Lecture 03: Overview of Inflammatory Response in Immunology [SEQ 2]

Chemokines are a sub-group of cytokines that play a crucial role in leukocyte recruitment during inflammation. They act as chemoattractants, attracting leukocytes to the site of inflammation by creating a concentration gradient. Unlike other cytokines, chemokines specifically affect the mobilization of cells, causing them to adhere to endothelial cells, alter their movement, and migrate towards the chemokine gradient. Their structure is characterized by conserved cysteine residues, specifically CC or CXC, which determines their target leukocyte types.

During inflammation, endothelial cells express ICAMs (intercellular adhesion molecules), which bind to integrins on leukocytes. Initially, the interaction is weak, but cytokines trigger leukocytes to express high-affinity integrins, strengthening the bond. This firm adhesion allows leukocytes to stop and spread, preparing for diapedesis. Diapedesis, the process of leukocytes exiting the bloodstream, is then facilitated by the breakdown of endothelial cell junctions, allowing the leukocytes to pass through the vessel wall into tissue.

TNF (Tumor Necrosis Factor) and IL-1 (Interleukin-1) are proinflammatory cytokines that play crucial roles in leukocyte recruitment and activation. Released by macrophages and other cells, they trigger endothelial cells to express ICAMs , adhesion molecules that bind to leukocytes. They also induce the expression of chemokines, which attract specific leukocytes to the site of inflammation. Moreover, both TNF and IL-1 enhance the expression of integrins on leukocytes, further strengthening their adherence to endothelial cells, ultimately paving the way for diapedesis and leukocyte accumulation in tissues.

<p>Cytokine signaling is a complex process that involves multiple stages. It begins with an inducing stimulus, such as an infection or tissue damage. This stimulus triggers the cytokine-producing cell to activate its cytokine gene, leading to the production and secretion of the cytokine. The cytokine then travels to target cells, where it binds to its specific receptor. This binding initiates a signaling cascade, activating intracellular pathways that ultimately lead to the activation or suppression of genes, enzymes, and other cellular processes. This results in the biological effect, such as cell proliferation, differentiation, or death. In inflammation, cytokines play crucial roles in leukocyte activation, recruitment, and the overall inflammatory response.</p> Signup and view all the answers

<p>Cytokines are crucial for communication within the immune system. They perform a range of functions, including: - Changing cell adhesiveness: regulating the attachment and movement of immune cells, such as leukocytes. - Affecting enzyme activity: activating or inhibiting specific enzymes involved in immune processes. - Determining cell fate: regulating cell survival, growth, and death. - Altering gene expression: influencing the production of proteins involved in the immune response. These diverse functions contribute to the overall immune response by orchestrating the activation, differentiation, and recruitment of immune cells, leading to the elimination of pathogens and the restoration of tissue homeostasis.</p> Signup and view all the answers

<p>Extravasation is the process of immune cells exiting the bloodstream and entering the site of inflammation. It involves two main steps: rolling and adhesion. During rolling, neutrophils are activated by TNF released from endothelial cells, causing the expression of selectin molecules on the endothelial surface. Selectins bind to sugar molecules on the neutrophil surface, allowing for weak attachment and rolling. Adhesion is then initiated by stronger interactions between integrins on neutrophils and intercellular adhesion molecule-1 (ICAM-1) on endothelial cells. This firm adhesion allows neutrophils to stop rolling and firmly attach, eventually squeezing through the endothelial junctions and entering the inflamed tissue.</p> Signup and view all the answers

<p>Mast cells, residing in tissues, play a critical role in orchestrating the inflammatory response. Upon activation by PAMPS, cytokines, or antibodies, they release histamine and other inflammatory mediators. Histamine causes vasodilation by widening blood vessels, increasing blood flow to the area, leading to redness and heat. Additionally, histamine increases vascular permeability by widening the junctions between endothelial cells, allowing fluid and plasma proteins to leak into the tissue, resulting in swelling and edema. This increased vascular permeability also facilitates the recruitment of immune cells to the site of inflammation.</p> Signup and view all the answers

