I though we’d shift gears today and cover a disease that has been catastrophic and historic: Yersinia Pestis a.k.a. “The Plague”. This article will explain why the bacteria Y. Pestis is so lethal in humans. It uses our own immune response to multiply and continue the infection, thereby continuing its life. I hope you enjoy this post which is a trimmed down version of a much longer research paper that I have been working on:
► Hot LinksThis essay’s main topic will be a discussion on how the human immune system functions in a period of active infection. For this paper, Yersinia Pestis will be the highlighted pathogen. Human Y. Pestis can take three main forms: pneumonic, septicemic, and bubonic.Y. Pestis is classified by the CDC as a Category A pathogen with a mortality rate of 50-90% if untreated; 15% when diagnosed and treated. A pathogen is defined as any disease-producing agent, especially a virus or bacterium or other microorganism. Category A Pathogens are high-priority agents that pose a risk to national security, can be easily transmitted and disseminated, result in high mortality, have potential major public health impact, may cause public panic, or require special action for public health preparedness.
Y. Pestis as Plague is transmitted to humans by fleas or by direct exposure to infected tissues or respiratory droplets; the disease is characterized by fever, chills, headache, malaise, prostration, and leukocytosis3. The infected flea bites the human, the bacteria is forced past the mechanical barrier of the skin and enters the tissue and then begins to collect in the lymphatic system without causing a protective immune response upon initial introduction into the system. The chemical barriers such as sweat, lysozymes, defensins, play little or no role in the prevention of infection by Y. Pestis. Y. Pestis annihilates the first line of defense in the human immune system well before a full immuno-response can be generated.
When Y. Pestis is first active in the human body, it produces a protease that clears the capillaries and lymphatic stem of clots and then move into the regional lymphatic system where they are attacked by macrophages.
The first cells to attack Y. Pestis are the macrophages, these cells, as their name suggests, engulf and then digest the pathogen and then present the pieces of the pathogen to the T and B cells for the secondary immune response. Y. Pestiss is unlike most other pathogens that invade humans, Y. Pestiss uses the phagocytes, especially the macrophages to multiply and become more deadly. When the macrophage comes in contact with Y. Pestis uses a type-III secretion pathway to inject “Yops” or Yersina Outer Membrane Proteins” which interfere with normal Macrophage action by directly suppressing T-lymphocyte activation which would eventually kill Y. Pestiss. also this pathway uses a protein that causes the affected cells to release 40 times the normal levels on interleukin 10 which will suppress the immune response.
The temperature inside the mammalian host (37C) signals Yersinia Pestis to produce an F1 antigen that becomes part of the anti-phagocytic capsule, it becomes encapsulated and ready for full pathogen activity; the carrier flea’s body temperature is 26C, which does not trigger encapsulation and therefore is not a pathogen in the flea itself. Yersinia Pestis has the ability to survive inside the macrophage and force that cell to aid in the bacterial reproduction inside the very cell that was sent to kill it. This pathogen multiplies inside the macrophage and then the macrophage dies, releasing more Yersinia Pestis that are now activated and encapsulated, express Yops, pilus adhesin, compliment resistance, and heme storage for energy.
These newly released and activated Y. Pestis then continue moving in the lymphatic system following the lymph flow from distal to proximal or form the infection site inward toward the main lymph system, . Y. Pestis rapidly moves through the afferent lymphatic vessels toward the collecting ducts and the draining lymph nodes. Once in the subscapular sinus of the node, the bacteria rapidly multiply and spread through the node. This is the cause of the painful Buboles in Bubonic Plague. These Buboles contain extensive amounts of extracellular Y. Pestis, hemorrhage and fibrin, and necrotic lymph tissue. “Without early antibiotic treatment, bubonic plague usually progresses rapidly to septicemic plague, a form of the disease characterized by bacteremia, systemic spread, and life-threatening Gram-negative sepsis. Hematogenous spread to the lungs can also result in pneumonic plague.”
At this point he Spleen’s Red Pulp, which is the site of mechanical filtration of red blood cells and the reserve of monocytes, is filtering infected and dead macrophages, neutrophils, and dendridic cells. The B-Cells in the spleen, that reside in the White Pulp, have not been fully activated because the macrophages have not brought back enough material from digested Y. Pestis for a secondary immune response. The T-Cells in the Thymus at this point are not yet mature and ready to attack the pathogen. Yersinia Pestis as Bubonic Plague has a 50-80% mortality rate if left untreated, untreated Pneumonic Plague is always almost fatal. “Early antibiotic therapy is recommended for persons deemed exposed to or infected with plague. Tetracyclines (e.g. doxycycline), fluoroquinolones (e.g., ciprofloxacin), and aminoglycosides (e.g., streptomycin, although not widely available, and gentamicin) are all antibiotics that have been used for treatment of plague.”
