardium

pharyngitis

inflammation of the pharynx

tonsilitis

inflammation of the tonsils

hypersensitivity

is immune response that causes injury •Hypersensitivity is sensitivity to allergen •Normally harmless environmental substance •Usually involves IgE response

immunodeficiency is

lack of adequate immune responses

toxic dose

maximum dose tolerated by the patient

chemotherapeutic index

ratio of toxic dose to therapeutic dose

the higher the chemotherapeutic index,

the safer the drug

Amantadine

• is a specific inhibitor that prevents influenza virus from uncoating and exiting by changing the pH of the phagolysosome.

infectious mononucleosis

•"The Kissing Disease" •Signs and Symptoms •Appear after long incubation period, usually 30-60 days •Fever, soar throat covered with pus, marked fatigue, enlargement of spleen and lymph nodes •Epstein-Barr virus (EBV) •Herpes virus family •Shed in saliva •Fever, sore throat, enlarged lymph nodes, fatigue •Virus infects and replicates •Infects mouth, throat •Replicates is carried to lymph nodes •Infects B. lymphocytes •Can exist as a latent infection •Epidemiology •Worldwide distribution •EBV present in saliva for up to 18 months after infection -Occurs intermittently for life -Mouth-to-mouth kissing is important mode of transmission in young adults •By middle age, most have antibody, indicating infection •Treatment and Prevention •Antivirals -No activity against latent infection •Avoiding saliva of others, including contaminated items such as tooth-brushes, drinking glasses •No vaccine

Antibacterial Medications That Interfere with Cell Membrane Integrity

•A few antimicrobials damage bacterial membranes •Cause cells to leak, leading to cell death •Limits usefulness to topical applications Also binds to eukaryotic cells, through lesser extent -Daptomycin inserts into cytoplasmic membrane »Used against Gram-positives resistant to other antibiotics »Ineffective against Gram-negatives; cannot penetrate outer membrane

two-subunit AB toxins

•A subunit is toxic. •B subunit binds host cell receptors. •Many B subunits are complexes of five units arranged as a ring. •ADP-ribosyltransferase inactivates or alters target proteins.

pneumococcal pneumonia

•Account for ~60% of adult pneumonia patients requiring hospitalization •Signs and Symptoms: cough, fever, chest pain, sputum production (pus, other material coughed up from lungs) •Usually preceded by 1-2 days of runny nose, congestion that ends with sudden rise in temperature and chill •Sputum becomes pinkish or rust colored from blood •Severe chest pain worse when coughing -Causes shallow rapid breathing -Patient develops dusky color from poor oxygenation •Without treatment, survivors show profuse sweating and rapid return to normal temperature after 7-10 days •Causative Agent: Streptococcus pneumoniae •Thick polysaccharide capsule necessary for virulence •Pathogenesis: encapsulated pneumococci inhaled into alveoli multiply rapidly, cause inflammatory response •Capsule, and cell surface proteins interfere with complement system. Both block phagocytosis •Enzymes damages ciliated epithelium •Epidemiology: up to 30% of healthy people carry encapsulated pneumococci in throat; mucociliary escalator effectively keeps from reaching lungs •Risk of infection increases when escalator defense is impaired -for example, alcohol, narcotic use, viral respiratory infections -Also heart, lung disease; diabetes; cancer; over age 50 •Treatment and Prevention: antibiotics if not resistant to them •Vaccine available for 23 pneumococcal strains that cause over 90% of disease (PPSV23)

antibacterial medications that inhibit cell wall synthesis

•Bacterial cell walls are unique, contain peptidoglycan •Great target for medications: often have high therapeutic index

community acquired pneumonia

•Acquired outside of a hospital •Pneumonia: an infection that causes inflammation in the lung •Classified as typical or atypical •Atypical pneumonias affect multiple organ systems, usually produce a normal WBC count, and produce symptoms that appear gradually, mimicking upper respiratory infections at the onset. •Most common cause of typical pneumonia are organisms such as Streptococcus pneumoniae.

acne vulgaris

•Affects 60-70% of Americans at some point •20% will have severe acne •Results from blocked hair follicles or pores called comedones •Can be open (blackheads) •Or closed (whiteheads) •Inflammatory acne •Inflamed macules, papules, pustules, and nodules •Cystic or nodular acne •Most severe •Painful fluid-filled cysts or nodules ▪: commonly begins at puberty •Signs and Symptoms •Enlarged sebaceous glands, increased sebum secretion •Blockage yields large accumulations of sebum, produces blackheads and whiteheads •Causative Agent Propionibacterium acnes which multiplies in sebum ▪Epidemiology •Most people have P. acnes on skin •Higher incidence of acne during puberty likely due to excess sebum production due to increased hormones •Treatment and Prevention •Usually mild; medications available Squeezing lesions ill-advised, can rupture follicles •Factors that contribute to acne development are: •Genetic predisposition •Hormones •Gram-positive bacterium Propionibacterium acnes •Organism uses the triglycerides in sebum as a nutrient •P. acnes promotes inflammation by binding to Toll-like receptor 2 on macrophages and neutrophils, which then release proinflammatory cytokines.

human herpes viruses and latency

•After a primary infection, human herpes viruses become latent in host cells (nerve cells or white blood cells). •DNA circularizes and exists as an episome. •DNA integrates into host cell genome. •Latent virus can reemerge after years of latency and cause a new active infection.

antibacterial medications that inhibit protein synthesis

•All cells synthesize proteins •Can exploit differences between prokaryotic and eukaryotic ribosome •Prokaryotes have 70S, eukaryotes have 80S ribosomes •Mitochondria have 70S •May account for some Toxicity of these antibiotics

Penicillins, Cephalosporins, other β-Lactam Antibiotics

•All have β-Lactam ring •Competitively inhibit enzymes that catalyze formation of peptide bridges between adjacent glycan strands; disrupt cell wall synthesis

streptococcal pharyngitis

•Also known as strep throat •Contagious and spread through: •Person-to-person contact •Indirect contact with items contaminated by secretions •Causative agent is Streptococcus pyogenes •Symptoms include: •Sudden onset of high fever and sore throat •Tender, enlarged cervical lymph nodes •Exudate on tonsils •Absence of a cough •Some strains of S. pyogenes produce exotoxins. •Streptococcal pyogenic exotoxins (SPEs) •Can cause fever and a red rash called scarlet fever •Rash starts on the head and neck, then spreads to the trunk, then to arms and legs. •Some patients may also have a very distinctive red, bumpy tongue referred to as a strawberry tongue.

Mechanisms of antibiotic resistance

•Altered DNA gyrase no longer binds to quinolones. •Beta-lactamase (penicillinase) destroys penicillin. •Enzyme modifies and inactivates aminoglycosides. •Tetracycline resistance is due to an efflux pump.

lower respiratory tract

•Alveoli are small sacs where oxygen from inhaled air is exchanged for carbon dioxide. •All the respiratory tubes warm, moisturize, and remove impurities from inhaled air as it travels to the alveoli. ▪Lower Respiratory Tract: usually sterile •Larynx (voice box), trachea (windpipe), bronchi, lungs •Inflammation of larynx is laryngitis •Trachea branches into two bronchii; infection leading to inflammation is called bronchitis -Commonly from viral infection or smoking •Bronchioles end in alveoli, make up bulk of lung tissue -Inflammation of lungs is pneumonitis, often viral -Pneumonia is when alveoli fill with pus and fluid -Lung tissue contains many macrophages to prevent

rheumatoid arthritis

•Antibodies form immune complexes to connective tissue in joints and cause inflammation.

immune avoidance by viruses

•Antigenic variation: 100 known serotypes of rhinovirus; each virus has a unique capsid protein. Antibodies to one capsid protein are not effective on another. •Antigenic shift: two strains of influenza virus infect the same cell and the genomes get mixed. This makes a dramatically different virus. •Antigenic drift: random mutations can occur within the cell that a virus infects, creating small changes in virus proteins.

