Dr. Guy Shahar, from the department of immunology at the Weizmann Institute of Science, follows the cells of the immune system during their regular activity and during illness and from where they go, how they get to Hafzam district, and with whom they communicate
The immune system is a large and extremely complicated organization - a complex network that each of its components must perform its role efficiently and at the right time. Dr. Guy Shahar, from the Department of Immunology at the Weizmann Institute of Science, monitors the cells of the immune system during their regular activity and during illness. Using a sophisticated microscope (see frame) he finds out where they go, how they get to the district they want, and with whom they communicate.
One group of cells that Dr. Shahar follows are the dendritic cells. These cells wander in organs such as the intestine, the skin and the lungs - the book areas of the body, which are exposed to the danger of the penetration of various disease agents. They sample various factors they meet along the way in order to find out if they are ours or ours. In the event that further treatment is required, they take a sample of a substance - a piece of protein called an antigen - and bring it to the nearest lymph node. There they present the sample to immune cells (mainly T cells) that drive the immune response, destroy bacteria and cells that have been "occupied" by viruses, and recruit additional immune cells to the campaign - including B cells that produce antibodies.
Dr. Shahar studies the way in which the dendritic cells migrate from the skin, through the lymphatic vessels, to the lymph nodes. It is known that these cells do not migrate efficiently when certain receptors displayed on their membranes are blocked. These are receptors for two certain signaling molecules - one that pulls them towards the target, and another molecule that helps them stick to it. Dr. Shahar is trying to find out the exact timing at which these two molecules are activated: do they play a role in the early stage, of dendritic cells leaving their place in the skin or intestine, or in the later stage, of navigating the lymphatic vessels, or in the last stage, of entering the lymph nodes.
Sometimes it is a guerilla war, which gives a relative advantage to the invaders: for example, a very few malaria parasites transmitted by a mosquito bite are enough to cause a disease. If the immune system has not encountered these parasites before, only a few of the billions of T cells in the body will be equipped with the appropriate receptors to recognize the unknown danger. At this point in time, a race begins between the agents of the disease and the immune system: the agents of the disease will try to complete their destructive work before the entire system mobilizes against them. On the other hand, the few immune cells that have recognized the danger try to convince the immune system to mobilize for an all-out war in a short time.
Dr. Shahar and the members of the research group he heads suggest that the work of persuasion is done by combining forces between the T cells and the dendritic cells: the dendritic cells create networks that allow the antigen samples to be presented, and the T cells move along the network and locate the dendritic cell that presents the antigen in a way most useful for them. Now the researchers are examining how the coordination between the T cells and the dendritic cells is carried out. In another study, Dr. Shahar focuses on "killer" T cells, which function as a kind of elite units of the immune system. Laboratory experiments show that these cells succeed, among other things, in identifying and destroying cancer cells growing in culture. In the body, on the other hand, the cancer cells succeed in repelling the T-cells by secreting the substance TGF-beta - which is also produced normally by the body's cells - whose purpose is to provide immune responses. In order to investigate this phenomenon, the scientists examine the mode of activity of "super killer" T cells: these cells have undergone genetic engineering that causes them to ignore the moderator, so that they attack and destroy cancer cells very efficiently.
Immune cells involved in inflammatory diseases of the digestive system (including Crohn's disease) are another target of Dr. Shahar's research. Recently, evidence is accumulating that the cause of these autoimmune diseases lies in poor control of the immune responses against harmless microorganisms that live naturally in the intestines. This response involves interactions between three immune components: cells that cause inflammation, T cells that moderate the immune response, and dendritic cells. Dr. Shahar and the members of his research group created an experimental system in which the intestines of live mice can be observed using a microscope. They injected bacteria containing unique antigens into it, as well as T cells that recognize only these antigens - and react to them. The researchers believe that the dendritic cells play a central role in the threefold interaction, and that revealing the role they play will open the door to new treatment methods for inflammatory bowel diseases.
lifelike
When the 17th century English scientist Robert Hooke first observed a piece of cork under the microscope lens, he gave the small structures he saw the name "cells". In the years that have passed, the microscopes have become more powerful, revealing in great detail the hidden world of cells. But, until recently, when researchers wanted to observe cells deep within complex tissues, they had to freeze them in place, just like Hooke's cork cells.
New types of microscopes have made it possible in recent years to observe living cells in motion within living organisms. For this purpose, Dr. Guy Shahar uses a "two-photon microscope" that allows him to track immune cells in anesthetized mice. The method is based on a physical phenomenon in which two photons which hit certain molecules one after the other, cause them to glow momentarily with fluorescent light. This is how a color image is obtained using ultra-fast pulses of infrared laser rays on the cells.
The infrared beam is able to penetrate the tissue to a depth of several hundred microns, which allows Dr. Shahar to slice the tissue virtually without physically damaging it, and observe the cell activities over time.
in brief:
The question: How do a few immune cells that have recognized a foreign invader convince the immune system to mobilize for an all-out war in a short time?
The findings: The institute's scientists suggest that the work of persuasion is done by combining the dendritic cells that form networks that allow antigen samples to be presented, and the T cells that move through the network and locate the dendritic cells that present the antigens.
Dr. Guy Shahar was born in Jerusalem and grew up in Givatayim. After his service in the IDF, he received a master's degree in interdisciplinary studies and a doctorate in neurobiology from Tel Aviv University.
In this framework, he studied the interrelationship between the immune system and the nervous system. In the post-doctoral research he carried out in Prof. Michael Dustin's group at the New York University School of Medicine, he started working on imaging immune cells. In 2006 he joined the faculty of the Weizmann Institute of Science.
Dr. Guy Shahar is married to Keren, and father to Gal, about six years old, and to Amit, about four years old. He enjoys mountain biking and the Japanese board game "Go".
