IMMUNOLOGY

Adhesion Molecules on Lymphocyte B cell and T cell lymphocytes interact with a variety of cells as part of their immune function, circulating and homing in on specific stimuli in tissues like inflammatory signals. The interaction of lymphocytes with other cell types like vascular endothelial cells requires transmembrane adhesion molecules like VLA-4, LFA-1, CD44, CD31 and L-selectin. Each of these lymphocyte adhesion molecules interacts with specific ligands expressed on cells like endothelial cells to moderate adhesion between cells. Alternative Complement Pathway The complement system of plasma proteins is an important part of the immune system that forms a cascade of factors that lyses foreign cells. There are two branches of the complement system, the classical pathway that is initiated by antibody-antigen complexes on a cell and the alternative pathway that is antibody independent. Antigen Dependent B Cell Activation A key part of the immune system is the production of immunoglobulins (antibodies) by B cells to bind and inactivate specific foreign antigens. The body produces B cells with a wide range of antigen specificities in the immunoglobulin B cell receptor, one antigen specificity per cell. BCR Signaling Pathway The B cell receptor plays a key role in the immune system. The specificity of the receptor is governed by the binding site formed from the mature heavy and light chain. It is the ability of this receptor to bind a foreign target with the appropriate affinity that ultimately leads to the production of antibodies against that target. Upon binding of antigen the BCR triggers the activation of the cell through MAP Kinases and the PKC family. B Lymphocyte Cell Surface Molecules B cells must communicate with their environment to participate in the immune system as the source of antigen-specific immunoglobulins. Cell surface proteins on B cells receive signals from the exterior, adhere to other cells, and transmit signals to other cells. Bystandard B Cell Activation Expression of Fas-Ligand by T cells can induce apoptosis through interaction with Fas on the target cell. A target of Fas-mediated apoptosis is the B cell. Complement Pathway Classical Complement Pathway The complement system is part of the defense against invading cells and is composed of about twenty different proteins found in the plasma. When activated, complement proteins form a pathway of proteolytic reactions that culminates in the lysis of foreign cells.    CTL mediated immune response against target cells CXCR4 Signaling Pathway EGF Signaling Pathway Epidermal Growth Factor Receptor (EGFR) has a cytoplasmic tyrosine kinase activity that becomes activated upon EGF binding to the extracellular domain of this 175 kD receptor. EGFR signals its growth regulating effects to the cell through several major pathways including MAPK (ERK and JNK), Protein Kinase C, and JAK/Stat. EPO Signaling Pathway Erythropoietin functions to increase the number of red blood cells. Thus, it has found utility as a drug for those needing to replenish erythrocytes for a number of reasons. The signaling mechanism includes multimerization of the receptor upon ligand binding, activation of MAPK cascade, and phosphorylation and activation of Stat5. Fc Epsilon Receptor I Signaling in Mast Cells The Fc Epsilon Receptor 1 signaling pathway in mast cells uses multiple core signal path to achieve its necessary ends. Through the BTK protein and PKC Mast cells are able to degranulate, through the PKC and MAPK paths the cells are able to alter cytokine expression and arachidonic acid release. IFN alpha Signaling Pathway Interferon alpha plays a role in viral infections. Signaling takes place through an IFN Recpetor complex consisting of two alpha chains (Type I receptor) complexed with Jak1 and Tyk2. These kinases phosphorylate Stat1 and Stat2 respectively. IFN gamma Signaling Pathway Interferon gamma is secreted from CD4+ Th1 cells, CD8 cells, gamma/delta T cells and activated NK cells. It plays a role in activating lymphocytes to enhance anti-microbial and anti-tumor effects. In addition it plays a role in regulating the proliferation, differentiation, and response of lymphocyte subsets. Signaling takes place through a IFN Recpetor complex consisting of two alpha chains (Type I receptor) and two beta chains (Type 2 receptor). Upon phosphorylation by Jak1, Stat1(alpha) transduces the signal into transcriptional events. Lck and Fyn tyrosine kinases in initiation of TCR Activation T cell activation is initiated by recognition of antigen by the T cell receptor (TCR) in the context of Class II MHC on an antigen-presenting cell. The T cell receptor contains multiple subunits and interacts with several factors to transduce antigen-stimulated T cell activation. IL-2 Signaling Pathway Interleukin 2 (IL-2) is a potent cytokine that can lead to cellular activation and proliferation. IL-2 Receptors are