First off, this is geared for those that have read my fanfic Lethally Hot. This fanfic deals heavily with the immune system. However, for those that just wanna know a bit more about it, in Toboe LoneWolf style, then heyla, read on.
In my fanfic Lethally Hot, I talk about the "seven parts of the immune system." Now, I was only a sophomore in high school when I began to write that fic, and thus my research and understanding of the immune system was quite limited. In truth, there are a great deal more "parts" of the immune system. Some of them have different names now, some of them have been discovered, some of them relabeled, recategorized, and really confusing. XD
Oh, and as a warning: this is very geeky material. Basically I ramble about all the nuances and little thingys about the immune system. Obviously, a lot of this ties into Lethally Hot, but...*laughs* biology is complicated, okay?
PART ONE: THE PARTS
First off, there are two "ways" that the body defends itself: non-specific and specific.
Now, non-specific is like a good, all-around basic defense. Kind of like the police. They do everything.
There are two types of non-specific defense: external and internal. Your external defenses are your skin, your mucous membranes, and the secretions they produce. Yes, your sweat is a protective measure against bacteria. Granted, it's not the absolute best defense, but it serves its purpose as a basic barrier to Bad Stuff.
Your internal non-specific defenses...well, this is were it gets a bit complicated. Being "non-specific," this means they do not distinguish between one foreign material from another. They just destroy 'em all. Destroy first and ask questions later of the dead body, so to speak.
Just exactly what is this internal, non-specific defense? Weeell...
It is triggered by chemical signals and involves phagocytic cells and antimicrobial proteins that indiscriminately attack invaders that penetrate the body's outer barriers. The appearance of inflammation is a sign that this second line of defense has been deployed
XD A bit complicated, yes? How about we just forget that for a moment, shall we?
There are also chemical measures, such as lysozyme, gastric juice (stomach acid), interferons (more later), and the complement system (also more later).
Now for the third type of defense: the specific defense. This is called the immune system. (...Yeah. I know. Wow, big surprise. XD) Basically this is a better, more fine-tuned, and specific defense to foreign microorganisms, toxins, cancer cells, and other Non-You-Stuff.
You could describe the three lines of defense to be like a besieged city: first the city walls, then your basic ordinary soldiers, then your intelligence officers, high-tech robots, and marines. XD
Okay then. Now I'm just going to describe and attempt to categorize all the parts.
Now, way back in grade school your teacher probably told you that the immune system is made up of white blood cells. Well, by now scientists have found that there are many, many different types of "white blood cells." The fancy term for ALL "white blood cells" is leukocytes.
First off, the phagocytic leukocytes. These are the kinds of cells that actually eat stuff and go chomp-chomp and all that.
Probably the most "famous" of these types of cells are the macrophages. These are the largest phagocytic cells and are especially effective, long-lived phagocytes (thus the name "big eaters"). How they "work" is by sticking out a pseudopodia -- an "arm" kinda like an amoebae -- that attaches to the foreign material. Then the macrophage pulls it in and proceeds to destroy the offending bugger, using super-duper-powerful chemicals and poisonous forms of oxygen (you know how pure oxygen can make you light-headed? Yeah, that's the idea).
[Now I could go in real-depth here about how it does all that, and what happens afterwards, like MHC molecules and interlukins and stuff, but that's probably over the top. Only bio geeks like me would like that. XD]
Now, macrophages aren't just born. The immune system is perhaps one of the few systems that actually is "trained." (Your brain is another. XD)
In the beginning, all cell-thingys that are part of the blood -- you know, the red blood cells, white blood cells stuff you learned in grade school -- are "born" in bone marrow. You know those stories about leukemia patients needing bone marrow? That's because their bone marrow's messed up and can't make good blood cells; therefore they need some other guy's bone marrow.
Among other things, the bone marrow "creates" monocytes. These are the baby forms of macrophages. They're smaller, and they're the ones that travel around the body before settling down in one general location. Then they mature into macrophages. Macrophages that stay in one place are sometimes given special names: in lung (alveolar macrophages), liver (Kupffer's cells), kidney (mesangial cells), brain (microglial cells), and connective tissues (histiocytes). Macrophages especially collect in the lymph nodes and the spleen. Not all macrophages stay in one tissue type.
[This is probably what I was referring to as "microphages" in Lethally Hot. Way back in sophomore year, I'd only had freshman biology. Not to mention, the research about the immune system has grown leaps and bounds since then.]
There's one last type of phagocytic leukocyte: the neutrophil. Recently, it's been discovered that neutrophils play a critical part in the immediate immune system response. Things that get past these cells will often cause sickness. There's an article in the Medical Science News titled "Neutrophils dictate whether our immune system will permit or prevent bacterial infections" (got that off the 'net, published May 5, 2005). They constitute the biggest part of the immune system too -- about 60% to 70% of all white blood cells are neutrophils.
