Seeking a better understanding of the immune system.

May 10, 2012 6:51 PM

Seeking a better understanding of the immune system. As I understand it: #1 I am exposed to bug. #2 I get bug. #3 I am now immune to bug. I understand that open wounds, chemo, or ailments that suppress the immune system would cause a person to fall ill more easily. How could a product effect a person's immune response?
posted by kristymcj to health & fitness (13 answers total)

The human immune system is complex, and many parts of it are not fully understood. Instead of trying to write it all down, I'll link an overview.
posted by the man of twists and turns at 7:14 PM on May 10, 2012 [2 favorites]

kristymcj, that is true for some bugs but not for all bugs. Consider incurable bugs such as HIV, once you have that bug, it just eventually kills you. Not only that but if you get exposed to someone else's strain of the virus, you can get infected with that as well, even though you already have the bug.

Is there a specific product you are wondering about? Because your question will be difficult to answer otherwise. If a medication counts as a product, one example would be Neulasta (pegfilgrastim). It's a medication that increases white blood cell counts in people undergoing chemo, to help them fight off infection.
posted by treehorn+bunny at 7:26 PM on May 10, 2012

How could a product effect a person's immune response

By enhancing or degrading some aspect of the immune system. This seems obvious - maybe you need to clarify your question.
posted by HiroProtagonist at 7:38 PM on May 10, 2012

IANAImmunologist, but I think that immunity is less black and white than you think it is. That is to say, think of immunity to a bug in terms of your body knowing how to produce the necessary antibodies to fight the drug. Knowing how, and having the resources to do so, are two different things. When your immune system is stressed by, for instance, being exposed to Chemo treatments, it may not be able to produce the right antibodies in sufficient quantities, or to deliver them to the appropriate spot, to to address the infection / exposure.

I think this is how it works, and no doubt will be corrected below if I am wrong.
posted by gauche at 7:39 PM on May 10, 2012

How could a product effect a person's immune response?

Immune cells need to communicate, in order to coordinate the correct response — you don't want your immune cells to attack your own (self) cells, right? So there receptors on the cell surface and associated chemicals that mediate that kind of signaling between cells. One signal might be "make more of these cells" and another signal might be "make fewer of these cells". Drugs (products) can interfere with signaling of this kind, changing the instructions that immune cells receive. If you have a drug that tells immune cells to chill out (for example, corticoidal steroids) then you get a suppression of the immune system.
posted by Blazecock Pileon at 8:04 PM on May 10, 2012

wounds, chemo, or ailments that suppress the immune system

I don't have the time to give a lengthy explanation to the errors in your post, but I will address this one. Chemotherapy does suppress the immune system, but wounds or infections don't suppress the immune system, they activate it. The fever, chills, and other symptoms you get? Those are all caused by your immune system reacting against the infection. This is the basis for immune reconstitution syndrome: A person with AIDS (immune deficiency) who gets treated can paradoxically appear to get sicker, because as his immune system strengthens, it begins to react to the infections already present in him.
posted by qxrt at 8:05 PM on May 10, 2012 [3 favorites]

Open wounds make you more prone to infections, yes. But not by suppressing the immune system per se. Your skin is a barrier between the outside and a largely sterile area inside your body. When you have an area where your skin is broken, then microorganisms (fungi, bacteria, parasites, viruses) are more likely to colonize that area and cause an infection. As mentioned by qxrt, the symptoms of an infection are the result of what we refer to commonly as the immune system going bonkers to kill off these invading organisms but as a side effect of this process, you get an inflammatory response (rubor/redness, calor/heat, dalor/pain, tumor/swelling, and functio laesa/loss of function).

Chemotherapy is such a wide topic that I refer you to wikipedia for information. The bottom line is that most suppress DNA replication and synthesis--the immune response (especially the adaptive immune response) requires cells to actively synthesize new antibodies and cell-to-cell signaling molecules called cytokines and if you shut down dna replication and synthesis, you stop the immune response. Obviously it is MUCH MORE COMPLICATED than what I have described.

Diseases that "shut-down" the immune system or suppress it to the extent that make the body more susceptible to opportunistic infections come in a wide variety of forms and are the result of a diverse set of insults. See: immunodeficiency.
posted by scalespace at 8:19 PM on May 10, 2012

The immune system has two parts. There is the innate immune system which mostly looks at motifs common to many pathogens and responds in a non-targeted way (and which is what causes the majority of the symptoms you would associate with most illnesses). The Kahn acadamy people have a pretty good overview of the innate system (and a lead in on the adaptive immune system).

