Thread by @curexcomplex

So. Tweetorial 1.

I thought we would cover what happens during an adaptive immune response. .I'm going to break this up into parts over the next few days because this would be multiple lectures tbh

We're going to start with a basic concept in immunology, that is going to end up resulting in something very complex...but its the 'domino' activation of immune cells. I like to teach this as the idea of transmission of instructions along a production line.

Adaptive immune responses are responses to specific little nuggets of proteins called 'antigens.' These are little chunks of protein stuff, they can be from you, from a bacteria, from a virus.

An immune response begins with an antigen presenting cell, a Dendritic Cell (DC). They are everywhere. In all your organs and tissues constantly sampling their environment. Once activated they pick up sticks and fly to the nearest lymph node, and can do 2 things.

They can be tolerogenic where they teach your immune system the antigen isn’t dangerous (I actually work on this) or immunogenic, where they then activate the rest of the immune system and choreographed hell breaks loose. Lets focus on them.

DC eat things, smash it to bits, and then 'present' the antigen on its surface on molecules called "major histocompatibility complex"s. These MHCs is actually what is matched during organ transplant etc, in order to help minimise immune rejection.

There are 2 types of MHC, which are creatively named MHC Class I, and MHC Class II. I is recognised by CD8+ "killer" T cells, and II is recognised by CD4+ "helper" T cells.

Yes. It's back to front. I don't know why. This happens a lot in immunology. We suck at naming things.

Side note: CD4 and CD8 are the co-receptors for the T Cell Receptor. Both cells have the same T Cell Receptor (TCR). The TCR is the same. The Co-receptor helps "stabilise" the TCR-MHC interaction, think of it as a stabaliser. CD8 stabalises TCR:MHC II and CD4 TCR:MHC I.

These process is antigen presentation. The MHC+antigen is recognised by either the CD8 or CD4 receptor on T cells, depending on the type of T cell.

Alongside this, there are multiple "co stimulation" molecules. These provide additional instructions to the T cell.

When DC become immunogenic they increase expression of CD80/86. These bind to CD23 on T cells.

When you get MHC+antigen:TCR+coreceptor, and CD23:CD80/86, at the same time. The T cell gets the signal to turn on.

Both are required. One without the other will result in inactivation of the T cell.

We talk about these as "signals" so T cells need at minimum 2 signals to turn on.

This is a complex process, T cells and DC interact a lot. Think of it as a big make out session. This is sometimes called "the immunological synapse" because a large amoung of information in the form of receptor:ligand interactions.

Ok.

So now we have activated T cells. What's a T cell to do?

There is a signal 3.

These are in the form of cytokines, the things highlighted in yellow. These can help tell a T cell what action to take next.

Different combinations of cytokines, produced by the DC the surroundings etc, will give rise to different subtypes of T cells. You will get a mix of these during an immune response. They all have slightly different jobs.

This is the first step of a long process, we'll talk about B cells and antibodies tomorrow.

As you can see we've gone from a DC picking up an antigen to now a complex, multifaced T cell response, with controls built in to prevent activation.

Apologies this is late I have had a very anxiety and stress riddled week. How about we continue this since I was talking about antibody tests.

So how do we get from DC activating a CD4+ T cell, to an antibody, lets go.

This is complex, so I'm gonna start with this diagram and every time we add a new step I'll update it and we can go through this stage by stage.

Lets refresh, we have two types of T cells, CD8+ T cells, your cytotoxic killer T cells (we’ll cover these in the next tweetorial), and CD4+ T cells, your helper T cells.

B cells, are another type of white blood cell and are mostly responsable for antibody production. They live in the lymph node, and before they can shack up with their CD4 T cell buddy they need a few shots first to get their courage up.

B cells will also recognise bits of pathogens that DC's bring with them. They can bind bits of foreign antigen with their B Cell Receptor, this receptor grabs bits of antigen, and primes the cell for activation. This basically says; "oi, this things here, kick its head in."

Guess what B cells also have!

MHC Class II! Just like Dendritic Cells do! Good old MHC to the rescue again!

Like DC, B cells also "present" antigen through MHC Class II.

In order for a B cell to get the message, it also needs telt twice.

Once by detecting the antigen itself and presenting it, and secondly, by the matching T cell, also telling it the same thing. Again, this is a failsafe, if one happens without the other B cells do not (normally) activate and produce antibodies.

Again, two signals are needed.

It goes a little like this:

B cell: This is the THING right? The bad thing we need to get rid of? This is it? Right? Really?
T cell: Aye, aye thats it
B cell: You sure? Like DOUBLE sure?
T cell: Aye! C'mon move your arse theres antibodies you need to make.

B cell activation occurs in your lymph nodes mostly. Activated CD4+ T cells, move through the lymph node, looking for the B cell buddy. It’s a little like trying to find your pals at a concert after you’ve gone to the bar and they’ve disappeared off into the mosh pit.

This deliverance of signal 2 to B cells, again requires direct contact, and we end up with multiple receptors binding to each other, to pass along information from the T helper cell, to the B cell.

The B cell activates and gets down to work.

Once these cells activate they undergo a two step differentiation process.

Both short-lived plasmablasts for immediate protection and long-lived plasma cells and memory B cells for persistent protection are generated.

When turned on B cells start to divide and grow rapidly, again this is another example of clonal expansion. Plasmablasts that produce early, weak antibodies mostly of class IgM.

These IgM antibodies are not the best, but they are produced quickly and can help patch things before the B cells get down to serious business.

B cells are not here to play, they begin a process called class switching. They decide something stronger is needed.

They begin producing IgG antibodies. Then, they being to make these antibodies even more efficient through somatic hypermutation - where the DNA that encodes the antibody gets shuffled around to make it super efficient at targeting the thing it's fighting.

B cells then begin producing these new antibodies on mass. millions and billions of B cells in your lymph node all chugging out these antibodies at breakneck speed - hence why your lymph nodes swell up when you are sick. They're busy making antibodies.

To do this takes DAYS.

The process of physically manufacturing the volume of cells and antibodies needed to do this takes days, up to 10. Hence the lag between infection and the start of an immune response, and antibody production and pathogen clearence.

Antibodies can do a number of things, but prob the most important is that they bind to pathogens, covering them in antibodies, making it harder for viruses to infect new cells, and easier for the immune system to grab a hold of them and eat them and destroy them.

As the infection resolves, majority of these B cells will die, however some will persist as Memory B cells. These are capable of making efficient antibodies, so should you encounter the pathogen again – you are now so over levelled you can take it out easily.

Antibodies will also persist in your blood. We can test your antibody titre (level) by taking a blood sample and testing it – this will tell us if you have antibodies for a thing. You either have them because you have been exposed or you have been vaccinated.