---begin intro to pathobiology---

INTRODUCTION TO PATHOBIOLOGY
Dr Colin 
Johnstone
9.2.97 1 pm B101

Dr Johnstone is a parasitology teaching team 
member.
Today is an overview of three presentations. Much of the material 
we hear today will be new. But, today is an introductory symposium, and 
everything we hear today will be repeated again later. 

VETERINARY 
EDUCATION

three phases

* animal biology - study of normal healthy 
animals. anatomy, physiology, histology, embryology, biochem

* 
pathobiology - study of disease. study of causes and transmission of 
diseases as well as expression of dz process at cellular, tissue, organ 
levels. pathology, microbiology, parasitology

* clinical studies - 
medicine, surgery, etc. pinnacle of pyramid. learn to diagnose disease in 
living animal. learn to acheive glory by learning how to tx and control 
various ailments pests and pestilences that afflict our animal 
companions.

PATHOBIOLOGY

interface between normal and sick animal. 

* 
pathology: general and systemic

* microbiology: bacteria, viruses, fungi 
- etiology of diseases

* parasitology: arthropods, protozoa, helminths


each subject is taught separately but we must integrate them, as they are 
often linked in significant ways. 

there are three important examples of 
diseases we'll discuss

* LYME DZ
* BOVINE VIRAL DIARRHEA (BVD)
* 
HEARTWORM

LYME DISEASE:

in 1975, an unusual cluster of cases of 
arthritis in kids occured in lyme, CT. it included other features, 
atypical of pediatric arthritis, like a circular rash, and a fever, and 
flulike symptoms. left untreated, dz progressed into chronic form 
affecting nervous system, heart, joints. cases were seasonal, onset in 
summer, peak in fall. clusters were suburban/urban. The seasonal onset 
with peak in summer/early fall is typical of arthropod associated dz. The 
tick ixodes scapularis was ultimately incriminated as the vector of this 
unidentified dz. in 1982, a new spirochete, borrelia burgdorferi, was 
isolated from ticks in the area of Lyme CT. 

a veterinary dimension to 
this dz was also discovered, which includes important links between 
parasit, pathology, and microbiology.

Dr. Thomas Van Winkle will discuss 
the pathology of the disease affecting the dog "Spiro"

Dr Schifferli 
will discuss how the pathogen was microbiologically isolated

Dr Lok will 
explain how the tick functions as a vector, how parasites infect hosts 
and cause disease.

PATHOLOGY of lyme disease:

first, some reminders. 
pathology includes many aspects of study of disease. ETIOLOGY: cause of 
disease. PATHOGENESIS: series of steps occuring which lead to changes 
seen with disease. we're going to follow etiology through pathogenesis in 
this disease. in general path, we discussed cell injury, death, necrosis, 
etc. inflammation, hypersensitivity, repair, hemodymamic disorders, 
neoplasia, etc. these will all come up again every day for the next 40-60 
years of our lives so you should know about them.

biological agents seen 
in microbiology and parasitology cause the diseases we see the effects of 
in pathology.

"SPIRO" 5 yr old male labrador. presented at VHUP with 5 
wk hx anorexia, vomiting, lethargy, wt loss. was lame on LR leg sometimes 
in past 3 mos. was PU/PD.  also had proteinuria and cellular casts in the 
urine. bloodwork: BUN and creat were both elevated, BUN 226, creat 12. 
Albumin was very low - 1.8 hypoproteinemia. PCV was also low. So we know 
there is a kidney function problem. The very low albumin accounted for 
the development of edema and ascites, which did occur during the 
hospitalization. Spiro wasn't eating or drinking. was put on IVs. got 
worse and worse. the owners elected euthanasia and agreed to a necropsy. 
so far, we know Spiro had a "protein losing nephropathy." The necropsy 
showed bilateral ulcers below the tongue, and uremic mineralization of 
the ribs. but the kidneys were worst. smooth, yellow-tan, approx normal 
size. histologically, we saw severe thickening of the glomeruli, largely 
dilated tubules with basophilic cells with large nuclear: cytoplasmic 
ratio - tubular necrosis and regeneration. inflammation in interstitium 
and tubular atrophy. severe membranoproliferative glomerulonephritis and 
something else i didn't see. now, they know they only have these two 
things at the same time in dogs from lyme endemic areas. 

clinical 
association with borreliosis: all dogs from lyme endemic areas
13 dogs 
had concurrent or recent lameness. 100% of dogs tested were positive for 
exposure. 6 of them had been vaccinated against lymes disease.

