NERVOUS SYSTEM
Neurons –
highly specialized.
Not much capacity to regenerate
Specialized chemicals for nerves to talk to each other- nervous system must be isolated.
no normal flora.
Barrier for isolation –
in a “plastic” bag
Brain and spinal cord
meninges : dura matter, arachnoid matter, pia matter (outside to inside).
bag filled with fluid. Fluid mostly between arachnoid and pia matter = cerebral spinal fluid. Nutrients and oxygen enter via blood to brain. Vessels must reach deep into brain. CSF –shock absorber, mechanical + chemical barrier. Not a molecular barrier.
Molecular Barrier at Blood Vessels
Lining cells of capillaries -very densely packed, forms blood/brain barrier. Oxygen nutrients pass. Stops MOST microbial infection.
Brain has just been discovered to have lymphatic circulation [June 2015]. The interaction with the menigeal fluid is not defined yet.
CSF tested by lumbar puncture.
Normal–very little protein, few antibodies, very few white cells.
Inflammatory Process or Blood/Brain Breach: abundant protein and antibodies, cells, WBC, lymph, + macrophages.
BRAIN – generally organized with nerves inside and cell bodies outside.
SPINAL CORD – Nerves out, cell bodies inside
NEURONS – sensory, signals in; motor, signal out.
Infections of PERIPERAL NERVES
BACTERIAL:
LEPROSY – (Hansen’s disease)
– 2 types Caused by Mycobacterium leprae. Schwann cells. Picked up by nasal secretions. Causes nerve damage by inflamed granuloma near those nerves.
1. Tuberculoid leprosy –
The outcome is much like Mtb. Occurs if the immune response activates macrophages. A strong delayed hypersensitivity reaction but a weak antibody response. lymphocytes forming granulomas. Relatively few bacilli are seen in tissues because production of cytokines mediates macrophage activation, phagocytosis and bacillary clearance.
2. Lepromatous leprosy –
occurs if the immune response activates antibodies. This is the most infectious form of leprosy. Damage is due to nerve destruction.
culture difficult: grows in.……..
Nov 2015 new research
Also remember Clostridium Botulinum and Tetanus
VIRAL
HSV –
Initiated by direct contact, dependant on infected tissue.
Causes direct cytopathology. Avoids antibody by cell-cell spread.
Latency occurs in neurons. Reactivated by stress or host compromised.
Cell mediated immunity is necessary to rid the infection. Both NK cells and T cells
POLIOMYELITIS –
caused by polio virus, enterovirus; picorna. Enters through the gut, the virus spreads from the blood to anterior horn cells of spinal cord + motor cortex of the brain. Severity of the paralysis depends on neurons affected.
fecal-oral route.
Vaccination:
Salk – killed virus in suspension
Sabin – live virus, only infects gut cells. Colonizes the gut, this causes generation of antibodies which protect neurons from infection of the wild type.
Polio History and current vaccine recommendations for children in the US
RABIES –
rhabdovirus; transmitted by animal bites.
Virus multiplies at site of inoculation remains localized for days to months, before infecting the peripheral nerves.
Once virus reaches spinal cord rapid infection of brain follows. Virus then disseminates from the CNS via afferent neurons to highly innervated sites. Antibody can block the spread of the virus to CNS and brain, if present during incubation.
Hydrophobia – stemming from pain associated with attempts to swallow water, due to spasms in the throat =”foaming at the mouth”.
MENINGEAL INFECTIONS
Bacterial Meningitis
Strep. pneumonia – common inhabitant of throat and nasopharynx.
Haemophilus
E. coli – causes neonatal meningitis.
Neisseria meningitis – Encapsulated, G negative, diplococci.
Can asymptomatically colonize the nasopharynx of healthy people or cause meningitis. Pathogenisis by three factors:
– 1) ability to colonize nasopharnyx
– 2) systemic spread [ if no antibody-mediated phagocytosis] (capsule)
– 3) expression of toxic effects.
Attaches selectively to specific receptors for menigoccocal pili. Binds to nonciliated columnar cells of the nasopharynx. The anti-phagocytic characteristic of the polysaccharide capsule protects it from phagocytosis. The diffuse vascular damage is in large part because of the lipopolysaccaride endotoxin. Serum bactericidal antibodies are important for preventing systemic disease.
