August 17, 2014

Crash Course – Epidemiology

this is how I feel when someone coughs without covering their mouth

Alright party people, let’s get right down to it. The Ebola outbreak is on everyone’s mind right now and I felt obligated as your friend and favorite science blogger (let me have my dream) to clear up a few key concepts that get tossed out by the media like candy wrappers. Epidemiologists (scientists who study disease) have their own technical lingo when it comes to disease and GOSH DARNIT I want you to know it too. Hey, look at me…I care.

The terms of the trade…

Agent – the thing that causes the disease, or put another way, the element that is always present with the onset of the disease and whose presence is essential for the disease to occur.

Reservoir – the habitat where the infectious agent lives and thrives. This can be a stagnant, jungle pond or the intestinal tract of a human being

Carrier – person or critter (bat, monkey, bird) that can harbor the infectious agent and is capable of giving it to others. The carrier often lacks any signs or symptoms of having the disease.

Host – Any living thing that can be infected by a disease causing agent under normal conditions. If it’s a brisk November morning and you’re reading “Horton Hears a Who” to a small room of kindergartners on the carpet and half of them have the sniffles, then you are the perfect host for the Rhinovirus (cold). All the conditions are perfect.

Vector – living intermediary between a reservoir and a host. Mosquitoes are classic vectors, especially since they’ll suck blood from a variety of victims. They are equal opportunity pains in the butt.

Transmission – the mode or mechanism by which the disease causing agent is spread (air, water, food, person to person contact, contact with object)

Virulence – refers to the infectious agent’s ability to cause disease. I think of it as a measure of potency. On the other hand, infectivity describes that pathogen’s ability to spread disease to other hosts. When Chicken Pox shows up at a party it doesn’t just stand in the corner by itself. It turns the music up, heads to the center of the floor, and tries to dance with everybody.

Zoonoses – infectious diseases that are transmissible from animals to humans.
It’s funny just how foreign this term is for many of us, since there are so many devastating diseases to the human population (Avian flu, Swine Flu, Black Plague, Rabies, Lyme’s) that we acquire from other species.

Morbidity – is essentially an assessment of just how sick the disease in question makes you. It also has a statistical value representing the relative occurrence of disease in a population.
The definition of morbidity has a wonderfully legal sound to it, but the further a disease moves you away from your normal, healthy physical or mental state the higher the morbidity of that disease is. It is the degree of transformation your body goes through in the course of a disease.

Let’s put it all together…

Gina flew in yesterday from Boston on a late flight back to Georgia. The 5 year old behind her showed her all of his limited edition Shrek action figures on the ride back. One of them was sticky from the gummy worms he’d eaten earlier. She’d gotten back at 10pm but her college peeps were in town and the beers at Karma Mike’s Grill were still half priced until midnight. Work came way too early that next day. She only slept 3 hours and the AC in her office was at full blast.
By noon the sneezes started and her nose would not stop running. Around 2:30 all the name brand, instant coffee in the world could not keep her eyes open to read through all her emails. Later that night her throat felt scratchy and her muscles ached as if she’d lost a cage match. That’s when she remembered the kid on the plane and the suspiciously sticky Shrek. Suddenly Gina understood everything that was happening to her.

Our Cast…

Gina – Host

5 year old – Asymptomatic carrier

Shrek action figure – mode of indirect transmission

Respiratory tract – reservoir of virus

Rhinovirus – infectious agent

I hope this helps. Stay curious, stay classy, and never stop learning my friends 🙂

June 2, 2014

Malaria II – Full Circle

Hello party people! So we’re back to finish up our chat about malaria. Last week I took you behind the scenes with the curious parasite (Plasmodium falciparum) that causes malaria, and its obnoxious insect carrier, with the face for radio, the Anopheles mosquito. Today I want to focus on the disease itself. Sure, having a parasite that rapidly divides in the liver and spreads through the blood stream clearly doesn’t sound as fun as dinner and a movie but how exactly does our body respond to these microscopic freeloaders?

Fun fact – Mosquitos do not depend on blood as their primary food
source. Most of the time they eat like vegan, yoga instructors,
feeding on sap and flower nectar for carbohydrate fuel to power their
airborne lifestyle. Blood becomes a necessary source of protein for
developing eggs. So it is actually the female Anopheles that goes buzz
in the night.