Tissue distribution, metabolism, and excretion

•Antimicrobials differ in behavior in body •Only some medications cross the brain-blood barrier important in treating meningitis. •Some unstable at low pH, must be injected.

adhesin

•Any microbial factor that promotes attachment •Types of adhesins: •Pili •Nonpilus adhesins

hashimoto's disease

•Autoantibodies bind and damage the thyroid, causing hypothyroidism.

grave's disease

•Autoantibodies bind to the thyroid-stimulating hormone receptor, causing hyperthyroidism.

viral infections of upper respiratory system common

•Average peson in U.S. gets two to five per year •Hundreds of kinds of viruses involved; symptoms similar •Infections usually subside without treatment or permanent damage, but can impair defenses •Allow for more serious bacterial infections •Common cold most frequent, accounts for >1/2 •No fever unless secondary bacterial infection •Symptoms mostly gone within a week •Mild cough may persist

antibodies and viruses

•Avoid antibodies by moving cell to cell or cause cell fusion (syncytium) •Modify surface antigens (proteins), outpace body's capacity to produce effective antibodies •Use antibodies to facilitate macrophage uptake

avoiding immune responses

•Avoiding the Antiviral Effects of Interferons •Viruses may block expression of host genes or block activation of enzymes

antibiotic resistance

•Bacteria have evolved resistance to cell wall‒inhibiting antibiotics through HGT or mutation followed by natural selection. •Acquisition of a gene for an enzyme called beta-lactamase, which breaks beta-lactam ring. -This destroys the β-lactam antibiotic •Random mutation in a gene for a penicillin-binding protein, in the cell wall, prevents penicillin from binding and halting peptidoglycan synthesis.

influenza

•Based on antigenic determinants •Type A •Can infect a variety of animals as well as people •Is constantly changing •Type B •Found primarily in humans and usually results in a milder illness •Type C •Causes only mild disease •Pathogenesis: inhalation of droplets or transfer to eyes, nose from contaminated fomites •Virus attach to specific receptors of respiratory epithelial cells; enter cells via endocytosis •Host cell protein and nucleic acid synthesis stops; rapid synthesis of viral RNA and proteins begins •Infected cells die, slough off, destroy mucociliary escalator •Individuals susceptible to secondary respiratory infections •Epidemiology: usually only small percentage die •But many cases, so overall number of deaths high •Most deaths due to bacterial infections (for example, pneumonia) (problem with mucociliary elevator) •Epidemics occur annually; pandemics periodically •Antigenic drift: minor gene mutations responsible for seasonal influenza (in the genes for proteins on outside of virus) •Antigenic shift: uncommon but causes pandemic influenza; mixing of RNAs from different flu viruses •Treatment and Prevention: antivirals, vaccines •Multivalent vaccines (against three most important strains in circulation) ~80-90% effective, but new one required each year because of antigenic drift

Rifamycin (rifampin)

•Binds to RNA polymerase and blocks transcription

spectrum of activity

•Broad-spectrum antimicrobials affect a wide range •Important for treating acute life-threatening diseases -Especially when no time to culture for identification •Disrupt normal microbiota that help in keeping out pathogens •Narrow-spectrum antimicrobials affect limited range •Requires identification of pathogen, testing for sensitivity •Less disruptive to normal microbiota than the broad spectrum

skin provides tough, flexible outer covering

•But exposed state makes vulnerable to injuries •Cuts, punctures, burns, chemical injury, and insect or tick bites can break barrier, provide entry for pathogens. •Staphylococcus aureus can enter surgical wound, invade bloodstream •Skin infections can occur when pathogens are carried to skin by bloodstream following entry from another site

S. pyogenes virulence factors

•Capsule: Helps organism avoid phagocytosis •Streptolysins: Lyse blood cells •Enzymes that degrade •DNA (DNAses), fibrin (streptokinase), and connective tissue (hyaluronidase), making pus less viscous

extracellular immune avoidance

•Capsules coat bacterial cell walls and can prevent phagocytes from binding. •Cell-surface proteins are components of the cell wall that prevent detection. •Bind to Fc region on antibodies •Alter their antigens to avoid antibody binding •Quorum sensing used to communicate with other pathogens about population size.

septic shock

•Catastrophic drop in blood pressure due to severe sepsis •Superantigens or PAMPs

mumps

•Causative Agent •Mumps virus •Highly infectious, self-limiting infection •Parotid glands •Shed in saliva •Spread via sneezing and coughing •Causes massive swelling of parotid glands and can cause harm if swelling of testes occurs •Vaccination has eliminated most cases •Signs and Symptoms •Onset marked by fever, loss of appetite, headache •Followed by painful swelling of one or both salivary (parotid) glands •Spasm of underlying muscle makes talking, chewing hard •Symptoms can arise elsewhere in body (sign of more serious infection) -Headache, stiff neck indicative of meningitis •Humans only natural host •Was common in the U.S. prior to routine vaccination •Treatment and Prevention •No effective treatment, but attenuated vaccine available in U.S. since 1967 as part of measles, mumps, rubella, and varicella vaccine (MMRV)

diphtheria

•Causative agent - Corynebacterium diphtheriae •Gram-positive rod •Antibiotics and antitoxin are simultaneously used •Vaccine is inactivated diphtheria toxin ▪Diphtheria is deadly toxin-mediated disease •Rare in U.S. because of immunization, found elsewhere •Signs and Symptoms •Mild sore throat, slight fever, extreme fatigue, malaise •Swelling of neck, formation of pseudomembrane on tonsils and throat or in nasal cavity -Made of dead epithelial cells, clotted blood, fibrin and leukocytes that accumulate -Can come loose and suffocate patient •Heart and kidney failure and paralysis may occur •Pathogenesis results from potent diphtheria exotoxin •A-B exotoxin: "B" chain attaches to cell receptors; entire molecule taken up by endocytosis -Cells lacking receptor are unaffected •"A" chain catalyzes reaction that inactivates the ribosome -Protein synthesis stops, cell dies •Epidemiology: humans primary reservoir •Spread by air; acquired via inhalation or from fomites •Direct contact with someone who has cutaneous diphtheria (found on skin) with chronic ulcers can be a source •Treatment and Prevention: •injection of antiserum •Delaying treatment can be fatal •Antibiotics can clear C. diphtheriae, but toxins already absorbed are unaffected •Immunization very effective (why it is not a big problem in US) •Even with treatment, ~10% mortality

lime disease

•Causative agent: B. burgdorferi •Signs and Symptoms (three stages) 1.Early localized infection: migraines, or circular skin rash, follows few days, weeks after tick bite •Nearby lymph nodes enlarge •Flulike symptoms: chills, headache, muscle pains 2.Early disseminated infection: 2-8 weeks later, nervous system affected, electrical conduction in heart impaired -Dizzy spells, fainting result; paralysis of face, severe headache, 3.Late persistent infection: ~6 months after skin rash, joint pain, swelling appear; slowly disappear over years -Chronic nervous system impairments may occur •Pathogenesis - humans are accidental host (vector disease) •Spirochetes introduced into skin by bite of infected tick •Multiply, migrate outward in circular fashion; LPS causes inflammatory reaction in skin •Enter bloodstream, disseminate •Immune system responds •Disease progresses through the three stages •Treatment and Prevention •Antibiotics effective in patients during early stages •In late disease, antibiotics less effective •Avoiding exposure to ticks •No vaccine available

