M1 macrophage #
A subset of macrophages that are present in tissues and are similar to macrophages activated by LPS and IFNγ in vitro. M1 macrophages produce high levels of IL-12, low levels of IL-10, and have pro-inflammatory and phagocytic functions that can have antitumor benefits. They also have anti-microbial activities. M1 macrophages are one end of a broad continuum of macrophage subtypes with different immunologic functions. M2 macrophages are at the opposite end of the continuum.
M2 macrophage #
A subset of macrophages that are present in tissues, and are associated with wound or tissue repair. M2 macrophages produce anti-inflammatory molecules such as IL-10, TGFβ, and only low levels of IL-12. Their phenotype can be enhanced with IL-4. M2 macrophages are often found to be associated with tumors and may promote tumor growth. M2 macrophages are one end of a broad continuum of macrophage subtypes with different immunologic functions. M1 macrophages are at the opposite end of the continuum.
A collection of genes coding for the major histocompatibility complex (MHC) molecules. MHC molecules are found on the surface of nucleated cells of the body. There are two classes of MHC molecules (MHC class-I and MHC class-II). Both are central to educating the immune system to recognize self and non-self molecules, and play a role in initiating immune responses to pathogens, variant or inappropriately expressed self molecules, or neoantigens (as in cancer cells), or self molecules in autoimmune diseases. Both types of MHC molecules are dimeric transmembrane glycoproteins.
- MHC class-I molecules are present on all nucleated cells and display peptides derived from normal intracellular self-antigens as well as from abnormal and nonself intracellular pathogens. Peptide–MHC-I molecules are recognized by CD8+ T cells.
- MHC class-II molecules are primarily found on the surface of “professional antigen-presenting cells”, e.g., macrophages, dendritic cells, and B cells, and display peptides from abnormal and nonself pathogen antigens. Peptide–MHC-II molecules are recognized by CD4+ T cells.
A class of MHC molecules that are made of an α chain coupled with the smaller β2 microglobulin. MHC-I α chains are encoded by autosomal, highly polymorphic genes. Within the human population, each individual typically has three different MHC-I genes (HLA-A, HLA-B and HLA-C) and hence, 6 MHC-I alleles in total. Mice have two to three different MHC-I genes (H-2K, H-2D, and H-2L), depending on the mouse model. The MHC-I α chain forms a cleft that displays short antigen peptides (epitopes), typically 8–12 amino acids in length, to the immune system. Peptides displayed by MHC-I molecules are derived from degraded cytosolic proteins that are transported into the endoplasmic reticulum (ER) by the TAP complex, and loaded in the ER onto MHC-I molecules by the peptide loading complex. Thus, peptides displayed on MHC-I molecules include those from cellular proteins and cytosolic pathogens. Peptide–MHC-I molecules are recognized by CD8+ T cells.
A class of MHC molecules that are made of an α and β chain that are similar in length. MHC-II α and β chains are encoded by autosomal, highly polymorphic genes. Within the human population, each individual typically has three sets of MHC-II genes (HLA-DR, HLA-DP and HLA-DQ, each with at least one separate gene encoding the α and β chains) and hence 12 or more MHC-II alleles in total. Mice have one to two sets of MHC-II genes (I-A and I-E), depending on the mouse model. The α and β chains of MHC-II molecules together form a cleft that displays short antigen peptides (epitopes), typically greater than 12 amino acids in length, to the immune system. Peptides displayed on MHC-II are derived from extracellular proteins captured by endocytosis, digested in lysosomes and loaded on MHC-II molecules prior to their migration to the cell surface. Thus, peptides displayed on MHC-II molecules include those from extracellular pathogens and cellular debris. Peptide–MHC-II molecules are recognized by CD4+ T cells.
Monocyte-derived Dendritic Cells #
A set of cells that have been considered to be a type of dendritic cells (DCs), though there is no clear consensus on their precise lineage. Surface markers and expression profiling support their DC characterization, but monocyte-derived dendritic cells (moDC) at sites of inflammation are heterogeneous and may also include cells with macrophage-like markers. Recent data show that moDCs or “inflammatory DCs” can develop independently of standard DC differentiation factors, FLT3 and GM-CSF. Thus, they are more likely a distinct type of cell of monocytic origin with some functionality shared with DCs. Monocytic DCs can cross-present antigen and have been used extensively as a source of ex vivo prepared antigen presenting cells for vaccines.
A mass spectrometry (MS) database search tool that identifies peptides from a protein sequence database by comparing their MS/MS spectra versus submitted data. It can use data from a variety of MS instruments and different experimental protocols. The software can be downloaded from Pacific Northwest National Lab.