L3: Molecular and Cellular Mechanism of Inflammation

What is inflammation?

The body's attempt to remove harmful stimuli and start the healing process by responding to pathogens, noxious stimuli, physical injury, hypersensitivity, and autoimmune diseases

What role do cytokines play in inflammation?

Cytokines are key modulators and regulators of inflammation, acting as chemical messengers.

What is the process of recognition in inflammation?

Involves identifying injurious agents through signals like PAMPs for infectious and DAMPs for sterile inflammation.

List some chronic inflammation types related to autoimmune diseases.

Examples include rheumatoid arthritis, systemic lupus erythematosus, metabolic syndrome, Alzheimer’s disease, asthma, ulcerative colitis, cardiovascular disease, and certain cancers like colon cancer

What are common symptoms of acute inflammation?

Symptoms include heat, redness ((dilation of small blood vessels in the area of injury)), swelling (increased permeability of blood vessels leading to a buildup of fluid), pain (bradykinin that stimulate nerve endings), and immobility.

Describe leukocyte recruitment during inflammation.

Leukocyte recruitment involves several steps: vasodilation, margination, rolling, adhesion, diapedesis, and chemotaxis.

Explain diapedesis in leukocyte recruitment.

Diapedesis refers to the migration of immune cells through blood vessel walls into tissues. It's facilitated by endothelial cell contraction and increased permeability.

What initiates vasodilation during inflammation?

Chemical mediators released as part of the inflammatory response attract blood flow to the affected area.

What is the purpose of chemotaxis in inflammation?

Chemotaxis involves the movement of leukocytes to the site of infection, guided by cytokines.

What are Neutrophil Extracellular Traps (NETs)?

NETs trap microbes using chromatin materials mixed with antimicrobial peptides and enzymes produced by neutrophils. This prevents microbes from spreading further within tissues.

How does phagocytosis remove causative agents during inflammation?

Phagocytosis involves recognition and attachment of microbes to phagocytes, engulfment via actin filament polymerization, fusion with lysosomes to form phagolysosomes where pathogens are killed using ROS and enzymes.

How does termination/resolution occur after an inflammatory response?

Termination occurs through depletion of chemokines leading to neutrophil apoptosis. Macrophages then clear apoptotic neutrophils while switching their phenotype from pro-inflammatory to resolution-phase macrophages.

How do cytokines function within the body?

Cytokines initiate autocrine, paracrine, and endocrine effects by binding to cell surface receptors. They facilitate T-cell proliferation (IL-2), pro-inflammatory responses (TNF-α, IL-1), and anti-inflammatory actions (IL-10).

What factors can induce chronic inflammation?

Chronic inflammation can be initiated by persistent infections, autoimmune responses, or non-degradable pathogens.

Describe the role of interleukins in inflammation.

Interleukins function in T-cell proliferation and modulating immune responses.

What is Systemic Lupus Erythematosus (SLE)?

SLE is an autoimmune disease characterized by immune-mediated tissue damage due to breakdown of self-tolerance.

What are the outcomes of acute inflammation?

Outcomes can include resolution, abscess formation, or progression to chronic inflammation.

How does cell senescence relate to inflammation?

Cell senescence results in increased expression of inflammatory mediators, contributing to chronic inflammation.

Identify the cells primarily involved in acute inflammation.

Neutrophils, monocytes, macrophages, basophils, eosinophils, and mast cells.

What triggers the recruitment of leukocytes during inflammation?

Blood vessel dilation and changes in endothelia allow leukocytes to migrate to the affected area.

What is the function of chemokines?

Chemokines are secreted to recruit leukocytes to sites of infection or injury.

What is the significance of hyaluronan in inflammation?

Hyaluronan is a large glycosaminoglycan that regulates inflammatory cell recruitment by binding to CD44 on cell surfaces. It influences tissue injury repair by modulating inflammatory gene expression.

How does cell senescence relate to inflammatory mediators?

Cell senescence leads to increased expression of inflammatory mediators such as TNF-α, IL-6, and IL-1β. This can be caused by age-related frailty or chemical injury.

Explain Systemic Lupus Erythematosus (SLE) as an example of an autoimmune disease involving chronic inflammation.

SLE is a Type II hypersensitivity reaction where there's a breakdown in self-tolerance leading to immune-mediated tissue damage. It involves autoreactive T cells and B cells with increased cytokine secretion affecting organs.

What is the pathogenesis of lupus nephritis in its acute and chronic stages?

Lupus nephritis involves an acute stage where nephrons are damaged by B and T cells, typically treated with immunosuppressive agents. The chronic stage leads to tubular atrophy and fibrosis, resulting in chronic renal impairment that may necessitate dialysis

How does the mechanism of lupus nephritis involve antibody binding?

The mechanism involves indirect binding where chromatin from dead cells acts as a bridge for anti-dsDNA antibodies to bind to the glomerular basement membrane (GBM), leading to glomerulonephritis. Direct binding occurs when antibodies attach directly to antigens on cell surfaces or extracellular matrices within the nephron