Why do immune reactions take place in the lymph nodes closest to the site of infection?

Submitted by arlomurfett t3_z1fohw in askscience

From what I learned in high school, every B cell in every lymph node is entirely unique since the structure of the surface receptors is randomly generated, causing each B cell to recognise a different antigen. However, whenever there is an infection in the body, it always seems like the closest lymph nodes are the ones active, eg. under the jaw during a cold, or under the armpit after a vaccine. Wouldn’t there be just as much chance that the B cell able to identify your sore throat antigens lives in a lymph node further from the site of infection like the groin, ect.? Does the B cell travel to a closer lymph node once activated? Or are there many different B cells that can recognise an antigen to varying degrees, and the closest ones mount the fastest immune response, even if a B cell further away could do a better job?

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Furrypocketpussy t1_ixaswyo wrote

Your body has dendritic cells in basically every tissue, so when an infection happens the dendritic cell will mature and lose its adhesion to the tissue. After that it will follow a chemokine trail to the nearest lymp node where it will present the antigen to mature B and T cells in the lymph node. Your lymp nodes also monitor the lymph for antigens, so the closest ones to the infection site will get the most of them and will react the most due to the higher concentration

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silent_cat t1_ixcimtd wrote

That's how I'd heard it explained: rather than having antigens spread across you body in the hope they match, they hang around in the lymph nodes and monitor the stuff coming past.

It's said the mammalian immune system is the second most complex known system in the world, after the brain. Every time I hear more about it I'm amazed.

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uuicon t1_ixc2u0e wrote

Wow, you explain this so well, I almost feel able to understand what you are saying.

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octopusgardener0 t1_ixdrlnv wrote

The neighborhood watch in parts of your body has people trained to look out for one thing, then when they see it they go down to the nearest police station who sends out officers trained to handle some common problems while beginning training new ones to help the first responders with that one thing

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GinGimlet t1_ixdeflh wrote

This is correct, also concentrating the cells presenting antigen and the cells that need antigen to activate/multiply increases the rate at which an immune response occurs. I can't remember the exact numbers but lots of T cells can contact dendritic cells per hour when they are stationary in a Lymph Node, increasing the odds that the correct ones are found; and then those activated T cells can go help other cells out, like B cells, which are also located in high numbers in the lymph nodes. It's essentially all about efficiency.

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DocJanItor t1_ixbjnvi wrote

The last sentence you wrote is essentially correct. The b cell that gets activated first, regardless of affinity, is the one that gets clonally replicated. Those clones have some randomization of their antigen matching site -> the ones that bind better get selected for future cloning -> ad infinitum until infection is clear.

Also, there are memory b cells of previous infections. Infections tend to be geographic; standard respiratory infections, hand infections, foot infections, etc. So those cells are already there for clonal proliferation.

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The-very-naughtyduck t1_ixc39wm wrote

In addition to the other answers, antigen naive (i.e. never-before activated) B and T cells circulate constantly between lymph nodes and blood. This maximises the chances of B and T cells finding their antigen and responding, even if the antigen is only found in those lymph nodes nearest to the infection.

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DooDooSlinger t1_ixcifcr wrote

The antigens carried by antigen presenting cells (dendritic etc) are drained through the lymph from the periphery into lymph notes, where various progenitors live. There they recognize antigens and proliferate. You don't want them to be in the periphery because they might miss antigens, and proliferating requires special structures, for example to avoid tissue damage.

So these lymph nodes are hubs where a huge diversity of progenitors is available to recognize any antigen, and which is able to see antigen coming from a significant area in the body. You can think of it as a scout discovering an enemy, bringing the news back to the local camp where all the officers can decide the best course of action.

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Content-Structure409 t1_ixet6nt wrote

Imagine you cut you finger, allowing some virus to enter your body. This infects some of your cells, forcing them to make more virus.

The damaged tissue leads to release of inflammation markers like interleukins, alerting your innate immune system to the situation. They hightail it to the site of the cut and pick up the fight. In essence, they try to kill all virus infected cells to stop the virus replication. Some cells can even signal to immune cells that they have been hijacked by a virus. The innate immune response is not enough to get you healthy again if it is a serious infection, but is a first effort and it buys you time. During this „battle“ a lot of debris is made. Remains of killed cells, components of the virus etc. Antigen-presenting cells (APCs) grab a piece of the rubble and the move to the next lymph node. A chemokine trail shows them where to go. Once there, they take this piece of debris and put it into a special protein on their surface called MHC. This allows them to present this antigen (piece of debris) to other cells.

In the lymph node, there are a lot of naive B and T-cells. Each of these has a different B or T-cell receptor. How it is shaped and what antigen it recognises is randomised at its “birth” through a process called VDJ recombination.

The antigen presenting cells now shows it’s piece of debris around to many naive T or B cell until one happens to bind it with its receptor. This cell is then rapidly copied millions of times. Once this army of T-cells is released into the blood, it can very specifically fight off any virus infected cells. B cells make antibodies and release that instead. That way, your immune system can fight even previously unknown invaders.

Your initial assumption can still be true - maybe the right T-cell lives in your leg at the moment you are cut. But the lymphatic system is all connected. APCs and other cells move through it as needed. This turns the node nearest to the site of infection into a sort of forward operating base that is still connected to the other nodes.

You also do not need a perfect match. If you found a T-cell or B-cell that can bind the antigen, the part it uses to recognise the virus can be optimised in a process called avidity maturation. You can also have many matches, with a number of different naive B cells or T cells being activated and then copied. This is the normal case. If you get infected, the antibodies in your blood are polyclonal, meaning they come from many different initial naive B-cells. Two different B-cells lines can make antibodies recognising the same or different parts of a virus. This redundancy is beneficial, it lowers the chance that a mutation of the virus allows it to escape the immune response, because the initially recognised antigen is no longer present. The process also continuously optimises the capability to recognise and fight the virus. Redundancy, with many parts trying to do the same task is key to not dying if the virus outsmarts any one system.

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