DiGeorge Syndrome

•Caused by mutations in several genes •Results in incomplete development or absence of thymus and parathyroid glands •Immunodeficiency includes T-cell deficiency and hypoparathyroidism •Treatment involves thymus transplant

nonpilus adhesins

•Cell wall associated proteins that bind to host proteins like integrin or fibroncectin

antibacterial medications target specific bacterial processes and structures

•Cell wall synthesis •Protein synthesis •Nucleic acid synthesis •Metabolic pathways •Cell membranes

delayed-type hypersensitivity in infectious diseases

•Cell-mediated immunity plays central role in combating intracellular microbial infections -Effector cytotoxic T cells destroy infected host cells -Prevents spread of infection, but also damages tissue; chronic infections yield extensive damage - -For example, damaged sensory nerves in leprosy •Contact Hypersensitivities (contact dermatitis) •Caused by effector T cells responding to small molecules that penetrate intact skin -Results in irritating rash, sometimes blisters

resistance to antimicrobials

•Certain bacteria have innate or intrinsic resistance •Type of resistance they are "born" with •Outer membrane of Gram-negatives blocks many medications •Bacteria may develop acquired resistance •Spontaneous mutations •Horizontal gene transfer

skin rash

•Change in color and texture of the skin •Exanthem: Widespread skin rash accompanied by systemic symptoms (fever, malaise, headache) •Enanthem: Rash on mucous membranes •These rashes are caused by an infectious agent •A reaction to toxin produced by •The organism •Damage to the skin by the organism •An immune response

antibiotics

•Chemical agents that target bacterial cells to inhibit growth or destroy the cell •Bacteriostatic drugs inhibit growth. •Bacteriocidal drugs are lethal. •Antibiotics are selectively toxic to bacteria without toxicity to other organisms. •"Magic bullet" concept •Antibiotics show a spectrum of activity. •Broad spectrum antibiotics are useful against a wide range of bacterial cell types. •Narrow spectrum antibiotics are useful against one or only a few types of bacterial cells.

respiratory infections

•Classified by whether they affect the upper or lower respiratory tract •Upper respiratory tract includes: •Upper airways (nasal passages) •Oral cavity •Pharynx •Larynx •Other structures that have direct or indirect communication with the upper airways include: •The passages to the sinuses •Lacrimal ducts •Inner ear

type 4 hypersensitivity

•Delayed-type hypersensitivity •24-48 hours •Triggered by antigen-specific T cells Example: Tuberculin skin test Site reddens, thickens = positive test •Attenuated strain of Mycobacterium bovis •Produced cell-mediated immunity •Memory T cells •Second exposure •Memory T cells activated •Elicit a localized reaction

polymixin

•Detergent action •Disrupts cell membranes

Antibacterial Medications That Inhibit Cell Wall Synthesis (Penicillins, Cephalosporins, other β-Lactam Drugs)

•Differ in activity •Peptidoglycan of Gram-positives exposed (more effective) •Outer membrane of Gram-negatives blocks (less effective) •The enzymes that synthesize peptidoglycan are different in Gram-positives vs. Gram-negatives

direct or indirect effects of an infection

•Direct (toxins produced) •Indirect (immune response) •Damage may help pathogen to exit and spread •Vibrio cholerae induces watery diarrhea, up to 20 liters/day, which contaminates water supplies •Bordetella pertussis triggers severe coughing, pathogens released into air

clinical considerations

•Drug concentration > Minimum inhibitory concentration (MIC) during treatment The tissue level of a drug over time (half-life) depends on how quickly the antibiotic is removed from the body via excretion by the kidney or destruction in the liver

hemmorrhagic fevers

•Ebola Virus Disease (EVD) and Marburg Virus Disease (MVD) •Signs and Symptoms •Causes severe, often fatal disease •Rapid onset of fever, headache, abdominal pain, joint and muscle pain, sore throat, macular rash, and bleeding •Virus causes capillary fragility and disrupts clotting; patients bleed from mucous membranes and body orifices; bloody vomit, diarrhea common •Causative Agents •Caused by Ebola virus, named after Ebola River Valley in Democratic Republic of the Congo •Named after Marburg where people got infection from green monkeys •Ebola Virus Disease and Marburg Virus Disease •Pathogenesis •Infect monuclear phagocytic cells (dendrites, macrophages) •Blood clotting is disrupted •Capillaries become leaky •Epidemiology •Prevention is difficult; natural reservoir is unknown •Ebola virus transmitted by contact with bodily fluids •Found in other animals including gorillas, chimpanzees; high mortality makes them unlikely reservoirs •Treatment and Prevention •Patients kept hydrated; blood O2 levels maintained •Plasma containing coagulation factors given •Vaccine is in use and over 95% effective

Endotoxin, Other Bacterial Cell Wall Components

•Endotoxin is lipid A (part of LPS) •Lipid A triggers inflammatory response »When localized, response helps clear infection »When systemic, causes widespread response: septic shock or endotoxic shock -Lipid A released following cell lysis -Activates innate and adaptive defenses -Heat-stable; autoclaving does not destroy

structure of skin

•Epidermis •Superficial •Five layers •Dead keratinocytes •Keratin •Dermis •Deep layer •Connective tissue •Cells •Blood vessels, nerves, hair follicles, sweat glands

transfusion reactions

•Erythrocytes (Red Blood CELL) have surface antigens • Major group is ABO, yields A, B, AB, or O blood types •Individuals have natural antibodies to the antigens they lack •Transfused Blood Cells are rapidly destroyed; debris can block vessels, start clotting; lead to kidney damage, fever, respiratory and digestive problems that may be life threatening

comparison of exotoxins and endotoxins

•Exotoxins from Gram-positives and Gram-negatives •Protein; potent; usually heat-inactivated •Endotoxins only from Gram-negatives •Lipid A component of LPS; small localized amounts yield appropriate response, but systemic distribution can be deadly; heat-stable

norovirus

•Fecal-oral route •Nonenveloped •Causes sudden onset of symptoms; can also cause fever, headache, and malaise •Outbreaks common on cruise ships

rotavirus

•Fecal-oral route •Nonenveloped •Enterotoxin that causes hypermotility of the intestinal tract •Vaccine prevents severe disease.

lower respiratory tract viral infections: respiratory syncytial virus (RSV) disease

•Fusion of adjacent infected cells into a syncytium, a giant cell containing many nuclei •Transmitted from person to person •Young, around age 2 •Infections occur when the virus comes into contact •With mucous membranes of the eyes •With mouth or nose •Through the inhalation of droplets from a sneeze or cough

complement deficiencies

•Genetic mutations •Can occur in either early complement components (C1-C4) or late complement components (C5-C9) •Patients are more susceptible to infections such as S. pneumoniae, S. pyogenes, H. influenzae, and N. meningitidis. •Treatment involves plasma. •Contains complement and antibiotics •Other aspects of humoral and cell-mediated immunity are intact.

