by One non horrible effect of the Covid 19 epidemic is that people have become interested in immunology. I am pleased by this, but have the sense that journalists over-simplify. Roughly they act as if the immune system consists of circulating antibodies and killer t-cells. I think this post might be of some interest to some readers. First acquired immunity does indeed come in two types called cellular and humoral. That does refer to killer t-cells vs immunity via antibodies (which are produced by b-cells). Another very important cell is the helper t-cell. They are very well known because HIV1 infects them and the loss of helper T-cells is called AIDS. b-cells make antibodies when stimulated. t-cells have on their surface a very
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One non horrible effect of the Covid 19 epidemic is that people have become interested in immunology. I am pleased by this, but have the sense that journalists over-simplify. Roughly they act as if the immune system consists of circulating antibodies and killer t-cells. I think this post might be of some interest to some readers.
First acquired immunity does indeed come in two types called cellular and humoral. That does refer to killer t-cells vs immunity via antibodies (which are produced by b-cells). Another very important cell is the helper t-cell. They are very well known because HIV1 infects them and the loss of helper T-cells is called AIDS.
b-cells make antibodies when stimulated. t-cells have on their surface a very important clump of proteins called a t-cell receptor.
Immunoglobulins (genes for antibodies) and t-cell receptors are unique, because the genes are not the same in every cell in the body. Each B-cell has two genes for antibodies (each antibody is made of 2 different proteins, the light chain and the heavy chain, which are stuck together in pairs, and then 2, 4 or 10 pairs may be stuck together for different kinds of antibody — the one you always see illustrated is IgG which has 2 pairs forming a Y. Your body has also made IgD with one pair, IgE with 2 pairs, IgA with 4 pairs and IgM with 10). These genes are different in different B-cells and different in B-cells than in all other cells. Each t-cell has two genes for t-cell receptor components which are different from those in different t-cells and from all other cells.
The huge range of the immune system is achieved through the creation of many different immunoglobulin genes and many different t-cell receptor subunits. The specificity of an immune response is achieved, because each b-cell makes on and only one immunoglobulin (variable region — sorry unclear but needed for accuracy) and each t-cell makes one and only one t-cell receptor. Immune memory is achieved through changes in the cells when their receptors bind to antigens (which just mean things specific immune cell receptors bind to). B-cells are stimulated when IgD on their surface sticks to something. T-cells are stimulated when their t-cell receptor sticks to something. (I *think* in both cases the point is that two receptors stick to the same molecule and are pulled close to each other — this is certainly the way t-cell receptors work).
An activated b-cell produces IgM. Also some go to germinal centers aka follicles where they hang out with helper t-cells. If the b-cell and the helper t-cell in a germinal center bind to the same molecule, then important and complicated things happen. The b-cell changes to make different kinds of antibody (always with the same variable sticky end) . I forget the exact sequence (M to E to A to G) but, if they stay in the germinal center, they end up making IgG. However, not all daughters make the exact same IgG. Crucially at that point small random changes to the immunoglobulin genes are made (called point mutations). This generates, among others, sticky parts which stick more tightly to the antigen. Inside the germinal center, the stickiest ones win the struggle for the attention of the helper t-cells (this is called immune dominance). This means that, over time, IgG molecules with higher and higher affinity for the antigen are produced. In the end, you get IgGs who stick to antigens about as tightly as anything sticks to anything else in your body (and much more tightly than almost anything else).
This two stage process explains why booster shots are so useful. The first shot gets the process going. The second provides antigen for helper t-cells and b-cells to stick to in the germinal centers.
At this point, b-cells can have two different fates. Some develope to make huge amounts of IgG — they are called plasma cells. Others just hang around waiting for stimulation. They are called memory B-cells. There are two specific cells which develope as a result of the process and, so far, two kinds of immune memory. Roughly there are the circulating antibodies made by the plasma cells and the memory b-cells.
Helper t-cells can go to many different states. They start out naive. When stimulated by antigen binding to their receptor, they can go into many different states (no I don’t mean like Maryland and Ohio). One of them is the one I discussed called Tf1. Another is they can circulate as memory helper t-cells. This is another form of immune memory separate from circulating antibodies and memory B-cells.
Now cellular immunity. Killer T-cells also start out naive with their unique t-cell receptor (which does not change — no point mutation process here). If their receptor binds to something, and nothing else happes, they become anergic (lazy like me). In contrast if they bind to activated antigen presenting cells, then they become very energetic. The antigen presenting cells are activated by helper t-cells whose receptors bind to foreign antigens stuck to a protein on the surface of the antigen presenting cell. The Killer Tcells receptors bind to a different bit of antigen stuck to a different protein which is found on the surface of antigen presenting cells and all other cells (except for red blood cells).
The activated killer can go off and kill every cell to which it’s receptor binds (except the antigen presenting cell, the cells in our corneas, and some cells in our gonads). This new state is called effector-memory. The key thing about how effector memory killer t-cells are different from naive killer t-cells is that if they bind antigen they kill and also replicate rather than becoing anergic (even if there aren’t the other signals from antigen presenting cells). Killer t-cells can also become central memory killer t-cells and immunologists understand the important difference between effector memory killer t-cells and central memory killer t-cells but I sure don’t.
So we are up to 5 kinds of memory: circulating antibodies (from plasma cells), memory b-cells, memory helper t-cells, effector memory killer t-cells, and central memory effector t-cells.
I get the impression that most popular discussion of immune memory considers only circulating antibodies and memory killer t-cells.
Roughly, my point (if any) is that when we are reinfected we make a whole lot more molecules of antibody than we make when convalescent. The titer goes up. This is an antibody dependent way in which previous infection or vaccination can prevent serious disease without completely preventing reinfection.
pointless appendix ————————————————————————————————————-
OK so how do antibodies work ? You do NOT want to ask that question. They work in many different ways and it is very complicated. How do killer t-cells kill. You do not want to ask this question either. It is less complicated, but also complicated. The one fun part is they secrete a protein called “perforin” which does exactly what its name suggests. But you don’t want to go down that TRAIL either (that was a pun — sorry).