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CYTOKINES Dr Dinesh Kumar Sharma Department of Microbiology Ch. Charan Singh University, Meerut.

[Audio] Cytokines are low-molecular weight regulatory proteins or glycoproteins secreted by white blood cells and various other cells in the body in response to a number of stimuli. These proteins assist in regulating the development of immune effector cells, and some cytokines possess direct effector functions of their own. The term "cytokine" is derived from a combination of two Greek words - "cyto" meaning cell and "kinos" meaning movement. Cytokines are cell signalling molecules that aid cell to cell communication in immune responses and stimulate the movement of cells towards sites of inflammation, infection and trauma. Cytokines exist in peptide, protein and glycoprotein forms. The cytokines are a large family of molecules that are classified in various different ways due to an absence of a unified classification system..

[Audio] Cytokines have high affinity for receptors and are active in picomole amounts. They are primarily produced by the immune system, but other organs like the liver, brain, and endocrine glands also produce them to influence the immune response. As soluble molecules, cytokines interact with their receptors on target cells, causing changes in the expression of adhesion molecules and chemokine receptors, allowing cells to move from one location to another. They can also signal immune cells to alter their effector functions, instructing them when to survive or die. All these processes occur through interactions between cytokines and their receptors, resulting in specific biological responses..

[Audio] Cytokines are small secreted proteins that mediate and regulate immunity, inflammation, and hematopoiesis. Their names were originally based on the activity they described or the cell type they derived from, resulting in a large number of three or four-letter acronyms. Despite this, cytokines play a crucial role in the immune response, acting by binding to specific cell surface receptors and triggering downstream signaling pathways. This process ultimately leads to changes in gene expression, influencing cell proliferation, differentiation, migration, and apoptosis..

[Audio] Cytokines bind to specific receptors on the membranes of target cells, triggering signal transduction pathways that ultimately alter enzyme activity and gene expression. The susceptibility of a target cell to a particular cytokine is determined by the presence of specific membrane receptors. Cytokines regulate the intensity and duration of the immune response by stimulating or inhibiting the activation, proliferation, and/or differentiation of various cells, by regulating the secretion of other cytokines or of antibodies, or in some cases by actually inducing programmed cell death in the target cell..

[Audio] Cytokines play a crucial role in our immune system's response to external stimuli. An inducing stimulus, whether it's an antigen or another cytokine, binds to a receptor on a cell, triggering the secretion of cytokines. These cytokines then interact with receptors on target cells, leading to specific biological effects. For instance, IL-2 can induce proliferation, differentiation, or even cell death, depending on the context. This process enables our immune system to mount an effective response against pathogens, ultimately promoting health and well-being..

[Audio] Cytokines have a crucial role in various cellular processes. They activate T-cells through interleukin-2, which also assists in activating B-cells. Moreover, cytokines can exert paracrine action on nearby cells, whereas they can also act on cells at a distance through endocrine action, transported via the bloodstream. Furthermore, autocrine action enables cytokines to influence the same cell that produced them. These actions underscore the significance of cytokines in diverse biological processes..

[Audio] Cytokines can act on nearby cells through paracrine action, or on distant cells through endocrine action. However, most immune system cytokines exhibit autocrine and/or paracrine action, with fewer exhibiting endocrine action. This means that they primarily interact with cells in their immediate vicinity, rather than being transported throughout the body to affect distant cells..

[Audio] Cytokines can have multiple effects on cells of the same type, but they also affect multiple cell types. This means that cytokines can act in concert on the same cell, influencing its behavior and function..

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[Audio] Cytokine-generating cells play a crucial role in both innate and adaptive immune responses. These cells include macrophages, endothelial cells, fibroblasts, T lymphocytes, macrophages, and natural killer cells. Macrophages, for instance, produce cytokines such as interleukins and tumor necrosis factor, which stimulate the activation of other immune cells. Endothelial cells, on the other hand, secrete cytokines like vascular endothelial growth factor, which promotes angiogenesis and inflammation. Fibroblasts produce cytokines like transforming growth factor beta, which regulates tissue repair and remodeling. T lymphocytes, including CD4+ and CD8+ T cells, generate cytokines like interferon gamma, which activates macrophages and other immune cells. Natural killer cells also produce cytokines like perforin, which mediates cytolysis of infected cells. The cytokines generated by these cells orchestrate the immune response, enabling the body to combat infections and diseases..