Weeell, there's actually one more type of phagocytic leukocyte, the eosinophils. Not much is known about this type of cell. What is known is that they help regulate the severity of allergic reactions and also kill a number of parasites.
Generally, "phagocytic" applies to a cell that can eat another cell. Macrophages and neutrophils fall quite nicely into this category, but scientists aren't quite as definite with eosinophils.
Just what do phagocytic cells do? Eat, of course. They just eat and eat and "eat," cleaning up bacteria, viruses, dead cell bits -- living vacuum cleaners. They're also the link for the specific defense.
Now we come to the more famous "grouping" : the lymphocytes.
Lymphocytes are part of the specific defense. They'll only take action if they "recognize" the enemy. While macrophages will attack anything, lymphocytes are very specific to their enemy. The lymphocytes are made up of five cells: the B-cell, the Helper T cell, the Killer T cell, the Inflammatory T-cell and the Suppressor T cell.
The B-cell makes antibodies. That's it. It's part of the humoral immunity. I'll talk about antibodies later. When the "war" is over, some of the B-cells that were activated turn into plasma cells. Plasma cells are basically memory cells -- they stick around and if they ever encounter the same thing they fought before, they'll turn "on" right away and your defense kicks in a lot faster.
The Killer T cell kills cells. They're also called cytotoxic T-cells. Has CD8 receptors. Unlike phagocytic cells, killer T cells don't attack the invader; they attack the cells that have become infected by the invader. In fact, it's not even "attack" per se, but rather Killer T cells give infected cells the command to self-destruct. If infected cells self-destruct...they take down the enemy with them.
The Helper T cell coordinates the cell-mediated immunity. Has CD4 receptors (probably drilled into your head by all the AIDS info.) If they recognize the enemy, they'll turn on their "partner" B-cells and Killer T cells. It starts the whole thing.
The Inflammatory T cell attracts inflammatory cells to the site of an infection or injury. Then the inflammatory cells pump out chemicals that start the inflammatory response. You know, swelling, redness, histamines, the whole gig. They do this by pumping out pyrogens (among other things, like histamines.) These cells call other cells, such as basophils and mast cells.
The Suppressor T cell is like the "opposite" of the Helper T cell. If the Helper T cell turns cells "on," the Suppressor T cell turns them "off." Otherwise, the B cells and Killer T cells would just keep on making antibodies and killing cells where there no longer is a threat -- and that would be a bad thing. Some scientists believe there's a balancing act between the Helper T cell and the Suppressor T cell -- if there's more signals from the "helper" cells then the B-cells and Killer T cells "attack," if there's more from the "suppressor" cells then the B-cells die off (though some turn into plasma cells) and the Killer T cells self-destruct (though again, some remain in an "off" state).
[What's with the T's? The T stands for "thymus." In the beginning, the bone marrow spits out an immature T cell or B cell. The T-cell travels to the thymus where it undergoes "training" and "specialization." More about this later.]
There's one more type of cell I haven't mentioned yet.
The Natural Killer cells, or NK cells for short. These are almost like Killer T cells, in that they kill body cells. They're mainly used to detect cancerous cells, and blow them up before they become tumors.
PART TWO: THE WORKINGS
So how does this all fit together?
Well, here's a scenario. There's a lot of examples out there that describe a bacterial infection, but that's boring. XD So I'll describe the common cold -- a viral infection.
So one of these viruses float around, get stuck, and make there way to the lining of your nose, where it's all warm and moist and full of blood cells. It's gotten past the external defenses -- skin, mucous, hairs, boogers XD -- maybe because you brushed your nose or something. Cold viruses are very sticky.
Attack.
Viruses get into a cell, hijack the cell's DNA, and tell it to start making more viruses.
However, infected cells (kind of) know they're infected. So they start making another chemical too -- interferon. Interferon are proteins made by virus-infected cells that stimulate other cells to make proteins that inhibit viral production. interleukin-1.
Interleukin-1 calls in the police forces -- macrophages, monocytes, neutrophils. They start eating away. Natural killer cells come in as well.
However, this probably isn't very efficient. After all, macrophages are meant to kill a wide variety of stuff, not just one thing. For efficiency, the immune system calls up the specific defense.
How they do this? Well, when a macrophage eats an "enemy," it takes a bit of the enemy's outer shell (it's protein coat, most likely), packages it with something called MHC II molecule (a molecule that is unique to You), and "displays" it outside. Kinda like a banner made out of your enemy's parts. Well, a macrophage "presents" it to a Helper T cell (...in the real world, they bump next to each other in the lymphatic system most likely). If this specific Helper T cell, which has a specific kind of receptor, matches with the MHC II + enemy bit combo, it turns "on" and starts pumping out chemicals that turn on its "brother" B-cells and Killer T cells. If not, the macrophage moves on...perhaps to another Helper T cell...
