The Immune System

Your immune system is what protects you from being used as an energy or nutrition source by microbes that might cause damage (pathogens). Like any defensive system, your body opts for "defense in depth". In other words, you have multiple layers of defense so that if one fails there is another, hopefully stronger, backup system. Obviously there is also a trade-off between the number of layers and the amount of energy that needs to be put into maintaining them. Our compromise is on two layers of defense--enough to handle most situations but not so much that you go "bankrupt" trying to build and maintain it. The first layer is part of the non-specific (or innate) defense; the second is the specific (or adaptive) defense.

A recent (summer 2020) article concerning COVID-19 treatment is a good overview of the immune system - The Pandemic's Biggest Mystery Is Our Own Immune System - The Atlantic.pdf

LAYER 1, PART 1--BORDERS (BARRIERS TO ENTRY):  The best defense in this case is to simply not let anyone in--put up a barrier that keeps most things out.  The skin and mucous membranes provide that barrier. Unbroken skin is an excellent barrier to entry--it is essentially bacteria and virus proof. The skin has a number of characteristics that make it an unfriendly place for most bacteria--dry, acidic, sloughs off regularly, fatty acid secretions, and antibacterial substances in sweat. It does not prevent all bacteria from living there as some are adapted to that environment. But it does keep most of them out. Unfortunately, your skin must have openings for oxygen and nutrients to get in and waste materials to get out. Each of these openings is a vulnerable spot for bacterial penetration.  They are all protected by mucous membranes which trap and sweep out particles as well secreting antibacterial substances. For a basic overview of the entire immune system that will supplement the text, use this link to an Online Biology Book (Links to an external site.). The preceding link can be used with each section of this information on the immune system. This site from the University of South Carolina Microbiology and Immunity Online Book (Links to an external site.) site covers barriers thoroughly.

This level involves an array of sensors and white blood cells and proteins in the blood that will attack antigens that have penetrated the barriers. These defenses are not specifically designed to counteract any particular antigen but attack most kinds of antigens. Like any generalist, they are somewhat effective against many things but not specialists on any particular antigen. The first sensor system involves toll-like receptors found on both the exterior and within phagocytic cells called macrophages and dendritic cells. They may be found in other cells but that is not yet known. These receptors recognize patterns there are unique to microbes such as the LPS layer from the outer membrane of gram negative bacteria, petidoglycan, or flagellin proteins. The second sensor system is the complement system. Complement is large number of proteins (at least 20) that form a cascade response--#1 attracts, that attracts # 2, then #3, etc.  Once complement is activated, there are three possible outcome and there are three alternate pathways or patterns of complement activation. Regardless of the pathway, the results are inflammation, lysis of foreign cells, or opsonization (complements molecules attract phagocytes). The Bite-Sized Immunity site has an overview of the complement system (Links to an external site.). A more detailed look is found at Doc Kaiser's Microbiology Web Site (Links to an external site.). University of South Carolina site also covers complement in detail--Microbiology and Immunity Online  (Links to an external site.)site. One other aspect of these non-specific responses is the inflammatory response. This response is a coordinated effort by the damaged cells, circulatory system, white blood cells (phagocytes), and complement. The Cells Alive site has an excellent presentation of the inflammatory response--see Ouch (Links to an external site.). The histamine released during this process increases fluid leakage from capillaries. When this occurs in the mucous membranes of the nasal passages, you get a thinner mucous and a "runny nose". This also helps physically remove pathogens. A fever (Links to an external site.) is also part of the normal response. The fever takes pathogens out of their optimal temperature, increases activity of the immune system, and makes you drowsy--you rest which leaves more energy for the immune process. It also limits iron availability for the pathogen (iron is the most scarce resource for bacteria inside the body and is required for growth of the bacteria). Over-the-counter-drugs that you may use to counteract these symptoms will make you "feel" better but may prolong the infection. The second protein usually discussed is  interferon. It is produced by virus infected cells and seems to slow down the ability of viruses to enter surrounding cells.