[Audio] Cytokines are part of a complex system that regulates the immune system. They are primarily produced by the immune system, but many other organs, including the liver, brain, and endocrine glands, also produce cytokines to influence the immune response..

[Audio] The immune system's cells are under control by a network of cytokine actions. Cytokines play a crucial role in regulating the immune response. They act as messengers between cells, transmitting signals that influence the behavior of immune cells. This network of cytokine interactions helps to coordinate the immune response, ensuring that it is effective against invading pathogens while minimizing damage to healthy tissues. Cytokines like IL-10, IL-2, IFN-γ, TNF-α, and others work together to regulate the immune response, promoting the activation of immune cells, modulating inflammation, and facilitating the clearance of pathogens. This intricate web of cytokine interactions is essential for maintaining immune homeostasis and preventing immunopathology..

[Audio] Cytokines have a vital role in stimulating the activation, differentiation, proliferation, and survival of immune cells like T cells, B cells, macrophages, dendritic cells, natural killer cells, and leukocytes. They also interact with one another and with other cells to regulate their functions. The diagram illustrates the intricate network of interactions between cytokines, immune cells, and other molecules involved in regulating immune responses. This visualization enables us to comprehend how cytokines collaborate to stimulate immune cell activation, differentiation, and function..

[Audio] Cytokines must first bind to specific receptors expressed on the membrane of responsive target cells. This binding event triggers a cascade of signals within the cell, ultimately leading to the activation of downstream pathways and the execution of specific cellular responses. The diversity of cytokine receptors allows them to interact with multiple cytokines, enabling cells to respond to a wide range of stimuli. Furthermore, the expression of different cytokine receptors on distinct cell types enables cells to selectively respond to specific cytokines, thereby allowing for precise regulation of cellular responses..

[Audio] The class I cytokine receptor family comprises receptors functioning in both the immune and hematopoietic systems. These receptors exhibit specific amino acid sequences within their extracellular domains, featuring four conserved cysteine residues and a tryptophan-serine-tryptophan-serine motif. All receptors for hematopoietins belong to this family, also referred to as the hematopoietin receptor family..

[Audio] Cytokines require specific receptors to bind to and initiate their biological responses. The receptor families identified include the immunoglobulin superfamily, class I cytokine receptors, class II cytokine receptors, TNF receptors, and chemokine receptors. These receptors play crucial roles in mediating the actions of various cytokines, including interleukins, interferons, and growth factors. The binding of cytokines to their respective receptors triggers signaling pathways that ultimately lead to changes in cellular behavior, such as proliferation, differentiation, and activation. The diversity of cytokine receptors allows them to interact with multiple ligands, enabling the regulation of various physiological processes..

[Audio] Cytokines play crucial roles in both innate and adaptive immunity. Innate immunity cytokines include Interleukin 1, Tumor Necrosis Factor, Interleukin 12, Interleukin 6, and Interferon. These cytokines are secreted by macrophages, endothelial cells, and fibroblasts..

[Audio] The interleukins are a group of cytokines that were first seen to be expressed by white blood cells, specifically leukocytes. These cytokines can be divided into four major groups based on distinguishing structural features. However, their amino acid sequences show only weak similarity, typically around 15-25% identity. The human genome encodes more than 50 interleukins and related proteins. The term "interleukin" was chosen in 1979 to replace the various different names used by different research groups to designate interleukin 1 and interleukin 2. This term derives from "(inter-)" meaning a means of communication, and "(-leukin)" deriving from the fact that many of these proteins are produced by leukocytes and act on leukocytes..

[Audio] IL-1 is a cytokine produced by macrophages and macrophage-like cells, as well as endothelial and epithelial cells. The two forms of IL-1, IL-α and IL-β, bind to the same receptors with different affinities. During development, IL-1 production up-regulates G-CSF production by monocytes. During inflammation, IL-1 promotes the expression of endothelial adhesive glycoproteins, such as ICAM-1, and stimulates the production of IL-6, IL-8, and other chemokines. Additionally, IL-1, along with TNF-α, induces prostaglandin E2 production in the hypothalamus, leading to increased body temperature..

