NEW BASOPHILS AND MAST CELLS

• Basophils

  True leukocytes = mature in the bone marrow
• Basophils


  • Circulate in the blood as mature cells with granules
  • Least numerous of the WBCs
  • Percentage of Circulating Leukocytes: 0% to 2%
  • Percentage of Nucleated Cells in Bone Marrow: Less than 1%
• Function of Basophils

  Play a role in immune response, particularly in allergic reactions and parasitic infections
• Basophil Development

  1. Derived from progenitors in the bone marrow

  2. Cell differentiation = Influenced by cytokines, particularly IL-3
• Immature Basophils

  • Nuclei: Round to somewhat lobulated with slightly condensed chromatin. Nucleoli may be present
  • Cytoplasm: Blue, containing large blue-black secondary granules
  • Primary Granules: Azure granules may or may not be seen
  • Granules: Water-soluble and may dissolve during staining, making them difficult to observe
• Mature Basophils

  • Nucleus: Lobulated, often obscured by granules. Visible chromatin pattern is clumped. Nuclear segmentation with visible filaments is rare
  • Cytoplasm: Colorless, containing large blue-black granules
  • Granules: Large blue-black granules, characteristic of mature basophils. If dissolved during staining, they leave a reddish-purple rim
• Basophil Kinetics

  Life Span: About 60 hours<|>Extended Life Span: Activated by IL-3, anti-apoptotic pathways prolong life span
• Functions of Basophils

  1. Involved in allergic reactions and parasitic infections

  2. Important in both innate and adaptive immunity

  3. Releasing large quantities of subtype 2 helper T cell (TH2) cytokines such as IL-4 and IL-13 that regulate the TH2 immune response

  4. Induce B cells to synthesize IgE
• Initiation of Allergic Inflammation

  1. IgE Receptors: Basophils have IgE receptors on their surface

  2. Activation by Antigen Cross-Linking: When antigens cross-link these receptors, it triggers granule release

  3. Non-IgE Mediated Activation: Can also be activated by parasitic antigens, lectins, and viral superantigens binding to nonspecific IgE antibodies
• Mediator Synthesis and Release

  1. Granule Proteins: Basophils can synthesize granule proteins in response to activation signals

  2. Granzyme B: Mediator of allergic inflammation

  3. Retinoic Acid: Regulator of immune and resident cells in allergic diseases, induced by mast cells

  4. VEGF (Vascular Endothelial Growth Factor): Basophils express VEGF and its receptors, contributing to angiogenesis
• Induction of IgE Synthesis

  B Cell Interaction: Basophils induce B cells to synthesize IgE, enhancing the allergic response
• Role in Helminth Infections

  1. Promotion of Eosinophilia: Basophils help increase eosinophil levels during helminth infections

  2. Macrophage Differentiation: Assist in the differentiation of alternatively activated macrophages in the lung

  3. Worm Expulsion: Contribute to efficient expulsion of worms
• Role in Acquired Immunity

  Tick Immunity: Basophils play a nonredundant role in mediating acquired immunity against ticks, as indicated by studies using basophil-deficient mouse models
• Basophil Activation Mechanisms

  1. Antigen-Specific Activation: IgE Cross-Linking: Specific antigens cross-link IgE receptors, triggering degranulation and cytokine release

  2. Non-Specific Activation: Parasitic Antigens: Bind to nonspecific IgE antibodies

  3. Lectins and Viral Superantigens: Can activate basophils in nonsensitized individuals
• Substances Released by Activated Basophils

  • Cytokines: IL-4, IL-13 (regulate TH2 response)
  • Granzyme B: Mediator of allergic inflammation
  • Retinoic Acid: Regulator in allergic diseases
  • VEGF: Involved in angiogenesis
• Basophil-Deficient Mouse Models: Helped in understanding the unique and nonredundant roles of basophils in immune responses
• Mast Cells


  Not considered leukocytes but tissue effector cells of allergic responses and inflammatory reactions<|>Derived from bone marrow and spleen progenitors<|>Major cytokine responsible for maturation is KIT ligand (stem cell factor). Maturation completes in the tissue microenvironment<|>Play roles in both innate and adaptive immunity, including allergic reactions and inflammation
• Mast Cell Activation and Mediators

  1. IgE-Mediated Activation: Cross-linking of IgE on the mast cell surface by specific allergens

  2. Mediators Released: Lipid Mediators: Leukotrienes and prostaglandins, which contribute to inflammation

  3. Proteases: Enzymes like tryptase and chymase, which degrade proteins and aid in tissue remodeling

  4. Proteoglycans: Heparin, which prevents blood clotting and facilitates mediator storage in granules

  5. Cytokines: Various interleukins (IL-4, IL-5, IL-6, IL-13) and tumor necrosis factor-alpha (TNF-α), which promote inflammation and immune response

  6. Non-IgE-Mediated Activation: Can be triggered by other stimuli, such as cytokines, physical injury, and pathogens

  7. Mediators Released: Similar to those in IgE-mediated activation, leading to inflammatory reactions
• Functions of Mast Cells in Immunity

  1. Innate Immunity: Inflammatory Response: Release of mediators contributes to the recruitment of other immune cells to the site of infection or injury

  2. Antimicrobial Activity: Release of proteases and other mediators can directly kill pathogens

  3. Adaptive Immunity: Antigen Presentation: Mast cells can function as antigen-presenting cells (APCs): presenting antigens to T cells and inducing differentiation of TH2 cells

  4. Cytokine Production: Production of cytokines that influence the differentiation and activity of various immune cells, including T cells and B cells
• Anti-Inflammatory and Immunosuppressive Functions of Mast Cells

  Regulatory Role: Mast cells can release anti-inflammatory cytokines (e.g., IL-10) and other mediators that suppress the immune response