microbiology final exam week 2

upper respiratory system (head and neck)

• common but usually not life-threatening

• viral or bacterial

• immune system clears in about a week

lower respiratory system (chest)(lungs)

• often serious and may be fatal

• viral, bacterial, fungal

sinusitis

inflammation with the sinuses (upper resp)

pharyngitis

inflammation of the throat (upper resp)

rhinitis

inflammation of the mucous membranes of nose (upper resp)

tonsilitis

inflammation of the tonsils (upper resp)

ottis media

inflammation of the middle ear

what does the upper respiratory tract do? (function?)

warms and moisturizes inhaled air

protective mechanisms of the upper respiratory tract?

• nasal hairs (catch particles)

• lysozyme

• igA

• saliva flushing

• coughing, sneezing, swallowing

• continuous sloughing of epithelium

• normal microbiota

• mucous and cilia (MUCOCILIARY ESCALATOR!)

normal microbiota of the upper resp tract or pathogen?

strains can be protective OR pathogenic or commensal depending on strain

moraxella

gram negative diplococci and diplobacilli

ottis media

haemophilus

small gram negative rods

meningitis

streptococcus

gram positive cocci in chains

10% strep pyogenes

corynebacterium

pleomorphic, gram positive rods; non-motile non spore forming

diptheria

staphylococcus

gram positive cocci in clusters

25% staph aureus

what causes fever, throat pain, and difficulty swallowing?

pharyngitis (inflammation of the throat)

caused by streptococcus pyogenes (treatment is penicillin or amoxicillin)

streptococcus pyogenes

• gram positive

• cocci that grow in chains

• encapsulated

• NON MOTILE

• group A carbohydrate

• B hemolytic

• “pyo" (pus)

causes strep throat (makes us sick)

what are the steps in the pathogenesis of infectious disease?

• entry

• attachment (M protein, F protein)

• multiplication

• invasion or spread (tissue degrading enzymes)

• evasion of host defenses

• damage to host tissues

what are the evasion of host defenses in pathogenesis of infectious disease?

• M protein

• streptolycin (leukocytes lyses or breaks open your immune cells)

• protein G (binds to antibodies)

• capsule (evade phagocytosis)

• C5a peptidase (avoiding of complement)

lysogenic phages encode what?

toxins in some strains

what are toxins?

superantigens

lead to… massive activation of T cells (MASSIVE INFLAMMATORY RESPONSE)

• scarlet fever

• toxic shock

• necrotizing fasciitis (“flesh eating disease”)

why can you get strep throat (pharyngitis) more than once?

we do not have a vaccine yet

• >80 types (antigenic variants) of M protein

• too many types to make a vaccine

epidemiology of streptococcus pyogenes

• naturally only infects humans

• spread by respiratory droplets or contaminated food

treatment and prevention of streptococcus pyogenes

• confirmation via diagnostic tests (rapid strep elisa) and throat culture

• treatment with penicillin and erythromycin about 90% effective

• prevents post streptococcal sequelae

why is it important to treat strep throat?

can lead to post-streptococcal sequelae (complications that happen after strep is gone)

post streptococcal sequelae

1. acute rheumatic fever (3%) → can lead to chronic rheumatic heart disease because antibodies to M protein cross react w/proteins on the HEART

2. acute post-streptococcal glomerulonephritis

   • antibody-antibody complexes activate complement → damages kidneys (rare)

(both sequelae are strain dependent!)

what is another bacterial pharyngitis?

diptheria

• caused by corynebacterium diphtheriae (do not leave throat BUT toxins circulate)

• strains carrying lysogenic phage produce toxin that can circulate in blood → shuts down protein synthesis in heart, kidneys, and nerves (damage!)

how do you prevent diptheria?

effective toxoid vaccine (DTaP)

• humans are the only reservoir

common cold causes

• mainly rhinoviruses (>100 types)

• infect respiratory epithelial cells → stop ciliary motion (more susceptible to 2ndary infection!)

average adult gets 2-4 colds each year, kids get 2x that number!

characteristics of the common cold

• short incubation period (1-2 days)

• non-enveloped (common, persist, resist dessication, stable)

• usually no fever

• first 2-3 days: nasal secretions contains high numbers virus

• portals of entry: eyes and nose

• prevention: wash hands, keep away from face, avoid crowds

• treatment: symptoms only: aspirin and ibuprofen may prolong duration

viral pharyngitis

• adenoviruses most common (>50 types)

• LONGER INCUBATION PERIOD (5-10 days)

• can also infect other tissues (eg. conjunctivitis)

• NON ENVELOPED, can remain infectious for long periods of time

corona virus

• upper respiratory viral infection

• many types

• cause 10-30% common colds

• can spread to lower resp tract

• fairly high mortality rate

• ANIMAL RESERVOIR (bats!)

what are the deadly coronaviruses?

