2 acute inflammation Flashcards
What is inflammation?
A local accumulation of fluid into tissue containing plasma proteins and WBCs.
Often a non-specific (innate) response.
A local physiological tissue response to injury, infection, and cell death
What are the main aims of inflammation?
Restrict damage or infection to a localised area.
Remove the causative agent and damaged tissue.
Promote immune cell and molecule access to initiate repair.
What are the three main causes of inflammation?
Physical (e.g., trauma, burns, radiation).
Biological (e.g., bacteria, viruses, fungi).
Chemical (e.g., toxins, acids, irritants).
How does the immune system combat pathogens?
Recognises and responds to invading organisms.
Avoids overreacting to harmless material or self.
Links innate and adaptive immune responses.
How is inflammation classified?
Acute inflammation: Immediate, transient response.
Chronic inflammation: Prolonged response following acute stages.
What are the cardinal signs of acute inflammation?
Heat
Redness (erythema)
Swelling (oedema)
Pain
Loss of function
Who first described the cardinal signs of inflammation?
Roman physician Aulus Celsus, over 2000 years ago.
What are the four main stages of acute inflammation?
Tissue damage.
Initial vasoconstriction followed by vasodilation.
Cell recruitment (phagocyte migration and margination).
Tissue repair.
What happens during vasodilation?
Small blood vessels dilate, increasing blood flow.
Nitric oxide (NO) relaxes smooth muscle.
Endothelial cells swell and retract, making blood vessels leaky.
What is cell recruitment in inflammation?
Circulating phagocytes adhere to swollen endothelial cells (margination).
They migrate through the endothelial cells (emigration) to the damaged tissue.
Phagocytosis of pathogens occurs.
What happens during tissue repair?
Example: Scab formation and regeneration of epidermis and dermis.
What are the benefits of acute inflammation?
Dilutes toxins.
Increases immune cell entry.
Delivers nutrients and oxygen to the site.
Forms fibrin to impede micro-organism movement.
Activates the adaptive immune response.
What are the downsides of acute inflammation?
Release of proteolytic enzymes damages healthy tissue.
Swelling can be harmful (e.g., airway obstruction, brain swelling in meningitis).
Inappropriate inflammatory responses (e.g., allergic reactions).
What is the role of mast cells in acute inflammation?
Key in inducing inflammation.
Activated by pathogen/damage signals (PAMPs/DAMPs) binding to pattern recognition receptors (PRRs).
Release inflammatory mediators upon activation.
Which innate immune cells are crucial in acute inflammation?
Mast cells
Neutrophils
Macrophages
Dendritic cells (DCs)
What mediators induce vascular dilation?
Histamine
Prostaglandins
Complement components (C3a, C5a)
What mediators increase vascular permeability?
Histamine
Kinins
Prostaglandins
What mediators promote leukocyte emigration?
C5a
Leukotrienes
IL-8/CXCL 8
What is normal fluid movement across capillaries?
Fluid moves out at the arteriolar end and back in at the venous end due to osmotic pressure.
What is oedema?
Swelling due to fluid leakage from capillaries.
What are examples of non-inflammatory oedema?
Pulmonary oedema (high-altitude sickness).
Ankle oedema (long-haul flights).
What causes inflammatory oedema?
Increased vascular permeability following tissue injury.
Mediator-induced endothelial cell retraction.
Which mediators are preformed in mast cells?
Histamine
Serotonin
Tryptase
What does histamine do?
Causes transient arteriolar dilation.
Increases vascular permeability in venules.
What are the four histamine receptors and their locations?
H1: Smooth muscle, endothelial cells.
H2: Gastric parietal cells.
H3: CNS.
H4: Mast cells, eosinophils, T cells, DCs.
What is arachidonic acid, and how is it involved in inflammation?
Derived from phospholipids in cell membranes.
Leads to production of prostaglandins, thromboxanes, and leukotrienes.
What does the cyclooxygenase (COX) pathway produce?