anthrax toxin

•Has two A subunits called edema factor (EF) and lethal factor (LF) •The B subunit is called protective antigen (PA). •Edema factor causes fluid loss to extracellular spaces similar to Bordetella. •Lethal factor destroys regulatory cascades and cripples the immune response.

chickenpox

•Herpesviridae family •Varicella-Zoster virus (VZV) •Initial exposure = chickenpox •Virus remains latent in the dorsal root ganglia. •Re-emerges later in life in about 20% of patients, which causes shingles •Shingles occurs more frequently in older individuals. •Cell-mediated immunity decreases. •Inhalation of infected particles from skin lesions •Virus replicates in the nasopharynx and infects the regional lymph nodes, leading to viremia. •Second round of viral replication takes place in the liver and spleen. •Followed by a secondary viremia 14-16 days postinfection •VZV invades capillary endothelial cells in the deepest layer of the epidermis. •Produces fluid accumulation and vesicle formation •Signs and Symptoms •Most childhood cases mild, sometimes go unnoticed •Rash starts as small red spots and progresses to small blisters and lesions -Occur anywhere on body -Lesions appear at different times •Lesions are pruritic (itchy); scratching can lead to serious secondary infection by S. pyogenes or S. aureus •More severe in adults; about 20% develop pneumonia •Damages lungs, heart, liver, kidneys, and brain in immunocompromised individuals; death results in ~20% •Major threat to babies, with case-fatality rate up to 30% •Reactivation of latent virus later in life produces shingles •Causative Agent •Varicella-zoster virus (VZV) of herpesvirus family •Pathogenesis •Varicella enters via respiratory tract, establishes infection, travels to skin via bloodstream •Virus enters nerve, travels to ganglia near spine -Shingles coincides with decline in cell-mediated immunity •Epidemiology •Transmitted by respiratory secretions and skin lesions •Humans are only reservoir •Highly contagious; incubation period averages 2 weeks •Most cases in winter and spring months •Ability of virus to form latent infection allows persistence in population; can reappear from shingles, which occurs in about 1/3 of individuals Chickenpox Treatment •Treated with antihistamines, oatmeal baths, and calamine lotion •Goal is to reduce and control the intense itching and use acetaminophen to reduce pain and fever. •Acyclovir is used to treat shingles. •Used only for severe or complicated cases of chickenpox •Varicella vaccination •Routine childhood immunization schedule •Varicella vaccine is a live, attenuated form of VZV. •Persons 60 years and older should be vaccinated with the zoster vaccine to prevent shingles.

whooping cough

•Highly contagious but preventable via vaccination •Gram-negative bacillus Bordetella pertussis •Acquired by inhalation of aerosolized droplets coughed by someone with the illness •Incubation period of 7-21 days. The disease progresses through •Catarrhal: symptoms of upper respiratory infection •Paroxysmal: a violent paroxysmal (rapidly repeated) cough, followed by a struggling deep breath that makes a whooping noise •Convalescent: paroxysms gradually disappear during the next 2-3 weeks as patient recovers

type 3 hypersensitivity

•Immune complex disease •Takes hours or days to develop •IgG antibody binding to soluble antigen forms an immune complex. •Immune complexes circulate in bloodstream. •Embed in vessel walls •Kidneys and joints •Bind complement •Polymorphonuclear leukocytes (PMNs) •Release proteases •Reactive oxygen species •Damage host cells •Inflammation

adverse (bad) effects of antimicrobials

•Include allergic reactions and toxic effects •Suppression of normal microbiota may allow dysbiosis (for example, Clostridium difficile increase) •Important to remember that antimicrobials save countless lives when properly prescribed and used

the upper digestive system

•Includes mouth, salivary glands, esophagus, stomach •The Mouth and Salivary Glands •Teeth protected by enamel •Proteinaceous material from saliva adheres, creates thin film (pellicle) -Bacteria attach, create biofilm called dental plaque •The Mouth and Salivary Glands •Damage to enamel allows microorganisms to enter tooth, cause decay or dental caries •Microbes can accumulate in gingival crevice •Gums become inflamed in response: gingivitis •Gums may recede from tooth root, allow bacteria access •The Esophagus •Mucus and saliva containing secretory IgA bathes lining -Microbial population relatively sparse (because of above) •Connects mouth to stomach; peristalsis pushes food •The Stomach •Most bacterial cells cannot survive, so normal empty stomach has few (because it is highly acidic)

bronchitis

•Inflammation of the bronchi •Acute and self-limiting •Multiple viral and bacterial etiologies •Productive cough is generally the only presenting symptom.

Platensimycin

•Inhibits fatty acid synthesis for facts in bacterial cell membrane •One of 4 entirely new (not just altering the old)antibiotics in last four decades

active immunization

•Injecting antigen •Stimulating immune system •Antigen-specific antibodies and T cells made

Aminoglycosides

•Irreversibly bind to 30S ribosomal subunit, causing it to distort and malfunction -Blocks initiation of translation -Causes misreading of mRNA by ribosomes past initiation

Legionellosis (Legionnaire's Disease)

•Legionella pneumophila •Aerobic, Gram-negative bacterium •L. pneumophila contaminates various water sources, ranging from lakes to the hot-water and air-conditioning distribution systems of large buildings. •Transmission via inhalation of contaminated water droplets •Intracellular pathogen •After phagocytosis, the bacterium prevents the fusion of the phagosome with the lysosome. •Epidemiology: found in natural waters, water systems •Aerosls from central air-conditioning systems, nebulizers, sprays to freshen produce, showers and water faucets, even car windshield sprays lacking detergent have spread •No direct person-to-person •Treatment and Prevention: (Antibiotics) •High doses of erythromycin and/or rifampin

hemolysin

•Lyses RBCs •These streptococci are subclassified into groups A-O according to cell wall antigens.

transplant rejection

•MHC recognition is an important part of self-recognition. •When transplanted tissue has a different MHC, rejection can occur.

imagine a world without antimicrobial medications

•Prognosis for people with common diseases (for example bacterial pneumonia, severe staphylococcal infections) was grim before availability of penicillin in 1940s •Physicians could identify cause, but only treatment was usually bedrest. •Misuse coupled with evolution of microbial resistance threatens these medications

passive immunization

•Protective antibodies are administered •Injection of immune globulin •Antitoxins •Breastfeeding

tuberculosis

•Mycobacterium tuberculosis •Multidrug resistant (MDR) tuberculosis •Produces rapid onset (fulminant) and fatal disease among patients with HIV •Highly infectious even to healthy people without HIV •Spread from person to person (no animal reservoir) •Aerosolizing of respiratory secretions Tuberculosis Pathogenesis •Bacteria enter lung, are phagocytized by macrophages, and survive sheltered within modified phagolysosomes. •A delayed-type hypersensitivity reaction develops. •Small, hard tubercules (granulomas) form around the site of the infection. •Tubercules develop into caseous lesions that have a cheese-like consistency and can calcify into hardened Ghon complexes seen on X-rays. •A. shows a cavity see via an X-ray •B. tuberculosis cavity in the lung (tissue examination)

