-many serotypes (1,2,5,6 in kids; 4,7 in military, crowds)

-linear, nonsegmented dsDNA

-genes transcribed in both directions; early and late phase and mRNA variable splicing

-nonenveloped icosadeltahedron with 12 pentons, one fiber

-terminal protein attached at 5' end= primer for replication

-the fiber has viral attachment proteins (hemagglutinin)

-fiber and base are toxic and inhibit mRNA transport, protein synthesis, cause tissue damage

-fiber interacts with coxsackie adenovirus R or MHCI-R

-penton base acts with alpha-v integrin-->cell-mediated endocytosis in clathrin coated vesicles

-pH breaks up capsid, lyse endosomal vesicle, capsid to nucleus for replication

-lytic virus in respiratory and GI tracts and conjunctiva) or can be latent in lymphoid cells

-translates its own DNA-dependent DNAP (early protein)

-E1A gene (early)-->E1A transactivator protein (an oncogene); binds p105RB (retinoblastoma), inhibit apoptosis

-E1B protein (early) binds p53 to prevent cell apoptosis

-capsid/structural proteins are late phase; made in cytoplasm and assembled in nucleus

-spread by aerosol, close contact, fecal-oral, direct inoculation

-acute febrile pharyngitis

-pharyngoconjunctival fever

-can get conjunctiva + diarrhea

-can look like strep throat so culture it

-can form pertussis-like illness with true viral pneumonia

-have live oral vaccine for serotypes 4 and 7

-a pico-RNA-virus (small and RNA)

-small, (+)sense ssRNA

-naked icosahedral capsid

-four virion polypeptides (VP1-VP4)

-5 VP subunits associate into pentamers-->12 pentamers associate into procapsid-->genome inserted-->VP0 cleaved

-best invades/replicates in nasal mucosa b/c is cooler

-can't replicate in GI tract, labile to acidic pH

-VP1 at vertice binds ICAM-1 (on epi, fibroblasts, B cells), VP1 creates channel in cell being invaded

-then VP4 is released, weakens virion

-genome injected across membrane through VP1's channel

-genome binds to ribosome (even though no 5' cap)

-synthesize polyprotein

-VP1 binds ICAM-1...gets into target cell

-VP2 and VP4 are formed when cleave VP0 (then can finish making capsid)

-genome encodes own RNA-dependent RNAP

-VP4 is released when enters cells, weakens the virus

-common cold in early autumn, late spring in temperate climates

-hands are major vectors

-most viral replication in nose-->cells release histamine and bradykinin-->runny nose

-IFN limits progression of virus but also makes symptoms worse

-cytokine release-->enhance expression of ICAM-1-->more can adhere to target cells

-do get transient immunity by IgA and IgG

-see antigenic drift, no vaccine

-enveloped

-longest (+)sense ssRNA, glycoproteins on envelope surface = club-shaped (look like solar corona in EM)

-has 5'cap and 3'tail

-genome associates with N protein to form helical nucleocapsid

-common cold or SARS

-unclear exactly how gets into host cell

-replication occurs in cytoplasm and envelope comes from ER -enters cell--> genome translated to polyprotein --> polyprotein cleaved to RNA-dependent RNAP-->get (-)RNA template

-L protein uses template to replicate new genome in cytoplasm

-virus assembles and gets envelope in ER

-E1 = transmembrane matrix protein

-E2 = viral attachment, membrane fusion, Ab target

-E3 = hemagglutinin-neuraminidase

-core nucleoprotein

-like rhinovirus, replicates in nasal mucosa b/c cooler temp

-longer incubation period than rhinovivrus

-see in infants, kids

-SARS = atypical pneumonia

-spread by aerosols and in large droplets

-parainfluenza

-respiratory syncytial

-human metapneumo

-(-)sense ssRNA -helical nucleocapsid with envelope

-nucleocapsid composed of: RNA, nucleoprotein, phosphoprotein, and large protein

-nucleocapsid associates with matrix protein (lines inside of envelope), fusion protein, and viral attachment protein (hemagglutinin-neuraminidase, hemagglutinin, or G protein)