[Audio] Cytokines play a crucial role in various cellular processes, including cell activation, proliferation, differentiation, and survival. Interleukin-1 (IL-1) and IL-6 stimulate the maturation of immune cells such as macrophages and T-cells. These cytokines promote population expansion of activated cells, leading to increased numbers of immune cells. Activation of these cells results in the production of immunoglobulins, which are essential for humoral immunity. Macrophages undergo increased activation upon exposure to cytokines, leading to enhanced phagocytic activity and cytotoxicity against pathogens. Adequate cytokine signaling is necessary, as deficiencies or dysregulation can impair immune function and increase susceptibility to infections. Cytokines have been implicated in the pathogenesis of various diseases, including autoimmune disorders and cancer. Understanding the interactions between cytokines and their receptors is essential for developing effective therapeutic strategies..

[Audio] Interferons were first discovered in 1957 by Isaacs and Lindenmann through an experiment using chicken cell cultures. They found a substance that interfered with viral replication and was therefore named interferon. Interestingly, Nagano and Kojima also made independent discoveries around the same time, identifying this soluble antiviral protein. This breakthrough discovery marked the beginning of our understanding of the role of interferons in the immune system..

[Audio] When a cell becomes infected with a virus, it releases interferons into the surrounding area, triggering nearby cells to boost their anti-viral defenses. This process helps to prevent the spread of the infection and protect the host from further harm. Interferons also activate immune cells like natural killer cells and macrophages, and increase the expression of major histocompatibility complex antigens on the surface of host cells. These actions help to enhance the body's natural defenses and promote the elimination of pathogens..

[Audio] IFN-alpha and IFN-beta are produced in response to viral infection, while IFN-gamma is induced by the stimulation of sensitized lymphocytes with antigen or non-sensitized lymphocytes with mitogens. IFN inhibits viral replication and exhibits various biological activities, including cell growth inhibition, immunosuppressive effects, and enhancement of macrophage, natural killer cell, and neutrophil functions. Additionally, IFN shows antitumor activity and is involved in the pathogenesis of various diseases. Moreover, IFN is currently being used in clinical therapy against viral infections and certain types of cancer..

[Audio] Interferons play a crucial role in enhancing the function of various immune cells, including B cells, NK cells, and macrophages. They increase the expression of MHC II on these cells, allowing them to present antigens more effectively, leading to increased antimicrobial and antitumor activities. Interferons stimulate the synthesis and expression of Fc-yR receptors on these cells, enabling them to recognize and bind to antibody-coated targets. Moreover, interferons inhibit migration and induce cytotoxic effects, making them an effective tool in combating infection and disease. However, some cytokines, like interferons, can induce delayed hypersensitivity reactions or suppress graft rejection. Overall, interferons play a vital role in regulating the immune response and maintaining homeostasis..

[Audio] "Οι κυτταροκίνες Δρ Δηνέσιος Κουμάρ, Σάρμα από το Τμήμα Μικροβιολογίας του Πανεπιστημίου Ch. Charan Singh στο Meerut παράγουν δύο τύπους ιντερφερόνης: τον τύπο Ι (IFN-α, IFN-β) και τον τύπο II (IFN-γ). Αυτοί οι τύποι παράγονται από μακροφάγους και κύτταρα που έχουν μολυνθεί από ιό. Η ιντερφερόνη αναστέλλει την ιοκυτταρική αναπαραγωγή μέσω των PKR και RNaseL και αυξάνει την έκφραση των MHCI για να βοηθήσει στην κινητοποίηση των Τ-κυττάρων. Επίσης, ενεργοποιεί την παραγωγή IFN-γ από ενεργοποιημένα Τ-κύτταρα και τα NK κύτταρα. Η ιντερφερόνη παράγεται κυρίως από Τh1 κύτταρα και χρησιμοποιείται για την παραγωγή της ICAM στα ενδοθηλιακά κύτταρα και την ενεργοποίηση των NK κυττάρων. Επίσης, αυξάνει την έκφραση των MHCI και MHCII για να βοηθήσει στην αλληλεπίδραση μεταξύ των Τh κυττάρων και των APC. Επιπλέον, προωθεί την διαφοροποίηση των Β κυττάρων σε πλασμακύτταρα και βοηθά στην διαφοροποίηση των κυττάρων διαμέσουύνης της κυτταροτοξικής Τ..

[Audio] When macrophages detect an infection, they release tumor necrosis factor to alert other immune cells and trigger inflammation. This process involves the production of various chemical signals, including myeloid colony-stimulating factors, interferon-gamma, interleukin-6, and other chemokines. The primary function of tumor necrosis factor is to regulate immune cells, inducing fever, apoptosis, and inflammation while inhibiting tumorigenesis and viral replication..