what 
next? immunohistochemistry of kidney. stain for IgG shows a lumpy bumpy 
deposition of IgG. Stain for IgM shows a similar pattern (in the 
glomeruli). We know that Ig's are usually bound to Ag's, right? now if 
they form Ag/Ab complexes and deposit in the kidney, we get activated 
complement. So they stained for C3, and found lots of it in the 
glomerulus. the complement, you recall, draws in neutrophils which can do 
a lot of damage....
so now the glomerulus is damaged, albumin is lost 
into the urine. 

we also used histochemical technique to find 
spirochetes in some of the kidneys. remember there are glomerular and 
tubular lesions. what causes the tubular lesions? maybe the spirochetes.


Now, a paper was studied on the epidemiological data and 
histopathological data.
we know that the spirochetes are found in the 
kidneys. we know that if you give this spirochete to the dog you will get 
lameness and arthritis. the epidemiological data is good. one other thing 
was done - they know there is Ab bound to Ag there. What if they can 
isolate the Ab and see what Ag it is bound to? So they pulled the Ab off 
the glomeruli, and found that they are in fact directed against borrelia 
burgdorferi. So that's good correlative evidence.

That's how they 
figured out that b.burgdorferi is causing these problems.

Now: 
MICROBIOLOGY takes over:

Dieter Schifferle (Swiss guy).

STAGES of lyme 
dz

Early: localized signs: erythema migrans
	   disseminated symptoms: 
skin, musculoskeletal, NS, lymphadenopathy, 				heart, eyes, liver, 
respiratory, genitourinary

Late: persistent: chronic arthritis, late 
neuralgic involvement, acrodermatitis

Spriochetosis! This was described 
in 1982 when Swiss scientist willy burgdorfer identified a borrelia from 
ticks - b.burgdorferi

transmission cycle: vextor==ixodes ticks. 
reservoir== mice, deer, birds, lizards, zoonotic cycle==cessential

what 
are spirochetes?
* bacteria
	-cellular organisms with ribosomes and are 
susceptible to antibiotics. NOT      viruses.
    -prokaryotes - NOT 
eukaryotes like fungi, parasites, algae, plants, animals

bacteria have a 
nuclear membrane, cell wall, peptidoglycans, different types of 
ribosomes, etc

bacteria come in many forms. they are larger than 
viruses, can see them with light microscope. can form cocci spheres, 
rods==baccili, fusilliform, filament, etc etc or spiral/coiled 
spirochetes.

SPIROCHETES are slender, flexible, helicoidal motile 
bacteria. slender, hard to grow, fastidious, require special things to 
grow. syphyllis, leptospirosis caused by spirochetes. they have two types 
of membranes. an inner cytoplasmic membrane and an outer membrane. in 
between is the periplasm, and you have a flagellum located in the 
periplasm. the flagellum has a motor that makes it turn, and the 
spirochete will spin and can move in a corkscrew fashion through a 
viscous medium.

NEW OR OLD DISEASE? well, in europe, symptoms were 
described as early as 1888 - called erythema chronica migrans. 2000 
cases/yr in switzerland. in North america, they found the spirochete in 
museum ticks from the 1940s. in the NE states, there was abandonment of 
farms, reforestation, increased deer population, proximity of suburban 
population...lyme is the most common vector borne dz in the USA.

it's a 
worldwide dz - russia, china, japan, australia, europe.

geographical 
variations: relative occurence of late symptoms: in america, more 
arthritis. in europe, more neuro and skin manifestations, why? 
phenotypic/genotypic heterogeneity of bacterial isolates. use of 
serotyping, plasmid profiles, RFLP, MLEE, ribotyping - shows that the 
spirochetes are actually different species. in USA we have b. burgorferi 
and garinii. but there is also andersonii and japonica and afzelii. all 
cause disease.

bacterial pathogenesis:

by using a vector, b burgdorferi 
can bypass host surface adhesion and colonization steps. it evades host 
defenses by covering itself with host proteins and hiding in closed 
compartments. 

many borrelia may be killed by host defenses but enough 
can hide in joints, kidneys, etc to cause dz.