Act I – Incubation stage

I don’t know about you, but if I just moved into a new apartment I need a few days to get settled in, unpack some boxes, and tape my Marley posters to the wall before I throw a party. Plasmodium falciparum is no different. At this point the Plasmodium is still hanging out in the liver cells. It can take up to 30 days after the
initial infection before the first symptoms appear, and those range in severity.

Act II – Blood stage

a closer look at the hemoglobin protein. P. falciparum converts the heme subunit to hemozoin.

The chaos ensues once the Plasmodium disperses from the liver and begins circulating in the blood stream. It’s the hemoglobin protein in our blood that they’re after. I don’t want to wander too deep into biochemistry, but if you recall from my earlier article on blood, each hemoglobin protein contains a vital compartment called a heme group. This contains a tiny molecule of iron at its core. This is what binds

the oxygen in our blood. Heme is also toxic when it is released from the hemoglobin. To get around this toxicity the Plasmodium can store heme molecules in their single-celled body in an insoluble, crystallized form called hemozoin. Inevitably the red cells lyse,
releasing the plasmodium along with all the waste products leftover from their hemoglobin feeding frenzy, to include hemozoin. This becomes bad news for us.

When it comes to our immune system our blood stream is a small town
and our white cells hate strangers with a passion. Eventually,
wandering T-cells with the right receptors will encounter Plasmodium
merozoites in the bloodstream (by detecting dsDNA on their membrane
surface) which triggers the release of pro-inflammatory cytokines. However the hemozoin that is released when the red cell ruptures seems to trigger an immune response on its own.

Unfortunately, our immune response is not always strong enough to
completely clear the infection. This is partly due to the many changes
the plasmodium goes through in its life cycle that allows it to dodge
the immune response. It goes through 7 stages, altering its
biochemistry a little each time.

One of the classic presentations of this disease is intermittent
fevers. Typically when your fever stops you start to feel better, but
with a malarial infection fevers often occur in waves every 48-72
hours. This is the result of the rupturing of blood cells as the
parasites continue to multiply and invade new cells.

Signs and Symptoms

That’s right, I know what you really really want…

Think back to the last time you or someone you’re close to had the
flu. When you get hit with the flu you typically look awful, drunk, and exhausted like you haven’t slept since the Spice Girls were last on tour. During classic cases of P. falciparum infections, patients will present with “flu-like” symptoms of high, persistent fever, headaches, chills, sweats, anemia, and vomiting. Remember that during the blood stage of the infection blood cells are being destroyed. So the patient is weak and essentially poorly oxygenated. It is basically a parasite-linked anemia.

Malaria can become deadly if left untreated when infected cells begin to clock capillaries of the brain (cerebral malaria). This can ultimately lead to brain damage, coma, or death.

Testing Methods

We can identify malaria directly from a peripheral blood smear where a
giemsa stain is added to a drop of infected blood on a glass slide and
examined under the microscope. This kind of testing is wonderfully
direct. The problem with poorly developed countries is that proper
testing facilities, microscopic equipment, and trained professionals
who know what to look for are in short supply. So there are RDT’s
(rapid diagnostic tests) available that can identify specific malarial
antigens in patient blood samples. Much like a Strep or flu test, the
patient’s sample is combined with a reagent in a tube or cassette
where a qualitative reaction (positive or negative) can be observed.
However, depending on the concentration of Plasmodium in the blood a
patient may have a false negative. So there is still a need for
confirmatory testing, especially in areas of the world (I’m looking at
you Africa) where drug resistant cases are high.

Treatment

Good Ole Chloroquine…

So we know the plasmodium needs to break down the hemoglobin in order to use those lip-smacking amino-acids while not poisoning themselves with the heme that gets released. So they form hemozoin crystals of the heme to disarm its toxicity.
Welcome to the wonderfully clever world of chloroquine. This drug diffuses into the Plasmodium, halting their ability to form hemozoin crystals. This allows the heme to build up in their nasty little bodies, shutting down their metabolism. Sadly, chloroquine resistant malaria is common place in malarial hot zones. In these cases patients require drug combinations like quinine sulfate and tetracycline.