tooth decay

•Normal flora include: •Streptococcus •Lactobacillus •Peptostreptococcus •Veillonella •Diphtheroid species •Dental plaque begins as biofilm. •Bacteria undergo metabolism. •Produce acids •Dental caries = tooth decay •Signs and Symptoms •Usually advanced before symptoms develop •Discoloration, roughness, defect; tooth may break •Severe throbbing pain of toothache usually first sign •Causative Agent •Streptococcus mutans; in body they live only on teeth -Thrive in acidic environments -Produce lactic acid from fermentation •Pathogenesis •Streptococci adhere to tooth, create plaque •Split sucrose into glucose and fructose; polymerize glucose into glucans and ferment fructose to lactic acid -Lactic acid lowers pH; glucans create thicker biofilm (allows the bacteria to stick together) •Epidemiology •Worldwide distribution; sucrose consumption, access to preventative dental care, genetics important factors •In the U.S., ~60% of teenagers have tooth decay •Treatment and Prevention •Drilling out cavity and replacing with filling •Restricting dietary sucros •Fluoridation in U.S. has reduced dental caries by 60% •Brushing, flossing

upper respiratory tract

•Nose and nasal cavity, pharynx (throat), and epiglottis •Lined mucous membranes •Traps air-borne dust and particles including microbes •Mucociliary escalator (elevator) propels mucus, trapped particles out of respiratory tract •Normally keeps lower respiratory tract free of microbes •Tonsils are secondary lymphoid organs, come into contact with microbes entering upper respiratory tract •Important in immune response

streptococcus pneumoniae

•Occurs mostly among the elderly, smokers, and immunocompromised individuals (such as diabetics and alcoholics) •There are 91 serotypes of S. pneumoniae that frequently colonize our airways. •Humans are the only natural reservoir.

Smallpox (Variola)

•Only known reservoir is humans •Eradicated from population in 1979 •Virus is divided into two variants •The variants are very similar to each other and to another virus called the vaccinia virus (cowpox). •Was used to make a vaccine against smallpox •Killed 10% of world population at one time •Smallpox was a devastating disease. On average, 3 out of every 10 people who got it died. Those who survived were usually left with scars, which were sometimes severe. •The last reported U.S. case came in 1949. Spurred by two new technological advances and the World Health Organization then launched a global immunization campaign in 1967 with the goal of wiping out smallpox once and for all. That year, there were 10 million to 15 million cases of smallpox and 2 million deaths, according to WHO estimates •Transmitted by direct or indirect contact •Happens when a person inhales small aerosolized particles or handles fomites containing the virus •Virus replicates in the lymph nodes and lymphoid organs; through two sequential viremias, infects internal organs and bone marrow, showing up as •Small spots on the oral mucosa (enanthem) •The pox pustule on the skin (exanthem) Treatment/ Prevention •Diagnosis can be made based on viral cultures and serology •No FDA approved treatments for smallpox •We no longer vaccinate against smallpox. •Government officials have stockpiled vaccine in strategic centers all across the United States. •2 labs have stocks of this virus •one in US and one in Russia

endotoxin

•Part of the outer membrane of the Gram-negative cell wall that includes lipopolysaccharide •Fever, activation of clotting factors, activation of complement, vasodilation, shock, and death may result when endotoxin is released into the blood.

intracellular pathogens

•Pathogens that seek refuge inside a host cell •They are not detected by many components of the immune system when inside the host cell. •Facultative intracellular pathogens can invade host cells but can also survive outside the host cell. •Ex: Salmonella, Shigella, Listeria •Obligate intracellular pathogens invade and reproduce inside of a host cell only. •Ex: Rickettsia, Coxiella, Bartonella ▪Hiding Within a Host Cell •Allows avoidance of complement proteins, phagocytes, and antibodies •Bacteria wanting to "hide" in a cell must: 1.Avoid destruction when lysosome fuses with vesicle or 2.Breakout before fusing with lysosome or 3.Prevent fusing with lysosome. Hiding Within a Host Cell After avoiding destruction bacteria can: 1.Move from 1 cell to the next cell without by passing thru the membrane (FATE 3) or 2.Move out of cell within the vesicle and exit the vesicle into the extracellular space 3.Once in the extracellular space bacteria can encounter and survive in macrophages and then spread though out body.

streptococcal sequelae: after the strep throat

•Pathological conditions result after a primary disease has run its course. •Sequelae from streptococcal infections •Caused by the immune response to the bacteria •Antibodies cross-react with host cells in an autoimmune reaction, resulting in serious sequelae. Post-streptococcal sequelae include: •Rheumatic fever (a cardiac disease) - Carditis develops and can lead to chronic rheumatic heart disease •Young children, 4-9 years of age •High fever •Damage to heart, joints, skin, or nervous system •Cross reactive antibodies, T cells, and complement •Glomerulonephritis (a kidney disease) - inflammation of kidneys

bacterial infections of the heart

•Pericarditis: Infection of the sac surrounding the heart •Myocarditis: Infection of the heart •Endocarditis: Inflammation of the inner layer of the heart •Symptoms can be vague and intermittent • •Subacute bacterial endocarditis (SBE) •S. mutans • •Acute bacterial endocarditis (ABE) •S. aureus

examples of virulence factors

•Pili •Enzymes that harm the host or prevent detection •Proteins that disrupt normal cellular function •Capsule •Enzymes that inactivate antibiotics

Avoiding Immune Responses Regulating Host Cell Death

•Prevent or delay apoptosis •Block MHC class I presentation •Present "fake" MHC class I molecules

plague (black death)

•Signs and Symptoms 1.Following flea bite, symptoms appear within 2-6 days -Enlarged and tender lymph nodes buboes; bubonic plague -High fever, shock, delirium, patchy bleeding under skin 2.Following inhalation of respiratory droplets from infected patient or animal, pneumonic plague may develop -Cough, bloody sputum arise within 1-3 days 3.If spread by bloodstream, septicemic plague may develop -Endotoxin released causes shock -Bleeding into skin and organs, produces red or black patchy rash •Causative Agent •Yersinia pestis •Certain dyes stain ends more intensely; safety pin appearance pathogenesis Forms biofilms in digestive tract of infected fleas, blocks it -fleas starve, increasing likelihood of feeding -causes bacteria to be regurgitated into bite wound •Infected macrophages die, release bacteria •Lymph nodes become necrotic -Dark hemorrhages and dusky skin, mucous membranes probably inspired name "black death" -10-20% infect lungs, leading to pneumonic plague •Epidemiology •Endemic in rodent populations worldwide except Australia •In U.S., mostly occurs in about 15 states in the West -Prairie dogs, rock squirrels, their fleas main reservoir »Rats, rabbits, dogs, cats can also be hosts •Treatment and Prevention •Antimicrobial medications especially if given within 24 hours of onset symptoms •Rat control measures (garbage disposal, rat-proofing buildings, rat extermination programs) important •Bubonic plague has ~50-80% mortality without treatment •Pneumonic plague has ~100% mortality if untreated •No current vaccine, but new genetically engineered vaccines being evaluated u