-binding of viral attachment protein to sialic acid on target cell-->fusion protein causes envelope & plasma membrane to fuse-->forms syncytia-->RNAP enters cell as part of nucleocapsid-->transcription, protein synthesis, replication all in cytoplasm-->new genomes associate with nucleoprotein, phosphoprotein, and large protein to form nucleocapsid--> nucleocapsid associates with matrix protein on modified plasma membranes-->mature virions bud from host cell plasma membrane

-fusion protein activated by proteolytic cleavage of F1 and F2 glycopeptides held together by disulfide bond

-hemagglutinin+, neuraminidase+, fusion protein+

-type of paramyxovirus

-serologic types 1-4

-see paramyxovirus for details

-infect epithelial cells of upper resp tract-->giant cell formation-->cell lysis

-rarely causes viremia

-the cell-mediated immunity it elicits causes the damage; short-term protection though b/c cell-mediated immunity manipulated for limited memory

-types 1-3 -infants and young kids: severe lower resp tract infxns (not as many as with RSV though)

-laryngotracheobronchitis/croup (subglottal swelling can close airway and cause hoarsness and seal bark and retractions; must distinguish between H. influenzae infxn)

-may see pneumonia in elderly

-can cause mild upper resp tract infxn, bronchiolitis, wheezing, bronchitis in older kids and adults

-type 4 -mild upper resp tract infxn with cold-like symptoms in kids and adults

-types 1 and 2 seen in autumn; type 3 seen year-round -can get pn

-type of paramyxovirus

-hemagglutinin-, neuraminidase-, fusion protein+

-most common cause of fatal acute resp tract infxn in infants and young kids

-by 2yo all kids infected

-see in winter, highly contagious even by fomites

-infxn localized to resp tract; see viral invasion of resp epithelium then have damage from cell-mediated immunity (see necrosis, mucus plugs)

-can cause infxn from common cold to pneumonia

-in older ppl: see upper resp tract infxn with prominent rhinorrhea

-in infants see severe lower resp tract infxn (bronchiolitis), air trapping, and decreased ventilation

-can treat with ribavirin and passive immunity in premature babies

-type of paramyxovirus

-can be asymptomatic, cause common cold, serious bronchiolitis, pneumonia

-ubiquitous

-only member of orthomyxoviridae

-only A and B cause significant human disease; C and D affect children (says our tutor)

-pleomorphic enveloped, segmented (-)sense RNA

-RNA-dependent RNAP carried in

-segmented genome leads to new strain development

-only A has genetic shift

-influenzae has genetic shift and drift

-RNA-dependent-RNAP but uses host RNA primer to get going

-hemaglutinin: viral attachment protein, binds sialic acid on epithelial cell receptors, promotes fusion of envelope to cell membrane; agglutinates RBC; has antigen changes

-neuraminidase: forms tetramer, has enzyme activity to cleave glycoprotein sialic acid, helps viral release from infected cells; has antigen changes; binds NANA residues of sialic acid on host cell and release virus into host cell 

-membrane protein: forms proton channel and promotes uncoating and viral release

-matrix protein: promotes virion assembly 

helical nucleocapsid segments containing (-)RNA with nucleoprotein and transcriptase with RNAP components

-local upper resp tact infxn

-target mucus-secreting, ciliated and other epithelial cells

-can cause severe desquamation of bronchial or alveolar epithelium is spread to lower resp tract

-may also get pneumonia

-have inflammatory cell response to mucosal membrane

-get submucosal edema and may see hyaline membrane disease

-host can get anti-hemaglutinin and anti-neuraminidase antibodies for each strain of influenza

-also get cell-mediated immune repsonse (cytotoxic T cells)