surface exposed 
lipoproteins are the first molecules to interact with host molecules. 
these are very important molecules. some have been used in vaccine 
development. some vaccines seem to work in beagles, but not sure about 
other dogs. b.burgdorferi persists in the host despite a strong Ab 
response. there is differential expression in host/vector of the surface 
exposed lipoproteins. some are expressed only in certain compartments of 
host or tick. antigenic variation by recombination betwen an expression 
locus and a silent locus. antigenic variation occurs within a single 
host. you have genes which express a certain protein, and other genes 
which are silent, but may be exchanged with the first genes. so it is 
hard to know what Ag to use to make vaccine.

the genome of borrellia is 
special, atypical of bacteria. there is a linear chromosome, a couple 
small circular plasmids, and a couple more small linear plasmids. now, 
there may be essential genes on these plasmids, so maybe they are 
actually chromosomes...but that's another story.

so, you have a 
relapsing/remitting fever disease which is better studied than lyme 
disease. in that dz, the agent enters host, makes Ag, host makes Ab, gets 
better. then spirochete makes 2nd Ag, animal gets sick again, host makes 
Ab, gets better. etc etc - relapsing/remitting.

B. Burgdorferi causes 
disease by being an invasive organism. no toxin produced. it binds host 
plasminogen, which gets activated to plasmin, allowing the pathogen to 
disseminate by digesting extracellular matrix proteins. plasmin digests 
ECM proteins, see. migration seems more efficient than bloodborne spread. 
in blood, spirochetes are susceptible to macrophage killing. But the 
spirochete can hide from mphage. also spirochete induces an inflammatory 
repsonse, damaging the host. neutrophils migrate due to bacterial 
invasion of endothelial cells and activation of adhesion mols, and 
bacterial induction of synovial linings to express IL8, chemotactic for 
neutrophils.

ETIOLOGIC DIAGNOSIS:
find out if there is an infectious 
agent involved.

why? optimal preentive and therapeutic measures

How? 
Henle-Koch's postulates. 1883.

to recognize an organism as the etiologic 
agent of dz:

pathogen should be present in all cases of dz
must be 
isolated in pure culture
should be able to reproduce the dz

diagnostic 
tools: for lyme, very difficult. hard to isolate the agent, long 
halflife, hard to get from host because is in low concentration. 


cultivation: low concentration in clinical specimens, long generation 
time, complex growth requirements, difficult growth on solid media


serology: crossreactive ag, insensitive early in infxn, long lasting 
titers. western blot to confirm...but, problem with standardization due 
to crossreactive Ags. moreover, the agent itself doesn't cause a strong 
Ab response early in dz. when patients are suspected of having lyme, 
because they used to have lyme, it is hard to tell if they are having a 
recurrence or something else - because the titer persists for so long.


PCR: genetic heterogeneity of isolates

---break----

so, we know that 
b.burgdorferi is causing lyme disease. but how is it getting into the 
host, and where does it hang out? 

PARASITOLOGY: life cycle of the 
vector
we've heard the term vector used already - but what does it mean?

vector == transmitter. an animal which carries an etiological agent from 
a donor to a host in a directed fashion. movement of the etiological 
agent from vector to host comes about due to specific behavior patterns.


the vector here turned out to be a group of ticks which have a combined 
geographic range almost identical to the range of the disease itself. 


ixodes scapularis is a tick, an arthropod related to spiders, scorpions. 
ticks pass through a series of life stages, each punctuated by a meal of 
vertebrate blood. during its life cycle, a tick may parasitize more than 
one host. eg, rabbits and cows, at different stages of life cycle. so the 
tick can move pathogens frmo one animal reservoir into another animal 
host. and this is what happens with b.burgdorferi

ticks can act in this 
way because of a specific relationship with vertebrate hosts. ticks are 
parasites. a parasite == an organism which lives temprorily on or in 
another living organism (plant or animal host) for the purpose of 
obtaining nourishment. ticks are ectoparasites: live on surface of host, 
skin, haircoat, feathers. endoparasites live within the host's body.


parasitology==science that deals with the interactions between an 
individual host and its population of parasites as well as the 
interactions of host populations and the parasites that infect them. 
parasitology limits itself to the study of eukaryotic 
organisms...protozoans, helminths, and arthropods.

examples: 

single 
celled eukaryotes: protozoa eg trypanosomes which live in blood
helminths 
eg worms, eg flukes (platyhelminthes)
tapeworms (also platyhelminthes)

nematodes (roundworms aka ascarids)

also include some arthropods eg 
fleas, ticks, mites

some parasites like the screwworm depend totally on 
vertebrate host - can never free live outside of the host. other 
parasites like a related fly larva, the wool maggot of sheep - can live 
outside of hte host in a free living situation.

