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Inflammation is characterized by increased ___________ with leakage of __________, often accompanied by ______________.
vascular permeability; plasma; WBCs migrating to the perivascular space
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Inflammation of the grey matter of the brain.
polioencephalitis
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Inflammation of the white matter of the brain.
leukoencephalitis
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Inflammation of the spinal cord.
myelitis
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Inflammation of the peripheral nerve.
neuritis
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Inflammation of a nerve root.
radiculoneuritis
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Suppurative exudate contains ____________; it occurs due to __________; there may be accompanying ___________.
neutrophils; bacterial infection; tissue necrosis
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Non-suppurative exudate contains __(2)__; it occurs due to... (3)
lymphocytes and histiocytes; viral infections, immune-mediated processes, or certain parasitic diseases.
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Granulomatous exudate is __________ of ___________; occurs in the CNS due to __(2)__.
focal accumulations; macrophages; mycoses and some bacteria
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Eosinophilic exudate occurs with ___________.
parasitic infections
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Fibrinous exudate reflects a ___________ insult, which may suggest certain _____________.
severe vascular; infectious agents
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_____________ are the accumulation of cells in the perivascular space and may be the result of __________.
Perivascular cuffs; cellular efflux or influx
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Infiltrating cells associated with perivascular cuffs include... (4)
lymphocytes/plasma cells, eosinophils, monocytes.
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Cellular efflux results in perivascular cuffs when _________ attempt to move back into circulation, but this process is compromised b/c of their ____________, therefore they accumulate in the perivascular space.
gitter cells; extreme cytoplasmic engorgement
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Why is a spinal tap diagnostic for CNS inflammation but not localizing of the lesion?
perivascular space communicates with the subarachnoid space; therefore, cells accumulating in perivascular space can get into the CSF
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The specialized lymphatic vessels lining the dural sinuses drain to the ______________, where immune responses can be primed.
deep cervical lymph nodes
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What are risks associated with having the potential to initiate and maintain immune/inflammatory responses in the CNS? (2)
cells lost may not be replaceable, CNS contains privileged antigens that may initiate autoimmune reactions
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Tissue-specific antigens are sequestered in the CNS during _____________; inappropriate presentation of these antigens to the immune system can result in _____________.
T cell maturation; immune-mediated neurologic disease
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How does the CNS support inflammatory responses and avoid undue damage in the process? (3)
restrict antigen presentation in the CNS by limiting MHC I and II expression, Tregs suppress inflammatory responses, cells are resistant to cytotoxic compounds released by I cells
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__(2)__ of the CNS are invisible to the immune system due to their poor expression of MHC.
Neurons and somewhat oligodendrocytes
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MHC I may be induced in __(2)__.
astrocytes and oligodendrocytes
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MHC II may be induced in _________.
microglia
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__(2)__ are the major APC of the NS.
Endothelial cells and CNS macrophages
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__(2)__ are a good place for intracellular infectious agents to persist in the CNS.
Neurons and oligodendrocytes (invisible to the CNS b/c do not express MHC)
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What is the most common route of infection for CNS inflammation?
hematogenous
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Infectious organisms localize wherever __________ is high and __________ is small, such as in the... (4)
vascular density; vessel caliber; leptomeninges, choroid plexus, subependyma, grey-white junctions
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Factors affecting distribution of infectious agents. (2)
size of particles, tropism for specific vascular beds
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Neural distribution of infectious agents occurs by ___________; 2 examples of agents that use this methods include...
retrograde axonal transport; rabies, listeria
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Direct extension of infectious agents from surrounding structures occurs near the __________ and extension from the _____________.
nasal turbinates; otitis meda/interna
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2 ways bacterial infection is spread.
hematogenous and direct extension
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Suppurative meningitis is secondary to ____________; it is generally a disease of _____________ animals, which as those with __(2)__.
septicemia; young, immunocompromised; FTPI or SCID
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With suppurative meningitis, _______ infectious particles are __________ aggregated by antibody and ___________ distributed in circulation to ____________.
small; minimally; widely; multiple organ systems
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Organ systems commonly affected by suppurative meningitis include... (3)
synovial membranes (polyarthritis), serosal membranes (serosal petechia), kidneys, and CNS
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A CNS lesion associated with suppurative meningitis is ______________; exudate is __(2)__.
cloudiness of the meninges; bacterial or sterile (bacteria have been cleared)
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____________ associated with suppurative meningitis occurs due to increased intracranial pressure, which is exacerbated by periventricular encephalitis and/or choroiditis, which directly ____________.
White matter edema; obstruct CSF flow
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With meningoencephalitis, seeding of the CNS structures is by __________ particles that are __________ distributed in circulation; there is __________ of antibody aggregation.
moderately-sized; sporadically; a greater degree
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The primary site of infection is more/less readily defined with meningoencephalitis than with suppurative meningitis.
more
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Extension of meningoencephalitis to involve the brain is facilitated by ________________.
capillary embolization/ venous thrombosis
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With meningoencephalitis, the agent may have a tropism for __________, thus promoting __(3)__.
brain endothelial cells; vasculitis, thrombosis, and infarction
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Infectious agent of bovines that has a tropism for brain endothelial cells.