You also have to manage the mosquito side of the disease. Spraying for mosquitos to control the population has been effective in many urban settings. We also have to understand the behavior of the mosquito. Anopheles prefers to feed at night until the wee hours of the morning. So distributing sleeping nets in malarial hot zones can literally save lives.

The CDC has mapped out malarial zones around the globe. So travelers are encouraged to seek malarial prophylaxis to prevent infections.

Here’s the bad news you already know..

– Children are the most at risk from malaria. In fact it kills more children globally than anything else.

– Diseases thrive in areas where the population is dense and the
availability of adequate healthcare is scarce. This creates a scenario
where the mosquitos are more likely to bite infected individuals. An
infected population left untreated inevitably leads to a more
resistant disease.

Luckily we don’t live in a vacuum and we can contribute. There are a number of organizations out there committed to finding solutions for this global problem. Here’s one organization I happen to like (no, I’m not affiliated with them)

http://www.malarianomore.org/pages/the-challenge

Hopefully I cleared a few things up about this topic. If you have questions please leave me a comment.

As always, stay curious, stay classy, and never stop learning my friends 🙂

May 12, 2014

Malaria – The Viscious Cycle

definitely not a mosquito

Anopheles would make a beautiful name for a daughter wouldn’t it? I mean if my friends set me up on a blind date and they told me that her name was Anopheles I would envision this mind-numbingly gorgeous, Greek goddess of a woman. However, 5 seconds into a google search you would very quickly realize that the name Anopheles has another meaning entirely, a dark, strangely complex story that has shaped human civilization over the eons. (I get so dramatic after I’ve watched “Game of Thrones.”)

This is the story of humans, mosquitoes, and a curiously well adapted parasite responsible for causing a disease known far and wide as “malaria.”
I’ve said it before; we are not alone, and I don’t just mean in the universe. Hell, we aren’t even alone sitting in the bathroom with a Vanity Fair magazine. There are microbes on the sink faucet, and in between the fibers in the carpet. There are viral particles, and fungal spores floating in the air, and no matter how thoroughly you wash your hands with cucumber melon scented soap the bacteria in your gut and the staph bacteria in your mouth could not be happier. Yes my friends, each of us is our own zip code.

So once upon a time our ancient ancestors were dropping like flies from a mysterious disease with no name…well, it had names like “curse from the Gods” and “bad air,” as in Mala = bad + aria = air, but none of those were terribly scientific. Of course, we eventually caught on to the fact that it was mosquitoes that were spreading the disease to humans. Mosquitoes don’t just feed on humans but anything with blood coursing through its veins, also known as “everything.” This makes them the perfect vectors for blood borne diseases. We recognize Anopheles as the genus of mosquitoes that commonly infects humans with malaria, but what exactly is the mosquito carrying?
One of the most ancient and devastating infectious agents to plague humankind is not a bacteria or a virus but a protozoa called Plasmodium falciparum. That’s right a protozoan, one of those curious creatures you read about in biology class and never mentioned again. The chapter on protozoa is like a TV show that only lasted for one season, but they’ve always been here, lurking in the shadows.

Plasmodium gametocyte shown here dead center. At this stage it can be taken up by a mosquito to begin the cycle again.

Plasmodium falciparum (the deadliest form of malaria) is a single, eukaryotic cell that’s life cycle is completely dependent on two hosts. The life cycle of the Plasmodium is pretty freaky stuff. It reads like the plot of a B-rated, 80’s Sci-fi movie starring Matthew Broderick. Its success as a species is completely dependent on the fact that mosquitoes feed on human blood. At one stage male and female gametes of the plasmodium develop in the gut of a mosquito where they have a little, kinky get together to produce fertilized versions of plasmodium. These will form cysts along the walls of the gut like time bombs that eventually rupture to release a demon horde of sporozoites inside the mosquito. These juveniles move into the salivary glands where they can be passed easily into the bloodstream of an unsuspecting human the next time the mosquito feeds.

Once the Plasmodium sporozoites reach the human blood stream they make a mad dash to the liver. They develop in the hepatocytes, dividing until their massive numbers rupture the liver cells, releasing them back into the blood stream where they now invade red cells. Some of these will differentiate yet again into male and female gametocytes. Yes, this is one of those déjà vu moments. If another mosquito drinks the blood of this infected human the cycle will begin again.

