2.3 Leukocyte trafficking and lymphatic system
3 min read•july 25, 2024
Leukocyte trafficking is a vital process in the immune system. It involves a complex dance of cells moving from blood to tissues, guided by adhesion molecules and chemokines. This intricate system ensures immune cells reach their intended destinations to fight infections and maintain surveillance.
The lymphatic system plays a crucial role in immune function. It acts as a highway for immune cells and antigens, connecting tissues to . This network allows for efficient immune responses and helps maintain fluid balance in the body.
Leukocyte Trafficking
Mechanisms of leukocyte trafficking
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Top images from around the web for Mechanisms of leukocyte trafficking
Frontiers | Vascular Endothelial Galectins in Leukocyte Trafficking View original
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Frontiers | Leucocyte Trafficking via the Lymphatic Vasculature— Mechanisms and Consequences View original
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- Leukocyte adhesion cascade orchestrates leukocyte migration from blood to tissues
- Tethering and rolling mediated by selectins slows leukocytes in bloodstream
- Activation triggered by chemokines enhances integrin affinity
- Firm adhesion achieved through integrin-ligand interactions
- Transmigration () allows leukocytes to squeeze between endothelial cells
- Adhesion molecules facilitate cell-cell interactions during trafficking
- Selectins (E-selectin, P-selectin, L-selectin) mediate initial rolling
- Integrins (LFA-1, VLA-4) enable firm adhesion to endothelium
- Immunoglobulin superfamily (ICAM-1, VCAM-1) serve as ligands for integrins
- Chemokines guide leukocytes to specific tissues
- Classification based on cysteine motifs (CC, CXC, CX3C, XC)
- Chemokine receptors (G protein-coupled receptors) transduce signals
- Chemokine gradients direct cell movement towards higher concentrations
- Endothelial cell activation upregulates adhesion molecules
- Cytokine-induced expression of E-selectin, ICAM-1, VCAM-1
- Shear stress and blood flow dynamics influence leukocyte adhesion and rolling
Lymphatic System
Structure and function of lymphatic system
- form network for fluid and cell transport
- Initial lymphatics (lymphatic capillaries) absorb interstitial fluid
- Collecting lymphatics propel lymph towards lymph nodes
- Lymph nodes filter lymph and initiate immune responses
- Lymph composition mirrors interstitial fluid, contains immune cells
- Antigen transport crucial for immune surveillance
- Soluble antigens carried by lymph flow
- Cell-associated antigens transported by dendritic cells
- Immune surveillance maintained through cell migration
- Dendritic cells migrate from tissues to lymph nodes
- Lymphocyte recirculation between blood and lymphoid organs
- Secondary lymphoid organs organize immune responses
- Lymph nodes strategically located throughout body
- Spleen filters blood-borne antigens
- Mucosal-associated lymphoid tissues (MALT) protect mucous membranes (tonsils, Peyer's patches)
High endothelial venules in lymphocyte homing
- Structure of HEVs specialized for lymphocyte
- Specialized endothelial cells with distinctive cuboidal shape
- Located in paracortex of lymph nodes for efficient lymphocyte entry
- Adhesion molecules on HEVs capture circulating lymphocytes
- PNAd (peripheral node addressin) binds L-selectin
- MAdCAM-1 (mucosal addressin cell adhesion molecule 1) interacts with integrin
- Lymphocyte receptors ensure tissue-specific migration
- L-selectin (CD62L) mediates initial tethering to HEVs
- integrin targets gut-associated lymphoid tissue
- Chemokines guide lymphocytes across HEVs
- CCL21 attracts naive T cells and dendritic cells
- CXCL12 promotes B cell migration
- Lymphocyte extravasation through HEVs follows multistep adhesion cascade
- HEV phenotype regulated by local microenvironment and lymphotoxin signaling
Lymphatic vessels for fluid drainage
- Interstitial fluid dynamics governed by Starling forces
- Balance between hydrostatic and oncotic pressures
- Tissue hydrostatic pressure influences lymph formation
- Lymphatic vessel structure optimized for fluid uptake
- Specialized endothelial cells form button-like junctions
- Discontinuous basement membrane allows fluid entry
- Anchoring filaments prevent vessel collapse under pressure
- Lymph formation and propulsion maintain fluid balance
- Primary valves in initial lymphatics prevent backflow
- Secondary valves in collecting lymphatics ensure unidirectional flow
- Intrinsic (lymphatic muscle contraction) and extrinsic (skeletal muscle movement) pumping mechanisms
- Immune cell migration through lymphatics crucial for immune surveillance
- Dendritic cells use CCR7-dependent mechanisms
- T cells and B cells recirculate via afferent lymphatics
- Lymphangiogenesis expands lymphatic network
- VEGF-C and VEGF-D signaling stimulates lymphatic endothelial cell proliferation
- Lymphedema impairs immune function due to compromised fluid drainage and cell trafficking
Key Terms to Review (14)
Autoimmune diseases: Autoimmune diseases are conditions where the immune system mistakenly attacks the body's own cells and tissues, treating them as foreign invaders. This misdirected immune response can lead to inflammation and damage in various organs, highlighting the complex interplay between immune regulation, self-tolerance, and disease pathogenesis.
