Monday, October 3, 2011

Immunology researchers win Nobel Prize

Bruce Beutler, Jules Hoffmann and Ralph Steinman have won this years Nobel Prize for medicine. Beutler and Hoffman have collectively discovered the existence and function of Toll-like receptors. They function in recognizing certain sugar molecules on bacterial surfaces, which causes activation of the immune system to get rid of the invading microbes. Steinman is responsible for discovering dendritic cells (DC), that also have a role in the immune system. DC reside in various tissues where they 'eat' microbes, and consequently 'present' it to specialized cells of the immune system, which in response launch a response against the invaders. This proces is called phagocytosis, and DC are named after their ability to form long tree-like appendices that aids in engulfing  foreign material.

Hoffmann discovered in 1966 that the efficiency of the immune system is affected by the function of a gene named Toll. Two years later, Beutler discovered that Toll functions as receptor-like molecules on white blood cells, demonstrating their function in the immune system. We now know there are many forms of Toll-like receptors, that each recognize different parts of foreign material. Most well-known is a sugary molecule called LPS, which is found on the outer layer of most bacteria. Once the molecule is recognized, the receptors activate various mechanisms in the immune system to get rid of the infection, a process that is called inflammation. This is aided by the production of chemicals that promote inflammation: cytokines. The most well-known pro-inflammatory cytokines are called interleukines (IL). There is a wide variety in cytokines, which collective function is immensely complex and is regulated in various pathways. Next to LPS, various Toll-like receptors recognize viral genetic code, fungus and certain molecules we produce in our own body.
DC also play a role in triggering inflammation. These 'all-eaters' engulf foreign material, which is consequently destroyed inside the cell, whereafter parts of the microbial molecules are processed to be mounted on a specific receptor on the DC surface. These receptors are called MHC, and play a very important role in communicating with other immune cells. By mounting foreign material on MHC, the DC are basically presenting their findings to other cells, so that they may respond in order to launch a full immune response.
Toll-like receptors and DC are part of the innate immune system. This means that we are born with it, and their ability to recognize foreign molecules and microbes is built in. They are important in initiating a full-scale immune response, which also involves the adaptive immune system. This part of our body's defence needs to learn: lymphocytes that are used for killing (T cells) and for antibody production (B cells) are specific for one molecular signature, which is called an epitope. With the aid of DC and the production of inflammation inducing chemicals in response to Toll-like receptor activation, the T and B cells can become activated, which means they will clone themselves rapidly and start wearing off the infection.

The discoveries of the three researchers have aided us in better understanding how our immune system recognizes microbes and consequently launches an attack against the intruders. This paved the way for research in how auto-immune diseases develop, and how we can reinforce a weakened immune system. Because our immune system is also involved with recognizing cells that are dysregulated and in need of clearing from the body, their discoveries also shed light on the development of cancer.

1 comment:

  1. Hello,

    Thank you for sharing such relevant topic with us. Toll-like receptors play a crucial role in the recognition of invading pathogens and the activation of subsequent immune responses against them. Individual TLRs recognize distinct pathogen associated molecular patterns...