Microbiology Final

• Indigenous or resident biota
• The large and mixed collection of microbes adapted to the body
• The native microbial forms that an individual harbors
• Includes bacteria, fungi, protozoa, some viruses and arthropods

Microbes that attempt to colonize the body but are rapidly lost

• Microbes capable of causing disease in a healthy person with normal immune defenses
• Generally associated with a specific, recognizable disease

• Cause disease when the host's defenses are compromised or when they become established in a part of the body that is not normal for them
• Not pathogenic to a healthy person
• Usually do not possess well-established virulence properties

• Locations in areas near and continuous with the outside of our bodies
• Upper respiratory tract (oral & nasal cavities)
• Skin and mucous membranes
• GI tract
• Outer openings of the urethra
• External genitalia
• Vagina, External ear canal
• External eye (lids, conjunctiva)

• Skin: organisms must be able to survive dry conditions, wide temperature range, salty, lower pH, available nutrients
• Oral cavity: survive mechanical actions of tongue/teeth, biochemical secretions of saliva
• Intestinal tract: withstand mechanical motility, presence of bile, anaerobic conditions
• Upper respiratory tract: be able to attach and not be carried away by mucociliary system, secretions of defensins
• Urogenital tract: attach to withstand flushing action of urine, lower pH

• Mouth population changes when teeth erupt (new sites for anaerobic organisms)
• Intestinal tract changes from Bifidobacterium to others with introduction to solid foods
• Vagina changes with change in pH at puberty

• Removing space and nutrients from harmful microbes
• Prevent overgrowth
• Development of our organs

When a microbe invades a location and becomes established or implanted

A condition in which pathogenic microorganisms penetrate the host defenses, enter the tissues and multiply.

A deviation from health, the pathologic state that results from the cumulative effects of the infection, damage or disrupt tissues and organs

Infections caused by biota already present in the body (normal biota or a previously silent infection)

• Portal of entry: how a microbe enters the tissues of the body, usually a cutaneous or membranous boundary, usually the same anatomical regions that also support normal biota
• Attaching to host: adhesion, how microbes gain a more stable foothold on host tissues, binding between specific molecules on host and pathogen, limits what a particular pathogen can bind to
• Surviving host defenses: antiphagocytic factors, killing phagocytes outright, secreting extracellular surface layer (slime/capsule), surviving inside phagocytes
• Cause disease: virulence factors, damage through exoenzymes/toxins or indirectly when their presence causes excessive/inappropriate host responses, spreading/multiplication
• Portal of exit: how pathogens depart the host, in most cases shed/released through secretion, excretion, discharge or sloughed tissues, in most cases is the same as portal of entry

• ID is the number of microbes it takes to produce an infection
• The more virulent the organism the lower the ID

Develops rapidly, severe but short lived

Develops slowly, progresses and persists over a period of time

Organism remains in one location

Organism in several locations, usually via bloodstream infection

Organism starts localized and then spreads systematically from that location

The first infection, from pathogenic cause

Infection by a second organism occurring later due to an aspect of the first infection, such as a bacterial infection following a viral infection

One that can be spread from an infected host to another host where it can now establish an infection

disease that does not arise through transmission of the infectious agent from host to host, infection and disease are acquired through other circumstances

The number of new cases per susceptible persons at X time (must define time), also called case or morbidity rate

The total number of cases of a given disease per total in the population

Any objective evidence of a disease as noted by an observer (more reliable)

The subjective evidence of disease as sensed by the patient

• Incubation - no symptoms
• Prodromal - symptoms appear, short, 1-2 days
• Invasion Period - height of invasion, then levels off
• Convalescent period - symptoms decline, recovery
• Graph

Habitat in the natural world where a pathogen originates, soil, water, air, environment

An infection indigenous to animals but naturally transmissible to humans

• Source: individual/object from which an infection is actually acquired 
• Carrier: individual who inconspicuously shelters a pathogen and spreads it to others without any notice