Escherichia coli Gastroenteritis

•Signs and Symptoms •Depend on strain; some cause watery diarrhea, others dysentery •Causative Agent •Escherichia coli: Gram-negative rod •Pathogenesis •Strains based on their virulence factors Enterotoxigenic E. coli (ETEC) •Causes secretory, watery diarrhea •No animal reservoirs Enteroinvasive E. coli (EIEC) •Causes bloody diarrhea similar to that caused by Shigella Enterohemorrhagic E. coli (EHEC) •Shiga toxin •Causes bloody diarrhea In severe cases EHEC can lead to hemolytic uremia syndrome and thrombocytopenic purpura •Epidemiology •Based on symptoms and pathogenesis of infecting strain -Example: STEC strains foodborne; epidemics have involved ground beef, unpasteurized milk, apple juice, green leafy vegetables; initial source often untreated cow manure •Treatment and Prevention •Most cases self-limiting, so antibiotics not routinely used -Worsen outcome in patients with STEC infections •Replacement of lost fluid important •Handwashing, pasteurization of drinks, cooking of food

subacute bacterial endocarditis (SBE)

•Signs and Symptoms •Noticeable fatigue, slight fever •Typically become gradually ill and slowly lose energy over weeks or months; may suddenly develop a stroke • •Causative Agent •Usually normal microbiota of mouth or skin such as Streptococcus viridans and Staphylococcus epidermidis •Pathogenesis •Bacteria enter blood during dental procedures, tooth brushing, or trauma; can get trapped in thin blood clots that form around deformed heart valves -Multiply, form protective biofilm -Pieces of infected clot can break off, block important blood vessels, lead to tissue death •Treatment and Prevention •Long term antibacterial medications •Artificial implants often must be replaced •No methods to prevent

sepsis and septic shock

•Signs and Symptoms •Severe sepsis results in violent shaking, chills, fever -Often rapid breathing, anxiety •If septic shock develops, urine output drops, respiration and pulse increase, arms and legs become cool •Causative Agents •Systemic infection by any microorganism can cause •Most fatal cases involve Gram-negatives due to endotoxin •Pathogenesis •Almost always from infection site other than bloodstream (infection set up somewhere else and spread to bloodstream) •Lung, urinary tract, meninges, surgical wounds •Pathogenesis •Bodies response to microbes can yield devastating outcomes -Activation of coagulation cascade causes small clots to form in capillaries; blockage leads to hypoxia, necrosis -Widespread clotting; may lead to multiorgan failure •Treatment and Prevention •Antimicrobial medications to clear causative organisms -Bacteriocidal antibiotics often lyse cells, increase risk of endotoxin from Gram-negative organisms •Sepsis prevented by quick identification, treatment -Identifying localized infection before it becomes worse •Treatment of predisposing conditions

general characteristics of all lower digestive infections

•Signs and Symptoms (lower digestive system infections) •Diarrhea, loss of appetite, nausea and vomiting; fever •Incubation period is a day or two but varies with dose •Infection of small intestine: copious watery diarrhea •Infection of large intestine: smaller amounts containing mucus, pus, sometimes blood -Dysentery refers to illnesses with blood, pus in feces •Termed gastroenteritis or "stomach flu" • •Causative Agents •Enterobacteriaceae: Shigella, Salmonella, E. coli; also Vibrio cholerae, Campylobacter jejuni, Clostridium difficile •Pathogenesis •Different approaches; strains within species can differ, and individual strain may use multiple mechanisms •Attachment often prerequisite, typically adhesins on pili •Additional mechanisms are toxin production, alterations in epithelial cells •Epidemiology •Transmission via fecal-oral route commonly from food or water contaminated with animal or human feces •Intestinal pathogens sensitive to acid usually have high infecting dose, since most are destroyed by acid -Generally transmitted by contaminated foods, water •Acid-resistant pathogens have low infecting dose -Transmitted through direct contact or foods, water ▪Treatment and Prevention •Oral rehydration therapy (ORT) used to counteract loss of fluid and electrolytes from diarrhea -Water alone insufficient; cannot be absorbed quickly -Glucose increases absorptive capacity of intestine -Oral rehydration salts (ORS) is glucose plus sodium chloride, potassium chloride, trisodium citrate •Sewage treatment, handwashing, chlorinating drinking water important control measures •Antibacterial medications usually not helpful, may prolong •A few pathogen-specific vaccines; limited effectiveness

lower digestive tract

•Small and large intestines, pancreas, liver •The Small Intestine -As stomach contents enter, pancreas and liver add alkaline digestive fluids that neutralize acid -Villi, microvilli increase surface area to about 250 m2 »Major role in nutrient and fluid absorption: ~9 liters/day •The Large Intestine •Main function is to absorb water, vitamins •Bacteria make up about one-third of fecal weight •Within the large intestine: -Bacteria degrade wide variety of foods including substances (for example, fibers) indigestible by stomach, small intestines -Bacteria important to human health: synthesize niacin, thiamine, riboflavin, pyridoxine, vitamin B12, folic acid, pantothenic acid, biotin, vitamin K -Bacteria prevent pathogens from colonizing; stimulate mucosal immunity; opportunistic pathogens

staphylococcal skin infections

•Staphylococci associated with skin infections include •Staphylococcus epidermidis •Staphylococcus aureus •Normal inhabitant of the nares (nose) •Can infect a cut and gain access to the dermis via a hair follicle •S. aureus possesses enzymes that contribute to disease. •Coagulase coats the bacteria with fibrin and walls off the infection from the immune system and antibiotics, promoting abscess formation. •Staph infections routinely require surgical drainage and antibiotic therapy. •Exotoxins damage host tissue and weaken host defenses. •S. aureus infection of hair follicles can be superficial or deep resulting in: •Folliculitis (superficial) •Boil or furuncle (deep) •Carbuncles are boils joined together •Methicillin-resistant S. aureus (MRSA) •Strain that has emerged over the past decade •Resistant to the antibiotic methicillin •Interfering with cell wall synthesis •S. aureus strains (~60%) have now evolved to resist methicillin. •Vancomycin is the treatment of choice. •First appeared as nosocomial infections •Today, MRSA is no longer confined to the hospital. •Individuals who have not been in a hospital are being infected with MRSA in what are being called "community acquired infections" at an epidemic rate in the U.S.

Staphylococcal Food Poisoning

•Staphylococcus aureus •Gram-positive, cocci •Causes Intoxication (caused by toxins) •Symptoms are seen within 2‒6 hours upon ingestion •Toxin is heat stable

systemic infection

•Starts in one part of the body and then spreads to other sites ▪Supplies nutrients and O2 to cells, removes waste •Also heats, cools to maintain optimum temperature •Infections can be serious, since infectious agents can become systemic, or carried throughout body •Conditions named after infectious agent •Bacteremia, viremia, and fungemia -person can become transiently bacteremic after brushing teeth

type 1 pili

•Static, hairlike appendages used only for attachment

Steptococcal skin infections

•Streptococcus pyogenes •The human nasopharynx and parts of the skin are the natural reservoir for S. pyogenes •Necrotizing fasciitis, also known as flesh-eating disease •Therapy includes antibiotics. •The incidence of necrotizing fasciitis has risen recently due to an increase in the use of NSAIDs, which accentuate a person's susceptibility to infection by S. pyogenes.

