RT4 by Like Mike Flashcards
bordatella toxins
TCT = tracheal cytotoxin; PT = pertussis toxin; ACT = adenylate cyclase toxin; DNT = dermonecrotic toxin; LOS = lipooligosaccharide FhA = Filamentous haemagglutinin
advantage of FhA
Multiple binding sites enables attachment to multiple cell types such as ciliated epithelial cells and macrophages
Stages in B. pertussis pathogenesis
- transmission
- adhesion (using virulence factors FHA, PT, Fimbriae)
- growth and toxin release (using virulence factors PT, ACT and TCT)
- Local and systemic pathology (using virulence factors TCT, PT, DNT, LOS)
- Bacterial clearance
Whooping cough stages (symptom based)
- incubation (0-1 days)
- catarrhal (signs of common cold, 1-2.5 days)
- paroxysmal (cough, vomiting, trouble breathing due to constriction, bacterial growth. difficulty INHALING (get whooping inspirational noise)
can cough so hard they vomit
can be fatal due to respiratory insufficiency, 2-4 days) - convalescence (~4-7 days)
culturing and identifying B. pertussis
take sample from nasopharyngeal swab or secretions
don’t due throat swab
is sensitive to lipids which are in cotton swabs so don’t use cotton swabs
so use alginate/special bordatella swab
is nutritionally fastidious so use charcoal blood agar + cephalosporin (slows growth of background bacteria). example media: bordet-gengou
DaPT vaccine for Pertussis
“aP” in DaPT vaccine
use accelular components, e.g. Fha, PT. lower rate of side effects than whole cell vaccine
viral agents for infectious bronchitis and bronchiolitis
influenza virus
adenovirus
respiratory syncitial virus
bacterial agents for infectious bronchitis and bronchiolitis
bordatella pertussis
mycoplasma pneumonia
chlamydophilia pneumonia
most common infectious agents causing bronchiolitis are bordatella and mycoplasma
Bordatella pertussis (general info)
clinical syndrome: whooping cough (chronic bronchitis)
small, gram -ve coccobacillus
typically occurs in unvaccinated children
adults important as reservoir
highly communicable
HPIV (general info)
clinical syndromes: laryngotracheobronchitis (croup), bronchitis
virus family: paramyxoviridae
enveloped
glycoprotein with Hemagglutinin-Neuraminidase (HN) activity
fusion factor (F): involved in viral entry. ABs against F protein are neutralizing
Paramyxoviridae overview
2 subfamilies:
-paramyxoviriniae: has genera respirovirus and rubulavirus. respirovirus has species HPIV-1 and HPIV-3. Rubulavirus has species HPIV-2 and HPIV-4
-pneumoviriniae: has genera RSV, mPV (metapneumovirus )
Genetic material of HPIV
Linear ss (-) sense RNA Release of nucleocapsid into cytoplasm occurs following fusion of viral and host cell envelopes
Key Viral Proteins of HPIV
P/F proteins: Immune evasion
F Proteins (fusion proteins): role in syncitium formation
HN Protein Structural: Hemagglutinin and Neuraminidase activity
L Protein: Multifunctional Polymerase
M Protein Matrix: Structural Protein
Croup aka laryngotracheobronchitis (important)
commonly caused by respiratory viruses (HPIV, Pneumovirus, RSV)
most common in young children and infants
swelling and narrowing of airway, distinctive cough (sounds like seal barking)
rarely can be fatal
seasonal variability of RSV
peaks around december through january
immunopathological component of RSV infection
suggested role of CD8+ T cells
subsequent disease shown to be ENHANCE (i.e. make it worse) when children vaccinated with heat-killed vaccine
Epidemiology of Influenza
an epidemic disease
epidemic flu is transmitted amongst people (no animals needed)
transmitted via respiratory droplets (virus survives drying for ~24 hrs)
epidemics rarely continue in community for >4-6 wks (most ppl recover spontaneously and develop long-lasting (but weak) immunity to that particular strain)
Flu symptoms in adults
rapid onset after incubation of 1=4 days
sudden malaise and headache lasting a few hours
abrupt rise of fever, chills sever muscle aches. loss of appetite, non-productive cough (these symptoms can last 3-8 days)
