A lot of lab cell lines divide happily in flasks because they come from cancer cells cultured from actual people. For example, Nalm6 is a precursor B cell leukemia cell line and Jurkat is a T cell leukemia cell line. So you could inject Nalm6 cells in a mouse and then see if a CAR-19 T cells can clear the cancer.

You can also administer carcinogens to cause the specimen to develop cancer on its own, without the need to culture and graft the cells. Based on the type of carcinogen and where/how it is administered you end up with different types of cancer.

Back when I was in grad school one of my colleagues injected a carcinogen via catheter to promote bladder cancer for example.

As to your questions about ethics: in my experience at least yes, researchers take the ethics of what they are doing extremely seriously, and the university has an elaborate oversight and approval system which monitors for ethical lapses. We were taught that an animal could only be used if there was no other way to collect the data we needed, and that the study should always be designed to minimize the animal’s suffering

How interesting! Wow have they always cared to conduct studies while being ethical? Or is this a recent change that scientists intentionally approach these experiments with ethics/compassion in mind?

The simplest algorithm used for basically every student-level task in my youth was "backward propagation of errors".

To run this model, you need three things: a big multi-layered filter (which will be our "AI"; a set of matrices that the initial data is multiplied on, and an activation function to mix some non-linearity in), a sufficient set of input data, and a sufficient set of corresponding output data. Sufficient for the system to pick on the general task.

Basically you take initial (empty or random) filter, feed it a piece of input data, subtract output data from corresponding desired result (finding what we call "error", i.e. difference between actual and desired result), and then you go backwards through the filter, layer by layer, and with simple essentially arithmetic operations, adjust the coefficients in a way that IF you fed the same data again, the "error" would be smaller.

If you "overfeed" one and the same input to this model 10 million times, you'll end up with the system that can only generate correct result for this, specific input.

But, when you randomly shift between several thousand options of inputs, the filter ends up in "imperfect but generally optimal" state.

The miracle of this algorithm is that it keeps working no matter how small the adjustments are, as long as they are made in the right direction.

One thing to keep in mind is that this particular model works best when the neuron activation function is monotonic, and the complexity of the task is actually limited by the amount of layers.

As a student, I made a simple demonstration program on this principle that was designing isotropic beams of equal resistance in response to given forces. During this experiment, I have proven that such a program requires two layers (since the task at hand is essentially a double integration).

I'm putting this response in because no-one seems to have mentioned backwards propagation of errors; modern and complex AI systems, especially working on speech/text, actually use more complex algorithms; it's just that this one is most intuitive and easiest to understand for humans.

I think it depends on who you ask, but most likely the people engaging in this work would believe that it is necessary at the moment to move medicine forward. There are panels that oversee the experimental design of any such study and I can assure you that they take their job very seriously. My PI in grad school was roasted by them during a meeting because he had not adequately outlined a pain management protocol for the mice in our study that were getting an experimental cancer drug. Everything in these studies is done with ethics at heart

Amongst that scientific community, is this considered ethical or a necessary evil?

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Cancer cells are grown in vitro and then injected into the animal at the desired location of the tumor. For most reliable model systems the parameters for what cell subtype to use and how many cells to inject are known and published

>That’s a bit different from what OP was asking.

I'm aware, that's why it was a reply to the mention of that assay and not a direct post towards OP. I work with TM-proteins and do quite a lot of labeled Ab assays to indirectly prove something's there as it's just too small to see;)

We're also talking about humoral immunity, which relies on antibodies. There is no self recognition involved there. As for cell-mediated immunity, it's true that the self MHC is part of what's required for recognition, but MHC alone is not sufficient - you need the foreign antigen loaded into the self MHC for recognition.

As for MHC and HLA, they are not two different molecules. MHCs are HLAs.

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That is absolutely wrong. The immune system HAS to recognize self in order to attack the non-self. It does so mostly through two self-identification molecules (Human leukocyte antigens [HLA], and the major histocompatibility complex [MHC]). When the immune system doesn’t recognize the body’s own cells you get autoimmune diseases.

The agglutination test at the bio labs for first year students don’t allow you to see individual cells. You simply see a reaction or lack thereof. That’s a bit different from what OP was asking.

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With modern understanding of pharmakinetics, researchers already have an idea of how drugs will act in mammals based on already understood compounds in or similar to the study drug. They can sometimes already tell what the half life is as well (this is how quickly the chemicals decay, or essentially stop working), so they know how long it will take for the drug to stop having an effect though it can behave differently in the body.

Study drugs are first administered to animals to determine potential AEs (adverse events, like side effects) and continue to study the half life by collecting blood and/or urine at specific intervals of time. Say they give the study drug at 8:00 am, they may draw blood or collect urine every 2 hours over the course of 12 hours. There will be less of the drug as time goes on, and they are using the blood/ urine samples to determine specifically how quickly it is passed though the body and how strong/ effective the medication is based on amount present in the sample.

Then they do the same thing in volunteer humans that get paid to be in a trial. They follow very strict procedures, the volunteers stay at the research facility 24/7 for a set period of time (could be a day could be 40 days) and are given the same food. The procedures (which includes when they administer the study drug or placebo, when they take blood or urine, when they take vital signs, EKG, weight, etc) are written out by the pharmaceutical company who developed the drug and are followed down to the second. Volunteers even need to pee at specified times. All adverse events (side effects) are recorded and there are usually follow up visits after the study volunteer is done with the initial stay to continue monitoring until the drug is no longer affecting them.

There are multiple arms of in-human studies where they do the same thing but with different diets, ethnicities, etc to see how the drug may be impacted by different factors.

So yes, they do a lot more than just blood testing and it is at very, very specific intervals of time. Usually vital signs, blood, urine, heart, etc are tested at specific times.

Antibodies are made by the immune system, specifically B-cells. They are used as targeting proteins so that your body can respond to diseases/pathogens. If they are expressed on the surface of the B-cell, then when they find and bind to something 'foreign', they can then cause the B-cell to proliferate (divide and multiply), meaning that your body can fight off the disease. They can also be secreted from other types of B-cells (plasma cells) which flat around to monitor your body, and then bind to foreign pathogens and act as a flag/beacon for other immune cells to come and investigate and attack (T-cells/NK cells).

In terms of what happens when they're not needed, the cell surface expressed antibodies will stay around as long as the individual cell lives (the cell probably recycles and makes more to put on the surface over it's lifespan) and the secreted antibodies will degrade over time or be processed and degraded by other immune cells. The plasma cells will tick over and are there to make more if the disease invades again.

Great answer, I didn’t know this much about blood cells. Unfortunately your answer doesn’t answer OP’s question. What are the physical differences between these antigens?

Edit: apologies your answer answers partially. You explained what those letters and signs mean.

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