How Vaccines Work

The human immune system is a complex network of cells and organs that evolved to fight off infectious microbes. Much of the immune system’s work is carried out by an army of various specialized cells, each type designed to fight disease in a particular way. The invading microbes first run into the vanguard of this army, which includes white blood cells called macrophages (literally, “big eaters”). The macrophages engulf as many of the microbes as they can.

Antigens Sound the Alarm

How do the macrophages recognize the microbes? All cells and microbes wear a “uniform” made up of molecules that cover their surfaces. Each human cell displays unique marker molecules unique to you. Microbes display different marker molecules unique to them. The macrophages and other cells of your immune system use these markers to distinguish among the cells that are part of your body, harmless bacteria that reside in your body, and harmful invading microbes that need to be destroyed.

The molecules on a microbe that identify it as foreign and stimulate the immune system to attack it are called “antigens.” Every microbe carries its own unique set of antigens, which are central to creating vaccines.

Macrophages digest most parts of the microbes but save the antigens and carry them back to the lymph nodes, bean-sized organs scattered throughout your body where immune system cells congregate. In these nodes, macrophages sound the alarm by “regurgitating” the antigens, displaying them on their surfaces so other cells, such as specialized defensive white blood cells called lymphocytes, can recognize them.

Lymphocytes Take Over

There are two major kinds of lymphocytes, T cells and B cells, and they do their own jobs in fighting off infection. T cells function either offensively or defensively. The offensive T cells don’t attack the microbe directly, but they use chemical weapons to eliminate the human cells that have already been infected. Because they have been “programmed” by their exposure to the microbe’s antigen, these cytotoxic T cells, also called killer T cells, can “sense” diseased cells that are harboring the microbe. The killer T cells latch onto these cells and release chemicals that destroy the infected cells and the microbes inside.

The defensive T cells, also called helper T cells, defend the body by secreting chemical signals that direct the activity of other immune system cells. Helper T cells assist in activating killer T cells, and helper T cells also stimulate and work closely with B cells. The work done by T cells is called the cellular or cell-mediated immune response.

B cells make and secrete extremely important molecular weapons called antibodies. Antibodies usually work by first grabbing onto the microbe’s antigen, and then sticking to and coating the microbe. Antibodies and antigens fit together like pieces of a jigsaw puzzle—if their shapes are compatible, they bind to each other.

Each antibody can usually fit with only one antigen. The immune system keeps a supply of millions and possibly billions of different antibodies on hand to be prepared for any foreign invader. It does this by constantly creating millions of new B cells. About 50 million B cells circulate in each teaspoonful of human blood, and almost every B cell—through random genetic shuffling—produces a unique antibody that it displays on its surface.

When these B cells come into contact with their matching microbial antigen, they are stimulated to divide into many larger cells, called plasma cells, which secrete mass quantities of antibodies to bind to the microbe.

Antibodies in Action

The antibodies secreted by B cells circulate throughout the human body and attack the microbes that have not yet infected any cells but are lurking in the blood or the spaces between cells. When antibodies gather on the surface of a microbe, it becomes unable to function. Antibodies signal macrophages and other defensive cells to come eat the microbe. Antibodies also work with other defensive molecules that circulate in the blood, called complement proteins, to destroy microbes.

The work of B cells is called the humoral immune response, or simply the antibody response. The goal of most vaccines is to stimulate this response. In fact, many infectious microbes can be defeated by antibodies alone, without any help from killer T cells.

Clearing the Infection: Memory Cells and Natural Immunity

When T cells and antibodies begin to eliminate the microbe faster than it can reproduce, the immune system finally has the upper hand. Gradually, the virus disappears from the body.

After the body eliminates the disease, some microbe-fighting B cells and T cells are converted into memory cells. Memory B cells can quickly divide into plasma cells and make more antibody if needed. Memory T cells can divide and grow into a microbe-fighting army. If re-exposure to the infectious microbe occurs, the immune system will quickly recognize how to stop the infection.

How Vaccines Mimic Infection

Vaccines teach the immune system by mimicking a natural infection. For example, the yellow fever vaccine, first widely used in 1938, contains a weakened form of the virus that doesn’t cause disease or reproduce very well. Human macrophages can’t tell that the vaccine viruses are weakened, so they engulf the viruses as if they were dangerous. In the lymph nodes, the macrophages present yellow fever antigen to T cells and B cells.

A response from yellow-fever-specific T cells is activated. B cells secrete yellow fever antibodies. The weakened viruses in the vaccine are quicky eliminated. The mock infection is cleared, and humans are left with a supply of memory T and B cells for future protection against yellow fever.

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