You can literally drive yourself mad thinking about where the original Plasmodium came from. It’s a tragically elegant case of chicken and egg. Sure, the cycle starts with the gametocytes in the gut of the mosquito but the gametocytes can ONLY be produced in the human host cells. Where and how did this all begin?

Stay tuned for a part 2 where we will describe how Malaria affects the human body and how we combat it.

As always stay curious, stay classy, and never stop learning my friends 🙂

map depicting the tropical regions with the highest prevalence of malaria.

October 26, 2013

Cell Talk

Hello again fellow information addicts. Did you have a good week? Well mine was just bursting with fruit flavor (try not to look too far into that). Anyway, after our last chat about the role of our immune system in allergic response, Allergies Oh My, I felt this incredible need…I mean like a deep and real need to talk about another wild topic in immunology, communication, as in cell to cell communication. Believe it or not, our white cells are quite chatty with one another. They don’t talk about reality shows, how Sarah’s new hair style is “all wrong for her” or what horse they’re betting on at the track in Charleston this payday weekend. It’s a non-verbal communication (can I say body language without it being a pun?). No, when our cells talk to each other they only want to know one thing, “are you one of us?” That is the very definition of immunity, being able to distinguish the sharks from the minnows, what scientist refer to as “self from non-self.” Cells accomplish this without secret handshakes or gang colors. Instead, each cell comes equipped with a special membrane bound receptor that displays protein epitopes, portions of particular proteins that cell in question makes.

So the white cells are like Penn State campus security, floating around, approaching sketchy looking cells it hasn’t seen on campus before going “alright kid, let’s see some ID. What’s your major? Ok ok…looks good, move along.” Every nucleated cell comes equipped with a membrane bound receptor, a complex of proteins referred to as a Major Histocompatibility complex, or MHC. These receptors operate by aide of two major biochemical pathways, MHC I and MHC II. I think of them as having different versions of software. In fact, the nature of these receptors is profoundly Star Trek-ish and sophisticated. Here’s the situation…

See that orange socket wrench poking out of the cell? That’s the kind of receptor we’re talking about.

Cells have membranes made up of a ballpit of proteins, fats, carbohydrates, and lipids that form this semi-solid layer that keeps their insides from spilling out onto the dance floor. So anything that cell needs to take in must pass through the membrane. This includes information. For a cell, information comes in a molecular form just like everything else that has to be taken into the cell. There’s no high speed internet, no Wi-Fi, no Skype. It’s like having your mail served to you on a dinner plate along with your chicken tenders. So in order to communicate to a cell you would need to A) keep that message painfully simple and B) convert that message into a molecular form that can be readily passed through the membrane. One form of cellular message that white cells use are referred to as cytokines. Cytokines are both released by white cells and taken up by them and they trigger vital immune responses. For example cytokines are responsible for attracting white cells to the site of an infection as well as switching them on and kicking them into action. Let me put it this way, a white cell without cytokines is like a police department with no dispatcher. Now back to receptors.

MHC II pathway

This version is typically found on white cells that act as antigen presenting cells or, as I like to call them “instigators.” These are cells like macrophages, monocytes, and dendritic cells that spend their time gobbling up any weird cell, bacterium, viral particle, or whatever that doesn’t identify itself in a timely fashion or flash the right ID. After the cell has devoured it’s prey and digests it with its cellular stomach (lysozyme/peroxisome) the organic bits and pieces like amino acids, lipids, etc. get recycled and distributed. Some of those bits, epitopes get attached to the MHC II receptor.

I’ll bet you didn’t know your cells were pre-labelled

The cell has numerous receptors in fact and in this case the receptor is inside of the cell in the cytoplasm where all the action is happening. The MHC II/epitope complex makes it’s way up to the membrane surface of that antigen presenting cell for display like an Applebee’s appetizer sampler platter. Well, it’s a bit more morbid than that because remember, this is a sample of the enemy (very Silence of the Lambs). So it’s floating around flashing the ID to other white cells “have you seen this guy before?” until it meets a T-cell (a CD4 cell to be exact) that says “oh yeah, I’ve met this guy and he’s a total D-bag. I’ll let everybody know.” In the case of an adaptive immune response that white cell will seek out a B-cell holding the same epitope, release cytokines to activate that B-cell to produce antibody against the invading microbe.

