Inflammation and Repair | Medical Science Optional Notes for UPSC PDF Download

Inflammation

Components of Acute Inflammation

Adhesion Molecuies

Inflammatory Cells

Chemical Mediators of Acute Inflammation

NET'S

• Neutrophil extracellular traps (NETs) are intricate networks of extracellular fibers that deliver a concentrated dose of antimicrobial substances to infection sites, impeding the dissemination of microbes by ensnaring them in the fibrils.
• Neutrophils generate NETs in response to the following stimuli:
  a) Infectious pathogens, primarily bacteria and fungi;
  b) Inflammatory mediators, encompassing chemokines, cytokines (especially interferons), complement proteins, and reactive oxygen species (ROS).

Upon the initiation of NETs production, the neutrophil nuclei are forfeited, resulting in the demise of the neutrophils. The extracellular traps form a dense mesh of nuclear chromatin that binds and concentrates granule proteins, including antimicrobial peptides and enzymes. Among these are antimicrobial proteins such as neutrophil elastase, cathepsin G, and histones, which exhibit a strong affinity for DNA.

In terms of clinical significance, the nuclear chromatin within NETs, encompassing histones and associated DNA, is suggested to serve as a source of nuclear antigens in systemic autoimmune diseases, notably lupus. In these conditions, individuals mount immune reactions against their own DNA and nucleoproteins.

Granulomatous Inflammation

A distinct pattern of chronic inflammation characterized by formation of granulomas

Granuloma

• A locus of chronic inflammation characterized by a small cluster of macrophages undergoing transformation into epithelium-like cells (epithelioid cells), encircled by a rim of mononuclear leukocytes (comprising lymphocytes and, at times, plasma cells).
• Giant Cells: Epithelioid cells commonly merge to create giant cells, often located at the periphery or occasionally in the center of the granuloma.

• Epithelioid cells exhibit minimal phagocytic activity and primarily function as secretory cells.
• Through the release of inflammatory mediators, they contribute to the sustained tissue damage resulting from inflammation.

Granulomatous Inflammation - Examples

Tissue Repair

Repair, often referred to as healing, involves the reinstatement of tissue architecture and function following an injury. This process manifests through two types of reactions:

• Regeneration of the damaged tissue
• Formation of scars through the deposition of connective tissue

Role of ECM in Tissue Repair

The process of tissue repair relies on both the activity of growth factors and interactions between cells and components of the extracellular matrix (ECM). An intact ECM is essential for tissue regeneration, and in instances where the ECM is compromised, the only viable means of repair is through the formation of scars.

The extracellular matrix (ECM) comprises three fundamental components:

• Fibrous structural proteins, including collagens and elastins, providing tensile strength and recoil.
• Water-hydrated gels, such as proteoglycans and hyaluronan, enabling resilience and lubrication.
• Adhesive glycoproteins that establish connections between matrix elements and facilitate adherence to both one another and to cells.

Functions of ECM

• Providing mechanical support for cell anchorage and migration, as well as upkeeping cell polarity.
• Regulating cell proliferation by binding and presenting growth factors and signaling through cellular receptors, primarily those of the integrin family. The specific ECM proteins can influence cell differentiation within the tissue, predominantly through interactions with cell surface integrins.
• Serving as a scaffold for tissue renewal, where the maintenance of normal tissue structure necessitates a basement membrane or stromal scaffold. The integrity of the basement membrane or stroma of parenchymal cells is crucial for the organized regeneration of tissues. While labile and stable cells can regenerate, disruption of the ECM leads to the failure of tissue regeneration, resulting in repair through scar formation.
• Establishing tissue microenvironments, where the basement membrane acts as a barrier between the epithelium and underlying connective tissue and also contributes to the filtration apparatus in the kidney.

Types of Wound Healing

Inflammation and Repair - Repeats 

1. Define inflammation. Describe the vascular phenomenon of the inflammation (1994).
2. Explain the role of extracellular matrix (ECM) in tissue repair. (2009) 
3. Discuss role of mediators in different reactions of inflammation. (2013) 
4. Define granuloma. Give the mechanism of formation of granuloma and give examples of granulomatous diseases. (2012) 
5. Enumerate the chemical mediators of acute inflammation. Give their mechanisms of action. (2015)
6. Describe the pathogenesis of granulomatous immune response in tuberculosis. Discuss gross and histopathological features of central nervous system (CNS) Tuberculosis. (2018)