Prostacyclin (PGI2): Inhibits platelet aggregation, vasodilation.
PGE2, PGF2, PGD2: Increase vascular permeability.
Thromboxane TXA2: Platelet aggregation, vasoconstriction.
What does the lipoxygenase pathway produce?
Leukotrienes (LTC4, LTD4, LTE4) that increase vascular permeability and smooth muscle contraction.
LTB4 stimulates neutrophil adhesion and chemotaxis.
What are the key inflammatory cytokines?
TNF-α: Mediates acute inflammation, promotes cell adhesion.
IL-1: Induces fever, acute-phase protein synthesis, and wasting.
What is the function of chemokines in inflammation?
Recruit immune cells to sites of infection.
IL-8/CXCL 8 is key for neutrophil recruitment.
What is acute inflammation?
initial, immediate, and often transient response to injury or infection.
What is chronic inflammation?
prolonged inflammatory response that follows acute stages and can lead to tissue damage.
What are the four main stages of inflammation?
Tissue damage
Initial vasoconstriction followed by vasodilation
Cell recruitment (phagocyte migration and margination)
Tissue repair
What happens during vasodilation?
Small blood vessels become dilated, increasing blood flow. Endothelial cells swell and retract, causing leaky vessels that allow the passage of fluids and proteins into the damaged area.
What is the function of nitric oxide (NO) in inflammation?
NO is a signaling molecule that relaxes smooth muscle, causing vasodilation and increasing vascular permeability.
What is margination and emigration in cell recruitment?
Margination: Phagocytes adhere to swollen endothelial cells.
Emigration: Phagocytes migrate through endothelial cells into the tissue.
What activates mast cells in acute inflammation?
PAMPs/DAMPs binding to PRRs (e.g., LPS/TLR-4)
IgE binding to FcεR
What are the key chemical mediators of acute inflammation?
Effect —- Mediators
Vascular dilation: Histamine, prostaglandins, C3a, C5a
Increased permeability: Histamine, kinins, prostaglandins
Leukocyte emigration: C5a, leukotrienes, IL-8
What is histamine’s role in acute inflammation?
Histamine increases vascular permeability and induces transient vasodilation.
What are the four histamine receptors and their locations?
H1: Smooth muscle and endothelial cells
H2: Gastric parietal cells
H3: Central nervous system
H4: Mast cells, eosinophils, T cells, dendritic cells
What are the two main pathways in arachidonic acid metabolism?
Cyclo-oxygenase (COX) pathway → Prostaglandins and thromboxanes
Lipoxygenase pathway → Leukotrienes
What is the role of COX-1 and COX-2?
COX-1: Produces prostanoids under basal conditions.
COX-2: Induced during inflammation.
What do NSAIDs like aspirin inhibit?
They inhibit COX enzymes, reducing prostaglandin production.
What are the functions of leukotrienes?
LTC4, LTD4, and LTE4: Increase vascular permeability and cause smooth muscle contraction.
LTB4: Chemotactic for neutrophils.
What is the role of platelet-activating factor (PAF)?
PAF dilates blood vessels, aggregates platelets, and triggers phagocytosis.
What is the function of TNF-α in inflammation?
Key mediator of acute inflammation.
Increases adhesion molecule expression on endothelial cells.
Upregulates chemokine secretion.
Induces fever and acute-phase protein production.
What is the role of IL-1 in inflammation?
Induces fever.
Stimulates acute-phase protein synthesis.
Causes metabolic wasting in severe cases.
What is IL-8’s role in inflammation?
IL-8 (CXCL-8) is a chemotactic factor for neutrophils.
What is an example of harmful inflammation?
Airway swelling in epiglottitis, leading to potential airway obstruction.
What is exudation?
The leakage of fluid, proteins, and immune cells from blood vessels into tissues.
What is the primary role of fibrin formation in acute inflammation?
Fibrin helps to impede microorganism movement, aiding phagocytosis.