MHC I pathway

This version is super friggin cool. It’s found in every single nucleated cell in the body. It’s function; display protein epitopes of what what that cell is producing. Yup, it’s like a show and tell receptor for cells. The cells say “look what I made in arts and crafts today.” If it’s something our white cells recognize than everything is gravy. Oh man, but if that white cell doesn’t like what it finds..well all hell kind of breaks loose. There is a no nonsense kind of white cell called a Cytotoxic T-cell, or CD8 killer. When it discovers foreign epitopes on a cell’s MHC I receptor it intiates a kind of self destruct command for that cell called apoptosis. To understand this you need to understand something about viruses. Viruses ONLY survive inside of a host cell…key word “inside.” They don’t just hangout inside the cell and watch sports center. They are up to no good, using the cell’s nuclear machinery and endoplasmic reticulum to produce viral proteins and essentially make new viruses. Once a cell is hijacked and turned into a viral production line there’s no going back. So like the sad scene in a zombie apocalypse film the CD8 takes the poor, infected cell out of it’s misery, which halts the replication of the viral particle. Our immune system evolved in this way because it has witnessed what viruses are capable of and has learned not to hesitate to pull the trigger.

Well my friends I’m off to go make a difference (get Thai food). As always stay curious, stay classy, and never stop learning 🙂

September 28, 2013

Allergies Oh My!

Hello Internet! No, I missed you more. Let’s chat about allergies shall we

Let me set the scene…

It’s a beautiful morning in March. No scratch that, it’s a perfect morning. It’s the kind of day that wakes you up before your alarm clock and you are surprisingly ok with it. You’re even singing in the shower (if I don’t sing in the shower I don’t feel quite as clean). So you kick the door open to get outside and get this day started when it hits you, allergies, Mother Nature’s “you don’t belong here” bitch slap to the senses.

First it’s a sneeze, a harmless little sneeze that triggers 3 more sneezes. Then your nose starts to run in that “get me a Kleenex or I’m wiping it on my sleeves and I don’t care who sees me” kind of way. Of course, the last straw…the absolute take me out back and put me out of my misery moment is when the eyes start their itchy, watery awfulness. So you look around to see if this is happening to anyone else…if anyone is hurt…if there is a special report on channel 6 about bio-terrorism attacks in your neighborhood. No one else seems to be effected and it’s not terrorists or a demon possession. Here’s what happens…

I’m fine! It’s just allergies ok.

The Super Condensed Cliff Notes Version

Allergens in the environment stimulate our B-cells to produce IgE that builds up in our bloodstream eventually attaching to Mast cells and basophils. Upon subsequent exposure, the allergens bind to the membrane bound IgE on the surfaces of the Mast cells and Basophils triggering the release of histamine filled granules, initiating the localized inflammatory response we all love to hate.

Your White cells are angry (localized immune response to allergens)

Alright I’m sorry but I’ve got to review a few things with you people.We learned as kids that our blood is composed of red cells that carry oxygen and white cells that help fight infections. The truth is we have a variety of white cells (leukocytes) that each has its own, nifty G.I. Joe-like skills at combat. Let me draw your attention to 3 cells for now; B-lymphocytes, basophils, and mast cells.
Your B-cells A.K.A B-lymphocytes develop from stem cells in the bone marrow and later hang out in the lymphatic organs (like your lymph nodes) where they are educated in the ways of antigen recognition (sort out the good from the bad) and are armed with the black magic ability to produce antibody for whatever ails you.

If you recall, antigens refer to any substance that can elicit an immune response. Antigens can be composed of carbohydrates, lipids, proteins, or anything that triggers the cascading effects of your immune cells (leukocytes) when they come into contact with it.
Antibodies are highly specialized, fancy-pants proteins produced by B-lymphocytes that have the ability to bind to the antigens of foreign invaders (pathogens) that slip into the bloodstream (Bacteria, viruses, microscopic fungi). The pathogens that invade our bodies display antigenic molecules on their surfaces, which is how they get spotted in the first place. If our B-cells make antibody that fits that antigen molecule (which it pretty much always does) our white cells will begin beating down that pathogen in a large-scale battle royale that involves cell divisions and some serious Pacman-like chomping action.
That’s right, your white cells divide and conquer. That’s why doctors are often expecting your white cell count to be elevated during and infection. They are quite literally forming a clone army.