1. SARS (sudden acute respiratory syndrome)

   • bats, cirets, high mortality rate

2. MERS (middle east respiratory syndrome)

   • bats, camels, high mortality rate

upper respiratory infections can spread to?

sinuses, middle ear, and lower resp system (bronchitis, pneumonia)

causative agents of lower respiratory infections?

• bacteria

• viruses

• fungi

infections of the lower respiratory tract?

1. bronchitis (infections of bronchi, larger airways)

2. bronchiolitis (infection of smallest airways)

3. pneumonia (alveoli filled w/fluid and pus)

pneumonia can spread to?

• CNS (meningitis)

• heart (endocarditis)

• blood (sepsis)

pneumonia can result from?

• inhalation of pathogen

• spread from upper respiratory infection)

• aspiration of foreign material

• periodontal disease

• blood infection

how can a lung infection spread?

short distance for bacteria to travel from blood into lungs or vice versa

protective mechanisms of the lower respiratory tract?

• mucociliary escalator present in trachea, bronchi, and bronchioles

• few normal microbiota

• macrophages waiting in alveoli are able to phagocytize and get rid of foreign material

streptococcus pneumoniae

most common cause of community acquired pneumonia

• ~60% hospitalizations

• 30% indiv carry encapsulated s.pneumoniae (dont develop disease)

symptoms of s.pneumoniae infection

• fever

• cough

• chest pain

• productive cough

• shallow and rapid breathing

• fatigue

(because of small air sacs filled w/fluid from inflammatory response)

treatment for s.pneumoniae infection

antibiotics but resistance is rising

who should get vaccinated for s.pneumoniae?

• children (under 5)

• anybody 65+

>90 different capsular serotypes; vaccines contain COMBINATIONS (w/capsular fragments from many serotypes)

klebsiella pneumoniae

• soil organism

• often a HAI

• damages lung tissue

• high mortality rate

• antibiotic resistance (eg. carpenum resistant entobacteriaceae) to almost all antibiotics

• cough up red currant jelly

mycoplasma pneumoniae

• “walking pneumonia”

• generally mild

• small infectious dose (droplets)

• patient infectious for many weeks

• treatable, NO CELL WALL (so you could NOT treat with beta lactam…)

bordetella pertussis

• very rare in US

• characterized by violent coughing (whooping cough)

• bronchioles blocked

• PREVENTED BY DPT OR DTaP VACCINATION

legionella pneumophila

• causes legionnaire’s disease in compromised hosts

• vulnerable are those really young and over 65+ (DEPEND ON HERD IMMUNITY!)

• ubiquitious, found in nature and ponds

what is one of the world’s deadliest diseases?

tuberculosis

• 1/3 of the world’s population is infected

• 4,000 people die each day

• active TB has a high mortality rate

cause of tuberculosis

mycobacterium tuberculosis

• aerobic

• rod shaped

• acid fast streptobacillus (doesn’t stain well in gram stain, very THICK mycolic acid well wall

transmission of tuberculosis

humans are reservoir

• airborne

• droplet spread

• quite resistant to drying, antibiotics, and disinfectants

pathogenesis of tuberculosis

• entry: inhalation of airborne particles or droplets carrying bacteria

• attachment: binds to alveolar macrophages

• avoiding host defenses: phagocytosed by alveolar macrophages but PREVENTS FUSION OF LYSOSOMES WITH PHAGOSOME

• damage: infected macrophages lyse inducing inflammation; tubercles (granulomas) can block alveoli and bronchioles. the bacteria can sometimes spread to other organs like kidney, brain, spinal cord, bone, or skin…

facultative intracellular pathogen

mycobacterium tuberculosis has acid fast cell wall

• resist digestion

• bacteria can multiply within human macrophage cells (use it as host)

• thick waxy wall prevents many antibiotics and disinfectants from entering bacterium; resist desiccation

droplet transmission

5 minutes of talking generates 3000 droplet nuclei

latent infection tuberculosis

• 90-95% infected individuals

• no symptoms

• non infectious

• usually positive skin test

• chest x ray and sputum normal

active infection tuberculosis

• 5-10% infected individuals

• symptoms

• infectious to others

• positive skin test

• chest x ray may be abnormal

• positive sputum sample

• can spread BEYOND LUNGS

result of active TB disease?