• Asymptomatic: infected but show no symptoms
• Incubating: spread infectious agent during incubation period
• Convalescent: Recuperating with no symptoms but continues to shed microbes and convey the infection to others
• Chronic: Shelters the infectious agent for a long period after recovery because of latency
• Passive: Picks up pathogens mechanically and accidentally transfers to others without becoming infected themselves

• Direct: contact (kissing, sex), droplets (air), vertical, biological vector
• Indirect: fomites (inanimate objects), food, water, biological products, air (aerosols/droplets)

The study of the frequency and distribution of disease and other health-related factors in defined populations

Research and provide basic information about a disease, i.e. incidence, mortality/fatality rate, transmission, risk factors

Tracking the spread of diseases, maintain databases, follow reported diseases, see if increase, clusters

Investigate outbreaks and determining cause, determine index case, source of outbreak, implement ring vaccination

Tracking/preventing nosocomical (hospital) infections

• Compromised hosts: hospitals represent pools of susceptible individuals - sick, immunosuppressed, antibiotics
• Microbe Prevalence: Pathogenic/opportunistic organisms, antibiotic-resistant strains - urinary tract
• Chain of transmission: Invasive procedures/insertion of medical equipment (surgical sites), direct/indirect contact with other patients (respiratory)

• Standard precautions: handwashing
• Contact precautions: if infection can spread via direct contact, gloves/gown
• Droplet precautions: spread via respiratory droplets, add mask
• Airborne precautions: negative pressure rooms and special masks
• All levels use universal blood and body precautions, protocols for medical asepsis

Immunities that occur during the normal life course

Born with it

One person receiving preformed immunity made by another person

Consequence of a person developing his own immune response to a microbe

Acquired through the normal life experience of a human, not induced by medical means

Produced purposefully through medical procedures (immunization)

• If a certain percentage of the population is immune to a disease, epidemics don't occur.
• Childhood vaccinations also prevent disease in elderly whose immunity is decreased, protects the 2 most vulnerable groups

• - Killed (bacterium) or inactivated (virus), fixed with formaldehyde or phenol
• - Live "attenuated" or weakened, have mutations or lack plasmids so not virulent, or antigenically similar but not pathogenic

• From cells or viruses: acellular (pieces of bacterium), capsule carbohydrates, spike protein
• Recombinant vaccine: components made using recombinant vaccine
• Toxoids: inactivated exotoxins, anti-disease approach
• Conjugate vaccine: antigen of interest conjugated to a protein

• Whole agent: polyclonal, more than 1 type of antibody, life more effective than dead more effective than attenuated, revertants from attenuated vaccines, reactions to dead whole organisms
• Subunit: Not as many antibodies, only seeing 1 piece, protein stimulates the biggest response

• Degree of immunity developed determines if boosters are needed and when
• Natural boosters occur by coming into contact with something you have already contacted

Exposing a person to a material that is antigenic but not pathogenic, provides long-term immunity

• Artificial, passive immunity
• A shot of IgG antibodies
• Not a vaccine
• When exposed and the vaccine is not available or  you haven't had immunization
• Instant immunity but short term, no memory

• Facilitate removal of antigen from the body
• Blocks the agent from causing disease

• Microbe hides inside the cell
• Does not damage cells directly but elicits enthusiastic immune response
• Need to control bacteria without strong inflammatory reaction
• Body has hard time eliminating the bacteria completely
• Natural immunity only lasts about 6 months

• Blindness
• Sterility
• Pneumonia
• Cardiovascular disease
• Can spread to others

Spore-like form invades (elementary bodies) → differentiate into noninfectious reticulate bodies in cell → block lysosome action → incite inflammation → avoid detection → 72 hours after initial invasion new elementary bodies break out possibly by apoptosis → infect solo cells or packaged into apoptotic bodies internalized by healthy cells