This level of the immune response uses both proteins and cells that are custom designed for one specific antigen. They are highly effective in most situations but are not produced unless the antigen for which they are "specific" is present. The specific immune system has four properties:  1.) It is highly specific--it exactly matches the 3-dimensional shape of a specific antigen. 2.) It can handle a diverse array of different antigens--a critical requirement because of the large number of different antigens in our environment. 3.) Since it destroys the antigen, it is important that it distinguish self from non-self so as not to attack normal body cells. 4.) It has a memory so that once an antigen is identified and responded to, the system does not have to start from scratch the next time it encounters that antigen. There are two primary portions of this response level.

One is the antibody mediated defense. It uses B-cells (lymphocytes--white blood cells--that mature in the bone marrow) and T cells (lymphocytes--white blood cells--that mature in the thymus gland). A B-cell can present antigens found to T-Helper (TH) cells. If the TH cell recognizes the antigen it secretes cytokines that activate the B cell. It responds by dividing into many more identical copies of that B-cell with a receptor that exactly matches the antigen (called clonal selection). Eventually some of these cells mature into plasma cells which produce antibodies. Antibodies are not living cells--they are proteins with a 3-dimensional shape that is the same as the original B-cell receptor; therefore, they also bind the specific antigen that started the process. Cells Alive (Links to an external site.) has an excellent  presentation on how antibodies are produced. I also recommend What the Heck Is an Antibody. (Links to an external site.)

Antibodies flood the fluid portions of the body and either destroy antigens, mark them for white blood cells, or attract complement proteins. The Howard Hughes Medical Institute has an animation that clearly presents information on B and T cells--Cells of the Immune System (Links to an external site.). Doc Kaiser’s site (Links to an external site.) has much information on the Antibody-mediated (also called Humoral) response.The National Institute of Allergy and Infectious Disease (NIAID) supplies a tutorial called Understanding the Immune System (Links to an external site.) that is also very well done and aimed at patients.

Major Histocompatability Complex (MHC) genes produce marker proteins on cells that display bits of protein from inside of the cell. These displays allow the immune system to screen cells for the presence of antigens in the cell. It is easy to see how this would identify infected or abnormal cells. There are two classes of MHC--Class I found on TC cells and all nucleated cells and Class II found on TH cells. In addition, macrophages, an amoeba-like white blood cell, patrol throughout the body. As they find bacteria, viruses, cell debris, etc, they engulf it and display pieces to helper T-cells. This allows the immune system to detect antigens before they are numerous enough to find their way into the lymph nodes and other lymph system organs where the B- and T- lymphocytes normally are found. I recommend What the Heck is an MHC Molecule for a clear description of their role.

The immune responses can be modified and/or misused. Immunization attempt to preloadthe immune system by presenting it with an antigen incapable of causing a disease butcapable of activating an immune response. This creates memory cells and allows a much faster response if and when the real pathogen arrives. Sometimes the immune system responds to a substance that is not dangerous; this response results in what we call  allergies. See What the Heck Is an Allergy for more information. The response to poison ivy is a similar problem--Poison Ivy:  An Exaggerated Response. If the immune system attacks normal body cells, you have an autoimmune disease. The reasons for this response are not understood, but many disorders are connected to this malfunction--Lupus, some kinds of diabetes, rheumatoid arthritis, some forms of muscular dystrophy and multiple sclerosis. More may be found. 

Immune deficiencies may be genetic or acquired. HIV/AIDS is probably the best known example; see Aids, HIV, and the Immune System for more information. Cells Alive also has an HIV Overview. For some other immune disorders, go to this NAIAD site.

There is also one area where I think your text is misleading. I assume they did this in an attempt to simplify the material; however, in that attempt they give incomplete information. The concept is self/non-self recognition. The text says that  immune cells recognize self markers on cells. There are a few instances of this. BUT, most of this "self recognition" develops during fetal and very early infant life as the immune system is being developed. During this time, the system generates many different receptors for B and T-cells. It then checks each new receptor configuration against the body's own cells. If there is a recognition with body's own cells, the new  B or T-cell self destructs--removing it from the pool. The end result is that there should be no cells that match (or would attack) the body's own tissues. Anything that is recognized by the immune system (a 3-D match) is foreign by definition. There is an outstanding animation of this process courtesy of Davidson College. It is complex but follow the B-cell through the three possible outcomes.