-Mx1 protein induced in macrophages by IFN(alpha and beta) to kill virus from within

-get the "flu" from IFN induction (fever, malaise, headache)

-spread by small airborne droplets (talking, breathing, coughing); can survive on counter for a day

-1-4 days incubation then have prodrome then abrupt fever

-in kids <3yo looks like severe resp tract infxn with bronchiolitis, croup, otitis media, vomiting

-can get secondary bacterial infxn-->pneumonia (usually w/ pneumonococcus or H influenzae or S. aureus)

-Reye's syndrome: encephalopathy, liver degenration

-lab tests reveal hemadsorption (RBC adhere to hemaglutinin + infected cells)

-Rx with amantadine/rimantadine  to inhibit uncoating in type A only; zanamivir/oseltamivir to inhibit neuraminidase in types A or B

-drift = slow; minor antigen changes from hemaglutinin and neuraminidase every 2-3 years; see with types A and B

-shift = fast; major changes from reassortment of genomes (b/c have 8 segments that can reassemble); see this with type A

-a bunyavirus

-enveloped, segmented (-)sense RNA

    -a large, medium, and small segment of RNA

    -associate with protein to form nucleocapsid 

-spherical particles

-envelope with glycoproteins (G1 and G2)

-glycoprotein G1

-glycoprotein G2

-RNA-dependent RNAP, L protein, nonstructural proteins all in the nucleocapsid

-does NOT have a matrix protein (UNIQUE)

-G1 interacts with beta-integrins on host cell-->virus endocytosed-->envelope fuses with endosomal membrane when vesicle acidifies-->nucleocapsid released to cytoplasm   -->steals 5'cap to prime mRNA (like influenza but this happens in cytoplasm not nucleus)

-medium RNA segment encodes nonstructural protein m, G1, and G2

-large RNA segment encodes L protein (RNA-dependent RNAP)

-small RNA segment encodes nonstructural protein s. 

-glycoproteins made and glycosylated in ER, then transferred to golgi-->virions assembled by budding into golgi--> released by lysis or exocytosis 

-rodents (deer mouse, peromyscus)

-no insect vector unlike other bunyaviridae

-see west of Mississippi river

-aerosols contaminated w/ infected urine and feces

-not person-to-person

-infection starts and remains in lung-->hemorrhagic tissue destruction and lethal pulmonary disease

-Hantavirus pulm syndrome: get prodrome of fever and muscle aches then interstitial pulm edema, resp failure, death within days (rare to have asymptomatic infection)

-no real treatment. 

Streptococcus Pneumoniae (S. pneumoniae, pneumonococcus): 

structure and identification 

-encapsulated gram+ diploccocci

-grow on enriched media supplemented with blood products

-alpha-hemolytic

-autolysis: will kill itself in stationary phase when culture

-has pili

-ferments glucose, produces lactic acid (if too much glucose when grow will get a lot of lactic acid and inhibit growth)

-quellung rxn +: mix Ab + bacteria-->capsule swells

-catalase(-) so high H2O2 inhibits growth

-polysaccharide capsule = virulence factor

-90 serotypes (1-8 cause pneumonia); lots of carriage in winter

-bile solubility test: are rapidly lysed after bile exposure

-optochin susceptible: optochin inhibits growth of S. pneumoniae and not of S. viridians

-polysaccharide capsule = virulent!!

-cell wall components: 

    -Peptidoglycan layer 

    -teichoic acid and lipoteichoic acid

          -both associate w/ phosphorylcholine (Unique!)

    -phosphorylcholine regulates cell; 2 choline residues on

     each carb repeat-->choline adheres to choline-binding

     receptors on target cell. 

     -phosphorylcholine required for the amidase autolysin

    -C polysaccharide excreted in urine, precipitates CRP in

     the presence of calcium 

-surface protein adhesions: bind epithelial cells

-normally s. pneumoniae spread inhibited if enveloped in mucus but to avoid this, the bug will utilize...

