Antibodies are like puzzles

I think antibodies are one of the COOLEST parts of human biology. You’ve likely heard of antibodies before, but you probably aren’t recognizing just how awesome they are. Let me fill you in.

An antibody is a large protein that recognizes a small part of a foreign invader, called the antigen. Invaders can be viruses, bacteria, fungi, or sometimes food particles. While one end of the antibody binds to its antigen like super strong Velcro, the other end sticks out and sends the signal, “I’ve caught one! Bring in the troops!”. The troops (other immune cells) swoop in to destroy the invader.

The amazing thing is that your body has the ability to generate antibodies to over 1,000,000,000 antigens!! How is this accomplished?

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“Puzzled” by Brad Montgomery on Flickr

Antibodies are generated by a type of immune cell called a B cell (B stands for bone marrow, where the cells originate).  The genes that make antibodies are actually referred to as multigene families because they are so large. There are three multigene families in human B cells, and each family consists of multiple family members, called gene segments. While each B cell is growing up, or maturing in the bone marrow, enzymes called recombinases actually shift the gene segments around like puzzle pieces. Because there are a so many gene segments, the number of possible combinations is mind-boggling. It’s a great thing, though, because it means we can fight off lots of foreign enemies.

Once a functional gene is pieced together, the DNA is transcribed and translated, and an antibody is born. The antibody is sent to the B cell’s surface where it sticks out to face the human body world. Before a B cell can be considered really mature, it has to undergo a check to make sure it’s antibody doesn’t bind to any self antigens. If this were to occur, your immune system would start attacking itself, and would result in an autoimmune disease, like lupus.

After passing this check point, the B cell hangs out in your lymph nodes and waits for the foreign invader that matches it’s antibody. If and when the invader appears, the B cell divides super quickly, producing more B cells that generate more and more of the same antibody. This B cell army then releases their arsenal of targeted weapons to destroy the intruder. The enemy is killed, and you never get sick.

This phenomenon of DNA rearrangement has not observed for the production of any other proteins besides antibodies. And this is why I think antibodies are so cool!

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Explainer: The Central Dogma

by Clarice on flickr

by Clarice on flickr

Today it’s raspberry walnut tart. I find the recipe on my computer, then jot down the ingredients and instructions on a 3”x5” card. I hurriedly take the recipe card to the kitchen where I begin collecting the ingredients – butter, flour, sugar, red raspberries and chopped walnuts. After 2 hours of mixing, kneading, spreading, baking and patient waiting, the tart is ready. And it’s delicious!  I like cooking for two main reasons: it gives me time to de-stress after work, and it gently reminds me of the basic biology which my thesis research is founded on.

The DNA contained inside each of the cells in our bodies is like an extensive cook book, called a genome. It contains thousands of recipes, called genes, which instruct our cells how to make proteins (instead of raspberry tarts). Because this recipe book of DNA is the essence of life, it is stored in a heavily guarded library in our cells, called the nucleus. In order to cook up a protein, our cells must first copy the recipe onto a recipe card, called RNA.

The act of copying the DNA recipe into an RNA copy is called transcription. This recipe card of RNA is then sent out of the library and over to the cell kitchen, the endoplasmic reticulum (ER). Small structures on the ER called ribosomes read the recipe copy, gather the ingredients and mix them together. Sometimes multiple ribosomes can read one recipe copy in succession, thereby doubling or tripling the batch of protein made. This process of reading the RNA and making a protein is called translation.

After translation, the protein is cooked so that the ingredients meld together, an action called protein folding. Without this step, the protein would be an inedible glob of dough instead of a delicious tart. The final step, called protein modification, is where the protein will get final touches, like a sprinkle of powdered sugar or a dab of icing. Collectively, these steps are the fundamental basis of biology, and are endearingly referred to as the central dogma.

Now that you’ve got this down, you will be able to understand other details of cell biology, so dig in!

How cells JUST KNOW

Domino by Bro. Jeffrey Pioquinto on flickr

Domino by Bro. Jeffrey Pioquinto on flickr

When I was in fifth grade, we had a program come into our classroom and teach us about the birds and the bees. We were told it was a very open environment and that we shouldn’t be afraid to ask any questions. Ask anything you want! they said. There are no silly questions. We each wrote a question on a slip of paper and handed it in.

The coordinators then read each question and answered them carefully. Kids asked about various body parts, rites of passage, weird dreams, and strange feelings. Then my question was read aloud: how do the sperm know where to go to find the egg? That’s right. Out of all the things about puberty and reproduction that confused me, I needed to understand how sperm KNOW where to find the egg. I knew that they didn’t have brains, so like, how did they KNOW what to do?!

The two women leading the program read the question aloud and laughed. They laughed! At my supposedly non-silly question! Then they explained that it’s probably like a stream and it just leads them to the egg. Besides being mortified that my question was laughed at, I wasn’t very satisfied with the answer.

Fifteen years later, after countless biology classes and the near completion of a PhD, I think I can provide a better answer to my own question. Cells don’t have brains, but they do have ways of sensing cues and responding to them, just like we can read a street sign and know where to turn. These cues come in the form of molecules of all types – chemical, protein, fat, sugar, or a combination. Once a molecular cue is picked up, a series of consecutive reactions will occur, like dominoes cascading down in a row. The end result of the chain reaction is the cell’s response to the original cue.

Actually, it’s a lot like this:

The cue is the car that starts it all off. The response is the band getting splattered with paint. None of the bowling balls, umbrellas, mannequins or pieces of confetti KNOW when or where to go, they are simply prompted to do so by the preceding reaction. This is how cells (like sperm cells) know exactly what to do, at exactly the right time.

And to all you fifth graders who have SILLY questions about how the world works, don’t give up on your inquisitiveness. You might find the answer you’re looking for down the road.