Jawed vertebrates (pretty much everything with a spine but lamprey) have an adaptive immune system which goes through a process of building specific antibodies against specific epitopes on one or more proteins of a pathogen. Antibodies can target a pathogen for destruction, but they can also neutralize it and prevent it from infecting you (thinking viri here) by binding the site which binds and infects your cells. A lot of the modern vaccines try to convince your immune system to produce exactly this kind of antibody.

As was said previously, there are a bunch of checks and feedback loops in the immune system making it complex (as opposed to just complex).

Staph toxin is in the big book of bioweapons (pdf) because of it's ability to activate T-cells without antibody recognition. Allergic response, including anaphylaxis, are also due to immune responses as is inflammation, so while it might seem like an activated immune system is a good thing, a little is more than enough.
posted by Kid Charlemagne at 8:20 PM on May 10, 2012

So this is a crazy complex topic, but I'll try to attack it by exploring the mechanisms of various drugs that modulate the immune system (usually by suppressing it). This will also help me study for my upcoming eight-hour exam so technically I'm being productive, right?

First, we need a little background: between the time that you're exposed to a bug and the time you develop an immune response to it, a lot of stuff happens. Antigen-presenting cells (thinkk of them as scouts for your immune system) sample little bits of the bug and show those bits to T and B cells-- the immune cells that actually do the fighting. Those T and B cells can do a few things: they can multiply, they can directly kill infected cells, they can produce antibodies that attach to cells and neutralize them or target them for destruction (opsonization), or they can send out signals that direct the body to respond in certain ways (fever, for instance). Most of these processes are directed by little tiny molecules called cytokines.

So based on that understanding, we can identify a few targets that modify immune function:

Screwing around with cytokines and their receptors:

IL-2 and T Cells: Cyclosporine, which was first isolated from a Norwegian fungus, stops the production of IL-2, a cytokine that encourages T cells to multiply. Tacrolimus also came from a fungus and does the same thing as cyclosporine but at a different point in the signal transduction pathway. Sirolimus, which sounds like Tacrolimus but comes from a bacterium that they found on Easter Island, blocks T cells' ability to multiply in response to IL-2. Daclizumab is a late-comer to the game because it's infinitely more complex than the first three drugs-- it's a monoclonal antibody, and it floats around in your blood, finds an IL-2 receptor, and blocks IL-2 from being received. Steroids, as mentioned above, dampen the immune system partially by telling T cells to stop making the IL-2 receptor (thus stopping IL-2 from triggering T-cell proliferation), and partially by stopping the production of a bunch of inflammatory molecules.

TNF-α: it stands for Tumor Necrosis Factor, but it's relevant to more than tumors-- it recruits white blood cells to fight just about anything and it also makes your blood vessels more permeable so that immune cells can get to the site of an infection. This is great when you've got a cut, but it's not so good when your immune system decides to fight innocent pieces of your body, like in Crohn's disease. For situations like that, there are a couple other monoclonal antibodies, infliximab and adalimumab (notice how all the Monoclonal AntiBodies end in =MAB?) that blow TNF-α out of the sky. There's even a weird one called etanercept that's actually a fake TNF-α receptor-- flood the body with those and the TNF-α never makes it to the real receptors.

Stopping immune cells from proliferating

ANTIMETABOLITES: All cells need to make DNA to grow and proliferate; immune cells proliferate faster than just about any cell in the body, so we can take advantage of their increased need to synthesize DNA by making fake DNA building blocks, or antimetabolites. Azathioprine, for instance, looks a hell of a lot like adenine or guanine-- enough so that immune cells try to use it and gum up all their machinery, effectively stopping proliferation. 5-Fluorouracil does basically the same thing, but is used more in cancer treatment. Of course, there are other cells in your body that also replicate quickly (hair, bone marrow, the lining of your gut), so it's important to make sure that you don't mess up too many of those cells.

OTHER WAYS to stop cells from dividing: Beyond synthesizing a whole new copy of DNA, dividing cells also need to, you know, actually divide. This requires them to make all sorts of structural proteins such as tubulin and mitotic spindles. Colchicine, a drug used in gout attacks, prevents neutrophils from dividing in this way and thus dampens the inflammatory response.

AND A SIDE-NOTE about your bone marrow: Most of these drugs that target expanding cell populations are also toxic to your bone marrow. It just so happens that your bone marrow is a super-important immunological organ. Among other things, it makes those white blood cells we mentioned above. Kill your bone marrow and you kill an important part of your immune system. Don't kill your bone marrow. Also don't kill your spleen with lupus, sickle cell anemia, or trauma. That's important for fighting encapsulated bacteria.