Group A Streptococcal "Flesh-Eating Disease"

•Streptococcus pyogenes commonly infects wounds •Generally easy to treat: susceptible to penicillin •Occasionally, severe infections can progress rapidly •Invasive, spread into tissues and organs, cause pneumonia, meningitis, puerperal fever, necrotizing fasciitis (flesh-eating disease), streptococcal shock •Signs and Symptoms •Appear suddenly, are very serious •Severe pain at wound site •Swelling stretches, discolors skin •Fever develop •Without treatment, shock and death usually follow shortly •Epidemiology •Cases in U.S. generally sporadic -Less than 2% of deaths from S. pyogenes infections are due to necrotizing fasciitis (death of tissue/inflammation of the tissue under the skin that surrounds muscles, nerves, fat, and blood vessels "fascia") •Risk factors include diabetes, cancer, alcoholism, AIDS, recent surgery, chickenpox, injected-drug abuse; invasive infections rare in healthy individuals •Treatment and Prevention •Toxins spread so rapidly that immediate surgery often essential to remove dead tissue and reduce pressure •Penicillin effective early in infection but ineffective against streptococci in necrotic tissue; no impact on toxins

actions of bacterial exotoxins

•Superantigens are cell surface antigens that trigger systemic responses. •S. aureus TSST-1 toxin and exfoliative toxin •B. anthracis lethal toxin

outermost layers bathed in secretions

•Sweat delivered via fine tubules from sweat glands; evaporates, leaves salty residue that inhibits microbes •Normal microbiota adapted to dry, salty, cool habitat •Use substances in sweat, sebum as nutrients •Too dry, salty, acidic, and toxic for most pathogens -Those that tolerate often shed with dead skin cells •Normal microbiota can be troublesome (opportunistic)

Antibacterial Medications That Inhibit Nucleic Acid Synthesis

•The Fluoroquinolones inhibit topoisomerases •Topoisomerases are enzymes that maintain supercoiling of DNA -KEEP DNA FUNCTIONAL •Bactericidal against wide variety of bacteria

common cold

•The most frequent viral infection of the upper respiratory tract •200 viral subtypes •Rhinoviruses •The most common cause of colds •Other prominent players include: •Coronaviruses •Influenza •Parainfluenza •Respiratory syncytial virus •Pathogenesis of Rhinoviruses •Attach to receptors on respiratory epithelial cells, infect •Ciliary motion of infected cells stops; cells may die •Damage leads to release of cytokines, inflammation •Inflammation leads to increased nasal secretions, tissue swelling, sneezing •Infection can spread to ears, sinuses, lower respiratory tract epidemiology •Humans only source; spread by close contact •Airborne droplets inhaled; Direct contact then touching eyes, nose •Transmission much more likely during first 2-3 days of infection when virus concentrations in nasal secretions high •Only need a few virions to infect •No relationship between exposure to low temperatures and development of colds; emotional stress can double risk •Treatment and Prevention •No proven treatments only can reduces symptoms •Viruses not affected by antibiotics, antibacterial medications •Prevention of spread effective: handwashing, avoiding touching face, avoiding crowded places and infected individuals in first few days of symptoms •No vaccine due to large number of different viruses •Analgesics, antipyretics can reduce symptoms but may prolong symptoms and duration

salmonellosis

•Two major diseases are typhoid fever and enterocolitis. • •Typhoid fever •No animal reservoir •Associated with food preparation •Intermittent fevers and diarrhea for 1‒3 weeks • •Enterocolitis •Associated with animal contact •Short-term illness lasts 6‒48 hours

four types of hypersensitive reactions

•Type 1: Immediate, antibody mediated •Type 2: Cell surface antigens, antibody mediated •Type 3: Soluble antigens, antibody mediated •Type 4: Delayed, cell mediated

diabetes

•Type I occurs in childhood when T cells attack the islet cells of the pancreas.

type 2 versus type 3 hypersensitivity

•Type II hypersensitivity occurs when antibody binds to antigen on a cell surface. •Type III hypersensitivity occurs when antibody binds to soluble antigen.

measels (rubeola)

•Very contagious (8‒10 day incubation period) •Portal of entry is respiratory or conjunctiva •Replicates in the lungs •Moves to regional lymph nodes •Produces a viremia that spreads throughout the body •Prodromal period starts with cold/flu-like symptoms. •High fever (40°C/104°F) •Koplik's spots •White spots on the buccal mucosa •On inner cheeks •Immunocompromised patients can develop serious complications •Death •Blindness (ulceration of the cornea) •Myocarditis or pericarditis •Variety of GI maladies •Serious complications include •Acute disseminated encephalomyelitis (ADEM) •A delayed complication called subacute sclerosing panencephalitis (SSPE) •Signs and Symptoms •Fever, runny nose, cough, and swollen, red, weepy eyes •Fine red rash appears within a few days, lasts ~1 week •Often secondary infections lead to earaches, bacterial pneumonia •Measles increases risk of miscarriage, premature labor, low birth weight •Causative Agent •Rubeola virus •Pathogenesis •Acquired via respiratory route; spreads to lymphatic tissues, eventually all parts of body •Rash results from cell-mediated immune response in skin •Koplik spots of mucous membranes identifying feature •1/1,000 cases fatal in U.S. and can be as high as 10% if healthcare is inadequate •Epidemiology •Humans only natural host of rubeola virus •Prior to vaccination, probably less than 1% of global population escaped infection since so contagious •No longer endemic in Western Hemisphere -Worldwide, ~160,000 people die from measles (2011) •Treatment and prevention •No antiviral, but attenuated vaccine can prevent (1960s) •Incidence in the U.S. is on the rise: cases on the rise as some parents refuse to vaccinate their children •In 1980, worldwide incidence ~100 million with 5.8 million deaths; vaccination programs have dramatically lowered

binding to host cells and invasion

•Viruses attach to target cells via specific receptors

B-Cell Disorders

•X-linked agammaglobulinemia (Bruton's disease) •Mutations in Bruton tyrosine kinase (Btk) gene on X chromosome •Lack of B-cell development and maturation •No or little immunoglobulin is made •Any of a class of proteins present in the serum and cells of the immune system, which function as antibodies •Recurrent pyogenic lung, sinus, and skin infections •Treatment includes IVIG and antibiotics.

herd immunity

•develops when critical portion of population is immune to disease; infectious agent unable to spread due to insufficient susceptible hosts •Responsible for dramatic declines in childhood diseases -Diseases sometimes reappear and spread as result of failure to vaccinate children •Effective vaccines should be safe, have few side effects -Give long lasting protection -Ideally low in cost, stable, easy to administer •Only possible for diseases that are contagious and transmitted between humans •Estimates are three-fourths of a population or more must be immunized to reduce disease through herd immunity. •This varies with each pathogen.

antagonistic drugs

•drugs interfere with each other and decrease effectiveness. Ex: penicillin + macrolides

synergistic drugs

•have greater effectiveness when used together (combined effect is greater than additive effect). Ex: aminoglycoside + vancomycin

immunization

•is process of inducing immunity o has probably has greatest impact on human health of any medical procedures

gramicidin

•protein that forms a channel in the membrane

Streptococcal pyogenic exotoxins (SPEs):

•superantigens; massive amounts of cytokines released in response to SPEs can produce high levels of inflammation and lead to shock. •SPEs are associated with scarlet fever, streptococcal toxic shock syndrome, and necrotizing fasciitis.

