Cells of the Immune System and AIDS

by James E. Riggs, Ph.D.
Rider University, Lawrenceville, New Jersey

First the bad guys. Viruses are nasty, virtually invisible bits of trouble that can be thought of, at least structurally, as "Tootsie Pops." The chocolate inside is their genetic material (DNA or RNA), containing the instructions necessary to make copies of them. The "candy coating" for the virus is a protein shell that protects the genetic material. (The props for the audience members who will be viruses are Tootsie Pops). Viruses need to get inside our cells, raid our genetic material and other cellular resources, make several (100-1,000) progeny and then "split." They are the awful party guests who come to your house, raid the refrigerator, trash the place and then leave you with a mess and the bill! Examples of viruses include influenza or the "flu," with which we all have had skirmishes; Herpaviruses known for chickenpox and infectious mononucleosis; and lastly, a focal point for this talk, human immunodeficiency virus (HIV), the virus that causes AIDS. (Depending on your audience you pick the pathogen, e.g., high school kids and STDs are always a good combo; adults--shingles, hepatitis A, B and/or C, HIV; kids--chickenpox, measles, mumps, flu.)

The next group of bad guys are the bacteria. Larger than viruses, but still smaller than the cells found in our body, bacteria are virtually everywhere. They are in and on our bodies and most are harmless and plenty are actually helpful. Still, there are a considerable number and variety of them that cause disease. They do this by rapidly multiplying, some doubling every 20 minutes (10 bacteria become more than 42 billion bacteria in less than 10 hours!) and by producing a variety of toxic byproducts some of which cause the body’s thermostat to rise (fever) or our bowels to attempt to flush them away (diarrhea). Like fruit, bacteria come in a variety of shapes, some of them with coats that are shed (peels = LPS/endotoxin) and themselves cause problems. (The prop for bacteria will be fruit: an orange can represent the germ associated with pneumonia, the peels represent the bacterial capsule or cell walls, which can play roles in the type of disease the bacteria causes. (Once again, depending on your audience, pick the pathogen and corresponding prop, e.g., high school kids and STDs [chlamydia, gonorrhea]; adults-- strep throat, Lyme disease [Borrelia]; kids--E. coli and uncooked hamburgers; Haemophilus [middle ear infections]; strep throat.)

Our last group of bodily invaders will be cancer cells or tumors. Cancer can be caused by a wide variety of factors working alone or in combination, including genetics (hereditary breast or colon cancer), environment (smoke and lung cancer), and diet (too much fat or salt). Cancer cells do their damage by hogging bodily resources and crowding out normal cells. (Our prop for cancer cells will be a clump of grapes, individual grapes representing clones [identical sons and daughters] of a parent cancer cell that keeps on dividing and making cancerous progeny.)

(Be creative with your educational aids! My point is to have memorable props. The talk has to have a life of its own beyond your one hour with the audience. An enlightened and entertained audience will remember the content of your presentation far longer than any technical presentation that you would present to your peers.)

To introduce the good guys, the cells of the immune system, let’s begin with the macrophages, literally "big eaters" that gobble up bacteria and viruses. Macrophages are found in all locations in the body where they await the entry of foreign material which they then wrap themselves around and ingest. (The prop for the macrophage will be a trash bag that can wrap around the various germs and make them disappear. Give a volunteer a trash bag to pull over his or her head, with a hole of course!) Macrophages break up these invaders into little pieces and then display them (much like a waiter/waitress showing you the dessert tray) to the most important cell in the immune system, the T helper cell. The little pieces of germs fit like keys into locks found on helper T cells, and thus "turn on" these cells. Once turned on, helper T cells then direct traffic in the immune system, using chemical messengers (called interleukins/lymphokines) to signal other immune cells to get involved in the battle. Being the "heart" of the immune system, we will use a heart symbol (cardboard cutout colored red) to denote our helper T cell and since I am the "know-it-all" traffic cop for this group, I will serve as the helper cell in this play. I will use my pointer as a "lymphokine wand" so that I can direct traffic in the immune system. (If there is a teacher or "leader" for the group you are speaking to, it is often useful to make him or her the T helper cell, orchestrating the behavior of the immune system that follows.)

Two important immune system cells that rely on the helper T cell for lymphokine directions are B cells and killer T cells. B cells, once given the proper information from helper T cells, secrete proteins called antibodies. Antibodies (which will be represented by toothpicks in our presentation) are missiles that move about our bodies specifically targeting foreign material. Their binding, in addition to neutralizing the germ, attracts other immune system components which facilitate the destruction of the antibody-labeled target. The other significant component of the immune response is the killer T cell. Once given the "go" signal from helper T cells, these cells will cozy up beside cancer cells or virus-infected cells and then "stab" them (demonstrate with a fake knife) so that the target cell ruptures and no longer serves as a reservoir for viral growth or as a cancer clone capable of generating more progeny. (provide toothpicks to a "B cell" audience member and provide a plastic knife to a "killer T cell" audience member.)