found on activated B-Cells, LPS treated Monocytes, and many T cells. The receptor is formed from three chains alpha (CD25), beta (CD122), and gamma (CD132). Primary signaling is through the JAK/Stat pathway and MAPKs. IL-3 Signaling Pathway Interleukin-3 promotes the proliferation and differentiation of hematopoietic cells through binding to its receptor. The receptor for IL-3 is a heterodimer with a ligand-specific alpha chain (70 kD, CD123) and a common beta chain (shared with IL-5 and GM-CSF). Signaling is believed to be primarily through Stat5 and the MAPK pathways. IL-4 Signaling Pathway Interleukin 4 (IL-4) is a cytokine that can lead to development of Th2 cells. The 140 kD IL-4 Receptor (CD124) is found on many cell types, even those of non-hematopoietic origen. The receptor is formed from two chains: IL-4R(alpha) and the IL-2R gamma chain (CD132). Primary signaling is through the JAK/Stat6 pathway and MAPKs. IL-6 Signaling Pathway Interleukin-6 (IL-6) is a cytokine that provokes a broad range of cellular and physiological responses. In addition to playing a role in inflammation and hematopoiesis, IL-6 is involved in other processes such as neuronal differentiation and bone loss. Lectin Induced Signaling Pathway Monocyte and Its Surface Molecules Monocytes are a class of phagocytes involved in non-specific immune defense that develop into macrophages. In plasma, monocytes ingest and destroy bacteria, and can form macrophages when they enter the extracellular space in tissues.Monocytes are a class of phagocytes involved in non-specific immune defense that develop into macrophages. In plasma, monocytes ingest and destroy bacteria, and can form macrophages when they enter the extracellular space in tissues. MSP/Ron Receptor Signaling Pathway MSP, macrophage-stimulating protein, acts through the transmembrane receptor kinase RON (Stk in mice) to play a role in inflammation and the response to tissue injury. MSP is secreted by the liver into the blood as pro-MSP, an inactive precursor form. Neuropeptides VIP and PACAP inhibit the apoptosis of activated T cells Vasoactive intestinal peptide (VIP) and the structurally related pituitary adenylate cyclase-activating polypeptide (PACAP), two neuropeptides present in the lymphoid microenvironment, elicit a broad spectrum of biological functions, including the modulation of innate and adaptive immunity. Neutrophil and Its Surface Molecules OX40 ( CD134 Signaling ) OX40 (CD134) is also known as Tumor Necrosis Factor Receptor Super Family member 5. Proteolysis and Signaling Pathway of Notch  NK (natural killer) cells are lymphocytes distinct from B and T cells that induce perforin-mediated lysis of tumor cells and virus-infected cells. NK cell-mediated cytotoxicity is activated by glycoproteins on the cell surface (activating receptors) and inhibited by MHC-1 with self-peptide bound. Ras-Independent pathway in NK cell-mediated cytotoxicity NK (natural killer) cells are lymphocytes distinct from B and T cells that induce perforin-mediated lysis of tumor cells and virus-infected cells. NK cell-mediated cytotoxicity is activated by glycoproteins on the cell surface (activating receptors) and inhibited by MHC-1 with self-peptide bound. TACI and BCMA signal transduction pathway that enhance cell survival TACI and BCMA signal transduction pathway that enhances cell survival APRIL and BAFF (also called TALL-I and BLyS) are TNF family members that act as ligands for the BCMA and TACI receptors. Both APRIL and BAFF bind to both the BCMA and TACI receptors to activate the humoral immune response, stimulating B cell immunoglobulin production and proliferation. T Cell Apoptosis T Cytotoxic Cell Surface Molecules T Helper Cell Surface Molecules TCR Signaling Pathway The T Cell Receptor plays a key role in the immune system. The specificity of the receptor is governed by the binding site formed from the mature alpha and beta chains (shown here) or gamma and delta chains in gamma/delta T Cells. It is the ability of this receptor to bind a complex of foreign peptide in the groove of an MHC molecule that leads to T cell activation. Upon activation the T cell can assist in activating other cells or carry out cytolytic attacks depending on the particular T cell type. The CD3 complex and CD4 (Th cells) or CD8 (Tc cells) work to transmit the activation signal to the T cell's transcriptional machinary upon engagement of the receptor. Th1/Th2 Differentiation The Co-Stimulatory Signal During T-cell Activation Toll-like Receptor The innate immune response responds in a general manner to factors present in invading pathogens. Bacterial factors such as lipopolysaccharides (LPS, endotoxin), bacterial lipoproteins, peptidoglycans and also CpG nucleic acids activate innate immunity as well as stimulating the antigen-specific immune response and triggering the inflammatory response.

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