natural killer cell

9

9 films that capture my aesthetic

melancholia (2011, lars von trier) • the cell (2000, tarsem singh) • oldboy (2003, chan-wook park) • enter the void (2009, gaspar noé) • spring breakers (2012, harmony korine) • only god forgives (2013, nicolas winding refn) • a clockwork orange (1971, stanley kubrick) • twin peaks: fire walk with me (1992, david lynch) • natural born killers (1994, oliver stone)

Innate Immunity - intro
  • First line of defence + first to act
  • A primitive response (exists in animals and some plants)
  • Non-specialised and without ‘memory’

Consists of:

  • Physical barriers (eg skin and mucosa//tight junctions, airflow)
  • Chemical barriers (eg enzymes, lung surfactant, antimicrobals)
  • Soluble mediators of inflammation (eg cytokines)
  • Microbal defence (eg commensal competition, secreted antimicrobals)
  • Cells (eg phagocytes)
  • Receptors to recognise presence of pathogen/injury - results in inflammation

Soluble Mediators

Complement Proteins

  • liver-derived 
  • circulate in serum in inactive form
  • activated by pathogens during innate response
  • functions include lysis, chemotaxis and opsonisation

Auxiliary Cells

Mediate inflammation as part of the immune response. The main auxiliary cells involved in the immune response are Basophils, Mast cells and Platelets.

Basophils 

  • Leukocyte containing granules 
  • on degranulation release histamineplatelet activating factor
  • causing increased vascular permeability and smooth muscle contraction
  • also synthesise and secrete other mediators that control the development of immune system reactions

Mast Cells

  • Also contain granules 
  • However they are not circulating cells - found close to blood vessels in all types of tissue especially mucosal and epithelial tissues.
  • rapidly release inflammatory histamine but this is IgE dependant so not innate

Platelets 

  • normally function in blood clotting
  • also release inflammatory mediators

Cytokines and chemokines

Produced by many cells but especially mØ (macrophages), initiate inflammatory response and act on blood vessels 

  • interferons - antiviral protection
  • chemokines - recruit cells
  • interleukines - fever inducing, IL-6 induces acute phase proteins 
  • IL-1 - encourages leukocytes to migrate to infected/damaged tissue
  • as does tumour necrosis factor (TNFa)

Acute phase proteins

  • Liver derived proteins 
  • plasma concentrations increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation
  • called the acute-phase reaction 
  • triggered by inflammatory cytokines ( IL-1, IL-6, TNFα)
  • help mediate inflammation ( fever, leukocytosis, increased cortisol, decreased thyroxine, decreased serum iron, etc)
  • activate complement opsonisation 

Inflammation 

Cells

Cytotoxic Cells

  • Eosinophils/natural killer cells, cytotoxic T cells
  • kill target via release of toxic granules 
  • dendritic cell derived IL-12 helps activate NK cells

Phagocytes

  • mono-nuclear = long-lived; polynuclear = short-lived
  • engulf, internalize and destroy 
  • phagosome forms around microbe
  • enzyme filled with lysosomes fuses to form phagolysosome
  • organism is digested
  • fragments are either ‘presented’ or exocytosed

phagocytosis requires recognition of microbe via receptors for

  • PAMPs (pathogen associated molecular patterns - eg flagella or capsule) - recognised by toll-like receptors 
  • activated complement
  • antibody

The innate immune response primes for the adaptive 

  • B-cells are primed by activated complement
  • Th1 cell differentiation needs pro-inflammatory cytokines

tohoxinki  asked:

hi! i sent u tht ask abt my mom having cancer, n i have a (rly dumb) question. i know shes on epoch-r, and i read about that, but im just. confused about how chemo in general works? ive tried looking it up but everywhere i looked says "chemo attacks cancer cells" and doesn't explain further.

hi hi hi!!! 

that’s totally not a dumb question. i’ve always been confused too, especially since there are so many cancer treatment terms and honestly it gets really confusing sometimes (like holy cow are cancer drug names awful to pronounce?)

historically, the term “chemotherapy” used to mean just any chemical compound (aka a drug) that can be used to treat a disease, such as antibacterial chemotherapy. and then the nomenclature slowly became known as just any drug that’s used to attack and kill cancer cells. this was way before anything like “targeted therapy” or “immunotherapy” was discovered, so you can look at chemotherapy being the grandfather or umbrella term for cancer-killing agents. 

