How your immune system works : The basics
The job of our immune system is to defend the body from invasion by foreign substances or organisms, such as bacteria or viruses. Think of the redness and swelling you experience when you get a splinter in your finger. Your immune system reacts to the splinter and the bacteria that enter the body with it by sending a range of immune system cells to the site of invasion or injury to fight infection. These cells produce a range of chemicals that serve as tools in fighting the invasion. The inflammation at the site of the splinter is a sign that your immune response is working.
The immune system: your body's police force
Think of your immune system as your body's police force. It is responsible for protecting your body from a range of harmful elements: viruses, bacteria, cancer cells—you can think of these as criminals that intend to rob you of your good health. Because your body is a very complex organism, protecting it effectively poses a big challenge to your immune system—as big a challenge as effective crime fighting poses to the police force in a big city.
Just as in a large police force, detectives, patrol officers, special intelligence units, SWAT teams, 911 dispatchers, crime labs, communications professionals, and others must all work together to keep the public safe from crime, your immune system must involve the coordinated efforts of many different specialized immune system agents. Immune cells and chemicals carry out these many specialized functions, including patrolling your body for signs of infection or invasion, serving as messengers to alert when suspicious activity is detected, and organizing a response to fight invasion.
How your immune system is organized
It's useful to know a few basic facts about your body to help understand how your immune system is organized. First, you may already know that your body is largely made up of water. About 70% of your body is fluid (or water). This fluid is located either inside your cells (intracellular fluid within the cellular membrane that encloses individual cells) or outside of your cells (extracellular fluid). This fact is vital to understanding how your immune system works because the immune system is divided in two branches: (1) the humoral branch, having to do with invasions that take place in the extracellular fluid, and (2) the cellular branch, having to do with invasions that take place within cells.
Immune system patrol
One of the most important groups of immune system cells is made up of cells that patrol the body and go to the site of invasion to respond to the invader. Included in this group, are white blood cells (also called leukocytes, from the Greek words, leukos for white and cytes for cells). These leukocytes are divided into two groups, the cells that are the body's first-responders and make initial contact with the invader, including neutrophils, monocytes, dendritic cells and macrophages (these derive from monocytes), basophils, and eosinophils, and the cells involved in later or delayed defense, including B and T lymphocytes (B- and T-cells, for short).1
Immune system cells produce a wide range of chemicals known as inflammatory mediators or soluble mediators of immunity. These serve as weapons against invading antigens. Some of the key mediators of immunity include a collection of serum proteins called complement and the cytokine network, a very large number of proteins produced by T-cells and macrophages that facilitate communication between cells. This last group includes interferons (IFN), interleukins (IL), growth factors, and tumor necrosis factor (TNF).1
B and T lymphocytes
Among leukocytes, B- and T-cells play a special role in the immune response. B-cells specialize in generating antibodies against specific antigens (whatever has invaded the body) and are designed to fight foreign invasion that occurs in the extracellular fluid. T-cells, of which there are two main types (helper T-cells [Th cells] and killer T-cells) specialize in neutralizing antigens that invade intracellular fluid, where B-cells are not effective.2,3
When an antigen (a foreign invader) is encountered during the initial response by the immune system, macrophages bring the antigen to B-cells and also display part of the antigen to circulating Th cells. The antigen is "fingerprinted" by the B-cell and this information is used to develop an antibody, a protein (specifically called an immunoglobulin [Ig for short]) that specializes in attacking that antigen. B-cells have the capacity to remember the pattern for antibodies that have been previously encountered. Our immune system contains "memory" B-cells that specialize in detecting specific antigens and evolving into plasma cells that produce antibodies that target those antigens.2,3
If the "fingerprint" of the antigen is unfamiliar, it takes the immune system longer to generate antibodies to the new invader. B-cells must be given the antigen "fingerprint" and develop an appropriate antibody. Therefore, the defense mounted by the B-cell is delayed. This is why a person who develops an infection from an organism they have never been exposed to may experience a period of fever, body aches, or other symptoms of infection before the delayed defense kicks in.
Sidebar: Fast Fact: Vaccines and Immunity
The ability of the immune system to "fingerprint" and remember an antigen is the idea behind vaccination. When you get a vaccine for the flu or another virus, your immune system is given a deactivated portion of the antigen that causes the infection. Your immune system studies that antigen and develops a matching antibody, so that when your body encounters the real virus, it can generate antibodies to fight infection caused by that virus.
Note that while normally antibodies are positive things that help us fight infection by any number of infectious microorganisms, people with RA and other autoimmune diseases develop antibodies that attack their own healthy tissues. These are called auto-antibodies, (auto means "self," so auto-antibody refers to antibodies against the self). Thus RA is an instance where an antibody can be destructive.
In addition to presenting the antigen to the B-cell, the macrophage also presents it to the Th cell (T helper cell). By closely examining the antigen, the Th cell determines whether it should stimulate production of B-cells for antibody production against an extracellular antigen or stimulate production of killer T-cells. Killer T-cells are produced if the antigen has invaded cells. The killer T-cell attaches itself to an infected cell and in most cases destroys that cell.2,3
The role of T-cells in RA is not fully understood, but large numbers of T-cells are routinely found in the synovial fluid of people whose joints are affected by RA.
Immune system communications
Just as clear and efficient communication within a police force is essential to combating crime, effective communication between cells in the body plays a critical role in immune system functioning. Immune system communication is divided into two separate functions: sending and receiving messages.
Immune cells (including the range of leukocytes) produce chemical messengers (most of these are proteins known as soluble mediators of immunity) that play the role of carrying information between cells. There are a large number of these messengers that are designed to carry out a broad range of functions, including promoting cell division, production of proteins that play a role in the immune response, and activation of B- and T-cells.1
Cell receptors, located on the surface of the cell, receive and interpret the messages carried by chemical messengers and also signal if a cell has been invaded by some foreign organism. Based on the nature of the invasion or the cell involved, the receptor may signal that a cell has been invaded and should be destroyed or call for certain leukocytes to prepare specific weapons to fight the invasion.1
Note that when we discuss drug therapy for RA, we'll talk about how many RA drugs have mechanisms of action that enable them to interfere with how cellular receptors work. By interrupting cellular communication, many RA drugs seek to dampen the immune response in RA, the out-of-control autoimmune response that threatens healthy tissue.
Immune system weapons
Immune system cells produce a wide range of chemicals known as inflammatory mediators or soluble mediators of immunity. These serve as weapons against invading antigens. Some of the key mediators of immunity include collections of proteins called complement and the cytokine network, a very large number of proteins produced by T-cells and macrophages. This last group includes interferons (IFN), interleukins (IL), growth factors, and tumor necrosis factor (TNF).1
1. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med 2011;365:2205-19. 2. Dörner T, Lipsky PE. The role of B cells in rheumatoid arthritis. In: Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH, eds. Rheumatoid Arthritis. Philadelphia, Penn: Mosby Elsevier; 2009:97-106. 3. Scheinecker C. The role of T cells in rheumatoid arthritis. In: Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH, eds. Rheumatoid Arthritis. Philadelphia, Penn: Mosby Elsevier; 2009:91-96.