Transmission is by respiratory droplets. Humans are only natural carriers.
review:
Listeria monocytogenes
facultative intracellular pathogen, motile, capable of growth in macrophages, epithelial cells and fibroblasts.
listeriolysin O, necessary for release of bacterium after phagocytosis made by all virulent strains
intracellular growth–breaks the phagolysozome which releases the bug. The bug then takes up actin and uses it to push through host cells. [spread!]
FUNGAL
Cryptococcus neoformans – fungus -yeast form. Capsular polysaccharide (acidic), critical for pathogenicity.
Lung -primary site of infection but spreads to the brain and meninges. –pigeon habitats. Can produce symptomatic pneumonia, also localize to bone infection.
PROTOZOAN
Toxoplasma gondii – causes meningo-encephalitis=infects meninges and brain. Most common reservoir is cats. Intracellular parasite. Humans become infected by 2 sources:
1) improperly cooked meats
2) infective oocysts from cat feces.
Illness is affected by immune status of the person
reactivation of previously latent infection common. Can be benign and asymptomatic with symptoms only occurring as the parasite moves in the blood to tissues where it becomes an intracellular parasite. Avoids phagosome fuse with lysosome –covers itself with the host’s protein called laminin.
VIRAL
caused by a flavivirus
Zika virus replicates in the mosquito’s midgut epithelial cells and then its salivary gland cells. After 5–10 days, the virus can be found in the mosquito’s saliva, which can then infect humans. If the mosquito’s saliva is inoculated into human skin, the virus can infect epidermal keratinocytes, skin fibroblasts in the skin and the Langerhans cells. The pathogenesis of the virus is hypothesized to continue with a spread to lymph nodes and the bloodstream. Flaviviruses generally replicate in the cytoplasm, but Zika antigens have been found in infected cell nuclei too.
from the NYer progress towards a vaccine 16Aug2016
microbiologists try a block at the level of mosquitoes
and PBS Ebola and Zika in the World
approach to quickly approved treatments
“We showed that neural progenitors can be infected by a strain of Zika virus that is currently infecting people in the Americas,” Dr. Schoggins said. “We found that the virus kills some neural progenitor cells, but not all. Other cells survive the infection, and surprisingly, continue to replicate the virus for many weeks. In addition, it appears that Zika virus does not stimulate much of an immune response.” –from ScienceDaily June 4, 2016
Encephalitis – arboviruses, host in arthropods; alphavirus and flavivirus. Attach to specific receptors.
The flavivirus attaches to Fc receptors on macrophages, monocytes, and other cells when they are coated with antibodies. The antibody enhances the infectivity of the virus by providing new receptors for the virus, promotes uptake into cells
The difference between alphavirus and flavivirus: the organization of their genomes and the mechanisms of protein synthesis. Both cause lytic or persistent infections. They make a nucleotide triphosphatase that degrades DNA. The virus infects the epithelial cells of the midgut of the mesquito and spreads through the basal lamina of the midgut to the circulation, then infects salivary glands. The virus sets up persistent infection and replicates to high titers. The mosquito inserts virus containing saliva into the victim’s bloodstream. The virus circulates free in the plasma and comes in contact with the target cells.
These viruses may cause mild systemic infections because of the inflammation due to induction of interferon. (like rhinoviruses)
SLEEPING SICKNESS
-caused by Trepansoma brucei, a flagellated protozoan
life cycle
– transmitted by bite of tsetse fly.
– infected state is trypomastigote, these enter the wound by bite and get into blood and lymph
eventually invading CNS.
constant fever and resultant sleepiness by TNFalpha, IL6 perhaps thyroid invovled
– Produces chronic and progressive disease.
-early sign of disease may be an occasional ulcer at site of bite
– ability to undergo rapid genetic modifications and change the antigen present on their surface
this means protective antibody resistance is limited.
mechanism pdf
SLOW VIRUSES (or PRIONS)
– are modified host proteins that leads to proteinaceous aggregates in the brain, which leads to progressive neuronal damage
– no immune response then no inflammation.
Types of spongiform diseases
Creutsfelt-Jacobs disease – a genetic predisposition. Transferred by contaminated
tissue, medical devices, and injection.
Kuru – found in New Guinea highlands. Transmitted by ritual cannabolism. Reading suggestion
Causes shivering and trembling.
Scrapie–disease of sheep
BSE–disease of cows
in human can be acquired by eating animals with the disease or by exposure to the protein by other routes
NOTE: No treatment for CJD or Kuru exists.