Inflammation and Mediators Overview

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Questions and Answers

What role does plasmin play in the inflammatory response?

It activates matrix metalloproteinases (MMPs) for tissue remodeling. (correct)

It limits the release of cytokines.

It directly promotes vasoconstriction.

It reduces vascular permeability.

Which of the following mediators is known for causing venous dilation?

Nitric oxide (NO) (correct)

Leukotrienes

Histamine

Cytokines

C3a and C5a are primarily involved in activating which cell-derived mediators?

T cells and B cells

Mast cells, basophils, and platelets (correct)

Neutrophils and macrophages

Endothelial cells

What is the consequence of the persistent accumulation of immune cells in chronic inflammation?

Inhibition of the repair response Signup and view all the answers

Which compounds are primarily responsible for causing inflammatory pain?

Platelet activating factor and leukotrienes Signup and view all the answers

Which mediator is involved in type 1 and type 2 hypersensitivity reactions?

Platelet activating factor (PAF) Signup and view all the answers

How is arachidonic acid related to inflammatory mediators?

It generates key inflammatory mediators like prostaglandins and leukotrienes. Signup and view all the answers

What triggers the rapid release of pre-formed histamine from mast cells?

IgE and complement proteins C3a/C5a Signup and view all the answers

Which of the following are considered cell-derived mediators of inflammation?

Basophils Signup and view all the answers

What is the primary function of kinins in the inflammatory process?

To facilitate vasodilation and increase vascular permeability Signup and view all the answers

Which component is NOT typically involved in the acute inflammatory response?

Lymphocytes Signup and view all the answers

Identify the sequence of events in the acute inflammatory response.

Tissue injury → cells release inflammatory mediators → vasodilation → recruitment of leukocytes Signup and view all the answers

What role does extravasation play in the inflammatory response?

It recruits immune cells to the site of injury. Signup and view all the answers

Which of the following best differentiates between acute and chronic inflammation?

Acute inflammation has a rapid response, whereas chronic inflammation is prolonged. Signup and view all the answers

Which of the following statements about the clotting system is true in relation to inflammation?

It helps to isolate damaged tissue and prevent infection. Signup and view all the answers

What is the primary source of bradykinin in the kinin system?

The enzymatic activity of specific serine proteases Signup and view all the answers

Which of the following accurately describes the role of kinins in inflammation?

They enhance the permeability of blood vessels and induce pain. Signup and view all the answers

Which of the following describes the main difference between acute and chronic inflammation?

Acute inflammation is a short-term response characterized by rapid onset, while chronic inflammation is prolonged with ongoing tissue damage. Signup and view all the answers

Which of the following is NOT a class of mediators involved in the inflammatory process?

Circulating antibodies Signup and view all the answers

Which cellular component primarily works to support the mediators of inflammation?

Immune cells Signup and view all the answers

What is the primary function of the complement system in inflammation?

To mediate phagocytosis and enhance immune response Signup and view all the answers

Which statement about the role of plasma-derived mediators in inflammation is correct?

They include components involved in clotting and the kinin system. Signup and view all the answers

Which of the following statements accurately reflects the process of extravasation during inflammation?

It allows immune cells to exit blood vessels and enter the injury site. Signup and view all the answers

Which substance is specifically produced during the activation of the kinin system?

Bradykinin Signup and view all the answers

What is the primary function of plasmin in the context of tissue remodeling?

Convert plasminogen to plasmin Signup and view all the answers

Which of the following mediators is involved in the chronic inflammation response due to persistent antigens?

Dysregulated immune responses Signup and view all the answers

What is the role of CCL3 (MIP1-a) in the inflammatory response?

Recruitment and activation of other immune cells Signup and view all the answers

Which of the following components is essential in the generation of prostaglandins and leukotrienes from arachidonic acid?

Arachidonic acid pathway enzymes Signup and view all the answers

What type of pain is associated with mast cell and basophil mediators like histamine and prostaglandins?

Dull, aching pain Signup and view all the answers

How do activated mast cells contribute to vasodilation during the inflammatory response?

Through degranulation and releasing histamine Signup and view all the answers

In response to which triggers do mast cells and basophils release leukotrienes and prostaglandins?

Immune complex activation Signup and view all the answers

What role does the Hageman factor (XIIa) play in the inflammatory process?