When they bind to a pathogen it allows white cells like macrophages to engulf them and also facilitates the killing action of another class of bad-ass, ninja protein referred to as complement that are always present in your bloodstream.
Our antibodies come in a variety of shapes, sizes, and classes based on complexity and specificity.
Keep in mind that there is a lot of crap floating around in the air, hanging out on table tops, Bank door knobs, and wherever 4 yr olds are running around, sneezing without covering their mouths.

Best Summer ever!

These microbes are just looking for their 15 minutes of fame and a chance to raise hell in our blood stream like a Girls Gone Wild, MTV beach house weekend.

So with so much diversity B-cells produce a very generalized, one size fits all, meat and potatoes class of antibody referred to as IgM. The structure of this antibody has a lot of arms that are well suited for grabbing hold of more than one antigen at the same time. Then there is the more specific IgG that gets produced in response to repeat offenders, meaning the body built up immunity to that invader and set aside memory b-cells armed to the teeth with antibody “made to order” for subsequent invasions.

yeah that's real clear. Those star fish looking things are the IgM antibodies and they help that enormous white cell to grab hold of whatever nasty bug they attach to

Uh yeah, that’s real clear. So those star fish looking things are the IgM antibodies and they help that enormous white cell to grab hold of whatever nasty bug they attach to

Let’s get back to Allergies!

that handsome devil in the center is the basophil. White cells are actually colorless until a stain is added to the slide. Basophils stain in basic (alkaline) pH, thus baso-phil.

When it comes to allergic responses IgE class antibodies are the usual suspects. They have the ability to activate distinct white cells in our body (Basophils in our blood and mast cells in our tissues) Both of these cells contain granules that when freed from their cellular cages unleash a potent substance called histamine which is primarily responsible for the classic symptoms of an allergic response. Your mast cells and basophils like to hang out on the mucous membranes of the nose, ears, throat, and eyes. These are the access points to your body, places of direct exposure to the outside environment. So these groupings of immune cells are just more likely to have a few run ins anyway with bad boys looking for a fight.

Behind the Scenes

D-awww adorable!

Let’s say you’re frolicking through the fields one day like a happy Jack Russell terrier, kick up some ragweed pollen and think nothing of it. For whatever reason ragweed pollen just rubs your white cells the wrong way (meaning white cells possess a membrane receptor that matches the antigenic determinant of the pollen granule and become sensitized on contact). Over the next few weeks your body will produce a line of B-cell clones that will only produce IgE for that pollen strain which will circulate in your blood stream attaching itself to the membranes of Basophils and Mast cells.

I mean if it’s a choice between land mines and funnel cake I choose cake not war.

These cells literally get coated in IgE like powdered sugar on funnel cake (man that sounds really good right now). So the next time that you’re exposed to ragweed pollen the IgE on those cell membranes grabs a hold of the antigen and triggers the basophils and mast cells to release their histamine granules like land mines.

When Histamine Attacks

The histamine released by your white cells acts on the cells of capillaries. It increases their permeability, opening up the blood vessels allowing white cells and plasma proteins access to the site of infection. This is what we call inflammation. So allergic responses to allergens are an inflammatory process. In the case of a runny nose it is the histamine released by mast cells in your nasal cavity acting on the vessels in your nose. The histamine molecule only has about 17 atoms so it passes quite easily through cellular membranes. A good portion of cold, sinus, and seasonal allergy medications available in the pharmacy section of your grocery store are “antihistamines” counteracting the effects of histamine to relieve your symptoms.

Anaphylaxis

So unfortunately the occasional runny nose isn’t all that allergic responses are capable of and in a select percentage of the population the triggering of inflammation can be a critical and often fatal, systemic reaction. I’m referring to anaphylaxis. This process reflects the most extreme form of immediate immune response whereby widespread inflammation can lead to severe swelling of the eyes, constriction of airways and even shock where the blood pressure drops. Yes, well you know how I like to end things on a light note so….take a look at this beagle puppy playing with a stuffed animal.

Stay curious, stay classy, and never stop learning my friends 🙂

Posted in Sweet Immunity
Tagged human biology, physiology, science
Leave a comment

February 28, 2013

Let’s Talk Immunity

professional bow tie models look just like bouncers don’t they?