Once a certain kind of helper T cell is activated, it multiplies and starts pumping out cytokines, like interleukin-2 (IL-2). This stimulates corresponding B-cells and killer T cells to divide and multiply. Plus, the antigen-presenting macrophage secretes interleukin-1 (IL-1), with activates the helper T cell to produce cytokines. Interleukin-2 also stimulates helper T cells itself to reproduce and produce cytokines -- it's all a cycle of self-stimulation. O_o
In any case, with all this activation and multiplying, the B-cells are pumping out antibodies and killer T cells are doing their thing.
The B-cells and their antibodies are part of the humoral immunity. This is the kind of immunity that can be briefly transferred to another, via plasma transfusions or mother's milk. See, plasma and mommy's milk both contain antibodies -- and these little things are what the humoral immunity work.
So how do antibodies work? Well, actually there are five different kinds of antibodies -- IgA, IgM, IgE, IgD, IgG... (the Ig stands for immunoglobin, the fancy name for antibodies). Different types of antibodies circulate in different parts of the body, and do different things.
In neutralization, antibodies block the activity of an antigen, such as when antibody covers the binding site of a virus. In opsonization, antibodies coat the antigen and make it more obvious to phagocytes. Some antibodies make the virus clump together -- the fancy word for this is agglutination. Others just make it blatantly obvious to phagocytic cells to "Eat This." And some activate the complement system.
The complement system is basically a cascade of enzymes -- proteins that do stuff -- that punch a hole in a cell wall. See, the antibody hooks up on the antigen (that's basically anything that activates the antibody). A protein that's part of the complement system hooks onto the other end of the antibody. You know the "famous" Y-shape of an antibody? Well, the bottom part of the "Y" hooks onto the antigen, and the top parts of the "Y" hook onto a protein.
This protein activates another protein, which activates another, until we get to the end, which basically blows a hole in the cell wall (bacteria) or protein coat (virus).
See, a cell wall/protein coat keeps the cell stuff inside and other stuff outside. Other stuff containing water, usually. Water exerts pressure. Now, a cell makes use of this pressure -- kind of like a dam. But if there's a whopping hole in the dam, water gushes in and wipes the cell out. For a virus, even though it's not alive, it still has a protein coat to protect the DNA -- so if there's a hole, bye-bye DNA, bye-bye virus.
Killer T cells work this way too -- by blowing a hole in infected cells. How do they tell which cell is infected or not? Same way the helper T cell got activated -- by recognizing bits of the antigen.
An (viral) infected cell basically works like this. Part of it starts manufacturing protein coats -- the shell of the virus. The other part makes copies of the viral DNA. The actual virus gets "packaged" together just outside the cell, and then buds out.
Parts of the protein coat of the virus become part of the protein coat of the infected cell. The killer T cells recognize this foreign stuff, and blow the cell -- and the virus.
The process of Helper T cells and Killer T cells, plus macrophages and neutrophils eating stuff up, is the cell-mediated immunity. Basically it's the defense system that's directed (mediated) by the Helper T cell.
Now, it's not all eating and blowing stuff up, when you've got a cold. You're feverish, your nose is running, and you're sick. (Well duh.)
Blame your inflammatory cells. They're the ones telling your nose cells to pump out mucous (trap viruses -- it does work), sneeze like crazy, and hype up the temperature. And your brain -- yes, your brain is part of your misery too. Since the temperature control panel is in your brain, that's how a fever begins. The immune system functions better at a slightly higher temperature than normal body temp, and the higher temp inhibits bacteria from multiplying.
Obviously the eating, sneezing, and blowing things up doesn't go on forever. Otherwise you wouldn't have a nose left -- your killer T cells would continue blowing cells up. This is where the suppressor T cell kicks in.
Suppressor T cell turns off helper T cell, which turns off B-cells and killer T cells. Thankfully, a killer T cell needs two commands in order to kill -- one from the helper T cell, the other from the infected cell itself. If one of the two commands aren't met, the killer T cell turns off.
The immune system cells recede. Some B-cells go into memory mode. Your nose stops running. The viral infection is over.
PART THREE: THE MESS-UPS
The immune system isn't infallible. Otherwise we'd live for a really long time.
You've probably heard of the HIV virus. I'm not going into that since there's a ton of books and stuff on that. However, that's not the only way the immune system can fail.
One way is when the immune system doesn't form properly. If one of the links don't work, the whole chain is messed up. No macrophages presenting stuff to helper T cells, chain broke. If the helper T cells don't turn on, chain broke. If the helper T cells don't stop, chain keeps going and chokes you.