Now that we have our cast of characters, let’s illustrate the interactions that lead to immune responses. Suppose our friend here (pick an audience member) is a nose cell, particularly a respiratory epithelial cell that just so happens to snuff up a flu virus (the Tootsie Pop person visits the nose cell person). We now have a virus-infected cell. What immune system cell will combat this? Correct, the killer T cell, but only after I (or the teacher/group leader), the helper T cell, the heart of the immune system and director of cellular traffic, tell that killer T cell to come here, front and center and deliver your lethal hit! (do so with lymphokine pointer). Suppose, instead, that we had the pneumonia bacterium (Streptococcus pneumonia), gain entry into our lungs, setting its sights on this location being its next home (a lung cell volunteer). The macrophage would be ready and waiting to envelope the microbe and then provide pieces to me, the helper T cell, to lead me to direct B cells to secrete antibodies that will bind this germ and participate in its demise. (carry out the series of steps directing the macrophage and B cell). Pieces of bacteria or virus from either scenario are mopped up by the macrophage scavengers. Finally, what of the cancer cell, sneaking along for years, making more and more grapes?! Under the best of situations, the cancer cell(s) eventually gives clues to the immune system that they are no longer self cells. Thus, killer T cells, with a little help from their friends, come to deliver the lethal hit and prevent the further expansion of the group of cancer cells.

What happens when the virus that causes AIDS, HIV, (it’s important to write these terms out on the board and, depending on the audience, explain the difference between someone being HIV+ and someone having AIDS) comes along and enters the picture? Unfortunately, what happens is a big problem, because HIV infects the most important cell of the immune system, the T helper cell, crippling the immune system and causing an immunological civil war where HIV-infected helper T cells may now be targeted by the killer T cells that they have helped to become killers! The helper T cell may actually contribute to its own demise! The death of the helper T cell leads to immunological paralysis, the traffic cop is gone (this is AIDS). Now when the virus or the bacterium or the cancer cell looks to increase its numbers it finds conditions are favorable because the macrophage, the B cell, and the killer T cell are no longer receiving the directions they need to orchestrate protective immune responses. (This point can be emphasized by the silencing of the speaker/teacher/group leader via insertion of the Tootsie Pop "virus" in his/her mouth. The seminar, as with normal function in the immune system, stops and the viruses, bacteria and cancer cells go about their business, feeding the audience and spreading the infection throughout the body.)

(Up to this point any immunologist could use the same talk. Depending upon his or her area of specialization he or she would insert necessary background information.)

My research is focused on how to solve this problem. The undergraduate researchers in my laboratory are helping me develop a mouse model for AIDS. In this model we take mice that, due to a genetic mutation, lack the B and T cells that we have just described. We transplant immune system cells into these mice, excluding the helper T cells. Thus, we biologically engineer a mouse that, immunologically, looks like an AIDS patient. Being in an undergraduate environment, we don’t work with HIV, for reasons that are obvious. However, the cells that we use to transplant into our immune-deficient mice have a virus in them that shares some of the properties of HIV, but is certainly not infectious in humans. Thus, our model recreates the immune-deficiency of AIDS with a virus being present. Our future studies (this summer’s projects for my research group) will be to find ways to add back helper T cells to these mice, to correct their immune-deficiency, but without feeding the virus! We have several tricks up our collective sleeves that I will tell you about the next time I get a chance to talk to you.

(I intentionally keep this portion short because the tendency to stray from simplicity and back to immunological jargon becomes most tempting when one begins describing one's specific research.)

My research has been supported with funds from the National Institutes of Health Academic Research Enhancement Award (AREA) program. Concurrent with exposing promising undergraduates to significant questions in research science, we are conducting studies that may contribute to the development of the means to fight AIDS. Your tax dollars fund such projects. The total monies invested in research science are very small, particularly that invested in programs such as ours. A remarkable number of research scientists, as well as a significant number of medical doctors, have had their first taste of research science, and thus their curiosity, flamed in the liberal arts college environment. We must continue to provide useful research opportunities for undergraduates thereby feeding more research scientists into the scientific careers "pipeline," be they doctors, researchers, or teachers at any level.

Thank you for your courteous attention. How about some applause for our fantastic audience participants!

To close, the knife can be used to cut up the various fruits. Put them on a tray with toothpicks and ask the audience to be macrophages and initiate immune responses and conversations (!) with all of the participants. There are many variations on this presentation theme and common questions will arise. Time does not permit me to expand on these but many questions are easily addressed and understood by the audience when the props/audience can be incorporated into the explanation. Leave at least 15 minutes for questions, you will get many and nothing could be better for getting the word out. Enthusiasm is necessary to reach the audience!