Once antibiotics are administered and begin to take effect in disrupting the cell wall protein production or DNA replication, or in the event that the infected person survives the first few days, the immune system can begin to respond to the infection with T and B cells. The antibiotics aid the immune system by destroying the bacteria outright. The immune system in the rare patient that has survived beyond the normal fatal period of a Y. Pestis infection without antibiotic treatment can fight back following a normal infection/immune-response pattern of primary/humoral response: Eventually, one of the bacteria cells will be met by a B-Cell that can effectively act on the bacteria, the bacteria may be weak or effected by the antibiotic, or it is a week into the infections and ht B-Cells are now active, regardless, what needs to occur is that the B-cells , which are matured in the bone marrow, and activated by a Th Cell (which mature in the Thymus), responds to extra cellular antigens/pathogens by proliferating and then differentiating into plasma cells that function as production sites for Y-Shaped proteins known as antibodies. These antibodies then bind to the pathogens at the external protein binding sites of the bacteria. This binding of antigens has the effect of blocking the entrance of the bacteria into a host cell, thereby preventing reproduction and encouraging phagocytosis. In short, the Th Cell checks the antigen as friend or foe, notifies the B-Cell to multiply and that the cell in question is an pathogen, and the B-Cell differentiate into plasma cells and they mark the pathogen for destruction with antibodies.
This above step that creates Humoral Immunity, or immunity and immune action outside of host cells. Innate, or immunity against pathogens that are already inside a host cell also depends on Helper T-Cells. In this case a pathogen is already inside a host cell and have left protein markers on the outside of that cell. A Dendridic cell activates Helper T-cells that then activate macrophages that engulf the specific anitgen that is already recognized as a threat by the dendritic cell. That dendritic cell also activates Cytotoxic T cells that, with the stimulation from Th Cells activate Tc (cytotoxix) cells that induces apoptosis in the infected host cell.
The B-Cells that have manufactured a given antibody now remain in the circulation for life, thereby granting almost life-long immunity in case of a re-occurrence of that pathogen in the system. The B-cells that are descendents of the activated B-Cells that have produced antibodies are then referred to as Memory B-Cells. These cells are very long lived and provide the memory of what antibodies to produce when a similar infectious agent is present again.
Immunity, infection, and exposure to a given pathogen will be often apparent in blood tests where certain types of Immunoglobulin are present in the test. These Immunoglobulin (Ig A/D/G/D/M) gamma globulin protein types are specific to the pathogen and act as markers for past/present infection or immunity depending on the disease and are produced by the plasma cells that come from the Acitvated B-cells. Generally, in the primary response, IgG and IgM are low, then the second time the antigen is present the IgG levels spike rapidly in response from memory to the antigen. Antibodies clearly contribute to defense against Y. Pestis but the mechanisms by which they do so in vivo remain to be established. It is accepted that the determination of efficacy of the humoral phase of immunity is based on the concentration of antibodies. However, the state of immunity against the plague is not determined by the blood concentration of the antibody. What appears to be the determinant factor is the availability of the anti-bodies the the regional lymph nodes. “ It is indeed significant that the immunity afforded by a virulent infection is greater than that conferred by vaccination with different avirulent strains, which in turn is more permanent than that produced by plague prophylactics consisting of antigens. Whether an infection in an immune animal stimulates the physiologic activity of the histiocytes and their related cells to produce antibodies more rapidly and more effectively than the susceptible animal has not as yet been determined. It is not unlikely that the immune state is further conditioned by an increased phagocytic capacity of the microphages and macrophages.”
The main reason Y. Pestis is so deadly is that it takes the human body up to 8-10 days to mobilize the T and B cells to fight the bacteria. By that time the host is most likely dead from septicemic or pneumonic plague. This bacteria shows us how the innate immune system works with macrophages, neutrophils, and dendritic cells, as well as how the adaptive immune system with the B and T cells functions. The adaptive system is much slower but far more powerful and specific.–Coldwarrior24JULY2010.
CDC Map
Tags: medicine, saturday lecture series
One of the resons I own property were there aren’t any dang furriners
Wow. Now if this infected someone with swine flu…
Not. A. Good. Result.
Scott Madsen wrote:
furriners dont have much to do with this…the US SW has y pestis all over the joint.
