Immunology

VIB-RUG Department of Molecular Biomedical Research

Molecular ImmunoBiotechnology Unit

A paradigm of immunology:

Our body has a natural defense system against dangerous invaders: our immune system. The immune system is a complex regulated interplay, which needs to avoid activation of killing of our own cells ("self"), and needs to trigger the correct response against a dangerous invader. To be able to recognize all possible invaders, we have T-cells (cellular killers) and B-cells (producing antibody) that all carry a different, unique receptor, which is randomly created. Those cells carrying a receptor that binds to a target, will proliferate and differentiate in to an activated immune effector cell, capable of killing a wide range of target cells. Since the receptors are varied randomly, a lot of these receptors are capable of recognizing our own cells! This is avoided by two mechanisms:

During their development, and before these cells come into circulation, a negative selection takes place. T- and B-cells capable of recognizing an antigen on the stroma cells of the thymus or the bone marrow die off.

Some self-recognizing immune cells do get past this first self/non-self selection and reach the periphery. But before they can do any harm, they need to be activated. These cells need a special code to be activated. This code consists of two signals that need to be present at the same time. Only professional antigen presenting cells (APC) can give this code. The first signal however can be given by any normal cell, and involves the binding of the unique receptor of the T- and B-cells. In the absence of the second signal, the T- and B-cells will be inactivated.

Antigen presenting cells can not distinguish "self" antigens from "non-self" antigens. They only present antigen in a correct way when they are activated themselves. This can be done in several ways, and is best described as a reaction to a "danger" signal.

APCs have several sensors for "danger": bacteria, viruses, trauma's, ... are unnatural situations where a reaction is usually appropriate.

Also other immune cells can pas an an activation signal to the APC. These are the cells of the "innate" immune system (as opposed to the adaptive immune system, consisting of the T- and B-cells). Innate immune cells have no unique receptor recognizing a unique antigen on the target, but have several receptors that recognize common antigens that are shared between large groups of bacteria. Or they respond to signals coming from normal cells infected with a virus, that releases a warning signal.

In summary, a danger signal activates an antigen presenting cell. This antigen presenting cell then goes and recruits those T- and/or B-cells that carry a specific receptor for the inflicting agent. Only APCs can activate the T- and B-cells.

Interesting reading:

THE REAL FUNCTION OF THE IMMUNE SYSTEM or TOLERANCE AND THE FOUR D's (danger, death, destruction and distress) by Polly Matzinger