Your body as watchdog

This exercise is a part of Educator Guide: Genes Foretell Flu Shot Response / View Guide

Directions: After students have had a chance to review the article “Genes foretell flu shot response,” lead a classroom discussion based on the questions that follow. Consider how these questions could lead to independent research for a science fair project.

BIOLOGICAL SCIENCES

Discussion questions:

1. What are genes and viruses made of and how do they replicate?

Genes in cells — everything from bacteria to human cells — are composed of specific sequences of molecular building blocks called nucleotides in deoxyribonucleic acid (DNA). DNA typically exists as a double-stranded helix, and each strand is a polymer made of a sequence of monomer nucleotides. Nucleotides are composed of a five-carbon sugar, at least one phosphate group and a nitrogenous base: adenine (A), cytosine (C), guanine (G) or thymine (T). The two strands of DNA are complementary: Each A on one strand pairs with a T on the other strand, and each C on one strand pairs with a G on the other strand. In order for DNA to replicate, the two strands are pulled apart and then special enzymes called DNA polymerases use each existing strand as a template to form two new DNA strands. The nucleotide sequences of the new strands are complementary to, or pair with, the original template strands. The end result is two complete DNA double-stranded helices.

Some viruses store their genes as DNA (either single-stranded or double-stranded, depending on the type of virus). However, many viruses store their genes as ribonucleic acid (RNA), which may be single-stranded or double-stranded depending on the type of virus. RNA is chemically similar to DNA but less stable, so RNA degrades more rapidly than DNA. RNA is also more prone to mutation than DNA. Each RNA strand is a polymer with a sequence composed of the nucleotides adenine (A), cytosine (C), guanine (G) and uracil (U), the RNA analog of thymine. Two strands of DNA and/or RNA can be complementary: Each A on one strand pairs with a T or U on the other strand, and each C on one strand pairs with a G on the other strand.

Viruses are unable to replicate themselves, so they must infect a suitable host cell to serve as a factory to produce more copies of the virus. Most RNA viruses make their own RNA polymerase, which uses an existing RNA strand as a template to bond individual RNA nucleotides to form a new complementary strand. RNA polymerases tend to be more error-prone than DNA polymerases, which greatly increase the frequency with which RNA viruses mutate. Most DNA viruses use the host cell’s DNA polymerase to replicate the viral DNA. Some viruses go through more complicated replication cycles involving strands of both DNA and RNA.

Extension prompts:

2. What do genes produce and how are their activity levels controlled?

Genes produce proteins through transcription and translation processes. The amount of proteins that genes produce, called gene expression, is controlled by specific sequences in the DNA and RNA, and by various enzymes.

In transcription, other types of polymerases copy DNA or RNA genes to produce complementary RNA strands. (In some RNA viruses, the genomic RNA itself serves as this resulting RNA strand.) Some of these RNAs include ribosomal RNA (rRNA), transfer RNA (tRNA) and messenger RNA (mRNA). They are involved in a second process called translation.

During translation, large enzymes called ribosomes, made of both rRNA and proteins, use the nucleotide sequence of mRNA to provide the code for making a protein with a specific sequence of amino acids.

3. How does the immune system specifically attack things that it recognizes should not be in your body?

White blood cells called lymphocytes help initiate an immune response. There are two main types of lymphocytes, B cells and T cells. B cells make different antibodies — proteins that bind to very specific receptors on foreign bacteria and viruses to make them ineffective. T cells have different receptors that sense specific shapes of molecules made by other cells, and kill cells that make molecules with the wrong molecular structure. Because B cells and T cells are so specific, they can only attack things that they have seen before and have learned to recognize. If they are confronted with a new substance, it usually takes your immune system a few days to initiate a response and fight off an infection — like trying all the keys on a key ring before you finally find the right one for a lock. You are generally immune to that same virus strain if you are exposed again afterward.

4. How do vaccines work?

A vaccine contains enough of a pathogen to teach your immune system how to recognize and fight the pathogen, but not enough to make you sick. The pathogen imitates an infection without causing one and initiates the production of T cells and antibodies. Some vaccines are killed versions of a pathogen — all parts of the pathogen are present so your immune system can learn to recognize it, but the pathogen is dead and therefore not able to replicate or turn on its virulence factors. Some vaccines are attenuated versions of a pathogen — the pathogen is alive but is not good at replicating itself or causing disease, so your immune system can both learn from it and kill it. Some vaccines contain just components of a pathogen — usually those parts of the pathogen’s molecular exterior that your immune system would be most likely to see during a real infection. More advanced vaccines can use a harmless organism or even your own cells to produce components of a pathogen and teach your immune system to recognize those components. Some vaccines must be given in a series of doses, or given again after a certain number of years, to teach your immune system what to recognize and to make sure it remembers.

