The Human Protein Atlas - Sponsored by Produced …The Human Protein Atlas () is an open access...
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Hematopoietic Stem Cell Common Lymphoid Progenitor Common Myeloid Progenitor Mastcell Myeloblast Erythrocytes Platelets NK cell B cell T cell Lymphocytes Basophil Neutrophil Eosinophil Monocyte Macrophage Myeloid Dendritic Cell Plasmacytoid Dendritic Cell 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 cell populations. In addition, the proteins actively secreted to blood (the Human Secretome) are described. Each node in this network shows the number of genes that are active in a specific immune cell population—both the number of genes enriched (high relative abundance of the protein) in a single cell type (red) and the number of genes enriched in several related cell types (yellow). For details and list of genes, see www.proteinatlas.org/blood. Function of blood proteins The liquid portion of blood is called plasma. It contains a complex mixture of proteins including clotting factors, antibodies, hormones, and enzymes, as well as sugars and fat particles. The abundance of blood proteins varies considerably, with only 10 proteins making up more than 90% of the total protein mass. Albumin is the most abundant, while signaling proteins like cytokines and hormones appear at much lower concentrations. The Human Blood Atlas lists the functional role of all proteins predicted to be actively secreted into the blood (figure on right) as well as their concentrations as determined by mass spectrometry and/or immunoassays (www.proteinatlas.org/blood). Blood disease and immune activation Certain proteins are essential for activating immune cells upon infection and their dysfunction leads to infectious disease susceptibility. Other proteins play critical roles in regulating immunity. Proteins with such activating or inhibiting functions are interesting targets for drug development. Examples of pharmaceutical drugs include anti histamines that control allergic reactions and biopharmaceuticals used to lower the levels of cytokines in autoimmune diseases, such as multiple sclerosis (TNF-α) and psoriasis (IL-17). In addition, targeting proteins that limit immune responses—so called checkpoint inhibitors such as PD-L1 and CTLA4—can 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. Blood cell types Ilya Ilyich Mechnikov Identification of phagocytic cells that engulf intruders Charles Richet Discovery of anaphylaxis, a life-threatening allergic reaction to toxins reflected in Nobel prizes awarded for discoveries involving blood cells and proteins A century of advances in immunology 1908 1913 1919 1930 1945 1948 1952 1955 1960 1972 1980 1984 1987 1996 2011 2015 2018 Paul Ehrlich Side-chain theory about how antibodies tackle invaders Jules Bordet Discovery of complement factors in blood serum 1926 The Svedberg for his studies of proteins using analytical ultracentrifuge methods Karl Landsteiner Discovery of human blood groups and the system for typing blood Alexander Fleming, Ernst Boris Chain, Howard Walter Florey for the discovery of penicillin and making it into an antibiotic to cure infectious diseases Arne Tiselius for his research on electrophoresis and the complex nature of serum proteins Selman Waksman for discovering streptomycin, the first antibiotic to work against tuberculosis Vincent du Vigneaud for the first synthesis of a polypeptide hormone 1957 Daniel Bovet for his work on antihistamine 1958 Fred Sanger the structure of insulin Frank MacFarlane Burnet and Peter Medawar Concept of immunological tolerance 1962 Max Ferdinand Perutz and John Cowdery Kendrew Structure of hemoglobin Gerald Edelman and Rodney Porter Elucidating the structure of antibodies 1977 Roger Guillemin and Andrew V. Schally for their discoveries of peptide hormone production Baruj Benacerraf, Jean Dausset, and George Snell Regulation of immune response by proteins on the surface of cells Nils Jerne Network theory for the immune system Georges Kohler and César Milstein Techniques for producing monoclonal antibodies Susumu Tonegawa Genetic mechanism for the construction of antibodies Peter Doherty and Rolf Zinkernagel How the immune system recognizes virus-infected cells 1999 Günter Blobel for the discovery of the signal peptide that directs the transport of