2011 Nobel Prize in Physiology or Medicine(2)
Reason for Award
for his discovery of the dendritic cell and its role in adaptive immunity
Laureates
Canada
Explanation
Inside our bodies there is a teacher-like cell called the dendritic cell that catches germs and shows them to other immune cells. Dr. Steinman discovered this dendritic cell and explained how it works in immunity. The cell carries information about microbes to lymph nodes and tells T cells, “Here is the enemy.” The T cells then power up to fight. Thanks to this finding, new kinds of vaccines and cancer treatments have been developed.
Related Keywords
dendritic cell
Dendritic cells (DCs) are antigen-presenting cells with tree-like projections found in nearly all tissues. Immature DCs capture pathogens via pattern-recognition receptors and migrate to lymph nodes where they mature and gain potent T-cell stimulatory capacity. By expressing high levels of MHC and costimulatory molecules, DCs are regarded as the only cells capable of priming naïve T lymphocytes. Cytokines and ligands produced by DCs steer T cells toward Th1, Th2, Th17, or cytotoxic fates. Multiple subsets—such as plasmacytoid DCs and Langerhans cells—have been identified, each playing distinct roles in disease and vaccination responses.
adaptive immunity
Adaptive immunity is mediated by antigen-specific T and B lymphocytes and creates memory for faster secondary responses. Dendritic cells initiate the process by presenting antigen and delivering costimulatory signals to naïve T cells. Helper T cells assist B cells in producing high-affinity, class-switched antibodies. Cytotoxic T lymphocytes eliminate infected or malignant cells, providing immune surveillance. Dysregulated adaptive immunity underlies autoimmune diseases, chronic infections, and tumor immune escape.
antigen presentation
Antigen presentation is the process of loading peptide fragments onto MHC molecules and displaying them to T cells. Dendritic cells can deliver exogenous antigens into both class I and II pathways through endocytosis and cross-presentation. Without sufficient costimulation, antigen presentation leads to T-cell inactivation or anergy. Enhancing antigen-presentation efficiency is pivotal for cancer and infectious disease vaccine design. Conversely, dysregulated presentation of self antigens can result in autoimmunity or graft-versus-host disease.
MHC class II
MHC class II molecules are expressed mainly on dendritic cells, macrophages, and B cells. They load peptides derived from lysosomally processed exogenous antigens after invariant-chain replacement and present them to CD4+ T cells. HLA polymorphisms influence peptide binding and susceptibility to autoimmune diseases. Expression is transcriptionally regulated by CIITA and modulated by the cytokine milieu. Transgenic mice expressing human class II molecules are invaluable for vaccine and immunopathology research.
immune tolerance
Immune tolerance denotes a state in which the immune system does not react against self or harmless antigens. When dendritic cells present antigen with low costimulation in a specific cytokine milieu, regulatory T cells (Tregs) are induced, establishing tolerance. Central negative selection in the thymus and peripheral checkpoints act in tandem to prevent aberrant responses. Breakdown of tolerance leads directly to autoimmune diseases and allergies. DC-based tolerance-induction therapies are being tested clinically for type 1 diabetes and multiple sclerosis.
vaccine development
The potent T-cell-activating ability of dendritic cells makes them the “commanders” of vaccination. Ex vivo-loaded autologous DCs reinfused into patients represent one form of cancer vaccine. mRNA vaccines are designed so that in vivo DCs translate and present the encoded antigen. Combining antigens with TLR-stimulating adjuvants drives DC maturation and yields stronger memory responses. Nanoparticles that target specific DC subsets are emerging as next-generation vaccine platforms.
cytokine
Cytokines are intercellular signaling proteins produced by immune cells, including interleukins, interferons, and TNF. Dendritic cells release IL-12, IL-10 and others to govern the direction of T-cell differentiation. Excessive cytokine production causes cytokine storms, a chief culprit in severe infections and CAR-T therapy side effects. Therapies that deliver or block specific cytokines have proven effective in autoimmune diseases and cancer. Quantitative mapping of cytokine networks is essential for predictive models of immune responses.