Cell Migration Signaling: Cell migration signaling refers to the complex network of molecular signals that guide the movement of cells, particularly immune cells, to sites of inflammation or injury. This process is crucial for leukocyte trafficking, which enables immune cells to respond effectively to pathogens and participate in tissue repair. Understanding these signals helps clarify how the lymphatic system supports immune cell navigation throughout the body.
Chemotaxis: Chemotaxis is the movement of cells towards or away from a chemical stimulus, often used by immune cells to locate sites of infection or inflammation. This process is crucial for the functioning of the immune system, as it directs leukocytes to areas where they are needed most to fight off pathogens and initiate repair processes.
Chronic Inflammation: Chronic inflammation is a prolonged and persistent inflammatory response that can last for months or even years, resulting in tissue damage and a variety of diseases. Unlike acute inflammation, which is a short-term and protective response to injury or infection, chronic inflammation often arises from the body's failure to eliminate the initial cause of inflammation, leading to continuous tissue injury and remodeling. This process is closely linked to various immune system activities, including leukocyte trafficking and the role of the lymphatic system in managing immune responses.
Diapedesis: Diapedesis is the process by which leukocytes (white blood cells) move out of the bloodstream and into surrounding tissues, allowing them to reach sites of infection or injury. This movement is crucial for immune response and inflammation, enabling leukocytes to migrate to areas where they are needed to combat pathogens and facilitate tissue repair.
Endothelial Adhesion: Endothelial adhesion refers to the process by which leukocytes (white blood cells) attach to the endothelial cells lining blood vessels. This interaction is crucial for the recruitment of leukocytes to sites of inflammation or injury, allowing them to exit the bloodstream and migrate into tissues. Understanding endothelial adhesion helps to explain how the immune system responds to various challenges, including infections and tissue damage.
Extravasation: Extravasation is the process by which leukocytes exit the bloodstream and move into surrounding tissues, a crucial step in the immune response to inflammation or infection. This movement is facilitated by a series of interactions between leukocytes and the endothelial cells lining blood vessels, allowing immune cells to reach sites where they are needed to combat pathogens or facilitate tissue repair.
Homing: Homing refers to the process by which leukocytes (white blood cells) navigate through the bloodstream and lymphatic system to reach specific tissues or sites of infection or inflammation. This directed movement is crucial for effective immune responses, allowing cells to locate and respond to pathogens or damaged tissues efficiently. Understanding homing is essential for grasping how the immune system maintains surveillance and manages tissue repair and immune defense.
IL-8: IL-8, also known as Interleukin-8, is a chemokine primarily produced by macrophages and other immune cells that acts as a potent attractant for neutrophils to sites of inflammation. This protein plays a crucial role in the immune response by mediating the trafficking and activation of leukocytes, helping direct them to areas where they are needed to combat infection or injury. Its significance extends to various diseases, including those involving chronic inflammation and autoimmune disorders.
Lymph Nodes: Lymph nodes are small, bean-shaped structures that are essential components of the lymphatic system and play a crucial role in the immune response. They act as filters for lymph fluid, trapping pathogens and foreign particles while housing immune cells that can respond to infections. These nodes are strategically located throughout the body, often clustered in areas such as the neck, armpits, and groin, enabling them to monitor and manage immune responses effectively.
Lymphatic vessels: Lymphatic vessels are a network of thin-walled tubes that transport lymph, a clear fluid containing immune cells, throughout the body. These vessels are integral to the immune system as they facilitate the movement of leukocytes and other immune components to and from lymph nodes, helping maintain fluid balance and support immune responses.
Neutrophils: Neutrophils are a type of white blood cell that plays a vital role in the innate immune response, acting as the first line of defense against invading pathogens. They are essential for responding quickly to infections, especially bacterial and fungal, and are characterized by their ability to migrate to sites of inflammation and infection through the bloodstream and tissues.
Signal Transduction: Signal transduction is the process by which a cell converts an external signal into a functional response, often involving a series of molecular events. This complex communication system allows cells to respond to various stimuli, including hormones, cytokines, and antigens, leading to cellular changes such as movement, activation, or differentiation. It plays a crucial role in various physiological processes, including immune responses, where it facilitates leukocyte trafficking, T cell activation, and B cell receptor signaling.
Vascular permeability: Vascular permeability refers to the ability of blood vessel walls to allow the passage of substances, such as fluids, proteins, and cells, into and out of the surrounding tissue. This process is essential for maintaining homeostasis and facilitating immune responses, particularly during inflammation when leukocytes need to migrate to sites of infection or injury.