L13 Flashcards
Three requirements to ensure successful infection of host:
- Sufficient virions available to initiate infection
- Cells at site of infection need to be physically accessible to virions, must be susceptible (bear receptors for entry), and permissive (contain intracellular gene products needed for viral replication)
- Local host antiviral defense systems must be absent or initially ineffective
Requirements for a successful infection simple
- Dose
- Access to target cells: be susceptible an permissive
- Absent or insufficient host immunity (innate not good enough for virus)
Transmission
Spread of virus from one susceptible host to another
Two patterns of virus transmission
- Perpetuation of transmission in one species (measles only in humans (are reservoir))
- Alternate infection of insect and vertebrate host (rabies from animals to humans but maintains in animals)
What is the term for a viral disease shared by humans and animals/insects
Zoonoses
The number of virus particles required to initiate and maintain infection depend on what three things?
- particular virus (how many virions needed to infect)
- Site of infection
- Age/physiology of host
A ___ virus particle can initiate an infection; complexity of the infectious cycle, and probability of a single virus particle completing the cycle is_____ 100%
single
not
In the initiation of an infection can defective virus particles be produced?
Yes
How can virus infectivity be determined?
- Tissue culture infectious dose
- Plaque assays
Virus entry into the respiratory tract
- Common
- large absorptive area (140m2) and high ventilation rate (6 Lair/in)
- So many foreign particles and aerosolized droplets introduced to the lungs with every breath
Respiratory tract defence mechanism
- mechanical barriers like the
- mucociliary blanket of ciliated cells
- Mucous-secreting goblet cells
- Subepithelial mucous secreting glands
All trap foreign particles and swallow or move them from lungs to throat. - Macrophages that line alveoli ingest and destroy particle
What form do virus enter the respiratory tract
Aerosolized form
The aero droplets expelled by an infected person cough or sneeze
What do goblet cells do
- secrete mucous that acts like a barrier to virus attachment
- Virions will pass though barrier and multiply in ciliated cells or pass between them
- Will then reach the basement membrane and virions taken to lympathic capillaries and reach blood
- Macrophages patrol tissue fluids and ingest foreign particles
Viruses can replicate that different levels of the respiratory tract
yes
What is the Alimentary Tract
Stomach
Virus Entry: Alimentary Tract
- Common route of infection and dispersal
- Extremely hostile environment for virions – stomach = acidic, intestine = alkaline
- Many digestive enzymes and bile detergents, intestine is lined by mucous, lumenal surface includes antibodies and phagocytes
What virus can replicate in lowpH of stomach
Poliovirus
Changes in capsid that occur under acid conditions are fully ___; low pH induces ____ disassembly of the rhinovirus capsid
reversible
irreversible
The intestine wall is made up of what?
epithelial, connective, and muscle tissues, made up of different cell types within an extracellular matrix.
What does a typical M cell have
surrounded by 2 enterocytes. Lymphocytes and macrophages move in and out of invagina&ons on basolateral side of M cell
Virus Entry Through Skin
- Skin of most animals is an effective barrier against viral infection – dead outer layer cannot support viral replication
- Entry through skin mostly occurs when integrity has been breached by breaks or punctures:
Entry through skin mostly occurs when integrity has been breached by breaks or punctures:
- Mechanical transmission eg.
1. by insect vectors such as arthropods, introducing virus into highly vascularized dermis
2. by hypodermic needle puncture into tissues below dermis.
Urogenital tract mucosal cells are protected by what?