• lungs damaged

• slight fever

• decreasing weight loss

• persistent cough (bloody sputum)

• night sweats

• can spread → military TB (problem for children!)

patients with latent tuberculosis do not have symptoms but are treated with antibiotics, why?

reactivation of tuberculosis

• infects CD4 pos cells (T helper cells)

• levels get low

• not able to keep TB infection in check

diagnosis for tuberculosis

• tuberculin skin test (mantoux)

• x ray

• sputum culture

• blood tests for interferon

treatment for tuberculosis?

3-4 drugs given in combination for many months

• wanna know if person with TB has significant number of resistance organisms (for someone with active TB!)

DOTS (directly observed therapy short course)

• for those not able to regularly get medication

multiple drug resistant TB

resistance to rifampin and isoniazid

• russia and soviet union

• extensively drug resistant (mycobacteria XDR: resistant to all 1st line drugs and many 2nd line drugs)

why doesn’t everybody receive the TB attenuated vaccine (BCG)?

prevents childhood TB but not latent tuberculosis later in life

vaccinated individuals test positive on skin test (disadvantage for false positive tests in future)

the majority of upper respiratory infections are caused by?

viruses

what is the key reason there is no effective vaccine against streptococcus pyogenes?

the number of antigenic variants (more than 80 types of M proteins!)

true or false, most people infected with M.tuberculosis develop active TB?

false (only 5-10%)

• some people with latent infections will go on to develop active TB if they become immunocompromised (ex: co infected with HIV)

mycobacterium can evade the host immune system by:

producing a large capsule

moving with flagella

reproducing inside macrophages

expressing different M proteins

reproducing inside macrophages

SARS-CoV2

• a corona virus

• several types of coronavirus infect humans: (4) cause a common cold, or severe symptoms (2, SARS and MERS)

structure of SARS-CoV-2?

RNA virus

• 4 structural proteins

• 1 single stranded viral RNA (ssRNA)

• membrane ENVELOPED (lipid bilayer comes from host cell membrane)

• the spikes (S) bind to HOST RECEPTORS (attachment!)

why are enveloped viruses easier to inactivate?

• more delicate than non enveloped

• don’t survive as long outside of host

• more likely to be inactivated by hand sanitizer!

what does SARS-CoV-2 attach to?

ACE2 (angiotensin converting enzyme 2)

• host receptor that is found on the surface of many cell types

(COVID-19 (illness) is caused by SARS-CoV-2!

why does COVID-19 affect multiple areas of the body

because Ace2 receptors are found in so many areas of the body

• throughout respiratory tract (sore throat)

• GI tract

• epithelial cells of veins and arteries (cardio and neurological symptoms)

• and more…

what is the updated COVID-19 vaccine?

bivalent, it targets the ORIGINAL SARS-CoV2 strain (Wuhan) AND OMICRON VARIANTS BA.4/BA.5

• made by pfizer and moderna

• BOTH ARE mRNA VACCINES

• contan SPIKE mRNA ENCLOSED IN A LIPID SHELL

• all persons 6 months and older should get at least one dose of the UPDATED BIVALENT vaccine (targets spike protein from 2 strains)

why do we need updated vaccines?

spike protein of the omicron variant:

• 32 mutations shown

• protective antibodies bind to the N-terminal domain (NTD) (prevent virus from successfully infecting the cells!)