This episode of Forgotten Physiology accepts the challenge of explaining cell mediated immunity in 5 minutes without the aid of caffeine! Grab some popcorn and don’t miss the action.

The body is a lot like an exclusive club in downtown D.C. No one gets in without an invitation (MHC receptor…every self respecting cell has one) and I do mean NOBODY. There are bouncers always watching the entrances and the exits (Dendritic cells, Macrophages) for shady characters looking to start trouble (viruses, bacteria, fungi, parasites). They are also constantly carding at the door for minors (immature red and white cells) or anyone who has an expired membership card (malformed cells, tumor cells, or any infected cells that make the wrong receptor).

Now these bouncers are pretty fierce. Good guys, but you don’t want to ever cross them because they will go Green Hulk on you expanding to sometimes 3 times their normal size and will literally (no really literally) eat you alive. They also have one hell of a temper and not only will they eat you but they’ll steal your wallet pass your picture to their friends so that anyone who even looks like you gets the gangland treatment. (sampling antigenic determinants from the bacterial cell for display to helper Tcells)

A Day in the Life of the Macrophage (cell-mediated immunity)

this picture is totally how your white cells look under 40x mag..trust me 🙂

Let’s ride along with the macrophage. This guy never stops working he pounds the pavement patrolling our peripheral blood circulation for strangers and shady characters (pathogens, toxins, foreign substances) that don’t belong and when it finds them it swallows them whole and digests them with a kind of industrial strength cellular stomach called a lysozyme, but it doesn’t stop there. Our immune system hasn’t learned about the infection yet it hasn’t hit the news. The macrophage must now present that antigen (foreign substance which elicits an immune response) to another kind of specialized cell the T-cell. That’s what a macrophage does it acts as an antigen presenting cell (APC to his friends). The way it does this is by binding some of the peptides of that antigen it swallowed with its own proteins (MHCII class) displays them on the surface of its membrane as receptors. Our macrophage now takes a little field trip to a nearby lymph node (a hot spot in town where all the young lymphocytes hang out) but he’s not just looking for any ole T-cell. Macrophage can only present antigen to a cell with matching receptors for it. He’s looking for “Misses Right.” Warning this next part is a little graphic. If and when our hero finds a T-cell they dock receptors (MHC II complexed with antigen T-cell’s CD4 receptor w/MHCII binding site) Macrophage passes along some IL-1 that stimulates that cell to switch on divide into daughter cells release its own IL-2 that stimulates those cells to divide. So the macrophage has now informed your T-cells, your effector cells about the infection and your T-cells produce an army of messenger clones all hard wired to manage the same infection.

Now the infection has reached the front page news. Meanwhile B-cell with the right receptors has encountered the same antigen that everybody is talking about. He has already processed the antigen bound it with his own MHC II protein. Now he’s watching for T-cell to switch him on, give him the software he needs (IL-2 helper cytokines) so that he can upgrade – switch from an IgM to a IgG antibody producing cell and divide into an army of plasma cell clones. So at this point you can imagine your lymph nodes are becoming a very crowded place and they are. Those lymph nodes begin to swell as thousands of activated lymph cells fight the active infection. These cells are short lived though many of your plasma cells spit out antibody and then die shortly after. Some of those cells live on inactive in your lymphatic system as memory cells. If that antigen returns they’ll switch back on and start spitting out high specificity IgG. This specialized antibody is many times more efficient at binding than the store brand IgM. Phew….now I need a nap. Until next time my friends. Stay classy and never stop learning.

February 18, 2013

Strep Poker

Don’t you hate it when you have a sore throat and half of your face falls off? That’s the worst!
source:http://www.aurorahealthcare.org

Not unlike blizzards or public radio telethon week, sore throats happen. Sure, you can eat all the right things, get plenty of exercise, wear a hat when it’s cold, and dry your hair when it is wet, but the honest truth is that sore throats will still happen. Whether it was the 5 yr old at the bank who never covered his mouth when he coughed or the fact that you never washed your hands before leaving the birthday party at Chuck E. Cheese, as far as your immune system is concerned, it is only a matter of time before an infection sets in. Thankfully, a number of safe, easy, and reliable testing methods have been developed in recent years to aid clinicians in identifying these elusive, agents of infection and help patients arrive at a speedy recovery.