      -secretory IgA protease: avoids IgA neutralization

      -pneumolysin:

            -binds cholesterol in host cell membrane, creates 

             pores and destroys ciliated epi and phagocytes

           -avoids classic complement???? 

-symptoms caused by host response, not by bug's toxins

-colonizes oropharynx normally, especially in kids

-aspiration-->pneumonia, especially lower lobar in elderly

-sinusitis, otitis media, pneumococcal menigits; all frequently preceded by viral infections 

-spore-forming, non-motile, nonhemolytic, gram+

-large single or paired rods or long, serpentine chains

-in peripheral blood can do gram stain

-on blood agar plates:

     -gray/white colonies w/ rough texture

     -ground glass appearance

     -comma-shaped outgrowths =Medusa head projects out

-has 2 plasmids 

     -pXO1 plasmid with protective Ag, edema factor, and 

      lethal factor

     -pXO2 with polypeptide capsule genes for inhibiting 

      phagocytosis

-3 toxic proteins on the pXO1 plasmid and their functions:

     -protective antigen (PA): binds host cell Rs

     -edema factor (EF):  calmodulin-dpdnt adenylate cyclase

      that increases intracell cAMP-->edema

     -lethal factor (LF):zinc-dpdnt protease that cleaves MAPK

      -->cell death

     -PA + EF = edema toxin

     -PA + LF = lethal toxin

-PA binds Rs on host cells-->host cell proteases cleave PA--> remaining PA-64 fragments associate into ring shape--> bind molecules of EF and LF (competitive binding)-->endocytosis   -->in acidic endosome the PA-EF and PA-LF complexes form transmembrane pores-->release EF and LF into cytosol--> cell death and edema

-polypeptide capsule with D-glutamic acid is another virulence factor on pXO2 plasmid: inhibits phagocytosis 

-see amthrax in herbivores (wool-sorter's disease)

-humans infected by inoculation, ingestion, inhalation

-Cutaneous anthrax: 

     -painless papule at inoculation site-->progress to ulcer 

      surrounded by vesicles-->necrotic eschar

-GI anthrax: depends on site of infection

-Inhalation antrhax: 

     -prolonged latent period

     -nonspecific symptoms followed by: fever, edema, 

      mediastinal lymph node enlargement, resp failure, 

      sepsis 

-spore-forming, motile, hemolytic, non-encapsulated gram+ rods

-penicillin-resistant 

-find in contaminated soil, rice, meates, veggies

-necrotic toxin: heat-labile enterotoxin

-cereolysin toxin: potentnt hemolysin

-PLC: potent lecithinase

-2 forms of food poisoning:

     -vomiting disease = emetic, heat-stable enterotoxin

     -diarrheal disease = heat-labile enterotoxin

-irregularly staining, non-spore-forming, pleomorphic, gram+ rod

-club-shaped in v- or l-shaped formation

-metachromatic granules

-identify based on:

     -presence of cysteinase

     -absence of pyrazinamidaze

-grow on blood agar and see small hemolysis zones

-grow on selective media and see black-brown halo

-tellurite plate = loeffler's medium for throat culture

-4 biotypes: gravis and mitis cause disease

-Diptheria toxin = major virulence factor

     -heat-labile polypeptide

     -produced at site of infection, disseminates via blood 

      so no need for organism to enter blood to get disease

-tox gene encodes the exotoxin:

     -gets into bacteria by lysogenic bacteriophage

     -gene gets proteolytic cleavage to become A-B exotoxin

-A-B exotoxin from tox gene has receptor binding and translocation region (on B subunit) as well as a catalytic region (A subunit)

-toxin binds to heparin-binding epidermal growth factor R

-B part binds and A part gets into cytosol

-A subunit terminates host cell protein synthesis by EF-2

-toxin 

-toxin synthesis is regulated by diptheria toxin repressor (DTxR), whcih is activated w/ high iron