Activates the clotting cascade and increases mediator release Signup and view all the answers

Study Notes

Inflammatory Mediators

Inflammatory mediators are crucial for the inflammatory process
They have key functions
Students should be able to list examples of inflammatory mediators and their key functions
Students should be able to overview the role of inflammatory mediators as key regulators of the chronic inflammatory process
Students should be able to discriminate between mechanisms in acute and chronic inflammation

Session Aims

Prepare students for the study of inflammatory immunopathologies and pharmacological modulators of inflammation
Build from year 1 consideration of inflammation with a deeper consideration of selected cellular mediators of inflammation (e.g. vasoactive amines and kinins)

The Inflammatory Process: Overview

Tissue injury (physical or chemical, or pathogenic microorganism) initiates the inflammatory response
Key signs include:
- Pain
- Heat
- Redness
- Swelling
- Loss of function
This process involves capillary widening, increased capillary permeability, attraction of white blood cells, Systemic response, increased blood flow, release of fluid, migration of white blood cells to injury, fever, and proliferation of white blood cells

The Inflammatory Process: Diagrammatic Overview (pages 4, 5)

Damaged tissues attract mast cells which release histamine, diffusing into blood vessels
Histamine causes vasodilation in vessels and increases capillary permeability, allowing complement proteins and phagocytes to enter
Blood plasma and phagocytes move into infected tissue from vessels
Phagocytes engulf bacteria/dead cells
Growth factors stimulate skin cell division for wound healing

Extravasation

Key process in inflammation
Recruits immune cells to injury site
Rapid action
- (low affinity) low affinity integrin rolling on endothelium,
- (high affinity) integrin activation by chemokines and sticking/stable adhesion to endothelium followed by transmigration through this endothelium

Cellular Components and Soluble Mediators

Cellular components of the inflammatory response are supported by soluble mediators of inflammation
Includes immune response, elimination of microbes/dead tissue, repair, inflammation mediators, source of mediators, and related structures

Mediators of Inflammation: Plasma Derived

Clotting system
Kinin system
Fibrinolytic system (plasmins)
Complement system

Mediators of Inflammation: Cell Derived

Auxiliary cells (basophils, mast cells, platelets)
Lymphocytes
Monocytes

Kinins

Enzymatic proteins involved in inflammation
Result in bradykinin and lysyl-bradykinin production
Powerful vasoactive peptide (venous dilation, increased vascular permeability)
Activated by Hageman factor (XIIa) in clotting cascade, plasmin system, and enzymes from damaged tissues

Plasmins

Originally identified as breaking down fibrin
Activated by soluble or tissue-derived plasminogen activators
Converts plasminogen to plasmin, which activates MMPs (tissue remodelling)
Promote angiogenesis via cytokine release

Cell-Derived Mediators (Mast Cells, Basophils, Platelets)

Activated by C3a and C5a (innate), and IgE (adaptive)
Rapid release of pre-formed histamine and serotonin (degranulation)
Result in vasodilation and increased permeability
Slow release (hours) of leukotrienes and prostaglandins
Activated by immune complexes (antibodies)
Platelet activating factor (PAF) from neutrophils, basophils, and macrophages
Involved in type 1 and 2 hypersensitivity
Recruitment and activation of other immune cells (CCL3 (MIP1-a), and B₄ (chemotactic for monocytes)
Chemokines and cytokines modulate local immune responses

Pain: Mast Cell and Basophil-Derived Mediators

PAF, histamine, serotonin, prostaglandins, and leukotrienes
Act on C fibers
Poorly localized, dull, aching pain (inflammatory pain)

Arachidonic Acid Pathway

Arachidonic acid is crucial for inflammatory mediators (prostaglandins, leukotrienes)
Key enzymes involved include cyclooxygenases (COX), lipoxygenases (LOX)

Chronic Inflammation

If antigens or insult persists, immune cells accumulate, response becomes uncontrolled/dysregulated, repair is inhibited
Chronic inflammation is a key cause of tissue damage and incapacity
Examples of chronic inflammation reaction sites in oral tissues

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Description

This quiz covers the role of inflammatory mediators in both acute and chronic inflammation. Students will explore key functions, examples of mediators, and their importance in inflammatory immunopathologies. Prepare to deepen your understanding of the mechanisms behind the inflammatory process.