Acute inflammatory response

CLASS: BSc. Biotechnology Ist Year

SUBJECT: Immunology

SUBJECT TYPE: Major III

COMPILED BY: Asst. Prof. Debosmita Saha

1. Mast Cells: The "First Responders"

Mast cells are granulocytes residing in connective tissues, particularly near blood vessels, nerves, and mucosal surfaces (skin, lungs, and gut). They are described as "hallmarks of innate immunity."

• What they are: Large cells filled with dense granules containing pre-formed inflammatory mediators.

• How they are activated: They have receptors (like TLRs—Toll-Like Receptors or Fc receptors for IgE) that detect pathogens or allergens. Your notes mention activation by cytokines like IL-12 and IFN-$\alpha$ (Interferon-alpha).

• What they release (Degranulation):

  • Histamine: A powerful vasodilator.

  • Heparin: An anticoagulant that prevents immediate blood clotting to allow immune cells to move.

  • Serotonin: In humans, it primarily acts as a neurotransmitter, but in some contexts, it aids in vasoconstriction/dilation.

  • Chemotactic factors: Signals that "call" other white blood cells to the area.

• Why they matter: They act as an "alarm system." Without mast cells, the body wouldn't know to start the inflammatory process at the site of a local injury.

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2. Acute Inflammation: The Process

Acute inflammation is a rapid, non-specific response to injury or infection. It aims to deliver defensive cells and plasma proteins to the site of trauma.

Phase I: Vascular Changes (Swelling and Redness)

When tissue is damaged (trauma/pathogen entry), the following occurs:

1. Vasodilation: Stimulated by Histamine and Nitric Oxide (NO).

   • Blood vessels (arterioles) widen.

   • Increased blood flow to the area.

   • Result: Rubor (Redness) and Calor (Heat).

2. Increased Capillary Permeability: Stimulated by Bradykinin and Prostaglandins.

   • The "tight junctions" between endothelial cells (lining the blood vessels) shrink, making the vessel "leaky."

   • To allow plasma proteins (antibodies, complement proteins) and fluid to exit the blood and enter the tissue.

   • Result: Tumor (Swelling/Edema) and Dolor (Pain) due to pressure on nerve endings.

Phase II: Cellular Phase (Leukocyte Recruitment)

Once the "gates" are open, white blood cells (WBCs), primarily Neutrophils, must move from the blood into the tissue.

• Margination: Due to slower blood flow (stasis), heavier WBCs move from the center of the vessel to the periphery (the sides).

• Rolling and Adhesion: WBCs use "sticky" molecules called Integrins and Selectins to attach to the vessel wall.

• Diapedesis (Extravasation): The WBCs squeeze through the gaps in the endothelial wall.

• Chemotaxis: WBCs follow a chemical "scent" (Cytokines like IL-8 or C5a) to the exact site of the pathogen.

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3. The Systemic Response (The "Whole Body" Effect)

Inflammation isn't just local. If the "alarm" is loud enough, the whole body reacts. This is primarily driven by Cytokines: IL-1 (Interleukin-1), TNF-α   (Tumor Necrosis Factor-alpha), and IL-6.

Feature	Mechanism	Purpose
Fever	Cytokines signal the Hypothalamus to reset the body's thermostat.	High temps inhibit bacterial growth and speed up metabolic repair.
Leukocytosis	Cytokines signal Bone Marrow to produce more WBCs.	To replenish the immune cells being used up at the injury site.
Acute Phase Proteins	Cytokines signal the Liver to produce C-Reactive Protein (CRP) and Fibrinogen.	CRP helps in opsonization (tagging pathogens for destruction).

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4. Outcomes of Acute Inflammation

1. Resolution: The best-case scenario. Pathogens are removed, debris is cleared by Macrophages, and tissue returns to normal.

2. Fibrosis (Scarring): If the tissue cannot regenerate (like heart muscle after a heart attack), the body fills the gap with Collagen (fibrous tissue).

3. Chronic Inflammation: If the agent isn't removed, the process continues indefinitely, leading to tissue destruction (e.g., Cirrhosis of the liver).

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Key Abbreviations

• WBC: White Blood Cells (Leukocytes)

• RBC: Red Blood Cells (Erythrocytes)

• IL-1 / IL-6: Interleukin-1 / Interleukin-6

• TNF-α: Tumor Necrosis Factor-alpha

• IFN-α: Interferon-alpha

• CRP: C-Reactive Protein

• DAMPs: Damage-Associated Molecular Patterns (signals from our own broken cells)

• PAMPs: Pathogen-Associated Molecular Patterns (signals from bacteria/viruses)

Comparison Table: Acute vs. Chronic Inflammation

Feature	Acute Inflammation	Chronic Inflammation
Onset	Fast (minutes to hours).	Slow (days to weeks).
Duration	Short-term (days to a few weeks).	Long-term (months to years).
Primary Cells	Neutrophils (the "first responders").	Macrophages, Lymphocytes (T-cells, B-cells), and Plasma cells.
Tissue Injury	Usually mild and self-limiting.	Often severe and progressive.
Vascular Changes	Pronounced (Vasodilation, increased permeability).	Less prominent; often involves Angiogenesis (new blood vessel growth).
Systemic Signs	Fever, Leukocytosis (elevated WBCs).	Low-grade fever, weight loss, anemia, fatigue.
Fibrosis (Scarring)	Minimal, unless the injury is severe.	Common and extensive (often leads to loss of organ function).
Examples	Bee sting, sore throat (pharyngitis), skin cut.	Tuberculosis, Rheumatoid Arthritis, Atherosclerosis, Cirrhosis.