within individual 
parasite lifestyles, parasites move from freeliving stages to obligatory 
endoparasite stages. so life cycles are important. much of the science of 
parasitology is organized around life cycles. parasitologists tend to be 
preoccupied with life cycles, justifiably so, because we're talking about 
the changes in form/number required for a parasite to complete its life 
cycle.

back to Lyme Disease and ixodes scapularis. the ticks start out 
as a larva hatching from an egg on the ground. the larvae parasitize 
small mammals eg whitefooted mice, squirrels, chipmunks, and sometimes 
birds. the whitefooted mice are the primary enzootic reservoir for the 
spirochete pathogen. they do not become ill. so the larvae engorge on the 
blood of the mice, picking up the spirochete. they then drop off and molt 
to the nymphal stage. the nymphs are less host specific. they will feed 
on the small mammals OR dogs, horses, people, etc. So the spirochete can 
go into human/domestic animal populations at this point. the nymph, after 
feeding, will return to environment, molt to adult stage, which will 
parasitize mainly white-tailed deer, but sometimes also horses, dogs, and 
man. so the deer is another reservoir. one way in which life cycles are 
important for us...lets talk about other types of parasite lifecycles 
we'll see.

protozoan life histories...sexual to asexual phases of the 
life cycle
nematode life cycles...larval stage from egg, to adult stages 
in gut or tissue
arthropods...simple metamorphosis as in sucking lice, or 
complete metamorphosis in fleas. flea is also a good reminder of how life 
cycle may encompass environment and host (larva and adult flea live in 
different places)

by knowing some of the tissue trophisms of parasites 
as they go through their life histories, we can predict the pathologies 
they will cause in the animal host. ascaris suum will start migrating 
through liver during first few days in the host - and these pigs get 
"milkspot dz" - granulomatous response in the liver to the migrating 
ascaris suum larvae. another example: if we know that a female sarcoptic 
mange mite lives in torturous canals in the epidermis of the host ,and 
that thousands of them live on the host, it isn't surprising to realize 
that mange will occur with awful skin reactions - because we know the 
mites are digging up the skin.

we can also generalize re: epidemiology 
of vector borne and parasitic dz by knowing about life cycle. eg, margins 
of wooded areas, border between meadow and woods  are typical areas where 
people get infected. 

when you are confronted with a life cycle like 
ixodes scapularis, it is kind of daunting to learn. we will become more 
and more convinced of this as we get into the course. what will help us? 
well, try to distill the life cycle down to a few points.

1. how does 
host acquire the infection? for lyme dz, host goes through wooded region 
and picks up a tick, which feeds on it.

2. what is predilection site and 
how does parasite get there? for ixodes, it's the skin/integument of host 
and it gets there by falling onto it or something

3. how does parasite 
get back to environment or to intermediate host? for ixodes, it just lets 
go of the skin and falls off.

4. what life stages are involved in 
entering and leaving the primary host?  usually the nymphal stage nails 
us, although adult can be infective as well.

relationship of parasitism 
to disease. in parasitism, infection !=disease. it isn't the same thing. 
some organisms, eg protozoa, eg say plasmodium, can self replicate in the 
host, and one infective stage can theoretically result in fulminant 
infection and disease. other organisms eg most nematodes do not self 
replicate in the host, and the presence and severity of clinical illness 
will be proportional to the infection pressure. parasitism is common in 
healthy animals.

---

BOVINE VIRAL DIARRHEA: BVD

Dr Perry Habecker, 
pathology
Dr Leonard Bello, microbiology

historical perspective: march 
1946. new transmissible dz in cattle reported in USA. first case in a 4yr 
old red devon cow imported from UK. cow had watery diarrhea, fever, loss 
of milk production, anorexia. dx dysentery, treated symptomatically. 
well, she died overnight, and because she was a pet she was buried in the 
yard w/o necropsy. but we knew she probably ddin't have dysentery. during 
next ten days, 5 other animals got sick. they also had mouth ulcers, 
leukopenia, and abortions. in these outbreaks, the same field service 
clinicians from cornell visited the affected farms about five days before 
the outbreak, and after treating the original sick cow. so it seemed 
certain to be a viral disease, adn was called virus diarrhea. 

in 1953 a 
second apparently new dz of cattle was reported from iowa. it was 
different from the NY cases because of low morbidity and high mortality, 
and because of mucosal ulcers present throughout gut

in 1956, in 
indiana, a disease was reported with same signs as ithaca outbreak, but 
also laminitis and lameness

all three disease ultimately found to be 
caused by same virus, and the disease came to be called BVD. the agent is 
called BVDvirus, BVDV.