• receptor binding domain (RBD) binds to the host ACE2 receptor

some mutations affect how well the spike protein binds to the ace-2 receptor…

what species does SARS-CoV2 infect?

it is ZOONOTIC (animal reservoir, animals → humans)

more species likely to infect:

• binturoung

• cat

• coatmundi

• deer

• dog

• ferret

• fishing cat

• gorilla

• etc…

in the US, what animal is a reservoir for SARS-CoV2?

white tailed deer

• new variants and mutants spread within deers that could spill over to humans

how could covid 19 be treated? (which drugs interfere with viral replication?)

remdesivir

paxlovid

block viral replication without harming host cells because remdesivir is selectively toxic for viral RNA polymerase humans dont have and paxlovid viral protease…

remdesivir

blocks RNA dependent RNA polymerase

• needs this bc RNA virus (RNA dependent)

• human cells dont have this

paxlovid

blocks viral protease → necessary for viral replication

• effective if given at beginning of covid infection

influenza virus

• A, B, C, and D types

• A causes the MOST SEVERE DISEASE IN HUMANS

• A INFECTS MULTIPLE SPECIES

flu vaccines contain which strains of influenza?

A and B

what type of virus is influenza?

RNA virus

• enveloped

• 4 structural proteins

• 8 single stranded RNA (ssRNA)(allows to mutate more dramatically)

• membrane envelope

• the spikes (hemagglutinin) BIND TO HOST RECEPTORS

how are flu strains named?

by the types of HA and NA proteins that are present

• 18 types HA

• 11 types NA (neuraminidase: protein required for viral exit from the cell)

humans are infected by which strains of HA and NA?

HA (hemogluttenin) 1,2 and 3

NA 1 and 2

ex: 2009 swine flu (infected humans) was H1N1

2015 avian flu (mainly infected birds) was H5N2

what are flu symptoms and treatment?

“FACTS”

F: fever

A: aches

C: chills

T: tiredness

S: sudden onset

drug tamiflu (neuraminidase inhibitor) can be used but only EARLY IN THE INFECTION

what is in the flu vaccine?

quadrivalent contains

• influenza A (H1N1, N3N2) and 2 strains of influenza B

why doesn’t the flu vaccine work better?

lots of variations and mutations as it spreads

egg adapted strains contain mutations (virus grown in egg embryos)

who gets vaccinated for flu vaccine?

80-90% should be vaccinated to achieve herd immunity

• unless immunocompromised or very young and eldery

• depend on herd immunity!

how does flu vaccination affect antibiotic resistance

• reduces spread of antibiotic resistance

• less clinic visits, less antibiotics prescribed inappropriately

• prevented 3.7 million office visits!

how do pandemic strains arise?

new strain could have N and HA spikes that recognize human receptors (zoonotic!)

rare occassions when animal like pig is infected w/2 different flu strains (1 from bird 1 from human)

antigenic drift

individual mutations (ex: change from A to C) occur frequently

respiratory syncytial virus (RSV)

• enveloped virus with RNA genome

• not zoonotic, humans only reservoir

• 7 structural proteins

• 1 single stranded RNA (ssRNA)

• membrane enveloped

• the attachment glycoproteins (G) bind to host receptors

what type of illness does RSV cause?

• spread by respiratory droplets and fomites

• leading cause of serous infections in infants, young children, and elderly

• infection in infants can lead to bronchiolitis caused by sloughed cells and inflammatory response; pneumonia in elderly and immunocompromised individuals!

• can cause common cold like symptoms in healthy adults

what is the new vaccine approved for adults?

RSV vaccine (adults only, not approved for infants)

• subunit vaccine consist of attachment and glycoprotein adjuvant

how can we prevent severe RSV illness?

• most people are infected multiple times

• avoid close contact with sick people

• hand washing and good hygiene

• avoid touching face with unwashed hands

• vaccination for adults 60 and older, those with underlying conditions

• antibodies for high risk infants and some children

fungal pneumonia

more rare

3 types

• coccidiomycosis

• histoplasmosis

• pneumocystis pneumonia

coccidiomycosis

“valley fever”

• US: arid regions of southwest

• usually self limiting

• fungal pneumonia

histoplasmosis

• mild illness in most

• fungal pneumonia

• found in soil contaminated with bat or bird droppings

• usually benign

pneumocystis pneumonia

• organism present in many people but does not cause disease

• only causes disease in immunocompromised individuals (AIDS)

• rare enough to be considered “AIDs defining”

• fungal pneumonia

flu infection directly damages these cells, which can lead to secondary bacterial infections

ciliated epithelial cells

true or false, the host specificity of a flu virus is dependent on its hemagglutinin (HA) type

true

• virus strains with H1 can infect humans, while strains with H5 infect birds