Receptor
Haemagglutinin
Receptor
Haemagglutinin Virus
Receptor
DC
The virus is bound by its haemagglutinin to receptors on the dendritic cell ( DC ) and channelled into the cell.
( → phagocytosis, → endocytosis ), migration ( → chemotaxis ) and the secretion of specific messenger substances ( → cytokines and → chemokines ). They also influence antigen presentation by dendritic cells to T cells in lymph nodes. lllll As they mature, DCs lose their ability to engulf pathogens ( phagocytosis ) but become capable of activating T cells. They can also activate natural killer cells ( → NK cells ). lllll DCs are not a uniform group of cells but rather a family with several different members. They do not arise from just one type of precursor cell. The best known are the conventional myeloid dendritic cell (mDC) and plasmacytoid dendritic cell (pDC). Both of these arise from blood-forming stem cells in the bone marrow. mDCs and pDCs circulate in the blood as DC precursors. Attracted by → chemotactic signals, the immature cells migrate into the tissues, where they adhere to → chemokines and become resident. → Langerhans cells are also considered to be a type of DC. Langerhans cells are present in the epithelium and mucosal membranes, which are particularly at risk of invasion by pathogenic organisms and therefore need effective sentinel cells.
Haemagglutinin Virus
DC Virus DC
Virus fragment Virus fragment Virus fragment
MHC molecule MHC molecule MHC molecule Membrane system
During its passage through the membrane system, the virus is broken down. Specific viral fragments are coupled to MHC molecules found on the inside of the membrane vesicle.
Membrane system Virus fragment Virus fragment Virus fragment
Membrane system MHC molecule MHC molecule MHC molecule
Transport vesicles carry the MHC molecules together with the viral fragments to the cell margins. Fusion of the membranes brings the MHC molecules to the outer surface of the DC so that it can now present these antigens to other cells.
Ralph Steinman – discoverer of dendritic cells
In 1970, Ralph Steinman, a Canadian immunologist, moved to the laboratory of the macrophage researcher Zanvil Cohn at the Rockefeller University in New York. While working there, Steinman described how cells engulf molecules. → endocytosis. lllll At the beginning of the 70s, immunologists developed cell culture systems to facilitate their research into the cellular basis of immunology. They soon realised that, besides the B and T cells, another cell type was necessary and called them accessory cells. In the lab, these accessory cells adhered to glass surfaces
and Steinman looked at them using various microscopic techniques. He discovered a new type of branching immune cell which formed rapidly changing protrusions. Steinman called them dendritic cells ( DCs ) because of their tree-like appearance ( Greek : dendron = tree ). He was convinced that these dendritic cells were the accessory cells. They were able to induce T lymphocytes to divide and T killer cells to react against antigens. He was also convinced that these accessory cells were not macrophages. lllll The scientific community was very slow in recognising the significance of his discovery. Steinman came under merciless criticism.
It seemed very far-fetched that, at a time when molecular cell biology was coming into its own, a new cell type could be discovered merely by looking down the microscope. lllll Steinmann persevered with his research on dendritic cells, however, and together with his co-workers was the first to describe the role of DCs in immune reactions. He demonstrated that DCs are also present in human blood. In animal experiments, he was able to induce immunity against tumours with antigenladen dendritic cells. He recognised that DCs could be activated by pathogenic organisms in order to induce immunity. lllll In 1868, Paul Langerhans
was the first to describe cells, subsequently named Langerhans cells, which he thought were part of the nervous system. They belonged, however, to the dendritic cells of the immune system, first discovered by Ralph Steinman and Zanvil A. Cohn in 1973. lllll Steinman was a basic research scientist but nevertheless he understood the enormous challenge involved in transferring laboratory findings into practice with patients. With the aid of dendritic cells he tried to produce → vaccines. For his work on dendritic cells, Steinman (1943-2011) was awarded the Nobel Prize in Physiology or Medicine in 2011. 11