MadSci Network: Immunology
Query:

Re: chemistry of antibodies and vaccines

Area: Immunology
Posted By: Mimi Mong, Staff Research Associate, University of California at Berkeley
Date: Fri Mar 28 16:16:40 1997
Message:

Immunization is the deliberate induction of an immune response against a disease-causing organism (a pathogen) by injecting a vaccine. Vaccines come in different forms (listed below). Each one contains something from the organism causing the disease, but in a form that should not make you sick. Your body's immune system prepares defenses against the "antigens" presented in the vaccine. If you become infected with a nasty microbe or virus containing these same antigens, your body thus has some defenses against it.

  1. Killed organisms (heat killed bacteria or viruses, e.g.).
  2. Live attenuated bacteria or viruses - "cousins" of a disease-causing strain.. allows the body to develop an immune response without actually making you sick.
  3. Purified macromolecules - some protein of importance required by an infecting virus or microbe to sucessfully colonize the host and cause disease. The molecule itself does not cause disease, but if the body can create antibodies against it, it can possibly fend off an infection from the whole organism.
  4. DNA-coated gold beads - genetic sequences from an organism.

Short Summary:
The vaccine consists of substances "foreign" to the body - things found in the pathogen, but not in you. It is injected into an individual to induce an immune response. The response activates white blood cells to divide, attack the foreign substance, and procude memory cells which will become activated should the body ever face a future challenge from the pathogen. The cells involved in the response include macrophages - "large cells" which engulf bacteria and foreign material, process their antigens and present them to T cells, T cells which come in two forms (as below), and B cells which produce antibodies to help trap the foreign substance. "Helper T cells" assist B cells to produce and secrete antibodies. "Cytotoxic T cells" can recognize and destroy a host cell that has been infected with a pathogen.

There is a lag of 5-10 days after vaccination for these processes to take place in full. Thus, vaccinating a sick person often has little effect (**in most cases**). Besides, the illness itself serves to elicit the production of memory cells for future use.

However, should you encounter the foreign substance again, your body's response will be faster (only 3-5 days), longer, and stronger because the generated memory cells are specific to that particular substance. Immunization can be thought of as training your body to combat pathogens by first giving you a less harmful form of a pathogen. When you encounter the real pathogen, your body is better prepared to fight it as the immune system has already been "trained and equipped." (Visit also Immunology and Vaccination )

Some basic concepts:
A foreign substance that elicits a specific immune response is called an antigen (contraction of antibody-generating.). Antigens include molecules found in and on viruses, bacteria, fungi, protozoans, and parasitic worms. Antigens also mark the surfaces of such foreign materials as pollen, insect venoms, and transplanted tissues, such as skin or organs. The immune system responds to an antigen by producing specialized white blood cells (lymphocytes) and specific proteins called antibodies. B cells and T cells are the two main classes of lymphocytes.

Brief details of the mechanism:
When foreign substance is injected via vaccination, cells called macrophages take the antigen up, internalize it, and break it into smaller pieces. The macrophages then present the processed antigen on their cell surface by attaching it to a glycoprotein called the major histocompatibility complex class II (MHC II). T cells carry a receptor (the T cell receptor - TCR) that recognizes this complex, but with a slight twist: every T cell receptor is slightly different. The differences arise from a complicated series of genetic events that take place before a T cell ever meets a pathogen. This generated "diversity" makes it possible for a subset of T cells to recognize the MHC-antigen structure presented by the macrophages. T cells capable of binding to this complex become *activated* and divide. This clone of cells combats the very antigen provoking their response. Some of these T cells secrete factors which selectively stimulate B cells that recognize that particular antigen to proliferate and grow. These B cells secrete antibodies into the circulation and give rise to long-lived memory B cells against that antigen. (T cells will give rise to memory T cells). If, during the lag time of first encounter of the invader, some cells were infected by the pathogen (a virus, e.g.), cytotoxic T cells can "kill" the infected cells to prevent further spread. When the same antigen enters the body the second time, B and T memory cells can react immediately, giving less time and opportunity for the invader to spread.

Small organic molecules such as arsenate and nitrophenyls do not provoke antibodies when injected by themselves. This is because MHC can bind only proteins. Since these small chemicals are not presented to T cells via MHC, T cells are inactive and unable to induce proliferation of B cells against the particular chemical. To solve this problem, small chemicals are covalently attached to a protein carrier. T cells can then be activated and help B cells specific to that chemical to grow and secrete antibodies.

An antibody does not usually destroy an antigenic invader directly. Rather, antibodies binds to antigen to form complex to clear the invaders. Once an antibody binds to an antigen the body has specific mechanisms to clear both the antibody and the antigen thereby removing the bacteria or virus from the body.

As far as a discussion about the chemical aspects of this whole reaction, realize that antibodies have a very specific chemical binding event that occurs with their specific antigen. This binding event has very high affinity and because of this the bacterial or viral antigen is bound up by the antibody. All of the antigen interactions with B cells, T cells and antibodies have an exquisite chemical specificity that can be altered by just small changes in the antigen. The key to vaccination is to inject people with molecules of bacteria or viruses that will cause an antibody and T cell response that will later recognize and attack the invading bacteria or virus that you have vaccinated against. To ensure that there is an appropriate attack against the bacteria or virus, a vaccine must contain chemically similar (if not identical) molecules that the bactera or virus has.

A good text covering this subject is Cellular and Molecular Immunology by Abbas, Lichtman and Pober (1994).


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