chemotherapy is also used to describe a treatment that’s given systemically–as in it goes everywhere in the body, usually through intravenous (IV) injections. therefore it’s pretty darn useful to, for example, treat cancers that have metastasized to different organs. (that’s not the exclusive use of chemo tho; patients with primary tumors that haven’t metastasized can still use chemo). this is in comparison to radiation therapy, which uses radiation to blast a very very specific area of the body where the tumor is. 

the majority of the time, chemotherapy is a group of drugs that kill cancer cells because they attack their more-or-less unique characteristic of being crazy fast cell dividers. these drugs will often go after the mitosis machinery, and cause so much chaos that the cells have no choice but to undergo apoptosis, or a type of programmed cell death. 

however, chemo can’t really tell the different between a cancer cell and a healthy normal cell; it just so happens to be more effective at killing cells that divide quickly. so that’s why chemo regimens aren’t given over a really long period of time (treatment usually only lasts days), and why patients can experience side effects such as immunosuppression and gastrointestinal issues, as the immune cells and the cells lining our intestines are also fast dividers. they’re civilian casualties, so to say :(

certain chemos tend to work better with certain cancers, which is why there are specific chemo regimens. chemos are oftentimes given as a batch rather than individually. for example, EPOCH-R is a combo of drugs that work as a team to attack different aspects of the NHL cells, and can achieve much better results than if any of them went on a solo mission. here’s a breakdown of what each drug does:

Rituximab: this is an antibody that can bind specifically to B-cells, which in NHL have gone rogue and replication-happy. B-cells have a very specific protein on their surface, CD20, and rituximab gloms on like velcro. This causes natural killer cells and macrophages to recognize the B-cells as “foreign” and attack them. It also causes the complement system to be activated by the B-cells, which also furthers destruction of the cell. The downside of rituximab is it doesn’t discriminate between cancerous B-cells and normal B-cells though. 

Etoposide: these dudes inhibit the topoisomerase, which is an enzyme that helps unwind DNA during cell replication. when DNA unwinds, the downstream strands tend to get tangled and bent (think of unwinding one of those old-school phone cords–the part of the cord you’re not straightening gets super stressed and coils in on itself). Cells don’t like that, so they tell topoisomerase to go in and form small harmless nicks in the DNA to help relax it, and then when the DNA is unwound, it seals back the nick again. That last step is pretty crucial; without that action, DNA will just be floating around in fragments and the cell can’t function and will undergo apoptosis. so by inhibiting topoisomerase, etoposide is able to kill the cell. like most chemos tho, it can’t distinguish between cancer cells and non-cancer cells, but because cancer cells replicate so much faster than normal cells, and thus rely on topoisomerase so much more frequently, etoposide should be more effective in killing the cancer cells. 

Prednisolone: i don’t think the exact mechanism of how prednisolone kills cancer cells is well known. it’s used generally in low doses to dampen the immune system during allergic reactions, but with a high dose during chemo, it specifically causes immune cells (like NHL cells) to undergo apoptosis. 

Oncovin: aka vincristine (which imo is a much prettier name). this drug binds to a protein called tubulin. tubulin is required during mitosis, or cell division, to form microtubules–think of tubulin as like the fibers of a rope. microtubules form the mitotic spindles which separates the two daughter cells during cell division, so without tubulin, the cells can’t separate, things go haywire, and the cells undergo apoptosis. again, this drug isn’t specific to cancer cells, but relies on the faster rate of cell division in cancer cells to “spare” as many normal cells as possible. 

Cyclophosphamide: this drug has a metabolite that’s formed in NHL cells that’s able to form crosslinks in the DNA, rendering it almost impossible for the cell to create RNA (and protein), or to replicate. without these functions, the cell undergoes apoptosis. 

Hydroxydaunorubicin: aka doxorubicin. this drug is able to interacalate DNA, which means it’s able to get all nice and snug inside the DNA strand, and now the cell can’t synthesize RNA or proteins, or replicate (much like the effect of crosslinking of DNA). it’s akin to getting a rock in your shoe, and the presence of the rock causes you to cease all normal function and undergo apoptosis. that’s one deadly rock. it can also prevent topoisomerase from sealing DNA nicks (much like etoposide).

I hope that was a bit helpful! i maaayyy have delved into more detail than what you were looking for, but it’s all just really fascinating stuff…and i hope it gives you something to launch off of if you’re curious to learn more (and also feel free to ask me any questions you may have!)

good luck to your mom! i’m still rooting for her <3

Preventing and Treating Winter Colds

By Michael Castleman

The signs don’t lie: scratchy throat, nasal congestion, watery eyes. It is, indeed, the start of another cold. If your first thought is to reach for the Airborne, that over-the-counter herbal cold remedy invented by a teacher, think again. It probably won’t make a dent.