• First cases in 1981 in LA and San Francisco then rapidly reported elsewhere (NY, Haitian population in FL, Paris)
• Called wasting disease in Haiti (1970)
• Index case in 1959 in Congo Republic
• SIV jumped to humans in approximately 1930 via hunter exposed to "infected blood", then jump occurred several times over a decade prior to spreading to city
• Lifestyle of patients and latent phase led to pandemic
• Spread via infected individuals moving and culture of promiscuity

• Humans are the only reservoir
• Transmission mainly by close contact - contaminated blood and blood products, sexual intercourse
• Blood, vaginal and rectal fluids most important source, semen more minor
• Portal of entry via breaks in anal/vaginal mucosa or needle

• Dendritic Cells: bind HIV and carry to CD4 cells in lymph nodes
• Also macrophages/monocytes

• First 1-2 Months: acute phase, flu-like, viral load increases, B & T cytotoxic decrease viral load, antibodies rise, enter asymptomatic phases, CD4 > 500, phases I and II
• Chronic Phase: 2-15 years, decreasing CD4 (200-499), latent, no symptoms but indicator diseases appear, phase III
• AIDS: phase IV, CD4 <200, viral load increases, overcomes immune system, opportunistic infections (aids defining illnesses) are the cause of death, common are TB, Kaposi's sarcoma, systemic candidiasis, herpes simplex ulcers, PCP

• HIV is present before antibodies are detected, time most likely to be infected
• Antibodies usually detected 6-18 weeks after infection
• Now with new testing 2-6 weeks so window closed a little bit

• Enveloped
• 2 spikes (GP-120 anchored by GP-41) and 2 capsid proteins
• 2+ ssRNA, reverse transcriptase, protease and integrase enzymes
• Absorption - CD4 binds GP-120, exposes co-receptor binding site on GP-120 to bind to host cell co-receptor (R4 or R5)
• Penetration - Co-receptor binding exposes GP-41 which inserts and stimulates fusion
• Reverse transcriptase is error prone so lots of mutations (could be one on every virus every day)
• RNA to DNA to provirus (integration)

• Normal job is cytokine receptors, signals of WBCs, stimulate maturation
• R5 - on macrophages, initial site of infection, STD strain
• R4 - on all CD4 t cells, second site of infection, usually blood-borne
• Later in infection virus that can use both receptors

• Highly active anti-retroviral therapy
• Use combination of 3+ drugs that target 2+ steps in virus life cycle
• Usually 2 reverse transcriptase and 1 protease inhibitor
• 3 drugs means 1/trillion chance of reverse transcriptase mutation, also more likely to decrease viral load
• Drug options - all inhibitors, reverse transcriptase, entry, protease, integrase, multidrug combination
• Problems - expensive, large number of pills daily, side effects, resistance, drug-associated diseases
• Length of treatment - latent virus is reservoir, established with the initial infection, mostly in memory cells, takes >50 years for reservoir cells to die, need treatment until gone

• Variability due to error prone reverse transcriptase causing mutations
• 2 distinct types, HIV-1 (US) and HIV-2 (W. Africa)
• HIV-1 has 4 groups, group M has 10 clades (7-12% variability within clades, more than 30% between clades)
• Need to find a region that does not vary to target vaccine

• Named for the site of inflammation, the same organism infects more than 1 location
• Most, human are the reservoir
• Common portal of entry, exit and transmission
• Transmission - contact (direct or droplet) and indirect (fomites, air as vehicle)

• If less likely to cause disease with age means we develop immunity, the organism is not variable (RSV)
• If still causes infections, no immunity, organism is variable (rhinovirus)

• Common → caused ≥ half of all colds
• Likes cold temperatures so stays in the nasal area

• Makes pus
• Beta hemolytic
• Type A antigen present so type A

• Pus
• Swollen tonsils
• Small hemorrhagic spots in back of throat
• Special sore throat
• Bad breath
• Caused by strep pyogenes
• Communicable for 10-21 days if untreated