[Audio] TNF-alpha, a pro-inflammatory cytokine, plays a crucial role in the body's response to infection, inflammation, and environmental stressors. Produced primarily by activated macrophages, but also by other cell types, TNF-alpha binds to its receptors, TNF-R1 or TNFR2, to elicit its biological effects. This cytokine is responsible for delivering various signals, including activation signals to neutrophils, endothelial cells, and osteoclasts, as well as increased expression of MHC glycoproteins and adhesion molecules in other cells. There are two members of the TNF family: TNF-alpha and TNF-beta, also known as Lymphotoxin-alpha or LT-alpha. Both are secreted as soluble proteins..

[Audio] TNF-alpha, a cytokine produced by activated macrophages and T-cells in response to microbial stimuli, plays a crucial role in the inflammatory response. It induces the production of various chemokines, including myeloid colony-stimulating factors, interferon-gamma, interleukin-6, and interleukin-8, which attract neutrophils and macrophages to the site of inflammation. TNF-alpha also stimulates the production of adhesion molecules, such as intercellular adhesion molecule-1, on the surface of endothelial cells and macrophages, facilitating the recruitment of these cells to the site of inflammation. Moreover, TNF-alpha causes fever through its direct action or indirectly through the activation of interleukin-1. The production of acute-phase proteins, such as C-reactive protein, is also promoted by TNF-alpha. Its roles have been implicated in various diseases, including rheumatoid arthritis, psoriasis, and tuberculosis..

[Audio] Macrophage activation plays a crucial role in the development of lymphocytes, particularly during the early stages of immune response. Activated macrophages can stimulate the proliferation and differentiation of lymphocytes, leading to the formation of effector cells capable of responding to specific antigens. Furthermore, macrophages can also produce cytokines that promote hematopoiesis, the process by which stem cells differentiate into various blood cell types. This highlights the importance of macrophage activation in the regulation of both adaptive and innate immunity..

[Audio] Chemokines play a crucial role in various biological processes, including angiogenesis and lymphoid organ development. These small proteins are produced by multiple leukocytes and other cell types, forming a large family of over 50 members. Despite their structural diversity, chemokines exhibit significant homology and overlapping functions. They are highly effective chemoattractants for various leukocytes, such as polymorphonuclear neutrophils, T-cells, and B-cells. This property enables them to recruit these immune cells to sites of infection and inflammation, facilitating the body's defense against pathogens. Furthermore, chemokines are involved in lymphocyte trafficking, wound healing, and even metastasis. Their multifaceted roles underscore the importance of understanding their mechanisms of action in maintaining immune homeostasis and responding to disease..

[Audio] Macrophages play a crucial role in regulating hematopoiesis by producing cytokines like M-CSF, which stimulates the growth and differentiation of monocytes into macrophages. This process is vital for preserving the immune system's integrity and ensuring proper blood cell production. The production of M-CSF is controlled by various factors, including IL-3 and SCF, which also influence the development of other hematopoietic lineages. The coordinated action of these cytokines maintains the balance between different hematopoietic cell types, thus preserving homeostasis in the bone marrow..

[Audio] Cytokines play a crucial role in the immune response by regulating the activity of immune cells such as T-cells and macrophages. En cov-es, also known as cytokine receptors, are proteins found on the surface of immune cells that bind to specific cytokines. This binding process triggers various cellular responses, including cell activation, proliferation, and differentiation. The cytokine receptor complex consists of two subunits, alpha and beta, which work together to recognize and respond to cytokines. In this context, IL-3, a type I cytokine, binds to its receptor, GM-CSF, leading to the activation of hematopoietic stem cells and the production of granulocytes. Norvvyte, a cytokine antagonist, can inhibit this process by blocking the binding of IL-3 to its receptor. The expression of cytokines is tightly regulated, with levels of cytokine production varying depending on the presence of antigens, inflammation, or other stimuli. Cytokines have been implicated in various diseases, including autoimmune disorders, cancer, and chronic infections. Understanding the mechanisms of cytokine action is essential for the development of effective therapies targeting these molecules..

[Audio] Cytokines are low-molecular-weight proteins that are produced and secreted by a variety of cell types. They play major roles in the induction and regulation of cellular interactions involving cells of the immune, inflammatory, and hematopoietic systems..

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