Monthly Archives: March 2015

Original Antigenic Sin

Friends,

I read a very interesting article in a recent issue of the Scientific American and I thought that I should tell you about it. The article was about a very interesting concept known as “Original Antigenic Sin” and it changed the way I look at how our immunity is formed and how it develops as we grow older. Let me also take this as a opportunity to recommend the Scientific American. It is fantastic magazine and if you have a love for science or want to inculcate the love of science in your family, you must subscribe to it.

Immunity is a fascinating concept. It is also a generally misunderstood concept. How do we become immune to something during our lifetime? What is the role of the environment in creating immunity against a certain disease or pathogen? Can we acquire immunity against a new disease when we become old? How much time after the beginning of a disease do we acquire an immunity against it? There are all very interesting questions. These are also very important questions because we are surrounded by new diseases like Ebola, swine flu and bird flu. And there are many other diseases which are on the verge of making a jump from other animals to humans by a slight change in their genetic code- a mutation. We absolutely need to know how immunity is developed if we want to save the billions of people on earth from global epidemics caused by crowded cities and the fact that millions of us travel everyday taking with us pathogens and diseases.

Before I read about the concept of Original Antigenic Sin, I thought that immunity can be built at any time during one’s life. I also assumed that if one is immune to some disease, and if a new disease strikes, the immunity can be built for the new disease without being biased by past immunities. But Original Antigenic Sin says that this is not true. The memory of earlier immunities affects the formation of immunities in the future. This effect is also known as the Hoskins’s effect.

Now let me describe Original Antigenic Sin. Let’s take two adults, Alice and Bob. Lets say that when Alice was a child she was infected with an Influenza virus of the type H7M7(I am just making up a name so as not to offend the sentiments of real diseases like H1N1 J ). Lets also assume that Bob has never had contact with H7M7 virus. When Alice was infected by the H7M7 virus her body responded by making antibodies against the antigens of the invading H7M7 virus. Lets briefly recall the terminology before proceeding further. An antigen is a substance that triggers an antibody generation. Antigens are parts of invading viruses or bacteria. For example, proteins on the surface of a bacteria are antigens. The body creates antibodies for the antigens on the germs that invade it. The antibodies have “binding sites” that allows them to bind to the antigens. The antibodies thus mark the invading germs by binding to their antigens and then the immune system unleashes its forces to kill the marked germs. Think of the antigen-antibody as a lock and key pair. The antibody that can bind to one kind of antigen cannot bind to another kind of antigen. So the body needs to make specific antibodies for the invading germ’s antigens else this system will fail because then the germs would not be marked. Now, armed with these basic concepts lets come back to our story of Alice and Bob. When Alice was infected by H7M7 in her childhood her immune system worked hard to fight the virus. It learnt to make antibodies for antigens on H7M7. After the infection was defeated the knowledge of what antibodies need to be formed for H7M7 virus was not lost. This remained with Alice’s immune system. So Alice’s immune system will always remember the H7M7 virus and antigens present on it. Alice’s immune system is always going to be prepared for H7M7 because it remembers H7M7 antigens and what antibodies to form to be able to bind to these antigens. But since Bob has never been infected by H7M7, his body does not know how to fight H7M7 ie his immune system does not know the antigens on H7M7 and what antibodies to create for these antigens.

Now lets ask: how does Alice’s immune system remember H7M7? This is done by memory B cells in her immune system. These memory B cells were formed  when H7M7 virus invaded Alice’s body and these will stay throughout her life. We all have memory B cells for every infection that has ever struck us. These cells help us to generate a fast and effective response to any infection that tries to strike us again. So Alice’s body has memory B cells for H7M7 but Bob’s body does not have memory B cells for H7M7. What will happen if H7M7 strikes Alice and Bob? You would agree that Alice’s body is prepared. Her immune system knows H7M7 antigens because of memory B cells for this virus. Her immune system immediately acts when it sees H7M7 virus and starts creating antiboidoes that bind to H7M7 antigens. The infection is soon defeated. But Bob’s body is not prepared. His immune system has to first learn about the H7M7 antigens and only then can it form antibodies. So time is spent and during this time the infection grows. Bob’s body had to fight longer to kill H7M7 and this results in Bob being sick for a much longer time as compared to Alice.

Now we come to the interesting part. Lets say that H7M7 mutates and there is now a new strain of virus known as H8M8. And lets assume that H8M8 has invaded the bodies of Alice( who has previously been exposed to H7M7) and Bob( who has never had any contact with H7M7). Who will have a better chance of effective defence against this new strain of virus? Would Alice’s previous exposure to H7M7 help her? Or would Alice’s and Bob’s immune system take the same time to understand the new virus and fight it?

The answer is neither of these. And that is because of the very interesting concept of Original Antigenic Sin. Alice’s body had been infected by H7M7 ealier and when the immune system was fighting the H7M7 virus it made a lot of memory B cells for H7M7. These memory B cells knew about the antigens on H7M7 and could quickly help in creating antiboidies to counter H7M7. So Alice’s immune system is very effective against H7M7. But this knowledge of H7M7 actually puts Alice at a disadvantage against the new strain of virus H8M8. When H8M8 enters Alice’s body, the memory B cells for H7M7 become active. The body thinks that H7M7 is the culprit, it does not realize that the virus has mutated. So when memory B cells for H7M7 become active they produce antibodies for H7M7 antigens. But the H7M7 antibodies cannot bind to H8M8 antigens because the mutation has changed the antigens on H8M8. So Alice’s immune system is completely ineffective against H8M8. Not only that, her immune’s system’s knowledge of H7M7 ( from memory B cells) causes the response to be wrong. Alice’s body wastes a lot of time in countering H8M8 with completely ineffective H7M7 antibodies. This allows H8M8 to grow and cause a lot of damage. On the other hand Bob’s immune system does not have prior knowledge of any flu virus and so can start understaning the antigens on H8M8 and then create an effective response in terms of antibodies. So Bob’s body responds better to H8M8 than Alice.

So the theory of Original Antigenic Sin refers to the ineffective response given to a new mutated virus because the immune system is trying to create antibodies of a virus that it had encountered earlier. This is similar to the adage that generals always fight the last war ie if a general has won a war he will keep using the same tactics in future wars even if those tactics are not suitable in the new situation.

The concept of Original Antigenic Sin is very important for vaccine research. If we make a vaccine for a particular strain of virus or bacteria, it may make people resistant for that specific virus or bacteria. But when that virus or bacteria mutates, the person who has been vaccinated would suffer the bad effects of the disease even more than the person who has never received the vaccine.

Kanwar

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Go wondrous creature, mount where science guides

go measure earth, weigh air, state the tides,

instruct the planets in what orbs to run

correct old time, regulate the sun

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