macrophages are awesome for many reasons, but unfortunately I can Not shut up about immunology ever, so please accept this unnecessarily detailed additional information about how the immune system responds to a cold, because there are So Many players here and macrophages are but one small part of a system that is unbelievably, mind-bogglingly complex at every turn:
ok so. you have a cold. how does your body figure that out? probably via PAMPs, or Pathogen Associated Molecular Patterns. essentially, your cells are filled with sensors that detect microbial byproducts and nucleic acid that is Not Supposed to Be There. so—depending on what type of cold you have—some viral RNA or DNA trips a PAMP and your cells start noticing that something is wrong. “hey,” they say, “that’s not supposed to be there. shit. that RNA isn’t mine”
so your infected cells have now noticed that something is wrong. they start producing these things called interferons, which interfere with viral replication. they essentially tell cells to shut down protein production, chop up RNA, and metaphorically board up their metaphorical doors
meanwhile, cells that have been infected are taking bits of virus and putting it on their surfaces. This is called MHC I presentation (this will be relevant later)
soon enough, the innate immune system arrives. these are your macrophages, eating gunk, but also your neutrophils, NK cells, and DCs
neutrophils are badass. when they’re fighting bacteria, they do this thing called NETosis where they explode their DNA all over the bacteria to trap them in NETs (NET stands for Neutrophil Extracellular Trap, but it’s more fun to think of them as literal nets). Unfortunately, viruses are generally inside of cells, so neutrophils can’t really do that here. but, like macrophages, they can help clean up debris
the real heroes here are the NK, or Natural Killer, cells. these cells are generalist killers that scan your other cells, looking for anything infection-y or cancer-y. what are they looking at? those MHC I things from before. if they see something weird on MHC I, they say “nope” and kill that cell so it can’t keep making virus
“aha!” say some viruses. “I can get around this by simply reducing MHC I expression! if there’s no MHC I for NK cells to look at, I can escape!” but no! they can’t. if NK cells don’t see MHC I, they treat its absence as suspicious and kill that cell too. NK cells don’t mess around
meanwhile, those DCs are busy. these are Dendritic Cells and their primary job is to wake up the adaptive immune system and activate the big guns (T cells and B cells). they do this by taking up information from the “battlefield,” as it were, and taking it to a lymph node. they’re little couriers
so eventually a DC makes it to a lymph node and presents whatever it found on its own, different MHC molecules (these are MHC II, which are different from MHC I. sorry. immunology names are dumb). in the lymph node, it looks around for the few rare T cells and B cells that recognize whatever viral bits it’s picked up
sooner or later, a T cell recognizes that virus, and a B cell does too. now Clonal Expansion begins. the T cell makes about a gazillion more of itself and the B cell gets T cell help and starts doing the same thing. this is why adaptive immune responses take days instead of hours—a small handful of cells that happens to recognize this cold has to expand 10,000 to 100,000-fold. your lymph nodes are growing an army
(how do you have T cells and B cells that recognize this cold despite you having never encountered it before? that is a completely separate and also absurdly complicated mechanism. T and B cell development is wild. ignoring that for now)
after a couple of days of Growing An Army, the adaptive immune system is up and running. Killer T cells start killing virus-infected cells more specifically. Helper T cells coordinate the response and communicate with other immune cells. B cells differentiate into plasma cells and start churning out antibodies. (they also get T cell help and optimize their antibodies with repeated rounds of mutation and evolution right there inside your lymph nodes. they mutate a little and see if they can recognize the cold better. and they do this over and over again. eventually, the mutations that recognize antigen better are selected for, so your B cell population gets more effective over time. they also switch which type of antibody they’re making depending on what the infection calls for—in a common cold, they’ll make a bunch of, say, IgA for example. There are 5 main antibody types [really just 4 that matter; sorry IgD] and they all do different things)
the antibodies neutralize whatever virus is floating around, block it from attaching to cells, and send Eat Me signals to the cells that eat stuff, like macrophages
after around a week, you start feeling better! because at this point, there’s just not enough virus still around to keep causing problems. (ironically, many of your cold symptoms are caused by your immune response to the virus, not the virus itself). soon, regulatory mechanisms start kicking in, and most of those immune cells die :(
BUT memory cells hang around, lurking, waiting for the next time that same cold tries to infect you. you’ll have some of these memory cells basically forever
… but there are like, one million types of colds. so you’ll keep getting colds. probably not This Specific Cold again, though.
and there’s your immune response to a cold! macrophages are absolutely involved, but so are NK cells, DCs, neutrophils, T cells of various subtypes (killer and helper, and certain specific helper subsets), B cells, etc.
so next time you get painful swollen lymph nodes, be gentle on your immune system. there’s a lot going on in there. one cell is trying to become 100,000 cells. B cells are mutating, trying to make the best antibodies. every cell is doing their best :)