CHEMICAL SCIENCES

You may want to check out Cancer’s Sweet Cloak Guide if you are interested in additional questions on protein composition and structure.

Discussion questions:

1. What is the difference between a physical change and a chemical change? Provide an example of each.

A physical change may alter the outward appearance of something, but it does not change the substance it is actually made of. The chemical composition of the molecules involved does not change. An example of a physical change would be water molecules changing from solid ice to liquid water to gaseous steam. The outward appearance and density of the substances change, but they remain water molecules, H2O, throughout the process.

A chemical change alters what substance something is made of, creating one or more new substances. The chemical composition of the molecules change. During a chemical change, chemical bonds — which are formed when atoms share or exchange electrons — are created and/or broken. This changes the initial chemical molecules into new types of molecules. An example of a chemical change would be the reaction that powers many rockets, in which hydrogen molecules (H2) and oxygen molecules (O2) react together to form water molecules (H2O) plus lots of energy to propel the rocket.

2. What are simple examples of physical changes and chemical changes for DNA?

One example of a physical change is pulling apart double-stranded DNA into two single strands by raising the temperature. Complementary bases in the two strands are attracted to each other by electrostatic, intermolecular attraction forces called hydrogen bonds. Hydrogen bonds are much weaker than actual chemical bonds in which electrons are exchanged or shared. Other examples of physical changes include precipitating DNA (making many DNA helices clump together to purify them in the lab), condensing DNA in the nucleus (changing how densely or loosely packed the DNA is, depending on whether it is currently needed for replication or transcription), supercoiling or kinking DNA strands and changing the DNA helix among the A, B and Z forms.

Examples of chemical changes include polymerases adding nucleotides to the end of a DNA strand, exonucleases removing nucleotides from the end of a DNA strand, endonucleases cutting a DNA strand, and mutating nucleotides within a DNA strand to create pyrimidine dimers from thymine or cytosine nucleotides, for example.

Extension prompts:

3. Many vaccines contain an adjuvant. What is that?

An adjuvant can be a chemical compound that helps the vaccine provoke a better immune response. For example, some adjuvants such as aluminum salts can generally irritate the immune system and thereby prompt it to pay more attention to the vaccine than it otherwise would. Other adjuvants such as oils or detergents can release the vaccine over a period of time or improve how the vaccine is absorbed by the body.

4. Why might it be undesirable to have too little or too much of an adjuvant in a vaccine?

With too little adjuvant, the immune system may not pay much attention to the vaccine, so the resulting acquired immunity would be less or short-lasting or would require a greater number of doses of the vaccine given over time. With too much adjuvant, the immune response to the vaccine might be too strong, causing side effects such as inflammation and fever.

ENGINEERING AND EXPERIMENTAL DESIGN

Discussion questions:

1. Why is it harder for researchers to identify genes that could predict how well older people’s immune systems respond to flu vaccines? How could a study deal with that problem?

Generally the immune system and other functions get weaker as a person ages, but some people experience more decline than other people of the same age. Moreover, different people can experience different alterations in their gene expression depending on their genetic makeup and the environmental stresses to which they have been exposed throughout life. Thus, a pool of older people could include a number of different subpopulations with various alterations in cellular functions and gene expression. A study would need to examine a very large number of older people, and it would need to look for patterns in gene expression that could help to group people into subpopulations and then identify the best predictive genes for each of those subpopulations.

Extension prompts:

2. “Genes foretell flu shot response” showed that analyzing how active certain genes are could predict how well a person would respond to the flu vaccine. Beyond what was mentioned in the article, what useful predictions could be made by analyzing gene activity?

Predicting in people, some animals or perhaps even plants: positive or negative immune system responses to other vaccines and various medications, susceptibility to various infectious diseases and non-infectious illnesses, previous exposure to various pathogens or chemical compounds, susceptibility of a tumor to various chemotherapeutic drugs or susceptibility of bacteria to various antibiotics, plus more.

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