Arthritis is basically the immune system messing up. The immune system thinks the joints are the enemy -- when they're not. So they're attacking themselves.
The distinguishing between self and non-self is Super Important. How else do they know what to blow up?
When a baby is forming, the immune system is forming too -- or going under training. A T-cell that doesn't understand self and non-self fails -- and dies. However, if a T-cell that doesn't get this link continues to live...that's a problem.
When people get older, their T-cells aren't as good -- heck, they're older, and their thymuses are shrinking (thymuses do that as you get older), and training isn't so good. So perhaps they attack joint tissue, thinking it's foreign, and that is a pain. Things get twisted and bent and Messed-Up. Arthrtis hurts.
A lot of problems with the immune system stem from the inability to distinguish self from non-self.
How do they distinguish self from non-self?
Well, just like how you have unique DNA, you have a unique MHC molecule. Well, almost unique. The instructions for making MHC molecules have lots of possibilities, and the chance of getting identical ones are slim to none.
Every cell in your body has that unique MHC molecule -- some are MHC class I, some MHC class II, but they've got the same base. Most cells have a MHC I molecule, macrophages have MHC II molecules. A cell that doesn't have that particular MHC molecule, isn't you.
A macrophage tests an antigen if it has that MHC molecule marker (among other markers) -- if it doesn't, it gets eaten.
So, the types of blood (A blood, B blood, O blood, AB blood) -- they're markers on a red blood cell. Protein coats on a virus -- a marker, and a foreign one at that.
When people need blood transfusions, they have to get the right type -- no mixing A with B, or you'll get an immune response. Which is bad, because the immune system rejects the blood transfusion, and basically fireworks are going off in your body.
Organ donors or marrow donors -- they have to be close to the patient's "marker." Even then, the patient will probably have to take immunosuppressants to suppress the immune system from reacting to the new liver or whatever.
And there are ways where the immune system doesn't mess up, per se, but rather thwarted -- by infectious diseases.
HIV hides within helper T cells, lying dormant.
Tuberculosis becomes impervious to macrophage's attempts to blow it up. So a macrophage turns itself into a prison, walling the tuberculosis bacteria in, while other macrophages patrol. But if the patrols drop, or are called away...the bacteria reactivates, and starts eating away...
Ebola manufactures a protein that neutralizes interferons, slowing down the immune system -- until it's too late.
And some simply overwhelm by sheer magnitude. Like the flesh-eating bacteria. Or the bubonic plague.
Some diseases we can hinder long enough for the immune system to kick in, by using antibotics. However, antibotics only work on bacteria -- not on viruses, and therefore not your cold, or the Ebola virus -- and far too many strains of bacteria are becoming antibotic-resistant.
And we are running out of antibotics to use against them. There are only so many ways to blow a hole into a bacterium using chemical means, and the pharmaceutical industry is finding that it is Expensive to manufacture new ways. Far too many doctors prescribe antibiotics willy-nilly, giving bacteria ample information to find new ways to thwart the antibiotics, far too many people don't take the antibiotics to their full term, giving time for bacteria to regroup, and far, far, too many people expect an antibiotic for everything -- when there isn't one.
Wake up, world.
The immune system isn't perfect. Good, yes. But there are way more bacteria, that are way faster at mutating into something that the immune system has to learn to defend against, and we are running out of time.
It's a war. A constant war between the immune system and the microorganismal world. The balance is constantly tipping.
War is hell.
TABLES:
|
Nonspecific Defense: |
||
|
External |
Internal |
|
|
Physical |
Chemical |
Cellular |
|
skin, mucous membranes |
lysozyme, gastic juice, interferons, complement system |
Phagocytes (see T2) |
|
Specific Defense: |
|
|
Humoral Immunity |
Cell-mediated Immunity |
|
B-cells, antibodies |
Helper T cell, Killer T cell |
Cell Types:
|
Phagocytes: |
|||
|
Macrophages |
Largest, most effective |
||
|
Monocytes |
smaller, travelers [microphage] |
||
|
Neutrophils |
Kamikazi, eat stuff |
||
|
Eosinophils |
Eat worms |
||
|
Lymphocytes: |
|||
|
B-cell |
Make antibodies |
[become plasma cells] |
|
|
Helper T cell |
Stimulate immune response |
Aka CD4 cells |
|
|
Killer T cell |
Kill infected cells |
Aka CD8 cells, cytotoxic T-cells |
|
|
Inflammatory T cell |
Stimulate inflammatory response |
||
|
Suppressor T cell |
End immune response |
||
|
Other: |
|||
|
Natural Killer Cell |
Kill infected cells |
||