since then, we've found that this virus is 
ubiquitous in cattle population. 70% of us cattle are seropositive. in 
1960s virus was grown in culture and vaccines made. two biotypes were 
found: cytopathic and noncytopathic. the cytopathic type caused 
vacuolation and cell death when grown in culture. note that this has 
nothing to do with ability to cause disease. both biotypes can cause 
disease.

in 1970s- vertical transmission was recognized. transmitted in 
utero. this led to a very significant discovery, which was that infection 
of a fetus in utero with a noncytopathic biotype during first 120-130 
days of gestation, results in a calf which is immunotolerant and becomes 
infected. the virus continues to replicate in the tissues of these 
animals, and is shed into the environment all the time.
immunotolerance, 
PI animals- persistently infected animals.
this is because the fetal 
immune system is not fully formed at this stage of development. so this 
noncytopathic biotype is important in that it creates PI animals.

two 
conclusions: one, the ability to produce PIs in animals means the 
noncytopathic biotype is predominant type in nature. also, re: 
controlling BVD, the key is to prevent fetal infecttions with 
noncytopathic biotype. PI cattle are the main reservoir of the infection.


[some statistics about biotypes i'm not writing down. hey, he said we 
didn't have to take notes on this anyway...]

mucosal dz: one of most 
severe forms of BVD, whether acute or chronic, it is invariably fatal. it 
only occurs in immunotolerant PI animals who have PI infections with 
noncytopathic biotype. when these animals become infected with the 
cytopathic biotype, they get mucosal disease. so for mucosal dz to occur, 
animal must be infected with BOTH biotypes, and it is the cytopathic type 
which causes the disease. how? well. immune system of PI animal doesn't 
recognize the cytopathic biotype as foreign, and doesn't mount an immune 
response, and gets sick and dies. the superinfective cytopathic biotype 
usually arises from a mutation of the cytopathic biotype already present 
in the animal. the mutation doesn't affect the antigenicity of the virus. 
so the biotype changes, but the antigenicity doesn't change.

---break---


now we launch into a description of pathological manifestations of BVD


BVD is very complicated
etiopathogenesis not fully understood.

virus 
needs to infect fetuses. at certain times, fetus will die. or can be 
persistently infected. or can be born with an Ab titer. after day 125, 
fetus is immunocompetent. after that time, can get abortions, PI animals, 
or normal calves with Ab. it is the PI animals which are infecting other 
animals. they usually die of mucosal dz by age two. 

MUCOSAL DZ

ulcerative and erosive oronasal lesions
mucopurulent rhinitis

ulcerohemorrhagic enterocolitis
cystic colitis
lymphocyte necrosis
etc 
etc

cow doctors will examine the mouths of sick bovids carefully. an 
erosive gingivitis may be seen. mouth may be full of erosions...may be 
seen on hard palate. slide: hyperemic tissue in cow mouth.

tongue may be 
affected. 
slide: diphtheritic membrane forming over necrotic peyers' 
patch in SI.
the virus kills the lymphocytes in the patches. the whole 
thing will collapse. this is due to cytopathic effects of the virus. 


mucosal dz is a rapidly evolving dz. animals die w/in 3-5 days (unless 
you euthanize them). sometimes they will go on chronically, with ulcers 
throughout GI tract, and also skin changes at feet, interdigital area, 
wasting away, intermittent diarrhea, crusting at eyes, nose. crusting 
dermatitis in inguinal region, on teats, etc. 

thrombocytopenia: 15 of 
146 bvd cases at cornell had severe thrombocytopenia, counts 2000-33000. 
all had bleeding problems. concurrent neutropenia and lymphopenia. 6 of 
the 15 survived. this form of BVD is due to a new type of virus- BVD type 
II, that doesn't require the PI state to inflict damage.

fetal 
mummification/fetal wastage. fetus dies in utero

BVDV is also a 
teratogen. can cause cerebellar hypoplasia, microencephaly, 
hydranencephaly, optic nerve hypoplasia, retinal dysplasia, cataract, etc 
etc. any congenitally deformed bovine is a likely BVD victim.


