Tutorial 1

Inflammation and cellular responses

Inflammation

• Is a protective response

• The body’s response to injury

• Interwoven with the repair process

Inflammation

• Types– Acute (sec, mins, hrs)– Chronic (days, weeks, months, yrs)

Causes of inflammation

• Bacterial• Viral• Protozoal• Metazoal• Fungal• Immunological• Tumours• Chemicals, toxins etc• Radiation

Acute inflammation

Inflammation

• The Cardinal Signs of Acute Inflammation

RUBOR

CALOR

TUMOR

FUNCTIO LAESA

Cardinal signs of inflammation

Cardinal signs of inflammation

Cardinal signs of inflammation

Cardinal signs of inflammation

Cardinal signs of inflammation

Cardinal signs of inflammation

Inflammation

The basis of the five cardinal signs

• Increased blood flow due to vascular dilatation gives redness and heat.

• Increased vascular permeability gives oedema causing tissue swelling.

• Certain chemical mediators stimulate sensory nerve endings giving pain. Nerves also stimulated by stretching from oedema.

• Pain and swelling result in loss of function.

The process of inflammation

Components of acute and chronic inflammation

Local manifestations of acute inflammation

Leukocyte migration in inflammation

Molecules modulating endothelial-neutrophil interactions

Chemical mediators of inflammation(local and systemic)

Plasma proteases

The complement system

Arachidonic acid metabolites

HETE = hydroxyeicosatetraenoic acidHPETE = hydroperoxyeicosatetraenoic acid

Cytokines (IL-1 and TNF)

Nitric oxide (NO)

Effects of inflammation and their major mediators

Vasodilation:Prostaglandins, NO

Increased vascular permeability:Histamine, serotonin, C3a, C5a, bradykinin,

Leukotrienes C4, D4, E4, platelet activating factor

Chemotaxis, leukocyte activation:C5a, lekotriene B4, bacterial products, chemokines (IL-8)

Fever:IL-1, IL-6, TNF, prostaglandins

Pain:Prostaglandins, bradykinin

Tissue damage:Neutrophil and macrophage lysosomal enzymes, oxygen metabolites

NO

Chronic inflammation

Cells of the chronic inflammatory response

• Lymphocytes

• Monocytes/ macrophages

• Plasma cells

Maturation of circulating monocytes to macrophages

Macrophage-lymphocyte interactions in chronic inflammation

Granulomatous inflammation

Bacterial:TB, Leprosy, Syphillis, cat-scratch disease

Parasitic:Schistosomiasis

Fungal:Histoplasma, blastomycosis, cryptococcus

Inorganics, metals, dusts:Silicosis, berrylliosis

Foreign body

Unknown:Sarcoidosis

Granulomatous inflammation: tissue effects

Healing and repair

The cell cycle

The major components of the extracellular matrix (ECM) required for

healing and repair

Major growth factors in wound healing

Critical steps in angiogenesis

Wound healing: critical steps

Outcome of healing and repair