• Strep throat with pinkish-red rash, strawberry tongue, nausea
• Caused by strep pyogenes
• Communicable so need treatment, usually penicillin to keep from spreading and to prevent post-infection complications

• Type II cytotoxic hypersensitivity, in appropriately targeting self cells
• Strep pyogenes
• Arthritis in joints, nodules on bony surfaces under skin
• Preventable if original strep infection is treated with antibiotics
• Do not treat because the bacteria is already gone

• Strep pyogenes
• Result of type III, antigen-antibody complexes in kidney glomeruli
• Nephritis, increased BP, blood in urine, heart failure occasionally
• Don't treat, the bacteria is already gone
• Only caused by nephrogenic strains

• Don't become immune to strep throat because that strain does not make the toxin
• Only get scarlet fever if you get the strain that makes a toxin
• 3 toxin types
• Toxins are antigenic, only get them once and then have immunity to that strain

• Primary: usually occurs in children, first infection, if healthy have acute response, infection becomes dormant but not killed, walled off of infected macrophages, tubercle or granuloma develops
• Progressive Primary: Inadequate T-cell response fails to control infection, tubercles rupture and infection spreads consuming more lung tissue, highly infectious, compromised immune individuals
• Secondary/Reactivation: Bacteria escape tubercle and hypersensitivity causes tissue damage down the road

• Multiple drugs (resistance and too long for sensitivity) and extended time (slow growing and inside tubercles & macrophages)
• Active treat for 2 months with 4 drugs and then retest
• If still positive treat 7 months with 2 drugs
• If negative (dormant) continue 4 months with 2 drugs
• Due to acid fast layer and slow growing, highly resistant to many environments
• Direct observed therapy (DOT), if needed to make sure people take drugs, if history of not taking or in situation not likely to take on their own

Productive cough (blood/sputum), fever, malaise, loss of weight

Enters the blood stream and disseminates to other locations

Not for routine use because it is only 50% effective and the person now tests positive on TB tests, can't be used to screen for new exposures

• RNA virus, 8 ssRNA each in its own helical capsid, all in a larger capsid
• Enveloped with spikes, H and N
• 3 antigenic types, A, B, C, based on differences in capsid proteins
• Epidemics prevented yearly by 3-4 inactivated strains in vaccine chosen by epidemiological prediction of what will be present the next year, at least 2 A and 1-2 B

Subtle yearly changes in H and N proteins of influenza envelope by mutation

• Dramatic influenza H and N changes
• 1 cause is mixing of avian/human genes in swine host, antigenically new
• Because some genes are now avian - reassortment
• Also from a purely avian virus that mutates enough to infect people
• H5N1 receptor is only in human lungs (very far down, difficult to get to)

• Type I: immediate, needs multiple exposure, IgE leads to mast cell degranulation that vies local or systemic reactions, 20 minutes
• Type II: Antibody-mediated, IgG or IgM, bind to cells recognized as foreign, good or bad, immune response is working normally, 5-12 hours
• Type III: Immune complex, antibody-antigen complexes lodge in basement membrane, lysosome granules digest these tissues and cause inflammatory reaction, acute/localized or chronic/systemic, 3-8 hours
• Type IV: Delayed hypersensitivity, not antibodies, T-cell mediated, T cells respond to antigens displayed on self or transplant tissue, too many macrophages being activated leads to tissue damage, memory cells, 24-48 hours

• Primes the body to react the next time it encounters allergen
• Type I - allergen → tissue fluids/lymphatics → lymph nodes: B cells → plasma cells → IgE → binds to mast cells/basophils
• Type II - immune system detects foreign factors and produces antibodies and memory B cells
• Type III - excess antibodies from "infection" form Ab-Ag complexes, overwhelm macrophages, acute(injection site reaction) or chronic (repeated exposures)
• Type IV - antigen exposure → dendritic cells → T helper cells → clone → sensitized memory cells → subsequent exposure memory is activated