Lost wrote:
now that would be nasty
updated with a map of distribution
ORANGE COUNTY, Fla. –
Dengue fever has infected a handful of people in Central Florida, health officials said.
“This is not a regular flu virus that you get, you feel a lot worse,” said Dr. Todd Husty.
“You get a real great fever, a horrible fever; it’s called ‘break bone fever.’ You feel like your bones are breaking, but it’s really joint pain,” Husty said.
@ coldwarrior:
I have read of the historical outbreaks in North America.
SW eh…..I heard TB is on the rise down there too.
Any vector corelation.
I’ll still take my mountaintop in WVa over East LA when there is pandemic outbreak
coldwarrior wrote:
That description is scary.
Scott Madsen wrote:
mice…mice…mice…rats…the fleas are the vector
@ Lost:
break bone fever sounds excruciating
Morning!
@ coldwarrior:
I understand that, and now I see that it doesn’t record south of the border. In fact, a very clear geographical dileniation is present at the border, therefore, is something not being reported from some agency foreign or domestic?
That it is a phenomenon present domestically on host animals is clear.
My concern is the same with the dirty ass person that coughed on me in the Robinson Wal-Mart last year during the flu scare….unhygenic personal habits/practices by two legged animals furriner and domestic.
If the stuff ever starts spreading beyond host animals through virulent humans, I will kill the cat and weather it out far away from Wal-Marts full Citizens of the Jerry Springer Nation, and cities full of third world peasantry.
@ Rodan:
was that u moving the posts around in the queue?
Morning Rodan!
@ coldwarrior:
Thinking of all these bugs makes me thankful for the fact that I’m healthy.
@ Scott Madsen:
now, if y pestis becomes pneumonic plague, then its all out pandemic. that stuff is way scary.
it has to be warm enough for fleas to survive, or the main vector is dead.
Lost wrote:
something will get us all in the end…
@ coldwarrior:
Not thinking of an end yet…I’ve got too much to do!
@ coldwarrior:
Oh, climate change means that it will be very warm and all the bugs with thrive! We’re dooooooomed!
/lvq mode off
coldwarrior wrote:
When my time comes, I hope I don’t get it the end.
Take note that I am reading this and watching a rerun of House at the same time…
Coincidence? I think not.
Bring out your dead.
huckfunn wrote:
these might get you in the end!
Carolina Girl wrote:
correlation may or may not be causation
@ Lost:
either tropic disease will get ya OR…you can freeze to death on a glacier!
man made global warming/cooling…pick one!
This is a cheery topic for a bright Saturday morning. Something even Obama can’t screw up: the Plauge! I bet he could find a way to fuck it up, though. That seems to be his only real talent.
coldwarrior wrote:
Egad! Hope not! My sister spent 2 years in Jordan with my Aunt who was a missionary doctor. Early 70′s. She came back with some sort of intestinal amoebic parasite and was laid up for months. I never axed her if it was worms.
coldwarrior wrote:
Totally lost my appetite.
@ coldwarrior:
Indecision may or may not be my problem.
Iron Fist wrote:
well, i could have written about ebola/hemorrhagic fever …
Lost wrote:
I almost said “glad he didn’t post any pictures” but then I realized it might be too great of a temptation so I didn’t say it.
Lost wrote:
yeah, but the parasites havent!
@ Iron Fist:
@ Iron Fist:Every one making more than 250k will be issued a flame thrower and be required to burn rats delivered by tandem load by the CDC on their estates to level the mortality field
@ Scott Madsen:
And the blue states get the vaccine and medicines first. Ooooo, sorry Alabama, looks like we’ve run out. Have to ration.
Scott Madsen wrote:
Yes; but will we get a tax break?
Carolina Girl wrote:
Thats when they’ll hear hoofbeats and it won’t be Sandy Claws
@ huckfunn:
Huck – saw your post on the Catsup thread about the long drive – and hell yeah to the XM radio. GREAT for the long hauls (I drive to L.A. a lot) and it’s great not to have to change stations to find decent stations. I fluctuate between the Patriot and Classic Vinyl, depending on whether I want to yell to myself in the car.
this is my ‘favorite’ disease for just shear ridiculousness of a prion causing it:
Creutzfeldt-Jakob (KROITS-felt YAH-kobe) disease is a degenerative brain disorder that leads to dementia and, ultimately, death. Symptoms of Creutzfeldt-Jakob disease (CJD) sometimes resemble those of other dementia-like brain disorders, such as Alzheimer’s, but Creutzfeldt-Jakob disease usually progresses much more rapidly.