A Storm on The Horizon

Morning is a cruel mistress

We can always feel it coming can’t we…that scratchy feeling in our throat, the dull twinge in our ears when we try to swallow. Oh yes, it’s sore throat time. Stayed out a little too late last night didn’t you? DIDN’T YOU?! Now just look what you did. That’s ok. Surprisingly, it is our body’s own immune response that produces the bulk of the drama when it comes to the really nasty cases of strep throat, especially in cases of neglected or under treated infections. Once the bacteria is recognized by our macrophages (the border patrol of our innate immunity) a cascade effect of cytokines, or cellular signals are released that bring about a variety of changes. Not only are white cells called to the site of the infection for a phagocytic schmackdown (when bacteria are either engulfed by macrophages or tagged by protective proteins for certain death by osmotic implosion), but inflammation is also induced by those white cells that are called to serve.

Blame those naughty antigens

The distinct molecular attributes of the streptococcus bacteria, or antigens, are largely to blame. The antigens (in this case, membrane bound proteins and carbohydrates that elicit an immune response) on the surface of the bacteria kick the immune system into overdrive, producing chemical cytokines or cellular signals that induce white blood cell action and inflammation (Phew…that’s technical!).This is what produces the characteristic soreness, swelling, and redness at the site of the infection. This not only makes swallowing difficult and painful but, lymph node glands can also begin to swell resulting in muscle ache in the neck. Fever and chills may also accompany the infection, as well as nausea and vomiting often in response to the persistent pain and discomfort. In the trade we like to refer to these as flu-like symptoms.

Sources of Infection

The bacteria can be spread from person to person by droplets from the cough or sneeze of an infected person. That’s right people, cover your pie holes! It is also possible to pick up the infection after touching contaminated surfaces like door handles or keyboards and then touching your eyes, nose, or mouth whereby the bacteria can easily gain access to the upper respiratory tract. Strep throat caused by S. pyogenes typically effects children or anyone with a weakened immune system. The infection can clear up on its own, however in some cases, S. pyogenes infections can lead to further complications, such as scarlet fever, toxic shock syndrome, and glomerular nephritis.

Behind the scenes

Typically when clinicians test for strep throat they are looking for the bacterium Streptococcus pyogenes. That is not to say that other bacteria as well as viruses are not just as capable of causing upper respiratory infections, but when it comes to the characteristically red, inflamed sore throats, in this region of the world anyway, it is S. pyogenes that usually gets called in for questioning. It is a handsome, frisky Group A, Beta-hemolytic strain of bead like bacteria that can produce mild to aggressive infections. “Beta hemolytic” refers to the ability of the bacteria to completely rupture (lyse) red cells on a culture plate, demonstrating a distinct, clear zone of red cell destruction. If you were to hold up an agar plate to the light it looks like someone took their thumb and rubbed the gel away where the Strep had been growing. Just think about the kind of damage something like that can do in your throat…ewww. That zone of hemolysis is a diagnostically reliable behavior that lab folks use to pick our star bad boy out of the line up.

Blinded by Science – Testing Principle

I hear lipstick models have really bad eyesight

There is a bargain bin of strep testing kits out there in the biotechnology market. They all tend to work off the same testing principle of immunofixation whereby a sought after antigen (in this case the S. pyogenes membrane bound carbohydrate) is bound to specific antibodies within the testing media. There is also a color indicator in the mix that forms a unique complex which displays the presence of that antigen. The color change is then interpreted as a positive result. It is way less dramatic and not nearly as fun as mystery flavor koolaide. These tests are limited by sensitivity, meaning that an individual can in fact have a Strep infection that is below the detectable limits of the test. This is why it is a good practice for the physician to order a follow up culture for negative rapid strep screens.

Penicillin to the rescue!

As mean as sore throat infections can be they are often easily treatable. If they do not clear up quickly enough on their own we can typically zap them with antibiotics in the form of our favorite cell wall attacking antibiotics like penicillin, amoxicillin, or any taster’s choice cephalosporin on the market. Just be sure to take your full prescribed dose. Those microbes are sneaky and like to play dead. Under treating an infection is the perfect real world example of “what does not kill us, makes us stronger” except in this case it’s the Strep that can come back stronger. Of course, antibiotic resistance will have to wait for another article.

Stay classy my friends and never stop learning.