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Phagocytic Cells and The Reticuloendothelial System (RES), Study notes of Physiology

Madhya Pradesh Medical Science UniversityPhysiology

A comprehensive overview of phagocytic cells and the reticuloendothelial system (res), which are crucial components of the immune system. It covers the different types of phagocytic cells, their functions, and the mechanisms of phagocytosis. The document also discusses the clinical relevance of phagocytic cells, including their role in immunodeficiencies, autoimmune diseases, cancer, and atherosclerosis. Additionally, it explores future research directions related to phagocytosis in aging, neurodegenerative diseases, and the potential for enhancing phagocytic function. The detailed information presented in this document could be valuable for students and researchers interested in immunology, cell biology, and the pathophysiology of various diseases.

Typology: Study notes

2023/2024

Available from 08/14/2024

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Phagocytic Cells and The Reticuloendothelial System (RES)
1. Phagocytic Cells Overview
Phagocytic cells are crucial components of the immune system. Their primary function is to
engulf and digest cellular debris, foreign substances, microbes, and cancer cells in a process
known as phagocytosis. These cells are essential for maintaining homeostasis and defending
the body against infections.
Types of Phagocytic Cells:
Neutrophils:
oThe most abundant type of white blood cells.
oFirst responders to infection sites.
oThey ingest and destroy bacteria and fungi.
Macrophages:
oDerived from monocytes that migrate from the bloodstream to tissues.
oPresent in virtually all tissues and are known by various names depending on
the tissue (e.g., Kupffer cells in the liver, alveolar macrophages in the lungs).
oInvolved in both innate and adaptive immunity.
oThey clear dead cells, pathogens, and present antigens to T cells.
Dendritic Cells:
oAct as messengers between the innate and adaptive immune systems.
oCapture antigens and present them to T cells in lymph nodes.
oFound in tissues that are in contact with the external environment (e.g., skin,
mucosal linings).
Eosinophils:
oPlay a role in combating multicellular parasites and certain infections.
oAlso involved in allergic reactions.
oThey release enzymes and toxic proteins that can kill parasites but may also
contribute to tissue damage during allergic responses.
Basophils and Mast Cells:
oLess commonly involved in phagocytosis but play a role in allergic reactions
and inflammation.
oRelease histamine and other mediators that contribute to the inflammatory
response.
2. The Reticuloendothelial System (RES)
The Reticuloendothelial System, also known as the Mononuclear Phagocyte System (MPS),
is a network of cells and tissues involved in phagocytosis and immune surveillance. It is
composed mainly of monocytes and macrophages located throughout the body in various
tissues.
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Phagocytic Cells and The Reticuloendothelial System (RES)

1. Phagocytic Cells Overview Phagocytic cells are crucial components of the immune system. Their primary function is to engulf and digest cellular debris, foreign substances, microbes, and cancer cells in a process known as phagocytosis. These cells are essential for maintaining homeostasis and defending the body against infections. Types of Phagocytic Cells:Neutrophils: o The most abundant type of white blood cells. o First responders to infection sites. o They ingest and destroy bacteria and fungi.  Macrophages: o Derived from monocytes that migrate from the bloodstream to tissues. o Present in virtually all tissues and are known by various names depending on the tissue (e.g., Kupffer cells in the liver, alveolar macrophages in the lungs). o Involved in both innate and adaptive immunity. o They clear dead cells, pathogens, and present antigens to T cells.  Dendritic Cells: o Act as messengers between the innate and adaptive immune systems. o Capture antigens and present them to T cells in lymph nodes. o Found in tissues that are in contact with the external environment (e.g., skin, mucosal linings).  Eosinophils: o Play a role in combating multicellular parasites and certain infections. o Also involved in allergic reactions. o They release enzymes and toxic proteins that can kill parasites but may also contribute to tissue damage during allergic responses.  Basophils and Mast Cells: o Less commonly involved in phagocytosis but play a role in allergic reactions and inflammation. o Release histamine and other mediators that contribute to the inflammatory response. 2. The Reticuloendothelial System (RES) The Reticuloendothelial System, also known as the Mononuclear Phagocyte System (MPS), is a network of cells and tissues involved in phagocytosis and immune surveillance. It is composed mainly of monocytes and macrophages located throughout the body in various tissues.

Key Components of RES:Monocytes: o Circulate in the bloodstream and migrate to tissues where they differentiate into macrophages or dendritic cells. o Act as a reservoir of phagocytic cells that can be recruited to sites of infection or injury.  Macrophages in Different Tissues: o Kupffer Cells: Liver macrophages that help clear pathogens from the blood. o Alveolar Macrophages: Present in the lungs, involved in clearing inhaled particles and pathogens. o Microglia: Macrophages in the central nervous system, involved in clearing dead cells and debris. o Osteoclasts: Bone-resorbing cells that are derived from macrophage precursors, involved in bone remodeling. Functions of the RES:Phagocytosis: Engulfing and digesting pathogens, dead cells, and debris.  Antigen Presentation: Processing and presenting antigens to T cells to initiate an adaptive immune response.  Cytokine Production: Secreting cytokines that modulate immune responses and inflammation.  Homeostasis Maintenance: Clearing apoptotic cells and maintaining tissue homeostasis.