proteins in the cell Bruce A. Beutler and Jules A. Hoffmann Activation of innate immunity Ralph M. Steinman Discovery of the dendritic cell and its role in adaptive immunity William C. Campbell and Satoshi Ōmura for a novel therapy against infections by roundworm parasites James P. Allison and Tasuko Honjo Discovery of cancer therapy by inhibiting immune regulators (checkpoint inhibition) Blood coagulation Complement pathway Acute phase Apolipoprotein Chemokine Interferon Interleukin Cytokine Growth factor Hormone Neuropeptide Transport Receptor Enzyme Enzyme inhibitor Immunity Defense Developmental protein Cell adhesion Other No annotated function GdTCR 10 44 Memory CD4 T-cell 16 Memory CD8 T-cell 11 7 13 12 Classical monocyte 18 10 8 15 266 97 Plasmacytoid DC Memory B-cell NK-cell 34 45 8 20 Naive CD4 T-cell T-reg 225 12 9 67 15 7 10 114 7 MAIT T-cell 15 Naive CD8 T-cell 19 22 7 Eosinophil 48 106 8 7 Basophil Naive B-cell 53 355 24 18 Neutrophil 54 8 40 68 24 21 22 Myeloid DC 9 38 51 7 35 Intermediate monocyte 15 Non-classical monocyte 42 17 7 Introduction to the Human Protein Atlas 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, 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, and basophils. Monocytes are the largest of the white blood cells and are involved in 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 adaptive immune response. Natural killer (NK) cells are involved in innate immunity and release cytotoxic granules to fight tumors and cells infected by a virus. B cells produce antibodies to fight infections as part of the adaptive immune response. T cells regulate the adaptive immune response and consists of many different cell types. The genes in human blood cells 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 blood cell populations that circulate throughout the body. www.proteinatlas.org Produced by the Science/AAAS Custom Publishing Office Sponsored by Rosalyn Yalow for the development of radioimmunoassays of peptide hormones Tu Youyou for a novel therapy against Malaria
Transcript of The Human Protein Atlas - Sponsored by Produced …The Human Protein Atlas () is an open access...
Hematopoietic Stem Cell
CommonLymphoid Progenitor
CommonMyeloid Progenitor
Mastcell Myeloblast Erythrocytes Platelets NK cell
B cell T cell
Lymphocytes
Basophil Neutrophil EosinophilMonocyte
Macrophage
MyeloidDendritic Cell
PlasmacytoidDendritic Cell
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 cell populations. In addition, the proteins actively secreted to blood (the Human Secretome) are described.
Each node in this network shows the number of genes that are active in a specific immune cell population—both the number of genes enriched (high relative abundance of the protein) in a single cell type (red) and the number of genes enriched in several related cell types (yellow). For details and list of genes, see www.proteinatlas.org/blood.
Function of blood proteinsThe liquid portion of blood is called plasma. It contains a complex mixture of proteins including clotting factors, antibodies, hormones, and enzymes, as well as sugars and fat particles. The abundance of blood proteins varies considerably, with only 10 proteins making up more than 90% of the total protein mass. Albumin is the most abundant, while signaling proteins like cytokines and hormones appear at much lower concentrations. The Human Blood Atlas lists the functional role of all proteins predicted to be actively secreted into the blood (figure on right) as well as their concentrations as determined by mass spectrometry and/or immunoassays (www.proteinatlas.org/blood).
Blood disease and immune activationCertain proteins are essential for activating immune cells upon infection and their dysfunction leads to infectious disease susceptibility. Other proteins play critical roles in regulating immunity. Proteins with such activating or inhibiting functions are interesting targets for drug development. Examples of pharmaceutical drugs include anti histamines that controlallergic reactions and biopharmaceuticals used to lower the levels of cytokines in autoimmune diseases, such as multiple sclerosis (TNF-α) and psoriasis (IL-17). In addition, targeting proteins that limit immune responses—so called checkpoint inhibitors such as PD-L1 and CTLA4—can 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.