BVD 
causes mild immune deficiency. May see secondary bovine pasteurellosis 
pneumonia with BVD as underlying cause.

lab tests: virus neutralization 
- least useful. if you find Ab you don't know if they're related to 
vaccine or mild infection or what. gold standard is viral isolation. time 
consuming and labor intensive. takes a few weeks. samples of blood or d/c 
swabs from live animals, or lymphocyte rich tissue or lung, kidney from 
necropsy. 

the immunoperoxidase monolayer assay is popular now. results 
in five days.

--change speaker--

now that we've seen all this stuff, we 
probably want to know more about the virus, right? we know that Dr 
Schifferle is not from Brooklyn, and that bacteria are not viruses from 
our other lecture. Now we find out that viruses are not bacteria. so what 
are they?

WHAT IS A VIRUS? well, a virus is a noncellular infectous 
agent containing

* nucleic acid (RNA or DNA but not both)
* protein (to 
protect nucleic acid, maybe also to contain attachment sites)
* lipid 
envelope (optional - also contains attachment sites)

nucleic acid will 
be encased in protein coat, or "capsid", together this is called a 
nucleocapsid. the smallest unit of the nucleocapsid is a capsomere.


viruses are small. you can't see them with a light microscope at all. you 
need an electron microscope. they're about the size of ribosomes. there 
is a size range. vaccinia virus is much larger than most other viruses. 
poliovirus is pretty small. 

viruses are classified into different 
families. they are either RNA or DNA viruses, and they are naked or 
enveloped, and they are single stranded or double stranded or circular 
nucleic acid type viruses, etc

BVD single stranded RNA virus

VIRAL 
REPLICATION

1. attachment (remember those attachment sites? they 
interact with receptors on 	host cells. this is critical)
2. penetration 
(often some kind of fusion event. virus must get into cell)
3. uncoating 
(virus strips down, disassembles.)
4. gene expression (critical. virus is 
going to hijack this cell's metabolism)
	a)synthesis of proteins needed 
for viral subunits (capsomeres)
	b)inhibition of host cell activities 
(variable)
5. synthesis of viral nucleic acid
6. assembly of capsomeres 
to form capsid around viral nucleic acid
7. release of virus from host 
cell (now infectious)

PROPERTIES OF BVDV

1. contains envelope derived 
from internal membranes of the infected cell
2. does NOT inhibit host 
protein synthesis
3. two biotypes:
	a) noncytopathic NCP
	b) cytopathic 
CP
4. nucleic acid == RNA
5. positive strand, 12.3 Kb
6. genome contains 
one large ORF (open reading frame)(3898 codons) coding for one large 
polyprotein which is cleaved during synthesis into the ten mature 
polypeptides found in infected cells. 

BVD contains an mRNA molecule 
which is its genome, basically. 

[he's going on about the synthesis in 
the cell of the virus. i'm not writing it down...]

the virus gets into 
the cell by receptor mediated endocytosis. enters endosome, fuses with 
membrane to get out into cytoplasm of cell, where it uncoats, etc etc. 
virus buds into intracellular vesicles and is transported to cell 
surface, where the vesicle fuses with plasma membrane, releasing viral 
particles. this is not killing the cell. it's just making it into a virus 
factory.

NCP biotype has no effect on tissue culture, but CP biotype 
kills cells in culture. p80 is associated only with CP strain. both 
strains are pathogenic in cattle. only NCP strain causes persistent 
infection, and both are involved in mucosal dz.

how do the NCP and CP 
biotypes different, and how were they generated?
the original NCP strain 
has had insertions into the p125 coding region, which create a new 
cleavage site (6) and formation of p80. this forms the CP biotype. so the 
NCP and cp strains are antigenically identical. immunotolerance to a 
specific NCP strain will result in immunotolerance to the homologous CP 
strain as well. Note that PI animals are not tolerant to DIFFERENT 
strains of BVD virus.  p80 is ALWAYS found in the CP strain. you do not 
see CP without a p80, and you do not see p80 in NCP strain. no new 
epitopes are formed with this mutation.

pregnant bovid...infected with 
NCP BVDV...fetus becomes PI with NCP and becomes constant source of 
infection to herd.....NCP mutates to CP, gets mucosal dz

type II 
bvdv...regular immunocompetent cow can get severe often fatal dz. low 
crossreactivity with type I. we're not sure how these strains differ yet.


---

CAL heartworm thing w/dr hendricks.
this is ELVIS. you should be 
able to find it in the computer lab.
[she's taking us through this 
computer program now]

it's a really good computer program. It's on all 
the computers in the lab under "elvis" and she's planning to put them on 
the web asap.
---end intro to pathobiology---