-poor urban areas with crowding

-humans = only reservoir

-see asymptomatic carriage in oropharynx, skin

-clinical presentation depends on infxn site, immune status, and organism virulence (the diptheria toxin is major virulence factor)

-Respiratory diptheria: airborne transmission with 2-4 day incubation period

     -replicate in epi cells of pharynx-->local damage due to 

      A-B exotoxin

     -see exudative pharyngitis with pseudomembrane 

      (UNIQUE) that can't be removed w/out causing bleeding

     -can see myocarditis and neurotoxicity 

-cutaneous diptheria: skin contact-->papule-->chronic nonhealing ulcer-->gets covered by grayish membrane

     -see in tropical environment

-treatment with early administration of diptheria antitoxin; have a DPT vaccine for kids

-exogenous (ubiquitous in soil)

-strict aerobe

-gram+

-cell wall with tuberculostearic acid --> weakly acid fast+

-trehalose linked to 2 molecules of mycolic acid

-catalase+, oxidizes carbs

-grow on nonselective media

     -see aerial hyphae (UNIQUE)

-N. brasiliensis is most commonly seen in N, C, and S America

-cord factor = virulence factor that prevents fusion of phagosome-lysosome so can survive intracellularly and replicate in the macrophage

-secretion of catalase and superoxide dismutase helps protect  bacteria

-broncopulmonary disease in immunocompromised pts

     -can spread to CNS or skin

-cutaneous nocardiosis: 

     -mycetoma: painless, chronic infxn of feet with local 

      swelling, suppuration, sinus tract formations

-lymphocutaneous disease:

     -nodules and ulcerations along lymphatics

-facultatively or strictly anaerobic

-non-spore-forming, gram+ rods

-not acid fast

-grow slowly in culture

     -delicate filamentous forms, hyphae

-produce chronic slowly developing infxns

-endogenous to oral cavity, cololinze upper resp tract, GI, female genital tract

-get disease when damage mucosal barriers

-chronic granulomatous lesions that can become suppurative, form abscesses and get sinus tracts to drain

-sulfur granules = yellow or orange masses of filamentous organisms connected by calcium phosphate

-cervicofacial type is most commmon (see nastiness on jaw)

-thoracid abscesses spread from lung to adjoining tissue 

-nonmotile, non-spore-forming, aerobic, slightly gram+ rods

-occasional branched filaments

-acid-fast b/c of mycolic acids

-identification by high guanine+cysteine content in DNA

-colonies = nonpigmented or light tan

-lipid-rich cell wall = hydrophobic, resistant to disinfectants

-plasma membrane has lipoarabinomannan

-PPD test of the transport proteins and porins in cell wall 

-when growing, use decontaminating agent, grow rapidly in broth cultures

-ziehl-neelsen, kinyoun, or truant acid fast stain

-TB penetrates into alveoli-->phagocytosed by macrophages   -->prevents fusion of phagosome with lysosome-->macrophages secrete IL-12 and TNF-alpha-->increase NK and T cell recruitment (get TH1)-->TH1 cells secrete IFN- gamma-->IFN-gamma makes macrophages better killers--> cycle continues with increased inflammation

-granulomatous lesions form and have central area of Langhan giant cells with tubercle bacilli surrounded by zone of epithelioid cells

-will later see tubercles: granuloma surrounded by fibrous tissue with central area of necrosis; healed and have more fibrosis and calcification 

M. Tuberculosis clinical disease:

-primary infection with localized focus usually around middle lung (this is a gohn focus); likely have at least one hilar lymph node with granuloma as well (makes it a gohn complex)

-insidious onset with nonspecific constitutional symptoms, including: malaise, weight loss, cough, night sweats, sputum may be scant, bloody, or purulent (if have cavitation)

-disseminated/miliary TB seen with immnocompromised or if primary infection takes over; no real lung disease