<p>Neutrophils and macrophages are both phagocytic cells that play vital roles in the inflammatory response. Neutrophils are the most abundant leukocytes and circulate in the blood, having a short lifespan of approximately 8 hours. They are the first responders to infection and injury, rapidly migrating to the site of inflammation and engulfing pathogens and cellular debris. Macrophages, on the other hand, are resident cells found in various tissues, including skin, lungs, and gastrointestinal tract. They have a longer lifespan than neutrophils and perform a variety of functions including phagocytosis, antigen presentation, and cytokine production. While both cells are phagocytic, neutrophils are primarily involved in early pathogen clearance, while macrophages play a key role in initiating tissue repair and orchestrating the adaptive immune response.</p> Signup and view all the answers

<p>Pattern recognition receptors (PRRs) are expressed on innate immune cells, such as macrophages and neutrophils, and act as sensors for pathogen-associated molecular patterns (PAMPS). PAMPS are conserved molecular structures found on microbes but not on host cells. When PRRs recognize PAMPS, they trigger a signaling cascade that activates innate immune cells. This activation results in the production and release of inflammatory mediators, such as cytokines and chemokines, initiating the inflammatory response. The recognition of PAMPS by PRRs ensures that the innate immune system can quickly and effectively respond to invading pathogens.</p> Signup and view all the answers

<p>The acute inflammatory response is a rapid and short-term response to injury or infection, characterized by the cardinal signs of redness, swelling, pain, and heat. This response is mediated by the release of inflammatory mediators and the recruitment of immune cells, primarily neutrophils, to the site of inflammation. Examples of acute inflammation include a cut on the finger or a bacterial infection. The chronic inflammatory response, on the other hand, is a persistent and long-term response to chronic injury or infection. It is characterized by the sustained presence of inflammatory cells, including macrophages, lymphocytes, and fibroblasts, and tissue destruction and fibrosis. Examples of chronic inflammation include arthritis and inflammatory bowel disease.</p> Signup and view all the answers

<p>Dendritic cells, resident in tissues, act as sentinels of the immune system, detecting danger signals and presenting antigen to T cells. They express PRRs that recognize PAMPS and danger-associated molecular patterns (DAMPs) released from damaged cells. Upon activation, they capture and process antigens from pathogens or damaged cells. They then migrate to lymph nodes, where they present these antigens to T cells, initiating an adaptive immune response. By bridging the innate and adaptive immune systems, dendritic cells play a critical role in orchestrating a targeted and specific immune response against pathogens.</p> Signup and view all the answers

<p>The release of inflammatory mediators, including cytokines, chemokines, and histamine, is crucial for orchestrating the inflammatory response. Cytokines, such as TNF-α and IL-1, are released from activated immune cells and induce a variety of effects, including vasodilation, increased vascular permeability, and fever. Chemokines, such as IL-8, act as chemoattractants, guiding neutrophils and other immune cells to the site of inflammation. Histamine, released from mast cells, further enhances vasodilation and vascular permeability, facilitating the entry of immune cells into the inflamed tissue. The coordinated release of these mediators ensures a rapid and efficient recruitment of immune cells to the site of infection or injury, enabling an effective inflammatory response.</p> Signup and view all the answers

<p>The complement system is a crucial part of the innate immune system, playing a significant role in the inflammatory response. Complement activation is triggered by the presence of pathogens or antibodies bound to pathogens. This activation leads to the generation of a series of protein fragments, including C3a and C5a. These fragments are potent inflammatory mediators, attracting neutrophils and other immune cells to the site of infection. Additionally, activated complement proteins can directly lyse bacterial cells, contributing to pathogen destruction. The complement system acts as a bridge between the innate and adaptive immune responses, enhancing the inflammatory response and facilitating pathogen clearance.</p> Signup and view all the answers

Signaling proteins that mediate communication in the immune response.

Process of leukocytes moving through endothelial cell junctions into tissues.

Subgroup of cytokines that act as chemoattractants to recruit cells.

Proteins on leukocytes that interact with ICAMs on endothelial cells for strong adhesion.

A proinflammatory cytokine released by macrophages and epithelial cells.

A complex cascade of immune reactions at the site of infection characterized by redness, swelling, pain, and heat.

The four primary indicators of inflammation: redness, swelling, pain, and heat.

The most abundant type of white blood cell, circulating in the blood and acting as phagocytes that die after about 8 hours.

Large immune cells that are the first to encounter microbes and act as phagocytes to engulf and digest pathogens.

The widening of blood vessels to increase blood flow to injured tissues, leading to inflammation.

The process where immune cells move from the bloodstream into the tissue during inflammation.

Resident cells in skin and mucosal tissues that release histamine and cytokines during inflammation.