@ coldwarrior:
Alzheimer like Dementia….Sponge Brain No Pants?
Carolina Girl wrote:
You drive to L.A. from where? I listen to Classic Vinyl, Classic Rewind, Water Colors, Pops and Coffee House. About the only time I go to old radio is when I’m trying to find Rush. I was able to listen to the whole show yesterday on an Amarillo station. Then back to Fox at 5PM for Special Report with Bret Bauer. Also, every year when renewal time comes around, they tried to hit me with that $135 BS. I have 2 accounts (one for me and one for the wife) and I tell them to cancel. They immediately jack it down to $77 per account. Works every time.
Scott Madsen wrote:
@ huckfunn:
I drive from the Sacramento area – clear shot down the I-5 and speeds up to 90 mph except through Fresno County – CHP there will ticket you in a heartbeat.
Scott Madsen wrote:
i gotta remember that one!
Carolina Girl wrote:
Wow! Dang near 500 miles. Most of the 4 lane West Texas highways have posted limits of 75, which means that you can go 80. I’ll put the hammer down if I have a good front door. However, I’m currently on speeding ticket probation, and I need to complete defensive driving by October and get no tickets. I’ll return to my lunatic driving in November. Tom Green County (San Angelo) is a notorious speed trap. I saw 4 troopers there yesterday, 3 of them with customers
coldwarrior wrote:
Everyone should have a favorite disease. My favorite is Hantivirus ‘cuz the mice are so cute.
@ huckfunn:
I have a female Maine Coon who averages about six rodents a week (if you count Chipmunks).
Our stupid township requies cats to be on leashes if outdoors. How the hell are you going to control vermin that way?
Scott Madsen wrote:
Gee! That’s a big honkin’ cat. I thought you were talking about a raccoon. Cat’s on a leash? Sounds like ya’ll need to clear some vermin at city hall.
@ coldwarrior:
What a great article. Very informative and fascinating. Pathogens want to live too. It is amazing how some of them circumvent our barriers, invade us, and wreak havoc on our carcasses like we’re not special beings.
The nerve.
I’ve read that if you get the plague in a 3rd world country you actually have a better chance of survival because doctors there recognize it immediately and begin life saving treatment. (if you can get the medicine, of course.)
Small pox is another ‘interesting’ bug that has tormented people.
@ huckfunn:
The dog people got pissy because they are require to leash and pick up spoil. Some garden society matron didn’t like finding little kitty cigars in her flower beds, and those poor cute Chipmunks and songbirds need a break.
Cats cull the weak and promote health in their prey species, it not like we have feral cats running around in this 85k mean income juristiction. They never think about the benifits, only their comfort and asthetics.
@ Scott Madsen:
I’m not much of a cat person, but requiring them to be kept on a leash is just dumb. Does anyone actually do that? My wife has a cat that’s 18 years old. She was an indoor-outdoor cat until last November when she crapped in our bed. She’s been an outdoor cat ever since. My wife thought that was harsh and said “she did that because she’s getting old”. I replied “so am I but I don’t poop in the bed; and if I do you can keep me outdoors, too”.
@ huckfunn:
I am on my second Coon, and it is the only cat I will own.
Mine have/will follow you around the block on a walk and come when called.
My older one would hang out on the back end (1500 feet from the house)of my brother’s property during bon fire parties like he was a Labrador Retriever or something
Oh yeah, we let them run free.
huckfunn wrote:
LOL I gotta a 16 year old kitty that pees when she sleeps. lol lol Talk about keeping up on the cleaning. I don’t even make my daughter’s bed anymore, just cover it with a vinyl table cloth. PS: My daughter no longer lives here so now it is Angel’s room. Boy does she piss the old man off….no pun intended. Funny what you told your wife +1
What do y’all know about the current plague sweeping through the military in Syria?
huckfunn wrote:
Amoebae are NOT worms. An amoeba is a one-celled animal, colorless and with no fixed shape. It is like a bag of protplasm that forms “pseudopods” in whatever direction it needs to move, multiplies by dividing, and feeds by engulfing pieces of food.
I got an amoeba infestation while studying Spanish in Guatemala (admittedly, I have a loooong way to go before I can achieve fluency, but at least I can READ Spanish now)…doctor there treated it with a medication that is safe, inexpensive, free of side effects, fast-acting, and widely used elsewhere but not available in the US. In the US, you have to take Flagyl, which is comparatively nasty stuff. An amoeba infection is dangerous because it can go through your bile duct and get to your liver, which it feeds on. Yuck…