• Produced by the ingestion of preformed toxins
• True food poisoning
• Rapid onset - staph 1-6 hours, botulism 12 hours

• Bacteria colonizing and establishing an infection
• Symptoms produced by (1) enterotoxins they produce causing damage or (2) bacteria invading and damaging/destroying intestinal mucosa/submucosa (treat with antibiotics)
• Usually 1-3 days after exposure

• Staph: head stable enterotoxin, rapid, 1-6 hr onset, last approximately 24 hours, nausea, vomiting, diarrhea, human host, treat with rehydration
• Botulism: heat labile, neurotoxin, usually poorly canned food, soil is host, onset 12-72 hours, blurred/double vision, dizziness, trouble swallowing, treat with antitoxin and respiratory support

• Food borne
• Caused by improper canning
• Prevent by heating food thoroughly and canning properly
• Other causes - wound infection and GI infection because of endospores
• Common in soil
• Normal flora may not outcompete

• Shiga toxin producing: human/cattle host, enterohemorrhagic strain, 1-3 day incubation, becomes systemic, mild enteritis to fever to dysentery, treat with antibiotics, dialysis, may last longer than 14 days
• Non-Shiga toxin producing: human host, 4 strains, 1-3 day incubation, profuse diarrhea, self limiting, treat with rehydration, enterotoxigenic - traveler's diarrhea, enteroaggregative - chronic

• Salmonelliosis
• Chickens/human hosts
• 1-3 days incubation
• Lasts 2-5 days, usually self limiting

• Shigellosis
• Primate/human host
• Shiga toxin
• Diarrhea, dysentery
• 1-3 day incubation
• Lasts 4-7 days

• Campylobacteriosis
• Human/numerous animal hosts
• 1-7 day incubation
• 7-14 days of symptoms
• Watery stool/dysentary

• Associated with having antibiotic therapy so common in medial settings
• common cause of endogenous/opportunistic infections
• Transmission by endospores shed in stool, need chlorine disinfectants, alcohol does not work. hand washing IMPORTANT

• Human reservoirs not as much of a problem in countries with good sanitation
• Animal/human reservoirs more problematic because spread through animals used in food

• Rotavirus (wheel): most common gastroenteritis in children 6 months to 2 years, 90% of children are immune by 3 years, not variable
• Norovirus: all age groups affected, highly variable

• Symptoms are fatigue, abnominal pain, fever, headache, jaundice
• Vaccines for A and B
• A and E spread fecal-oral
• B and C spread blood and vertical
• B spread by contact - direct sexual
• C rarely spread by sex, silent epidemic, 80% no signs or symptoms

• Hypersensitivity can cause the disease, the immune system overreacting causes the damage
• Type I - hay fever, damage not caused by allergen
• Type II - rheumatic fever
• Type III - acute glomerulonephritis
• Type IV - TB

• Transmission - indirect, food/water/fecal-oral
• Prevention - proper food handling and sanitation
• Symptoms - due to site of inflammation and damage in the same location

• Dental caries: S. mutans and S. sobrinus establish biofilm, then lactobacilli and others work together, lead to acid production, enamel destruction
• Gengivitis: plaque (biofilm) at gum line give access to microbes, pockets between teeth and gums is a nice environment for bacteria

• Tooth work can cause breaks in gum tissue, releases strep species into the blood stream
• Subacute endocarditis: fatal in months if untreated, bacteria lodge in heart tissue, more likely with abnormal heart valves
• Acute endocarditis: S. aureus is usually the cause, fatal in days

• Produces urease which neutralizes stomach acid
• Injects toxins into gastric cells, breaks down tight junctions, leads to PUD
• Ulcers can lead to gastric cancer

• Enteritis: small intestine
• Gastroenteritis: small intestine with vomiting
• Colitis: large intestine
• Dysentery: diarrhea with blood or mucus