Bacterial infections of lower respiratory system

▪ less common, usually stopped by immune defenses •Generally much more serious, however •Pneumonias: inflammatory diseases of the lung •Top the list of fatal community-acquired infections (in the general population) in the U.S.; common healthcare-associated infections •Whooping cough, tuberculosis, Legionnaires' disease also serious infections of the lungs

special case of delayed-type cell-mediated hypersensitivity is

▪ the rejection of transplant tissue (Type IV Hypersensitivities) •Most human transplants are allografts, which are tissues of donor and recipient are not genetically identical •Autografts (from elsewhere in body) and isografts (from identical sibling) avoid these problems (tissue rejection) •Xenografts (from animals) evoke vigorous response •Effector cytotoxic T cells, natural killer cells reject tissue •Minimized by matching donor and recipient, also indefinite use of immunosuppressive drugs -But increases susceptibility to infections and cancer

transmission of SARS-CoV-2

▪Coronaviruses can be transmitted through direct and indirect contact. ▪Coronaviruses are most commonly transmitted through airborne transmission. ▪Researchers have data to suggest that droplets can linger indoors for 2-4 hours but are inactivated by sunlight in 8-20 minutes. ▪On surfaces left in a chamber, the virus can be found up to 3 days later. •Proper cleaning of surfaces kills the virus. •UV light can also destroy the virus.

Pathogenesis of Streptococcus pyogenes

▪Enzymes (Dnase degrade DNA, and hyaluronidase/proteases degrade intracellular connections) degrade your cellular components and breaks blood clots (streptokinase) ▪Epidemiology of Streptococcus pyogenes •Naturally only infects humans •Spread by direct contact with infected person or respiratory droplets or contaminated food •Nasal carriers more likely to spread than pharyngeal •Individuals can be asymptomatic carriers for weeks ▪Treatment and Prevention •Confirmation via diagnostic tests (Rapid strep test) and throat culture •Treatment with antibiotics; prevents post-streptococcal sequelae

How SARS-CoV-2 Infection Causes Harm in the Human Body

▪How does SARS-CoV-2 enter the body? •Coronaviruses enter the body through the respiratory tract. •Once coronavirus enters, the virus infects the cells lining the respiratory tract. •The virus can also infect heart cells, kidney cells, and small intestine cells. ▪How does SARS-CoV-2 cause harm to the human body? •Viruses lyse (destroy) the host cell that they infect. ―Causes damage to blood vessels, lung tissue, and heart muscles due to viral binding of ACE2 receptor on these cell types •Our immune system recognizes the virus and causes inflammation. •Recruitment of immune system cells •Production of pro-inflammatory cytokines (chemical signals) •Increased production of mucus to help remove the pathogen

type 1 hypersensitivities: immediate

▪Localized Allergic Reactions •Hives: skin condition characterized by wheal (swelling) and flare (redness) •Seen in positive skin test for allergens •Blocked by antihistamines •Hay fever: itching, teary eyes, sneezing, runny nose following inhalation of airborne antigen •Blocked by antihistamines •Asthma: respiratory allergy •Inflammatory mediators cause spasms of bronchial tubes, and mucus production •Antihistamines not effective

type 1 hypersensitivities: immediate

▪Occurs within 24 hours, often within minutes ▪IgE antibody binds to mast cells or basophils ▪IgE functions as captured antigen receptors, allows mast cells and basophils to detect invaders ▪IgE is specific to a foreign particle (allergen) ▪Binding triggers release of inflammatory mediators »Inhaled substances such as pollen, pet dander, mold »Ingested substances such as peanuts, milk, seafood »Injected substances such as insect venom or drugs •Tendency to have type I reactions inherited •Specific allergen is due to environmental exposure ▪Systemic Anaphylaxis •Rare but serious form of IgE-mediated allergy •Antigen enters bloodstream, spreads throughout body •Extensive blood vessel dilation results in fluid loss, severe drop in blood pressure -Can lead to heart failure, insufficient blood flow to brain and other vital organs: anaphylactic shock -Bronchial tubes constrict, can cause suffocation •Examples: Bee stings, peanuts, penicillin injections account for most cases •HOW TO CONTROL SYSTEMIC ANAPHLAXIS •Can usually be controlled by injection of epinephrine -Epi-pen

bacterial pathogens entry

▪Penetrating the Skin •Difficult barrier to penetrate; bacteria rely on injuries •Staphylococcus aureus enters via cut or wound; Yersinia pestis is injected by fleas ▪Penetrating Mucous Membranes ▪Entry point for most pathogens ▪Directed uptake by cells ▪Pathogen induces cells to engulf via endocytosis

Importance of Childhood Immunizations

▪Prior to vaccinations, numerous deaths, disabilities •Many still become ill or die from preventable diseases •Vaccines victims of their own success, have lulled people into false sense of security; risk of vaccine seems greater than risk of diseases

lower respiratory tract viral infections

▪RNA viruses of greater importance than DNA •Infect more individuals, potential for serious outcomes •Influenza (Flu) infects ~20% of humans annually •Signs and Symptoms: ~2 day incubation period -Headache, fever, sore throat, muscle pain; peaks in 6-12 hours; dry cough develops and worsens over a few days -Acute symptoms last ~1 week; lingering cough, fatigue, weakness last additional days or weeks

type 2 hypersensitivities: cytotoxic

▪Response destroys cells: cytotoxic hypersensitivity ▪Antibodies react with molecules on cell surface •Antibody binding/reacting with cell surface trigger destruction of cells (via two ways) 1.Activate classical pathway of complement system, lead to lysis via membrane attack complexes (MACs) 2.Trigger antibody-dependent cellular cytotoxicity (ADCC), lead natural killer (NK) cells to binding antibodies that are bound to a target cell and deliver chemicals to destroy cell •Examples include transfusion reactions and hemolytic disease of the newborn, some autoimmune diseases •ABO blood typing •Rh incompatibility • •Four major groups are A, B, AB, and O •Incompatibility occurs •Specific antibodies in serum bind to antigen on foreign red blood cells (RBCs) Incompatibility example: •Individual with B blood type •Carries anti-A antibodies •Anti-A antibodies attack transfused RBCs with A antigen •Cell lysis •Complement activation

passive immunity

▪antibodies from other source •Natural: during pregnancy, mother's IgG antibodies cross placenta; breast milk contains secretory IgA •No memory; protection is lost once antibodies degrade •Artificial: injection of antiserum (contains antibodies) •Can prevent disease before or after likely exposure •Limit duration of certain diseases

active immunity

▪follows antigen exposure •Natural (infection) or artificial (immunization)

vaccine

▪is preparation of pathogen or its products •Used to induce active immunity •Protect individual; prevent spread in population

exotoxins

▪proteins with specific damaging effects •Secreted or leak into tissue following bacterial lysis •Foodborne intoxication results from consumption •Destroyed by heating; most exotoxins heat-sensitive •Can act locally or systemically •If the exotoxins are proteins, immune system can generate antibodies • •Many fatal before immune response •Exotoxins that are Membrane-Damaging Toxins •Cytotoxins that disrupt plasma membranes, lyse cells •Hemolysins lyse red blood cells

attenuated vaccines

▪weakened form of pathogen •Replicates in recipient; disease undetectable or mild •Advantages: single dose usually induces long-lasting immunity due to microbe multiplying in body •Can also inadvertently immunize others by spreading •Disadvantages: can sometimes cause disease in immunosuppressed individuals •Can occasionally revert or mutate, become pathogenic •Measles, mumps, rubella, chickenpox, yellow fever, rotavirus, nasal flu vaccine are examples