-weakly gram+, strongly acid-fast, aerobic rods

-lipid-rich cell wall

-get from contaminated water or food and sometimes aerosol

-chronic granulomatous enteritis (Chrone disease)

-in immunocompromised pts can see:

     -older men w/ smoking history and underlying pulm 

      disease; get slowly evolving cavitary disease that looks

      like TB

     -elderly female nonsmokers w/ lingular/middle lobe 

      infiltrate and patchy, nondular appearance with

      bronchiectasis 

           -indolent form called Lady Windermere syndrome if

            suppress the cough reflex

     -solitary pulmonary nodule formation 

-facultative aerobes

-gram- rods

-large polysaccharide capsule give mucoid appearance of isolated colonies 

     -polysaccharide capsule also gives virulence by impeding

      phagocytosis 

-large polysaccharide capsule impedes phagocytosis

-endotoxin causes fever and shock b/c of sepsis 

-upper respiratory tract infections

-may become pneumonia via aspiration or inhalation

-commonly causes community-acquired primary local pneumonia

-with pneumonia have necrotic destruction of alveolar spaces -->formation of cavities-->production of blood-tinged sputum

-ubiquitous (soil, vegetation, water, hospitals)

-opportunistic infections

-beta-hemolysis, green pigmentation, grape-like odor (UNIQUE)

-motile, straight or slighly curved, gram- rods

-arrange in pairs

-aerobic respiration, nonfermenters

-cytochrome oxidase+

-some appear mucoid b/c abundant polysaccharide capsule 

-type III secretion: exotoxin transferred from bacterium directly into adjacent cell to avoid Abs

-mucopolysaccharide capsule adherees to host cells via flagella, pili, LPS, alginate-->protects from phagocytosis

Various toxins and Enzymes make it pathogenic:

-exotoxin A: disrupt protein synthesis by blocking peptide chain elongation like diptheria toxin

-procyanin: blue pigment that color pus blue; catalyzes production of superoxide and hydrogen peroxide and stimulates IL-8 release

-pyoverdin: yellow pigment that fluoresces under UV light; binds iron for metabolism (siderophore) and regulates other virulence factor secretion

-alkaline protease = tissue desctruction, interferes w/ host response

-PLC = heat labile hemolysin that breaks down lecithin; contributes to tissue destruction

-exoenzymes S and T = extracell toxins with ADP-ribosyltransferase activity

-mutation of porin proteins = major mechanism of resistance

-enzyme LasA (serine protease) and LasB (zinc metalloprotease) degrade elastin, cause lung parenchymal damage and hemorrhagic lesions 

-highly resistant to antibiotics even as treat b/c mutation of porin proteins 

-infections in lower respiratory tract

-ecthyma gangrenosum: LasA and LasB degrade elastin, cause lung parenchymal damage, hemorrhagic lesions

-symptoms range from:

     -asymptomatic colonization

     -benign tracheobronchitis

     -severe necrotizing bronchopneumonia

-can infect wounds

-folliculitis from contaminated water

-osteochondritis if foot is penetrated (wear tennis show and step on nail)

-UTIs in patients with indwelling urinary catheters

-external otitis media (swimmer's ear) and corneal ulcers

-opportunistic

-see with pts with cystic fibrosis or chronic granulomatous disease

-infection called meliodosis

-suppurative cutaneous infxns with cutaneous lymphadenitis, fever, malaise

-pulmonary disease can range from mild to necrotizing pneumonia

-opportunistic infxn

-see in debilitated pts with impaired host-defense mechanisms

-resistance to beta-lactams and aminoglycoside antibiotics

-nosocomial infections: bacteremia and pneumonia

-strictly aerobic, oxidase-, plump, coccobacilli

-ubiquitous saphrophyties

-see in wet and dry places, including human skin and part of normal oropharyngeal flora