Histophilus somni
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With CNS abscess formation, _______ infectious particles are ___________ distributed in circulation; this may reflect the addition of ________ to the emboli.
large; sporadically; fibrin
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The primary site of infection with CNS abscess formation is often the ___________ due to ____________.
endocardium; bacterial endocarditis
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With CNS abscessation, infection does not spread beyond the ___________, which is ________ by _________.
devitalized tissue; walled off; fibrous astrocytosis
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With a brain abscess, the thin fibrous capsule may _______ with ________, leading to... (3)
break; head trauma; reactivation of infection, edema, and death.
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_____________ may represent a sequel to bacterial meningoencephalitis.
Meningeal abscessation
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What are the 3 syndromes associated with Listeria monocytogenes?
abortion, septicemia, encephalitis
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____________ permits overgrowth of Listeria, which enters branches of the _________ when eaten.
Inadequate fermentation of silage; trigeminal nerve (defects in oral mucosa, exposed dental pulp)
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Ascension of Listeria organisms from the __________ to the brainstem occurs via ____________, inciting __________.
trigeminal n.; retrograde axonal transport; encephalitis
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Brainstem lesions associated with Listeriosis are ______________, __________ formation, and _____________.
lymphocytic meningoencephalitis; parenchymal microabscess; lymphocytic perivascular cuffing
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What are the 2 requirements for a cell type to support viral replication?
target cell must express the appropriate surface receptors, target cell must be able to provide the appropriate intracellular metabolic environment
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With hematogenous viral spread to the CNS, viral particles are carried by __________ across the BBB, where they infect ___________; this is followed by direct infection of the ___________ and are shed in _______ to spread to the rest of the NS.
leukocytes; endothelial cells; choroid plexus epithelium; CSF
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What is required to create successful infection with retrograde axonal transport of viral particles?
some type of amplification post-inoculation
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A virus that can infect neural cells under natural conditions.
neurotropic virus
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Virus that is capable of entering the CNS from peripheral sites.
neuroinvasive virus
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Virus that is capable of spreading through CNS and thus causing disease.
neurovirulent virus
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A neurotropic virus with a low degree of neuroinvasiveness but a high degree of neurovirulence. [specific pathogen]
herpes simplex virus (always enter PNS but rarely enters the CNS...when it does, it replicates like crazy and causes disease)
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A neurotropic virus with a high degree of neuroinvasiveness and neurovirulence.
rabies virus
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Increased __(2)__ is observed in neonates because... (3)
neuroinvasiveness and neurovirulence; biological barriers are not fully formed, not fully immune competent, cell proliferation/tissue development ideal for viral replication.
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Viral gene infection resulting in death of the host cell.
cytopathic/lytic infection
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______________ typifies persistent infection; ______________ is characteristic of latent infection.
Low-level viral gene expression; no viral expression for extended periods of time
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RNA viruses replicating in the cytoplasm cannot undergo ____________.
latency
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What is the result of toxic effects of viral genes at low level expression?
sustained cell viability with loss of luxury functions, such as myelin production---> clinical neurologic disease with demyelination
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Cytopathic infection leads to _____________; therefore, ___________ is a continuum; the precise relationship is defined by _________.
persistent non-ctopathic infection; latent infection; host factors (age, immune status)
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Viruses that exhibit non-cytopathic infection in differentiated cells, but exhibit cytopathic infection in dividing cells.
radiomimetic viruses
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Cytopathic/lytic viral infection may result in __(2)__.
direct or indirect damage on CNS cells
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Describe how cytopathic viral infection can lead to indirect damage of the CNS.
highly inflammatory lesions resulting in extensive demyelination and productive infection of microglia; release of large amounts of antiviral antibody
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Highly inflammatory lesions due to viral infection result in the production of _________, which enhances microglial activation and __________, which can lead to ___________;
IFNγ; MHC II expression; demyelination
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Vascular lesions associated with viral infection can lead to __(4)__; the mechanism of damage involves... (2)
CNS edema, hemorrhage, thrombosis, and infarction; infection of vessel wall and deposition of immune complexes in the vessels.
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General features of virus infected tissues. (3)
non-suppurative perivascular infiltrates, necrosis of specific cell types, inclusion bodies
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Viral clearance is ________-mediated; clearance is correlated to a _________ activity and can occur without _____________.
