Inflammation

Overview of Inflammation

• Inflammation is a response to tissue damage that leads to observable signs.

• Key characteristics include:

  • Pain - one of the major characteristics.

  • Increased Temperature - often occurs with infections, especially from pathogenic bacteria.

  • Redness - results from vasodilation and increased vascular permeability, leading to more blood flow.

  • Swelling - caused by the accumulation of blood, plasma, and immune cells.

• Function of inflammation includes:

  • Clearing out pathogens (like splinters or bacteria).

  • Facilitating tissue repair after damage.

Mechanism of Inflammation Response

• Initial Stimulus: Can be an infection, like a virus or bacteria.

• Recognition and Response:

  • Macrophages recognize damage and release cytokines and chemokines.

  • This causes increased vascular permeability and basal dilation, leading to typical inflammatory signs.

• Recruitment of Immune Cells:

  • Major players include helper T cells and neutrophils, which work towards clearing the infection.

  • Complement system plays a pivotal role in signaling and recruiting immune cells.

Key Components and Players

• Complement System:

  • C5a is crucial for recruiting immune cells.

  • Helps in the coordination of the inflammatory response.

• Cytokines from Macrophages:

  • IL-1, TNF-alpha, IL-6 are significant for increasing vascular permeability and recruiting cells.

  • TNF-alpha's impact leads to systemic effects in severe infections.

• Local vs. Systemic Responses:

  • Local inflammation is beneficial for tissue affected (e.g., a cut).

  • Systemic inflammation can lead to severe symptoms like fever and septic shock in case of widespread infection.

Phagocytosis and Cleanup

• Phagocytes:

  • Recognize pathogens through receptors like mannose for recognizing sugars.

  • Engage in phagocytosis by engulfing and destroying pathogens with lysosomes containing antimicrobial components.

• Inflammation Outcomes:

  • Outcomes include edema, redness, pain, and influx of leukocytes (neutrophils, helper T cells).

Acute Inflammation Process

• Pathogen Entry:

  • Example: Bacteria introduce a rapid complement response (C3).

  • C3b marks bacteria for destruction by phagocytes.

• Macrophage Activation:

  • Macrophages produce cytokines that influence both local repair and immune function globally (e.g., liver and bone marrow).

• Endothelial Response:

  • Activation of endothelial cells leads to tighter binding of immune cells (via integrins), aiding in targeted recruitment during inflammation.

Chronic Inflammation

• Transition from Acute to Chronic:

  • If moisture remains due to continuous infections, inflammation can shift from M1 (pro-inflammatory) to M2 (anti-inflammatory and repair).

  • M2 macrophages contribute to the cleanup and restoration of tissue post-infection.

• Consequences of Chronic Inflammation:

  • Results in persistent immune responses leading to tissue damage, fibrosis, and potential complications (e.g., scars from repeated episodes).

  • Can be driven by ongoing infections or environmental factors like smoking or poor health.

Key Illustrations of Inflammation

• Acute Inflammation: Visible effects at the site of infection, with macrophages and neutrophils clearing pathogens.

• Systemic Effects: In severe cases, cytokine storms lead to extensive body effects, like fever or septic shock, indicating widespread inflammation.

• Long-Term Effects: Chronic inflammation can cause tissue changes and remodeling leading to diseases (for example, emphysema in chronic smoking).

Conclusion

• Inflammation is a complex process involving recognition, recruitment, and resolution.

• Both acute and chronic inflammation have distinct pathways and consequences.

• Understanding the balance between M1 and M2 macrophage functions is critical in addressing inflammation-related diseases.