Inflamacion Inata

INNATE IMMUNITY: ACUTE INFLAMMATION

Inflammation • Injurious stimuli cause a protective vascular connective tissue reaction called “inflammation.” – – – –

Dilute Destroy Isolate Initiate repair

• Acute and chronic forms

Inflammation. Response of tissues to the presence of microorganisms or to injury. Protective mechanisms are focused on a localized region of tissue.

Blood vessel

O

! ! h c u

Invading organisms or trauma

Vasoactive factors

Blood vessel

injury

Increased vascular permeability

Chemotactic factors

Phagocytes Neutrophils macrophages

migration Edema Swelling Pain

Antibodies and complement

Opsonization Phagocytosis Destruction

The essential features of acute inflammation

ESSENTIAL FEATURES OF ACUTE INFLAMMATION

pathogen-associated molecular patterns Mφ, DC and mast cells.

The major structural features of the cell walls of Gram-negative, Grampositive, and acid-fast bacteria. These conserved structural molecules serve as PAMP’s and can bind to pattern-recognition receptors such as the toll-like receptors.

ACUTE

ACUTE INFLAMMATION

The cardinal signs of acute inflammation

swelling

pain

heat

redness

Serous exudate/subcutaneous edema, photosensitization, skin of the nose and ears, ewe. The nonhaired skin of the nose is covered by a crust resulting from dehydration of the serous exudate released from injured blood vessels following a short exposure to the sun. The ears are edematous and droopy.

Catarrhal inflammation. Abomasum, cow. The mucosal epithelium is moderately thickened, covered by a glistening layer of clear mucus, and has a subtle nodular appearance caused by accumulation of mucinous secretory products (catarrhal exudate) in the gastric pits.

The principal cellular and vascular responses during the inflammatory response. The majority of leukocyte transmigration and hemorrhage occurs in the capillaries and postcapillary venules.

Blood pressure and plasma colloid osmotic forces in normal and inflamed microcirculation. Acute inflammation. Arteriole pressure is increased to 50 mm Hg; the mean capillary pressure is increased because of arteriolar dilation, and the venous pressure increases to approximately 30 mm Hg. At the same time, osmotic pressure is reduced (averaging 20 mm Hg) because of protein leakage across the venule. The net result is an excess of extravasated fluid.

The major local manifestations of acute inflammation compared with normal. (1) Vascular dilation (causing erythema and warmth), (2) extravasation of plasma fluid and proteins (edema), and (3) leukocyte emigration and accumulation in the site of injury.

How Invaders are Recognized?

1. The innate immunity “senses” that the body is being invaded. 3. The presence of strange material is detected by “sentinel” cells. 5. The sentinel cells are macrophages, dendritic cells and mast cells. 7. These cells have receptor that recognize molecules (PAMPs) normally found in many microorganisms but not in higher animals (NAG, NAM, LPS, CHO´s, etc.).

MAST CELL

nucleus

Metachromatic granules

scrolls

Mast Cells

Mast Cells

Some of the stimuli that make mast cell degranulate.

Normal mast cell

Degranulating mast cell

Vascular leakage Four mechanisms known to cause vascular leakiness 1. Histamines, bradykinins, leukotrienes cause an early, brief (15 – 30 min.) immediate transient response in the form of endothelial cell contraction that widens intercellular gaps of venules (not arterioles, capillaries).

Gingival edema. Dog.

VASOACTIVE MOLECULES HISTAMINE SEROTONINE

VASOACTIVE POLYPEPTIDES

KININS EICOSANOIDS PROSTAGLANDIN LEUCOTRIENS (B4, C4, D4, E4)

PLATELETACTIVATING FACTOR (PAF)

FIBRINOGEN BREAKDOWN PRODUCTS

C3a, C5a

VASOACTIVE LIPIDS

NEUTROPHIL-DERIVED MOLECULES

COAGULATION SYSTEM

COMPLEMENT

Vascular leakage

2. Cytokine mediators (TNF, IL-1) induce endothelial cell junction retraction through cytoskeleton reorganization (4 – 6 hrs post injury, lasting 24 hrs or more).

Vascular leakage

3. Severe injuries may cause immediate direct endothelial cell damage (necrosis, detachment) making them leaky until they are repaired (immediate sustained response), or may cause delayed damage as in thermal or UV injury, or some bacterial toxins (delayed prolonged leakage).

necrosis

necrosis

thrombus

lymphocyte

Mφ

plasma cell

PMN

Mφ

Vascular leakage 4. Marginating and endothelial cell-adherent leukocytes may pile-up and damage the endothelium through activation and release of toxic oxygen radicals and proteolytic enzymes (leukocyte-dependent endothelial cell injury) making the vessel leaky.

Vasodilation: leads to greater blood flow to the area of inflammation, resulting in redness and heat. Vascular permeability: endothelial cells become "leaky" from either direct endothelial cell injury or via chemical mediators. Exudation: fluid, proteins, red blood cells, and white blood cells escape from the intravascular space as a result of increased osmotic pressure extravascularly and increased hydrostatic pressure intravascularly Vascular stasis: slowing of the blood in the bloodstream with vasodilation and fluid exudation to allow chemical mediators and inflammatory cells to collect and respond to the stimulus.

Chemical mediators producing endothelial contraction include: histamine, leukotrienes, bradykinin, platelet activating factor, and the C3a and C5a components from complement activation. Mediators of this process over a longer term include tumor necrosis factor and interleukin-1. Chemical mediators that promote vasodilation include: histamine, prostaglandins, and nitric oxide.

Cell-membrane phospholipids

phospolipases

Arachidonic acid Lipooxigenase

Leucotrienes

Ciclooxigenase

Prostaglandins Thromboxans Protacyclins

Proinflammatory Proagglutination Thrombotic

The production of leucotrienes and prostaglandins by the action of lipooxigenase and cyclooxygenase of arachidonic acid.