T cell; cytolytic; destruction of infected neurons
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Accumulations of viral protein or mucoprotein in the nucleus or cytoplasm of target cells.
viral inclusion bodies
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Derivative of nucleoli and arise to supplement nucleolar function to support the increased metabolic demand placed upon cells by virus replication.
nuclear bodies
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CDV is caused by a __________ and it is a __________ disease; the extent of tissue destruction mediated by virus gene expression is a reflection of __(2)__.
paramyxovirus; multisystemic; host age and immune status
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With CDV, initial virus replication is in ________ tissues of the __________, which leads to ________ with seeding of ________ of the body; virus replication results in __________.
lymphoid; respiratory tract; primary viremia; lymphoid tissues; secondary viremia
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In what cells does CDV replicate?
tissues with cell proliferation or cells with a high degree of metabolic activity (radiomimetic)
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What is the key to viral shedding with CDV?
infection of epithelial tissues- bronchiolar, intestinal, cutaneous, urinary, odontogenic
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___________ is the common cause of presenting clinical signs of CDV.
Secondary bacterial infection (esp. respiratory and GI)
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3 types of clinically evident CDV CNS infections.
acute encephalopathy, subacute encephalitis, delayed onset encephalitis
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Acute encephalopathy associated with CDV is a ______________; it occurs in _________ animals that lack _________ from _________.
neuronal lytic infection; animals < 4weeks old; protective immunity from colostrum
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Describe the appearance of acute encephalopathy associated with CDV. (4)
rapid death, minimal structural evidence of infection, viral antigen is ubiquitous, inclusion bodies are RARE
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Subacute encephalitis caused by CDV is a ____________; it occurs in __________ animals that have a __________ but are ___________.
glial lytic infection; animals > 4 weeks old; mature immune system; immunologically naive to CDV
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With subacute encephalitis caused by CDV, progression of virus through nervous tissue is ___________, and as a result, infection of ___________ is apparent, clinically apparent CNS involvement may develop, including __(3)__.
protracted; non-neuronal; periventricular demyelination, glial inclusions, astrocytic syncytia
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How does CDV cause periventricular demyelination?
oligodendrogial damage and loss of metabolic support by astrocytes--> demyelinating encephalitis
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Delayed onset encephalitis caused by CDV is known as __________; what are the 2 theories of pathogenesis?
old dog encephalitis; viral persistence in neurons and reactivation, causing direct host cell damage; cumulative insults due to virus persisting in neurons and constant low level expression, leading to structural damage
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What features of old dog encephalitis are relatively constant? (2)
no prior clinical evidence of CDV, but antiviral antibody titers in serum and CSF are high
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Lesions of old dog encephalitis are characterized by... (4)
neuronal degeneration and necrosis, +/- intranuclear inclusion bodies, lymphoplasmacytic perivascular cuffs, gliosis
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Rabies virus infection results in ________________ with formation of ____________.
neuronal degeneration and necrosis; Negri inclusion bodies
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Rabies virus initial viral replication is at the site of _________; prior to the completion of this stage, ___________ may suppress __________.
entry; passive immunity; viral spread
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If point of entry of Rabies is by aerosol, initial replication takes place in ____________; if by bite wound, initial replication is in ___________ and ___________.
neuroepithelial cells of nasal mucosa; muscle cells and cells of the sensory spinal apparatus
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After initial viral replication of rabies, virus enters ______________ and ascends to the associated _________ by ____________ transport; this allows the virus to be _______________.
peripheral sensory nerve; paraspinal ganglion; retrograde axoplasmic transport; shielding from immune surveillance
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How does rabies virus get to the mandibular salivary gland for viral shedding?
axoplasmic transport carries virus to peripheral tissues from the CNS; goes o sensory ganglion of CN5 to mandibular salivary gland (also goes to mammary gland and gravid uterus)
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What makes up the clinically observed incubation time/eclipse phase of rabies infection?
viral replication at site of entry through transport to peripheral tissues from CNS
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Describe the onset of clinical signs associated with rabies infection. (3)
weakness or paralysis, difficulty swallowing due to laryngeal paralysis, death occurs when virulent strains reach the brain
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Location of viral inclusion Negri bodies in carnivores and herbivores.
carnivores: hippocampus, herbivores: Purkinje cells
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Les virulent strains of rabies virus will be stalled due to their tendency to _____________; this can lead to ________ restriction and _________ rabies; with this, there is decreased __(2)__.
incite a substantial inflammatory response; spinal cord; paralytic; formation of inclusion bodies and likelihood of salivary shedding
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What is "post-vaccinal rabies"?
we cannot be assured that a modified live vaccine approved for use in one species will be safe in another; modified live vaccine can lead to paralytic rabies
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How is rabies diagnosed? (4)
immunofluorescence staining for viral antigen, inclusion bodies in hippocampus, histopath, RT-PCR of viral RNA
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Equine herpes myeloencephalitis is a _________ infection of ___________; it is caused by ____________.
lytic; vascular endothelium; equine herpesvirus 1 subtype 1 (abortagenic strain)
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Equine herpesvirus 1 subtype 1 has a tropism for ____________ of ____________; infection of these cells results in ___________ with ___________.
endothelial cells; spinal cord white matter; vasculitis; hemorrhage
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Grossly, what does equine herpes myeloencephalitis look like?
diffuse red triangular foci of hemorrhage in spinal cord white matter, Wallerian degeneration
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Diagnosis of equine herpes myeloencephalitis is by...
gross and histopathology
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