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www.proteinatlas.org Blood cell types Hematopoietic Stem Cell Blood cells make up approximately 40% of the blood volume and originate from stem cells in the bone marrow, where they mature into erythrocytes (red blood cells), platelets, and a large number of white Common Common blood cell populations that circulate throughout the body. Myeloid Progenitor Lymphoid Progenitor Erythrocytes (red blood cells) are small non-nucleated cells that transport oxygen and represent the most numerous cell type in the blood.

Platelets circulate in the blood until they are activated by tissue damage, Mastcell Myeloblast Erythrocytes Platelets NK cell Lymphocytes where they aid in blood clot formation. Granulocytes are a category of white blood cells involved in defending against bacteria and parasites. They are characterized by the presence of granules in their cytoplasm that contain, e.g., defensins, lysozymes and histamines. Cell types include neutrophils (most common), eosinophils, Basophil Neutrophil Eosinophil B cell T cell and basophils.

Monocyte Myeloid Plasmacytoid Monocytes are the largest of the white blood cells and are involved in Dendritic Cell Dendritic Cell immune responses to bacteria, viruses, and fungi. They can differentiate into macrophages that can penetrate into tissues and perform defense functions.

Dendritic cells are regulators of immune responses. They engulf and present fragments of pathogens to T cells in lymph nodes, enabling the Macrophage adaptive immune response.

Natural killer (NK) cells are involved in innate immunity and release Introduction to the Human Protein Atlas cytotoxic granules to fight tumors and cells infected by a virus. The Human Protein Atlas (www.proteinatlas.org) is an open access database with RNA and protein profiles of all genes across cells, tissues, and organs in the human body. A subsection of this database, the Human Blood Atlas, focuses on the expression levels of all human protein-coding genes in major blood immune B cells produce antibodies to fight infections as part of the adaptive cell populations. In addition, the proteins actively secreted to blood (the Human Secretome) are described. immune response. T cells regulate the adaptive immune response and consists of many different cell types. 68 355 40 225 53 67 7 54 Eosinophil Neutrophil Basophil T-reg 35 24 9 20 Naive 42 8 CD4 T-cell 15 12 Intermediate 24 106 48 monocyte 18 7 Naive 15 Non-classical Naive CD8 T-cell The genes in human blood cells monocyte 7 B-cell 19 8 114 15 Each node in this network shows the number of genes that are active in a specific immune cell Classical 18 7 22 17 10 monocyte MAIT population—both the number of genes enriched (high relative abundance of the protein) in a Memory 7 T-cell B-cell single cell type (red) and the number of genes enriched in several related cell types (yellow). For 9 Plasmacytoid 34 8 7 details and list of genes, see www.proteinatlas.org/blood. 7 10 DC 45 Memory 44 38 CD8 T-cell 22 15 11 266 NK-cell 21 Myeloid Memory 10 12 13 97 51 DC 8 GdTCR CD4 T-cell 16

Function of blood proteins

Blood coagulation The liquid portion of blood is called plasma. It No annotated function Complement pathway contains a complex mixture of proteins including Acute phase clotting factors, antibodies, hormones, and enzymes, Apolipoprotein as well as sugars and fat particles. The abundance Other Chemokine of blood proteins varies considerably, with only 10 Cell adhesion Blood disease and immune activation proteins making up more than 90% of the total Developmental protein Interferon protein mass. Albumin is the most abundant, while Defense Certain proteins are essential for activating immune cells upon infection and their dysfunction signaling proteins like cytokines and hormones Immunity leads to infectious disease susceptibility. Other proteins play critical roles in regulating Interleukin appear at much lower concentrations. The Human immunity. Proteins with such activating or inhibiting functions are interesting targets for drug Blood Atlas lists the functional role of all proteins Enzyme inhibitor development. Examples of pharmaceutical drugs include anti histamines that control predicted to be actively secreted into the blood allergic reactions and biopharmaceuticals used to lower the levels of cytokines in autoimmune Cytokine (figure on right) as well as their concentrations as diseases, such as multiple sclerosis (TNF-α) and psoriasis (IL-17). In addition, targeting proteins determined by mass spectrometry and/or Enzyme that limit immune responses—so called checkpoint inhibitors such as PD-L1 and CTLA4—can immunoassays (www.proteinatlas.org/blood). Growth factor boost the efficacy of immune cells, leading to dramatic improvements in patients with certain blood cancers, as well as showing promise in the treatment of solid tumors. Receptor Hormone Transport Neuropeptide

A century of advances in immunology reflected in Nobel prizes awarded for discoveries involving blood cells and proteins 1977 1957 1962 Rosalyn Yalow 1984 2011 2015 Daniel Bovet Max Ferdinand Perutz and for the development of Georges Kohler and Ralph M. Steinman William C. Campbell 1945 radioimmunoassays César Milstein Discovery of the and Satoshi Ōmura 1908 Alexander Fleming, Ernst for his work on John Cowdery Kendrew 1999 2018 of peptide hormones Techniques for dendritic cell and its role for a novel therapy Paul Ehrlich Boris Chain, 1948 1952 antihistamine Structure of hemoglobin 1972 1980 1996 Günter Blobel James P. Allison producing monoclonal in adaptive immunity against infections by Side-chain theory about how 1913 Howard Walter Florey Arne Tiselius Selman Waksman 1955 1960 Gerald Edelman Roger Guillemin and Baruj Benacerraf, Jean Peter Doherty and for the discovery and Tasuko Honjo antibodies roundworm parasites antibodies tackle invaders Charles Richet 1919 1926 1930 for the discovery of for his research on for discovering Vincent du Vigneaud 1958 Frank MacFarlane Burnet and Rodney Porter Andrew V. Schally Dausset, and George Snell 1987 Rolf Zinkernagel of the signal peptide Bruce A. Beutler and Discovery of cancer Ilya Ilyich Mechnikov Discovery of anaphylaxis, a Jules Bordet The Svedberg Karl Landsteiner penicillin and making it electrophoresis and streptomycin, the first for the first synthesis Fred Sanger and Peter Medawar Elucidating the for their discoveries Regulation of immune Nils Jerne Susumu Tonegawa How the immune that directs the Jules A. Hoffmann Tu Youyou therapy by inhibiting Identification of phagocytic life-threatening allergic Discovery of complement for his studies of proteins using Discovery of human blood groups and the into an antibiotic to cure the complex nature antibiotic to work of a polypeptide the structure Concept of immunological structure of of peptide hormone response by proteins on the Network theory for Genetic mechanism for the system recognizes transport of proteins Activation of innate for a novel therapy immune regulators cells that engulf intruders reaction to toxins factors in blood serum analytical ultracentrifuge methods system for typing blood infectious diseases of serum proteins against tuberculosis hormone of insulin tolerance antibodies production surface of cells the immune system construction of antibodies virus-infected cells in the cell immunity against Malaria (checkpoint inhibition)