What Makes Me Tick - Part 7

Part 7 – The Human Immune System

Another system worth investigating is our body's immune system. The following three articles by Merch Manual, Khan Academy, and Assay Genie, respectively, offer an overview of the many facets of the human immune system: https://www.merckmanuals.com/home/immune-disorders/biology-of-the-immune-system/overview-of-the-immune-system; https://www.khanacademy.org/science/in-in-class-12-biology-india/xc09ed98f7a9e671b:in-in-human-health-and-disease/xc09ed98f7a9e671b:in-in-types-of-immunity-and-the-immune-system/a/adaptive-immunity; https://www.assaygenie.com/b-cells.

Our immune system utilizes and orchestrates many different kinds of cells. One of its processes involves B-cells which are produced in the bone marrow. Below, I will describe this B-cell response, summarizing the molecular biology delineated in chapter 6 of Darwin's Black Box.

B-cells are factories that each make one type of antibody. Each B-cell makes an oily tail that keeps its antibody connected to itself while roaming in the bloodstream. If a particular B-cell comes across an invader in the bloodstream that is a close enough chemical match to its attached antibody, then a molecular process begins.

The B-cell molecularly cuts a piece of membrane to wrap around the invader, takes the invader into its own cell, and then cuts the invader into pieces. The B-cell then binds a piece of the invader to another protein and attaches them onto its membrane. If a T-cell (produced in a different organ called the thymus) that has a molecular fit comes by (like a lock fitting on a key), then the T-cell secretes a substance called interleukin that causes a massive reproduction of individually specialized B-cell factories.

At first these new B-cell factories resemble the original B-cell, but then they are modified to become plasma cells. These cells each manufacture their antibodies, but without the oily tail. Now the antibodies produced are not attached to the cell factory, and will move freely and attach to the pathogens roaming in the body.

The antibodies bind to pathogens making antigen-antibody complexes. The immune system now begins to attack the antigen-antibody complex in a variety of ways (each type having their own cascades of molecular chemistries) in order to rid the body of the pathogen.

If the invader was bacteria, the following complement activation begins: A C1 antigen group binds to the antigen-antibody complex. The C1 group has 22 proteins that form a stalk. This stalk links to the antigen-antibody complex, wraps around, cuts, bends, and changes. Then groups C2, C3, and C4 are assembled with this chemical complex and are reshaped.

If any of these chemical components are too far away or too low in quantity, the process decays and no attack is made. Five chemical reactions later, the C8 group has reorganized itself into a tube shape that then pierces the invader. Pressure differential causes fluid to invade the pathogenic cell, swell, and rupture it.

Each step above not only has a list of proteins directly engaged in the complex, but also, each step has control points, switches, and activators which are all essential to the process. A much more thorough look into this process can be found at articles like this one by Karger, Journal of Innate Immunity, https://www.karger.com/Article/Fulltext/491439.


B-Cell Variation

The process of destroying invaders summarized above is chemically complex and dependent upon different organs. What perhaps is even more intriguing is another process that is set in motion before the complement activation begins.

Every B-cell is different from all other B-cells. Each B-cell manufactures an antibody that has a unique binding site, the place where the antibody attaches to an invader. Each antibody has a 1 in 100,000 chance of binding with a particular pathogen. The chemical match does not have to be exact; approximated matches can combine.

There are 10 billion different types of antibody binding sites that could be made. Our body does not have enough DNA to code all the possible variations of these 10 billion different types of B-cells. Actually, our body does not even have a separate code for each type of B-cell it generates. Instead, B-cells have a different process for multiplication.

When an invader binds with the antibody on the B-cell, and the factory reproduction process is initiated by the matching T-cell, the B-cell does not just self-replicate into identical B-cell factories; it does something more valuable. There are 400 genes in the B-cell's DNA that account for different antibody binding sites. Instead of making multiple copies of the same antibody that might not be the best fit for the invader, the B-cell makes a set of varied B-cell factories by splicing and reorganizing its antibody genes.

This process is not random though; the process only uses the subset of genes that will yield a variety of antibodies that all have the minimum matching requirement to bind with the invader, and some will bind even stronger. Therefore, with each invasion, the body not only produces a varied strategic attack, but also afterwards is armed with an even greater variation of defending B-cells. A much more detailed description of this process can be seen in the National Library of Medicine article found here: https://www.ncbi.nlm.nih.gov/books/NBK26860/.


The Lymphatic System

The B-cells only play one part in the body's defense against daily invaders. In the aforementioned article by Merck Manual, we discover the immune system (with its variety of defender cell types) works in conjunction with the lymphatic system, the bone marrow, the thymus, the spleen, the tonsils, the appendix, and Peyer patches in the small intestine.

The lymphatic system is a network of vessels and nodes which transports lymph throughout the body. Lymph is formed from fluid that permeates from the capillaries into the body's tissues, enters the lymphatic vessels, and later joins back with the subclavian vein returning to the bloodstream. Lymph transports foreign substances, cancer cells, or dead and damaged cells from the tissues to lymph nodes for the body to remove.

"All substances transported by the lymph pass through at least one lymph node, where foreign substances can be filtered out and destroyed before fluid is returned to the bloodstream. In the lymph nodes, white blood cells can collect, interact with each other and with antigens, and generate immune responses to foreign substances. Lymph nodes contain a mesh of tissue that is tightly packed with B cells, T cells, dendritic cells, and macrophages. Harmful microorganisms are filtered through the mesh, then identified and attacked by B cells and T cells." (Merck Manual, https://www.merckmanuals.com/home/immune-disorders/biology-of-the-immune-system/overview-of-the-immune-system)

The above is only a brief introduction to a portion of our immune system. To truly grasp even a small understanding of the complexity involved in this section, the reader is encouraged to research the article referenced above by Karger, The Journey of Innate Immunity (https://karger.com/jin/article/10/5-6/455/180323/Complement-and-Bacterial-Infections-From-Molecular).

The immune system depends on a very long list of proteins. In Part 8 we will investigate what is required to make and deliver proteins.  

What Makes Me Tick - Part 8

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