Skeletal Muscle Injury Repair

Skeletal Muscle Injury Repair

• Repair Process Following Muscle Strain or Contusion
  • Hemostasis and Hematoma Formation: Initial response to injury involves stopping bleeding and forming a blood clot.
  • Degeneration:
    • Necrosis: Tissue death occurs, with neutrophils being the first responders.
    • Chemotactic Agents: Released to attract inflammatory mediators to the injury site.
  • Inflammation:
    • Begins within 24-48 hours post-injury, crucial for healing.
    • Involves phagocytosis of cellular debris by immune cells.
    • Macrophages stimulate satellite cells to migrate, differentiate, and release various cytokines.
    • T-lymphocytes increase in number as macrophages decline, continuing to release cytokines.
  • Regeneration:
    • Typically occurs 6-8 weeks after the injury, followed by remodeling of the new tissue.
  • Fibrosis: Can develop, leading to less functional muscle tissue, but not always a consequence of injury.

Role of the Basement Membrane in Muscle Healing

• Integrity of Basement Membrane: Essential for regeneration; must remain intact.
  • Satellite Cell Division: Crucial for maintaining the basement membrane's integrity.
    • Satellite cells combine with other myogenic cells and fuse with remaining muscle fibers.
  • Consequences of Damage: If compromised, fibrosis occurs, resulting in decreased functional capacity and increased risk of future injuries.

Effects of Cytokines on Satellite Cells / Muscle Cells During Repair

• Enhanced Resistance to Oxidative Stress: Promotes cell survival during the healing process.
• Block Myofibrogenesis: Prevents irregular muscle fiber formation, leading to improved healing outcomes.
• Proliferation: Stimulates cell division to increase the number of muscle cells.
• Differentiation: Encourages fusion of satellite cells with myofibers for regeneration.
• Angiogenesis: Supports the formation of new blood vessels, ensuring adequate vascular supply to the regenerated muscle tissue.

Immune System Overview

• Innate immunity is non-specific and responds rapidly to pathogens, initiating adaptive immunity.
• Adaptive immunity develops specificity and memory for pathogens, requiring days to weeks for activation.

Key Components of Innate Immunity

• Exterior Defenses: Epithelial barriers, mucosa, and secretions protect against pathogens.
• Cellular Components/Phagocytes: Include natural killer cells, neutrophils, monocytes/macrophages, eosinophils, basophils, mast cells, and platelets.
• Soluble Mediators:
  • Complement: A protein system that induces inflammation and kills microbes.
  • Cytokines: Proteins that modify cellular behavior in response to infection.

Types of Cytokines

• Chemokines: Small proteins that promote leukocyte migration and enhance inflammation.
• Interferons: Produced by virus-infected cells, increasing resistance to viral replication.
• Acute Phase Proteins: Pro-inflammatory cytokines that alter metabolism, blood flow, and protein production.

Components of Adaptive Immunity

• Humoral Immunity: Mediated by antibodies produced by B cells.
• Cell-Mediated Immunity: Involves T cells responding to infected cells.

Antigens vs. Immunogens

• Antigen: Any molecule that binds to an antibody or T-cell receptor.
• Immunogen: A specific antigen that elicits an immune response, often aided by adjuvants.

Active vs. Passive Immunity

• Active Immunity: Long-lasting immunity gained through exposure to antigens, either naturally (e.g., infection) or artificially (e.g., vaccines).
• Passive Immunity: Temporary immunity acquired by receiving antibodies from another individual; can be natural (e.g., maternal antibodies) or artificial (e.g., antibody injections).

Structure and Function of Antibodies

• Antibodies are produced by B lymphocytes, featuring:
  • Fragment Antigen Binding Sites: Bind specific antigens with variable regions for specificity.
  • Constant Regions: Determine the antibody's class and function.

Major Immunoglobulin (Ig) Classes

• IgM: First antibody produced in response, activates the complement system.
• IgG: Major antibody in blood, provides long-lasting immunity, crosses the placenta.
• IgA: Predominates in mucosal areas and secretions, protects mucosal surfaces.
• IgE: Associated with allergies and responses to parasites, found on mast cells and basophils.
• IgD: Functions as an antigen receptor on mature naïve B cells.

Clinical Relevance of Cell-Mediated Immunity

• Important for defense against intracellular pathogens and plays a role in transplant rejection and autoimmune diseases.

Process of Cell-Mediated Immunity

• Antigen-presenting cells (macrophages, dendritic cells) digest pathogens and present antigens to T cells in lymph nodes.
• T cells matching the antigen expand and differentiate, aiding in pathogen destruction and the activation of B cells.

Formation of T-Lymphocytes

• Origin in bone marrow, maturation occurs in the thymus where T-cell receptors are formed.
• Cells that recognize self-antigens are eliminated to prevent autoimmune diseases.