-resistant to antibiotics

-strict aerobe, oxidase+, gram-, diplococci

-commonly cause bronchitis and bronchopneumonia, sinusitis, otitis

-many produce beta-lactamases and are resistant to penicillins

-small, pleomorphic, gram- rods on mucous membranes

-polysaccharide capsule

-6 serotypes and 8 biotypes

-serotype b = most severe infection

-to grow, require supplemental media with hemin, NAD for growth-stimulation; use heated chocolate agar

-grow colonies of S. aureus on unheated blood agar (satellite phenomenon); staph will provide needed growth factors by lysing RBCs and releasing X factor (hemin) and NAD (V factor)

-cell wall: impairs ciliary function, damages resp epithelium, enter blood by crossing epithelial and endothelial cells

     -more severe when not cleared well from blood

-major virulence factor of serotype b = polysaccharide capsule

     -capsule is antiphagocytic, has ribose, ribitol, and 

      phosphate (polyribitol phosphate)

-lipopolysaccharide lipid A-->meningeal inflammation

-IgA1 proteases-->can colonize mucosal surface 

-colonize upper respiratory tract in first few months of life and can spread to cause otitis media, sinusitis, bronchitis, pneumonia

-biotypes II and III mainly cause otitis media, sinusitis, lower resp tract infections

-meningitis: see in unimmunized children

-epiglottitis: see in unimmunized kids; see cellulitis and swelling of supraglottic tissues

     -life-threatening

     -pharyngitis, fever, difficulty breathing b/c obstruct 

      airway

     -called "cherry-red" epiglottis

-cellulitis: in kids; reddish-blue patches on cheeks 

-pneumonia: mainly in elderly w/ underlying chronic pulm disease

-for kids part of conjugated vaccine with diptheria toxin

-small, strictly aerobic, gram- coccobacillus

-forms acid, not a gas, from glucose and lactose

-susceptible to toxic substances and metabolits when culture

-bipolar metachromatic granules

-capsulated

-virulent (PT producing form) is hemolytic (???)

-virulence genes: bvgA and bvgS

     -S responds to environment; A responds to transcription

      activator 

-protein adhesions of capsule attach to ciliated epithelium of respiratory tract-->proliferate-->localized tissue damage and systemic toxicity

-pertactin and filamentous hemagglutinin w/ RGD motif--> promote binding to sulfated glycoprotein integrins on ciliated cells

     -pertactin and filamentous also bind CR3 on macrophages (so get phagocytosis but no oxidative burst)

-finbria helps with binding somehow

-pertussin toxin: an A-B toxin 

     -S1 = toxic subunit; S2-S5 = binding subunits

     -S1 has ADP-ribosylating activity, inactivates G-inhibitory 

      -->increases cAMP, respiratory secretions, mucus 

      production, promotes lymphocytosis, histamine 

      sensitization, enhanced insulin secretion 

-adenylate cyclase/hemolysin: toxin that catalyzes conversion of ATP to cAMP

      -inhibits leukocyte chemotaxis, phagocytosis, killing

      -important early in disease course

-Dermonecrotic toxin: heat-labile that causes vasoconstriction of peripheral blood vessels

     - at low doses: local ischemia, movement of leukocytes         to extravascular spaces, hemorrhage

     -at high doses caus fatal reactions and get tissue destroyed 

-Tracheal cytotoxin: cell wall monomer w/ affinity for ciliated epi cells

     -causes ciliostasis at low concentrations

     -causes extrusion of ciliated cells at high concentrations

     -interferes with DNA synthesis 

-2 distinct lipopolysaccharides (lipid A and lipid X)

-human disease, no other reservoir

-inhale aerosols

-3 stages of clinical presentation:

     -incubation period of 7-10 days

     -catarrhal stage: like common cold for 1-2 weeks

     -paroxysmal stage: ciliated epi cells extruded from resp

      tract-->mucus clearance impaired-->whooping cough

          -for 2-4 weeks  then move into convalescence 

-treatment is supportive

-vaccine combination with diptheria and tetanus (DTaP)