3. Mechanism of PhagocytosisChemotaxis: Phagocytic cells are attracted to the site of infection or injury by chemokines and other signaling molecules.  Adherence: Phagocytes recognize and bind to pathogens via pattern recognition receptors (PRRs) that detect pathogen-associated molecular patterns (PAMPs) or opsonins (antibody or complement-coated pathogens).  Ingestion: The phagocyte engulfs the pathogen or debris by extending pseudopodia around it, forming a phagosome.  Digestion: The phagosome fuses with lysosomes to form a phagolysosome, where enzymes and reactive oxygen species digest the contents.  Exocytosis: The digested material is expelled from the cell, or the antigenic fragments are presented on the cell surface. 4. Clinical RelevanceDefects in Phagocytosis: Can lead to increased susceptibility to infections and chronic inflammatory diseases.  Autoimmune Diseases: Abnormal phagocytic activity can contribute to the pathogenesis of autoimmune diseases, where the body's immune system attacks its tissues.  Cancer: Tumor-associated macrophages (TAMs) can promote tumor growth and suppress immune responses against cancer cells.

**d. Antigen Presentation:Major Histocompatibility Complex (MHC): o Fragments of the digested pathogen, especially peptides, are loaded onto MHC molecules. o MHC Class II: Presents antigens to CD4+ helper T cells, primarily by professional antigen-presenting cells (APCs) like dendritic cells and macrophages. o MHC Class I: Presents intracellular antigens to CD8+ cytotoxic T cells, primarily by all nucleated cells.  Role in Adaptive Immunity: o The presentation of antigens on MHC molecules is crucial for the activation of T cells, which are central to the adaptive immune response.

  1. Specialized Phagocytic Cells and Their Functions **a. Tissue-Specific Macrophages:  Kupffer Cells (Liver): o Involved in clearing pathogens and toxins from the portal blood. o Play a role in lipid metabolism and iron recycling.  Microglia (CNS): o Act as the primary immune defense in the central nervous system. o Involved in synaptic pruning during development and response to CNS injury or infection.  Alveolar Macrophages (Lungs): o Patrol the air spaces of the lungs, clearing inhaled pathogens and particulate matter. o Secrete surfactant proteins that have antimicrobial properties.  Osteoclasts (Bone): o Specialized cells that resorb bone tissue during growth and repair. o Derived from monocyte/macrophage lineage and are involved in maintaining bone homeostasis.
  2. Reticuloendothelial System (RES) Functions Beyond Phagocytosis **a. Iron Metabolism:  Heme Recycling: o Macrophages, especially in the spleen and liver, break down aged red blood cells, recycling iron from hemoglobin for reuse in the body.  Storage and Release: o Macrophages store iron in the form of ferritin and release it when needed for erythropoiesis (red blood cell production) or other processes.

**b. Lipid Metabolism:  Clearance of Lipoproteins: o Macrophages are involved in the clearance of modified low-density lipoproteins (LDL), preventing the formation of foam cells and atherosclerotic plaques. Role in Inflammation:  Macrophages secrete pro-inflammatory cytokines (e.g., TNF-α, IL-1, IL-6) in response to lipid accumulation, contributing to the development of atherosclerosis.

  1. Regulation of Phagocytic Activity **a. Cytokines and Chemokines:  Pro-inflammatory Cytokines: o Molecules such as TNF-α, IL-1, and IL-6 enhance the phagocytic activity of macrophages and neutrophils.  Anti-inflammatory Cytokines: o IL-10 and TGF-β act to dampen the inflammatory response, preventing excessive tissue damage. **b. Apoptosis and Clearance:  Efficient Removal: o Macrophages recognize and clear apoptotic cells, preventing the release of potentially harmful intracellular contents.  Immunological Silence: o The phagocytosis of apoptotic cells is typically non-inflammatory, promoting tissue repair and resolution of inflammation.
  2. Clinical Implications **a. Immunodeficiencies:  Chronic Granulomatous Disease (CGD): o A genetic disorder affecting NADPH oxidase, leading to defective ROS production and impaired bacterial killing. o Patients with CGD are prone to recurrent bacterial and fungal infections.  Leukocyte Adhesion Deficiency (LAD): o A defect in the adhesion molecules required for leukocytes to migrate to infection sites. o Results in impaired wound healing and recurrent infections. **b. Autoimmune and Inflammatory Diseases:  Rheumatoid Arthritis: