Inflammation Flashcards
What stimuli causes production of inflammatory mediators? What are the chemical mediators of acute inflammation and what are their actions?
- Inflammatory stimulated by
- Necrotic cells
- Tissue injury
- Mechanical irritation
- Microbial products
- Foreign body
- Immune reaction - Chemical mediators of acute inflammation
- Histamine: Increased vascular permeability, vasodilation
- Prostaglandin: Increased vascular permeability, vasodilation, pain, fever
- Leukotrienes: Increased vascular permeability, vasodilation, chemotaxis
- Chemokines: Chemotaxis, activates WCC
- Cytokines: Increased vascular permeability, vasodilation, fever, pain, hypotension
- Kinins: Pain, increased vascular permeability
- Complements: Chemotaxis, activates macrophage, cell injury
- Reactive oxygen species: Tissue damage, killing microbes
Describe the vascular changes in acute inflammation. What are the mechanisms responsible for increased vascular permeability in acute inflammation. Describe the role of the complement cascade in inflammation.
- Vascular changes in acute inflammation
- Transient vasoconstriction
- Vasodilation of arterioles and capillaries
- Increased vascular permeability -> Edema
- Stasis and congestion -> Erythema
- Margination of neutrophils - Mechanisms involved in increased vascular permeability
- Endothelial retraction/contraction -> Most common -> Due to mediators (histamine, prostaglandin) -> Forms gaps in venules
- Direct endothelial injury -> Trauma/chemical irritation damages endothelium
- Leukocyte-mediated injury -> Secretes mediators causing leaky vessels
- Increased transcytosis -> Formation of transendothelial channels
- Angiogenesis -> New vessels are fragile and leaky - Role of complement in inflammation
- C1 - 9 complement
- Once activated, amplifies complement cascade
- Begins with C3 -> C3a by 3 pathway (alternative, classical, lecithin)
- Causes
+ Inflammation: C3a, C5a being anaphylatoxins -> Recruits lymphocytes which secretes mediators causing inflammation
+ Opsonization: C3b opsonizes cell for phagocytosis by macrophages
+ Cell lysis: C5 - 9 forms MAC
Describe the main characteristics/major components of acute inflammation. How are leukocytes delivered to site of injury? Name some of the chemoattractants responsible for chemotaxis. What chemical mediators are responsible for fever, pain and tissue damage?
- Main characteristics of acute inflammation
- Rapid onset
- Vasodilation -> Increased blood flow
- Increased vascular permeability in the microvasculature
- Emigration of neutrophils to site of injury - Mechanism of leukocyte extravasation into site of injury
- Margination of leukocytes
- Rolling -> Transient attachment-detachment mediated by selectin
- Adhesion -> Firm attachment to endothelium mediated by integrin
- Pavementing -> Leukocytes line endothelium
- Transmigration/diapedesis -> Leukocytes crosses endothelium
- Chemotaxis -> Migration towards site of injury due to chemoattractants - Chemoattractants
- Exogenous: Bacterial products
- Endogenous (CILK): C5a, IL-8, Leukotrienes B4, Kallikriene - Chemical mediators causing fever, pain, tissue damage
- IL-1
- Prostaglandin
- Bradykinin
- Reactive oxygen species
What are the different types of acute inflammation? What are the outcomes of acute inflammation?
- Types of inflammation
- Serous inflammation -> Thin fluid from plasma -> Burns
- Fibrinous inflammation -> More severe trauma with larger vessel permeability -> Meningitis
- Suppurative inflammation -> Pus exudate, neutrophils infiltrate, necrotic cells
- Ulcers -> Local defect in surface of organ or tissue - Outcomes of acute inflammation
- Resolution and scarring
- Abscess formation
- Fibrosis
- Chronic inflammation
Describe the sequence of cellular events in acute inflammation. What leukocytes types are characteristics of acute inflammation? Why do neutrophils predominate in the first 6 - 24 hours? What is the role of leukocytes in acute inflammation?
- Sequence of events in acute inflammation
- 6 - 24 hours -> Neutrophils predominate
- 24 - 48 hours -> Macrophages predominate
- Vessel changes
+ Transient vasoconstriction -> Vasodilation -> Increased vascular permeability -> Stasis and congestion
- Promotes leukocytes
+ Margination of neutrophils to walls of endothelium
+ Rolling by transient attachment-detachment mediated by selectins
+ Adhesion mediated by integrins
+ Pavementing of neutrophils lining endothelium wall
+ Transmigration/diapedesis
+ Chemotaxis towards site of injury
+ Leukocyte activating for phagocytosis and release enzyme mediators - Types of leukocytes in acute inflammation
- First 6 - 24 hours -> Neutrophils
- 24 - 48 hours -> Macrophages
- Viral infection -> Lymphocytes
- Hypersensitivity -> Eosinophils - Neutrophils predominate in early inflammation
- More numerous in the blood
- Respond more rapidly to chemokines and cytokines
- Bind more firmly to adhesion molecules - Role of leukocytes
- Recognises opsonin and attaches to molecule
- Killing by engulfment or phagocytosis
- Release of products -> Reactive oxygen species, lysosomal enzymes
What cell types are present in chronic inflammation? What processes mediate the persistent accumulation of macrophages in chronic inflammation? What clinical conditions can cause chronic inflammation? What are the characteristics of chronic inflammation? What products are released by activated macrophages in chronic inflammation?
- Cells types in chronic inflammation
- Macrophages predominantly
- Lymphocytes
- Eosinophils
- Mast cells
- Plasma cells
- Very scarce neutrophils - Macrophages in chronic inflammation
- Continued recruitment of macrophages -> Continued expression of adhesion molecules and chemotactic agents
- Local proliferation of macrophages
- Immobilization of macrophages -> Inhibiting macrophages from leaving - Chronic inflammation seen in
- Persistent infection -> TB, syphillis
- Persistent exposure to foreign substance -> Lipid (Atherosclerosis), silica (Silicosis)
- Autoimmune disease -> RA, IBD - Characteristics of chronic inflammation
- Inflammation over prolonged period
- Predominantly macrophages involved with some lymphocytes and plasma cells
- Simultaneous tissue damage, inflammation and attempts at repair by connective tissue (fibrosis) - Activated macrophages release
- Products causing cell injury -> Reactive oxygen species, nitric oxide, protease enzymes
- Products causing fibrosis -> Growth factors (PGF, TGF)
What is the complement system? Describe the main pathways by which complement activation occurs. How do activated complement products mediate acute inflammation? Of the complements, which are the most important inflammatory mediators?
- Complement system
- Plasma protein system involved in immunity against microbes
- C1 - C9 - Pathways for complement activation
- Classical pathway -> Antigen-antibody complexes causing complement activation
- Alternative pathway -> Microbial surface molecules activating complement
- Lectin pathway -> Lectin binding to carbohydrate on microbe activating complement
- All 3 pathways cause cleavage of C3 -> C3a - Role of complement products in acute inflammation
- Inflammation: C3a, C5a -> Anaphylatoxins -> Increased vascular permeability, release of inflammatory mediators (histamine, prostaglandin)
- Opsonization: C3b -> Opsonizes microbe, activates phagocytes for phagocytosis
- Chemotaxis: C5a -> Chemoattractants -> Attracts leukocytes to site of injury
- Cell lysis: C5 - 9 -> Forms membrane attack complex (MAC) - Most important inflammatory mediator
- C3
- C5
Which mediators of inflammation are derived from cells? Which cells release histamine? What are the effects of histamine in an inflammatory response?
- Inflammatory mediators
- Pre-formed mediators: Histamine, serotonin
- Newly synthesized mediators: Prostaglandins, leukotrienes, cytokines, chemokines, reactive oxygen species, nitric oxide - Cells releasing histamine
- Mast cells
- Basophils
- Platelets - Effects of histamine
- Increased vascular permeability
- Vasodilation