recovery is complete in 7-10 days
pt is contagious FROM BEFORE SYMPTOMS APPEAR (end of day 1) for 1st week
risk of secondary infection highest from 6-12 days after infection
Flu symptoms in Children
same as those in adults plus these additional symptoms: higher fever G.I symptoms: (Vomiting, Abdominal pain) Earache (Otitis Media) Muscle pain and sometimes swelling Croup often Febrile Convulsions (Children under 3: Rare)
symptoms helping distinguish common cold from influenza
fever, headache and vomiting/diarrhea (rare in cold, common in flu) general malaise (slight in cold, common, severe and lasting weeks in flu) nasal discharge (common and abundant in cold, less common and not abundant in flu) sore throat (common in cold, much less common in flu)
complications of flu
Primary Viral Pneumonias
Secondary Bacterial Pneumonias
Muscle inflammation – Cardiac involvement
Rare Neurological syndromes: Guillain Barre’, Encephalitis,
Reye’s Syndrome in Children (made worse by aspirin containing drugs)
Influenza Virus Type “C”
cause mild illness
do not cause epidemics or pandemics
not classified according to subtype
Zoonotic transmission of influenza Virus Type “A”
a disease of birds (most commonly found in domestic ducks)
wild ducks and sea birds are reservoir–>associate with domestic ducks (competing for food, e.g.)–>domestic pigs, chickens and/or people get infection from domestic ducks
people can get infected from chickens, domestic pigs, too
chickens with flu can cause epidemics
most birds have no symptoms
Influenza B and Severe Disease
•Two lineages of influenza B circulate in the population— lVictoria-like
lYamagata-like
lonly 1 is covered by the trivalent seasonal flu vaccine. •Influenza B is not paid as much attention as the common A strain, notwithstanding influenza B’s ability to cause fulminant disease, precipitate Reye’s Syndrome, and result in fatal illness.
flu virus nomenclature
Nomenclature:
Type/Host of origin/Geographic origin/Strain number/Year of isolation plus antigenic description of HA and NA (type A only).
E.g., A/Avian/Hong Kong/03/68 (H3N3)
E.g., B/Kansas/246/76
lSub-grouping for Influenzavirus A = based on
surface antigens: Haemagglutinin (HA/H) Neuraminidase (NA/N)
H and N
15 H types
9 N types
Our bodies develop immunity to each separate type of H and N independently. (Immunity to H1 will not protect against H2 for example.)
how do we know influenza is an important human pathogen?
Humans have a gene encoding a protein which seems to be dedicated to preventing
influenza virus infection:
Interferon-inducible dynamin-like myxovirus resistance protein (MxA)
flu as stealth virus
HA and NA (proteins usually incorporated in vaccines) inducing less than expected immunogenicity:
examples of HA:
In H7N9/A/Shanghai/1/2013 (H7N9)
examples of NA:
A/California/07/2009 (HIN1)
A/Victoria/361/2011 (H3N2)
A/Shanghai/1/2013 (H7N9)
Structure of flu viruses
8 RNA segments (influenza A and B) 7 RNA segments (influenza C) M2: ion channel M1: matrix protein (inner lining to membrane, holds things in place) lipid envelop (outside of M1) NA HA
M2, NA and HA are antigens
HA more antigenic than NA
mechanism of influenza entry into cell
receptor mediated endocytosis
hemagglutinin
Rod-shaped.
25% of viral protein
Highly variable: responsible for evolution of new strains
Carried out by cellular proteases
Proteases probably define tissue tropism
HA spikes extend like springs during infection (changing their structure due to low pH), attaching and bringing host cell closer
HA aids in receptor mediated endocytosis (RME)
NA
Definition: Sialidase enzyme (removes terminal sialic acid residues from glycoproteins and glycolipids)
Functions/roles:
Enables release of newly formed budding virus from host cells.
Helps virus move through mucin layer.
Two subtypes described in humans: N1 and N2.
NO stimulation of neutralizing antibodies
role of immune response in flu pathogenesis (general)
immune response is protective to some degree but deeply involved in pathogenesis as well