-slender, pleomorphic, gram- rods

-look like short coccobacilli in tissue

-obligate aerobes; media must be supplemented with L-cysteine and iron 

-facultative intracellular parasites 

-culture = gold standard for diagnosis 

     -buffered charcoal yeast extract agar (BCYE)

     -can look in patient urine for serogroup 1-specific 

      lipopolysaccharide Ags

-parasite will bind complement to outer membrane porin protein--> deposit complement C3b on bacterial surface--> bacteria bind CR3 complement receptors on macrophages---> endocytosis-->phagolysosome fusion inhibited-->infected cells release cytokines to stimulate severe inflammatory response-->proliferate within intracellular vacuoles of macrophages--> kill host cell when vacuole lysis

-need cell-mediated immunity to kill it

     -TH1 cells activated the infected macrophages by IFN-

      gamma so can use oxidative burst 

-see in older men who smoke and drink

-see in AIDS patients, cancer patients, transplant patients or patients treated with corticosteroids 

-worldwide distribution found in natural bodies of water, air conditioning, cooling towers, condensors, hot tubs

-infxn commonly exposed to contaminated aerosols

-can survive at high temps and can live in amoeba in water

-symptomatic infections affect lung in 2 forms:

     -Pontiac fever: influenza-like, resolves spontaneously

          -fever, chills, etc. no clinical evidence of pneumonia

     -Legionnaires disease: severe atypical pneumonia 

          -dry, nonproductive cough, headach, multi-organ 

           disease with GI, CNS, liver, and kidneys affected

          -pneumonia with multilobar consolidation and 

           inflammation and microabscesses in lung tissue

Mycoplasma pneumoniae: structure and identification

-smallest free-living bacteria

-no cell wall (UNIQUE)

-cell membrane has sterols

-pleomorphic coccoid to rods

-M. pneumoniae is strict aerobe (other mycoplasmas are facultative anaerobes)

-grow slowly

-positive culture is insensitive for M. pneumoniae

     -homogenous granular appearance = mulberry shaped 

     -Ab-specific tests

     -cold agglutinins (auto-Ab against RBC during infxn)

-extracellular pathogen

-P1 adhesin binds sialated glycoprotein Rs on base of cilia of resp epithelium-->ciliostasis-->cell death-->interfere with normal clearance of of gunk from upper resp tract and infxn can move to lower resp tract (persistent cough)

-M. pneumoniae = superantigen 

-strictly human pathogen

-worldwide distribution year-round; see in kids and young adults

-colonizes nose, throat, trachea, lower airways

-spreads via resp droplets when cough

-Infection can range from:

     -asymptomatic carriage

     -tracheobronchitis with low-grade fever, dry and 

      nonproductive cough

     -acute pharyngitis

     -bronchial paassages get infiltrated with lymphocytes

      and plasma cells

     -can get atypical walking pneumonia

-extra-pulmonary manifestations:

     -stevens-johnson syndrome, erythema multiform,

      Raynaud's phenomenon, arrhythmias, hemolytic anemia,

      guillan-barre syndrome 

-obligate intracellular gram-negative

-diagnose with serology, don't culture

-inhale small cell varient (SCV), which is resistant to environmental stress-->phagocytosis-->rearranged into large cell varient (LCV)-->fusion of phagolysosome-->LCV replicates-->LCV reorganizes into SCV-->released into environment

-different LPS antigens in cell wall -- antigenic variation

     -highly infectious form has LPS with complex carb

-phase I antigen blocks Ab interaction w/ surface proteins--> surface protein undergoes a deletion mutation-->phase II Antigen (??????)

-Q (query) fever

-associated with ticks, contaminated environmented, unpasteurized milk, worldwide

-most patients have asymptomatic infection

-symptomatic infxns normally mild and flu-like

-rarely, pneumonia, hepatitis, subacute endocarditis 

-do vaccinations of animal herds to decrease prevalence