But other herbal and natural approaches do prevent colds—and if you do end up catching a cold, natural treatments can spare you considerable misery.  

Colds are humanity’s most prevalent illness. Caused by more than 200 viruses, each one technically causes a “different” cold. But because all colds produce similar symptoms, the malady is considered a single illness. 

Most colds start with a scratchy throat, and progress through nasal congestion, watery eyes and runny nose to a dry, hacking cough that may become bronchitis. Childhood colds may cause fever, but adult colds rarely do.

Medically, colds are minor and clear up by themselves in a week or so. But this minor illness causes major misery and is quite costly. Americans suffer 500 million colds annually and spend $17 billion a year treating them. Most of that money is wasted on over-the-counter cold formulas that suppress symptoms without spurring healing. Herbal and natural approaches are preferable because they provide real protection and/or speed healing.

Keep reading

Galectin-1

There are a ton of approaches to cancer… but the most promising now a days seem to be an immune response approach. Galectin-1 is a membrane protein that is missing in many cancer lines and by introducing it, it was able to completely eradicate the cancer cells in rats.

Before anyone thinks.. they cured cancer! Here are some things you should consider about these research. Lots of studies designed this way seem to show very good results, but it is partially due to their ability to introduce these interventions invitro before introducing them into the animal models. If we could get every tumor/cancer cell to express these proteins, there are a number of treatments that would work just as great (pTK, p53..) The main problem with cancer research now a days is actually being able to target them efficiently, while reducing toxicity. 

However, it is great to see such an approach work since it immunotherapy is such a hot topic. With the specificity and strength our immune system can provide treatments like this have a great future outlook. Take a look at the study below; I would love to get my hands on some of this plasmid!

Natural Killer Cells Eradicate Galectin-1 Deficient Glioma in the Absence of Adaptive Immunity

PMTH Morning Report: NK Cells

Good morning staff, zombies, and minions of Princeton Medbloro Teaching Hospital!

I am a baby medblr here, taking a stab at my first morning report. Today’s topic is…wait for it…my favorite cells…natural killer cells! Those bad ass little buggers whom you can thank your lucky stars for playing a role in keeping you a healthy, and relatively happy, humanoid. 

Give them credit because they truly are:

These lymphocytes don’t get as much credit as their ever so popular B and T cell counterparts, but don’t let the absence of genetic rearrangement deter your from what these gems do. They are a part of the innate immune system, and they are ready for action! Watch out infected cells, watch out neoplasms, NK cells are hunting you down!

How do you identify one of these super duper cells you ask? Well, lucky for us they are waving a giant flag. Thanks CD56! Of course, there are other markers but I like this one the best. Anyway, some NK cells let their CD56 shine more than others. What do I mean by that? You can see it with the use of our friend,flow cytometry!

But don’t think CD56 is all lonely on the surface…oh no. There’s a party going on. We have NKG2D getting all flirty with danger, and revving up the engines. All the while NKG2A is flirting’ with the HLA’s (Human Leukocyte Antigen) on cells passing by, and calming shit down. 

However, our party would not be complete without the KIRs (Killer Cell Immunoglobulin-Like Receptors) making everything more interesting. These aren’t generalists like NKG2D or NKG2A. Oh no, these dudes are picky. KIR2DL1 is looking for HLA-C2, KIR2DL2/3 is looking for HLA-C1, KIR3DL1 is looking for HLA-Bw4. But shhhh there’s a little secret that people don’t like to talk about…these KIRs can be frisky sometimes. I just listed the inhibitory KIRs, but substitute an S for the L (ex. KIR2DS1), and you’ve got yourself an activating KIR!

Yes, Yes, I know there is a lot of random information here. It’s important though because whether or not an NK cell kills, and how activated it is, depends on the BALANCE of those activating and inhibiting signals. 

Why do we give a shit about this? There are lot’s and lot’s of reasons, but I’ll list one. Tumor immunology! Turns out information about somebody’s HLA and KIR genotypes may be able to predict a patient’s response to immunotherapies, and maybe even outcomes in cancer patients. Pretty neat huh? 

Well, that’s all I’ve got. Be sure to grab coffee and an extra doughnut on your way out. 

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14LEFT(14레프트) - Natural Killer Cell