4.2-Inflammation

What type of chronic inflammation features collections of activated macrophages and T lymphocytes, often with or without central necrosis?

Granulomatous inflammation

What cell types characterize granulomatous inflammation?

Activated macrophages (epithelioid histiocytes), T lymphocytes, sometimes multinucleated giant cells

What is the key difference between foreign body and immune granulomas?

Foreign body granulomas lack T-cell mediated response; immune granulomas involve persistent T-cell mediated immune response

What causes foreign body granulomas?

Inert materials too large for phagocytosis (e.g., talc, sutures)

How can foreign body granulomas be identified microscopically?

Foreign material appears refractile under polarized light

What causes immune granulomas?

Persistent microbes (e.g., TB) or self-antigens

What cytokines are involved in immune granuloma formation?

IL-2 (activates T cells), IFN-γ (activates macrophages)

What type of granuloma is seen in tuberculosis and fungal infections?

Caseating granuloma (necrotizing)

What type of granuloma is seen in sarcoidosis and Crohn's disease?

Non-caseating granuloma (non-necrotizing)

Before diagnosing granulomatous disease, what must always be done?

Stain for organisms to rule out infectious causes

Which cytokines mediate the acute-phase response?

TNF, IL-1, IL-6

What is the most prominent systemic sign of acute inflammation?

Fever

What causes fever in the acute-phase response?

Pyrogens stimulate prostaglandin production in hypothalamus → resets body temperature

What liver-synthesized proteins increase during the acute-phase response?

C-reactive protein (CRP), fibrinogen, serum amyloid A (SAA)

Which cytokine stimulates CRP and fibrinogen production?

IL-6

Which cytokines stimulate SAA production?

IL-1 and TNF-α

How do CRP and SAA help fight infection?

Act as opsonins and fix complement

What acute-phase protein causes increased erythrocyte sedimentation rate (ESR)?

Fibrinogen, by promoting rouleaux formation

What is rouleaux formation?

Stacking of red blood cells that sediment faster, increasing ESR

Which protein reduces iron availability and causes anemia of chronic disease?

Hepcidin

What causes thrombocytosis in inflammation?

Increased thrombopoietin stimulates megakaryocytes

What WBC change is most common in bacterial infections?

Neutrophilia

What WBC change is common in viral infections?

Lymphocytosis

What WBC change occurs with allergy or parasitic infections?

Eosinophilia

What infections may cause leukopenia?

Typhoid, rickettsiae, some viruses, protozoa

Which cytokine is responsible for elevated ESR in a patient with chronic inflammation?

IL-6

Which cell plays the most important role in healing after a myocardial infarction?

Macrophages

How does chronic inflammation contribute to Alzheimer’s disease?

Microglia and complement system inappropriately prune synapses, promoting tau tangle formation

What microscopic features characterize Alzheimer’s disease?

Neuritic plaques, neurofibrillary tangles, cortical atrophy

What triggers inflammation in inflammatory bowel disease (IBD)?

Immune dysregulation in response to intestinal microbiota

What cancers are associated with chronic inflammation?

HCC (chronic HCV), gastric cancer (H. pylori), colon cancer (IBD)

What systemic markers of inflammation show health disparities by race and sex?

C-reactive protein (CRP) and interleukin-6 (IL-6)

How is chronic stress linked to increased inflammation?

↑ Amygdala activity → ↑ bone marrow inflammation → ↑ cardiovascular disease risk