Formation and Maturation of B-Lymphocytes

• Matured B cells express IgM and IgD, and upon activation, divide and produce antibodies.
• Differentiate into plasma cells that secrete antibodies and memory B cells for future rapid response.

Phases of the Immune Response

• Recognition: Identifying pathogens.
• Amplification: Boosting immune signals.
• Effector: Eliminating pathogens.
• Termination: Shifting off immune response.
• Memory: Retaining information for future pathogen encounters.

Primary vs. Secondary Immunodeficiency

• Primary Immunodeficiency: Congenital defects disrupting T/B cells or lymphoid tissues.
• Secondary Immunodeficiency: Resulting from conditions or treatments that suppress immune function.

Sources of Iatrogenic Immunodeficiency

• Cytotoxic drugs, corticosteroids, immunosuppressive drugs, radiation therapy, and splenectomy can weaken immune responses.

Definition of Hypersensitivity

• Increased immune response to antigens, resulting in undesirable clinical effects.
• Four types of hypersensitivity reactions can occur concurrently or overlap.

Types of Hypersensitivity

Type I – Immediate Hypersensitivity (Atopy)

• Elevated production of IgE instead of IgG.
• Primarily involves mast cell degranulation and histamine release.
• Triggered by allergens, commonly harmless substances such as:
  • Shellfish
  • Pet dander
  • Dust mites
  • Peanuts
  • Latex
  • Insect venom
• Anaphylaxis represents a systemic Type I hypersensitivity response.

Type II – Cytotoxic Reactions to Self-Antigens

• Immune response targets the body's own tissues.
• Mechanisms include complement activation, agglutination, and phagocytosis.
• Notable examples:
  • Hemolytic disease of the newborn.
  • Myasthenia gravis.
• Cross-reactivity occurs between foreign antigens and body tissues, exemplified by:
  • Hemolytic streptococci linked to mitral valve disease.
  • Guillain-Barre syndrome.

Type III – Immune Complex Diseases

• Characterized by antibody-antigen complexes depositing in small blood vessels.
• This leads to complement cascade activation, acute inflammation, and tissue damage.
• Examples of diseases include:
  • Rheumatoid arthritis.
  • Nephritis.
  • Pericarditis.
  • Vasculitis, as seen in systemic lupus erythematosus (where cell nucleus acts as the antigen).

Type IV – Cell-Mediated Immunity

• Exhibits a delayed hypersensitivity reaction, typically 48-72 hours post-exposure.
• Based on interactions between macrophages and T-cells, which require time to develop.
• Common examples include:
  • Transplant rejection.
  • Delayed contact dermatitis, such as reactions to poison ivy.

Definition of Hypersensitivity

• Increased immune response to antigens, resulting in undesirable clinical effects.
• Four types of hypersensitivity reactions can occur concurrently or overlap.

Types of Hypersensitivity

Type I – Immediate Hypersensitivity (Atopy)

• Elevated production of IgE instead of IgG.
• Primarily involves mast cell degranulation and histamine release.
• Triggered by allergens, commonly harmless substances such as:
  • Shellfish
  • Pet dander
  • Dust mites
  • Peanuts
  • Latex
  • Insect venom
• Anaphylaxis represents a systemic Type I hypersensitivity response.

Type II – Cytotoxic Reactions to Self-Antigens

• Immune response targets the body's own tissues.
• Mechanisms include complement activation, agglutination, and phagocytosis.
• Notable examples:
  • Hemolytic disease of the newborn.
  • Myasthenia gravis.
• Cross-reactivity occurs between foreign antigens and body tissues, exemplified by:
  • Hemolytic streptococci linked to mitral valve disease.
  • Guillain-Barre syndrome.

Type III – Immune Complex Diseases

• Characterized by antibody-antigen complexes depositing in small blood vessels.
• This leads to complement cascade activation, acute inflammation, and tissue damage.
• Examples of diseases include:
  • Rheumatoid arthritis.
  • Nephritis.
  • Pericarditis.
  • Vasculitis, as seen in systemic lupus erythematosus (where cell nucleus acts as the antigen).

Type IV – Cell-Mediated Immunity

• Exhibits a delayed hypersensitivity reaction, typically 48-72 hours post-exposure.
• Based on interactions between macrophages and T-cells, which require time to develop.
• Common examples include:
  • Transplant rejection.
  • Delayed contact dermatitis, such as reactions to poison ivy.

Explore the mechanisms involved in the repair of skeletal muscle after injuries such as strains and contusions. This quiz covers the stages of hemostasis, inflammation, regeneration, and the potential for fibrosis. Test your knowledge on the key processes that contribute to the healing of muscle tissues.