So that's a crazy incomplete answer to your question. There are tons of other ways to modulate your immune system. There's interesting research to suggest that zinc lozenges can help shorten the duration of colds. There are a bunch of pharmaceutical cytokines that tell the immune system to do one thing or another, (like make more thrombocytes/red blood cells, or grow more bone marrow, or whatever). Even your daily diet has some influence over how your immune system functions. But now we're getting way out of my depth and I'm done studying for the night.

posted by The White Hat at 8:24 PM on May 10, 2012 [6 favorites]

Immunology is one of the most complicated systems of the human body and it is actually one of the most dynamic areas of medical research (aka "translational" research) right now. Researchers are trying to actually use an individuals own immune system to kill cancer cells. (cf. NEJM, NYTimes references to recent advances in this area.)
posted by scalespace at 8:24 PM on May 10, 2012

Something I didn't say earlier, but is relavent - the immune system is not the sum of it's parts. It's the sum of the interaction between it's parts.
posted by Kid Charlemagne at 8:56 PM on May 10, 2012

Heya, I actually teach some immunology, so here's what I would tell my students, with the typical "you might learn something in more detail in a later class" caveat....

"Seeking a better understanding of the immune system. As I understand it: #1 I am exposed to bug. #2 I get bug. #3 I am now immune to bug."

Pretty much - when infected with an acute disease you either become immune or your become dead.

However, when you become immune to a bug, it might be quite specific - this is especially true for certain classes of pathogens, like RNA viruses, which mutate quite a bit. This is why you usually need a new flu shot every year and, as the posted above states, you don't become immune to HIV....the actuality is you do....but it embeds its genetic info into your DNA and churns out low-fidelity RNA copies at such a high rate that it eventually sends out a strain you can't fight. So while you might be immune to one strain of the flu, you may not be immune to another strain of it, and why some people have a much better ability combating HIV.

"I understand that open wounds, chemo, or ailments that suppress the immune system would cause a person to fall ill more easily. How could a product effect a person's immune response?"

An open wound does not "suppress" the immune system as much as damages it - our skin is part of our immune system! That part of the immune system (along with a few other features) is nonspecific. Chemotherapy, radiation therapy, and even medicines can prevent cell division. The adaptive immune system is specific, and relies on massive amounts of cell division by white blood cells - so that's the connection between the two. Your immune system needs new cells to work, and chemo stops news cells from forming. Other drugs or chemicals may affect energy output, which your cells also need to divide.

Some infections can also damage the immune system - these are called primary infections, and can lead to secondary infections. However, the way each works depends on what the primary infection is. With HIV as a primary infection, for example, the virus actually destroys the white blood cells that would "clean up" other microbes that would prevent disease. A fungal infection though, say, ringworm, might lead to a secondary infection by causing dryness and cracking of the skin, allowing bacteria in.
posted by Lt. Bunny Wigglesworth at 10:30 PM on May 10, 2012

As a child I caught a lot of colds (farming community in a cold climate, etc.). I haven't had a full on cold in a decade or more now as a result. I get the "first day" stuff (little weirdness with balance, back of the throat dryness), go to bed, and wake up feeling fine. Sometimes I'll get a second day of the first day symptoms, then go to bed again and wake up ok. So, lesson learned, my immune system knows a lot of bugs and such, and clobbers everything before they even get much of a chance to start.

A few months ago I was in the shower and found a golf ball sized bump in my arm pit that hadn't been there the day before. I didn't get to the doctor for another two days because it started to go down. What my doctor told me floored me. Basically something really really bad had got in, probably off of a small cut on my chest, and with my immune system as it is, it went into hella crazy mode. The lump was a lymph node that swelled massively and went to war. Typically a small cut won't do much with me, but for whatever reason, this one picked up something really bad...

So having an efficient immune system doesn't help me catch less colds and infections. I'm not even convinced I'm immune to many, but I do kill them way before most people would. Before I started worrying about hydration (few cups a day + regular intake, beer or two a week at most) and smoking I got caught colds like everyone else, so there's a safe data point. I also know I do not have the CCR5 delta 32 mutation (darn!). Of three markers for IgA deficiency (rs1990760, rs2187668, and rs9271366), I basically draw an even risk (no higher or lower than normal. And beyond that, no clue.
posted by jwells at 8:49 AM on May 11, 2012