mucous and low pH
Minute abrasions allow viruses to enter – may produce local lesions, spread to other organs
fact
Transplacental infection
- ZIKV infection can occur during any pregnancy stage
- By mosquitos
- ZIKV can breach the placenta barrier
Virus infect targets cells where
at site of entry
Progeny viruses remain localised and is contained within what
Epithelium by immune response and by physical structure of tissue
Virus spread: disseminated
They are spread beyond primary site and can lead to systemic infections
Virus spread: systemic infection
Many organs are infected
Polarized (directional) release of virus from cells
- Directional release of virus from polarised cells at a mucosal surface permits avoidance of shot immune response
- Will facilitate and spread within the body
Virus released at the apical surface will:
Establish localised infection where the underlying lymphatic and circulatory vessels rarely invade
Virus released at the basolateral surface of polarized epithelial cells are:
distant from def of the lumenal surface and can access underlying tissues and facilitate systemic spread
Haematogenous Spread
- Entry of virus to bloodstream results in disseminated infection
- Virus replicates at entry site and is released into extracellular fluid, which can be taken up by local lymphatic vascular system
- Lymphatic vessels drain into circulatory system -> viruses enter bloodstream
- In lymphatic system viruses pass through LN where they encounter migratory immune cells -> infected immune cells release virus into plasma or tissues
How can a virus enter the bloodstream
- directly through capillaries
- By replicating in endothelial cells
- by inoculation by a vector bite
Viremia
: presence of infectious virus in blood [virions may be free in blood or contained within infected cells, such as lymphocytes]
Ac.ve viremia:
when there is replicating virus in blood
Passive viremia:
introduc&on of virions into blood without replication at site of entry
Primary viremia:
progeny virions are released into blood aRer ini&al replication at site of entry
Secondary viremia:
Delayed appearance of high concentra&on of infectious virus in blood, following dissemina&on from initial entry site
Neural spread
- Virus spread from primary by entering local nerve ending
- If they infect NS - neurotropic
- Virus repliation first in non-neural cells to afferent (sense) or effected (motor) fibres that innervate infected tissue
Non- PNS then SC then brain
Herpes latency in PNS
Reactivationfromlatencyresultsinviralreplicationin primary neuron and transport of progeny virions back to peripheral tissue (to form a cold sore) , or to the CNS (to cause lethal viral encephalitis)
Organ invasion
- After spread from primary into blood virus needs to invade new tissue/cell
- Continuous endothelium and basement membranes
- fenestrated epithelium
- sinusoid
Found in CNS, CT, muscle, skin and lungs
Contin. endothelium and basement membranes
Found in choroid plexus, intestinal vili, renal glomerulus, pancreas, endocrine galnd
Fenestrated epithelium
Adrenal glands liver spleen and bone marrow
Sinusoid lined with macrophages of reticuloendothelial system
Adrenal glands liver spleen and bone marrow characterised by sinusoid with macrophages
Macrophage infected by virus present in blood will infect underlying cells
Kupfer inected (line liver) infect hepatocytes and cause hepatitis
Found in CNS, CT, muscle, skin and lungs characterised by dense basement membrane
- CNS basement mem is foundation of BBB
- Virus pass thru capiliary endothelium and enter stroma of choroid plexus, cross epithelium to CSF and infeact brain tissue
- Cross BBB or via transcytosis
Skin rashes
- made when virions leave blood
- In systemic infections (V)
*
Macules and papules
Small and flat non elevated
Small and swollen bumps
Macules and papules develop when
Infection in dermis with lesion confined in or near vascular bedV
Vesicles and pustules occur when
virus spread from capillary to superficial skin
Rash in mucosal tissue (mouth and throat)
Mealses infect vesicles of mouth and breakdown to become ulcers like koplik spots
Vasicular rash
Varicella zoster virus (chicken pox and shingles)
Maculopapular rash
Measules and zika
latrogenic
activity of health care worker leads to infection of patient
Nosocomial:
individual is infected while in a hospital or health care facility
Vertical:
transfer of infection between parents and offspring
- Horizontal:
all other forms of transmission
Germ line: transmission as part of host genome (eg. Integrated proviral DNA)
transmission as part of host genome (eg. Integrated proviral DNA)
How infection is a virus
*Viral infectiousness is quantified and viruses are assigned a reproduction number (Ro)
* Ro = average number of secondary cases generated by one primary case in a susceptible community (with no control measures)
- The higher the Ro value, the more persons can be infected from one case
- However, the incubation period in the host (and the vector where relevant) is also important
- Viruses with longer incubation periods and low Ro gives time for possible use of_____ to stop an outbreak eg. SARS
quarantine
- Viruses with high Ro and short incubation period are significant public health problems eg. Influenza
asdf
RO
hep C
Ebola
HIV
SARS
Measles
2
2
4
4
18