Blood cell types
Ilya Ilyich MechnikovIdentification of phagocytic cells that engulf intruders
Charles RichetDiscovery of anaphylaxis, a life-threatening allergic reaction to toxins
reflected in Nobel prizes awarded for discoveries involving blood cells and proteins
A century of advances in immunology
19081913
1919 1930
19451948 1952
1955 19601972 1980
1984
19871996
2011 2015
2018Paul Ehrlich Side-chain theory about how antibodies tackle invaders
Jules BordetDiscovery of complement factors in blood serum
1926The Svedbergfor his studies of proteins using analytical ultracentrifuge methods
Karl LandsteinerDiscovery of human blood groups and the system for typing blood
Alexander Fleming, Ernst Boris Chain, Howard Walter Floreyfor the discovery of penicillin and making it into an antibiotic to cure infectious diseases
Arne Tiselius for his research on electrophoresis and the complex nature of serum proteins
Selman Waksmanfor discovering streptomycin, the first antibiotic to work against tuberculosis
Vincent du Vigneaud for the first synthesis of a polypeptide hormone
1957Daniel Bovet for his work on antihistamine
1958Fred Sanger the structure of insulin
Frank MacFarlane Burnet and Peter MedawarConcept of immunological tolerance
1962Max Ferdinand Perutz and John Cowdery Kendrew Structure of hemoglobin
Gerald Edelman and Rodney Porter Elucidating the structure of antibodies
1977
Roger Guillemin andAndrew V. Schally for their discoveries of peptide hormone production
Baruj Benacerraf, Jean Dausset, and George SnellRegulation of immune response by proteins on the surface of cells
Nils JerneNetwork theory for the immune system
Georges Kohler and César MilsteinTechniques for producing monoclonal antibodies
Susumu TonegawaGenetic mechanism for the construction of antibodies
Peter Doherty andRolf Zinkernagel How the immune system recognizes virus-infected cells
1999Günter Blobel for the discovery of the signal peptide that directs the transport of proteins in the cell
Bruce A. Beutler and Jules A. HoffmannActivation of innate immunity
Ralph M. Steinman Discovery of the dendritic cell and its role in adaptive immunity
William C. Campbell and Satoshi Ōmurafor a novel therapyagainst infections by roundworm parasites
James P. Allison and Tasuko Honjo Discovery of cancertherapy by inhibiting immune regulators (checkpoint inhibition)
Blood coagulationComplement pathway
Acute phaseApolipoprotein
Chemokine
Interferon
Interleukin
Cytokine
Growth factor
HormoneNeuropeptideTransport
Receptor
Enzyme
Enzyme inhibitor
Immunity
DefenseDevelopmental protein
Cell adhesion
Other
No annotated function
GdTCR10
44
MemoryCD4 T-cell
16
MemoryCD8 T-cell
11
7
1312
Classicalmonocyte
18
108
15
26697
PlasmacytoidDC
MemoryB-cell
NK-cell
3445
8
20NaiveCD4 T-cell
T-reg
225
12
9
67
15
710
1147
MAITT-cell
15
NaiveCD8 T-cell
19
22
7
Eosinophil
48106
87
Basophil
NaiveB-cell
53
355
24
18
Neutrophil 54
8
4068
24
21
22
MyeloidDC
9
38
51
7
35
Intermediatemonocyte 15 Non-classical
monocyte
42
17
7
Introduction to the Human Protein Atlas
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, 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, and basophils.
Monocytes are the largest of the white blood cells and are involved in 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 adaptive immune response.
Natural killer (NK) cells are involved in innate immunity and releasecytotoxic granules to fight tumors and cells infected by a virus.
B cells produce antibodies to fight infections as part of the adaptive immune response.
T cells regulate the adaptive immune response and consists of many different cell types.
The genes in human blood cells
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 blood cell populations that circulate throughout the body.
www.proteinatlas.org
Produced by the Science/AAAS Custom Publishing OfficeSponsored by
Rosalyn Yalow for the development ofradioimmunoassays of peptide hormones
Tu Youyoufor a novel therapyagainst Malaria
