Acute Inflammation Flashcards
What are the primary cells in acute inflammation?
Neutrophils
What are the primary cells in chronic inflammation?
Lymphocytes
What are the 2 main causes of acute inflammation?
- Infection
- Tissue necrosis
Goal is to eliminate pathogen or clear necrotic debris
What will a patients white count be after an MI?
Raised (predominantly neutrophils)
What does innate immunity include?
- Epithelium
- Mucus
- Complement
- Mast cells
- Macrophages
- Neutrophils
What are toll like receptors present (TLRs) on?
Innate immune system cells
- Macrophages and dendritic cells
What do TLRs recognise?
PAMP
- Pathogen associated molecular patterns
What does CD14 on macrophages recognise?
LPS (lipopolysaccharide) on the outer membrane of gram -ve bacteria
- A form of PAMP
TLR activation results in the upregulation of what?
NF-kB
- Transcription factor
- Molecular switch which turns of acute inflammatory response - multiple immune mediators turned on
What enzyme releases arachadonic acid from the phospholipid cell membrane?
Phospholipase A2
What enzymes act on Phospholipase A2?
- Cyclooxygenase (COX)
- 5- Lipooxygenase
What does the cyclooxygenase pathway (from arachadonic acid) produce?
Prostaglandins (PG)
- PGI2, PGD2, PGE
What do PGI2, PGD2 and PGE3 mediate?
Vasodilation and increases vascular permeability
What prostaglandin mediates vasodilation, increases vascular permeability AND mediates fever and pain?
PGE2
- “E2 fEver”
What does 5-lipooxygenase produce?
Leukotrienes
What does LTB4 do?
Attracts and activates neutrophils
What do LTC4, LTD4 and LTE4 do?
- Mediate vasoconstriction
- Bronchospasm
- Increase vascular permeability (contraction of pericytes)
What are the 4 key mediators that attract and activate neutrophils?
- LTB4
- C5a
- IL-8
- Bacterial products
What cells lie below endothelial cells and are located above the BM?
Pericytes
What do pericytes do when contracted?
Opens up space between endothelial cells
- Allows leakage of fluid into interstitium
What are mast cells activated by?
- Tissue trauma
- Complement proteins C3a and C5a
- Cross-linking of cell-surface IgE by antigen
Where are mast cells found?
Widely distributed throughout multiple connective tissues
What do mast cells immediately release and what do these granules do?
Preformed histamine granules
- Mediates vasodilation of arterioles and increase vascular permeability (post-capillary venule)
What is produced by mast cells in the delayed response?
- Arachadonic acid metabolites
- Particularly leukotrienes
What is the classical pathway?
C1 binds to IgG or IgM that is bound to antigen
What is the alternative pathway?
Microbial products directly activate complement
What is the mannose-binding lectin pathway?
MBL binds mannose on microorgansims and activates complement
What are the convertases?
C3 convertase and C5 convertase
What does C5b complex with to create?
C6 - C9
- To create the Membrane attack complex
What do C3a and C5a trigger?
Mast cell degranulation
What complement product acts as a chemotactic factor for neutrophils?
C5a
What does C3b act as?
Opsonin for phagocytosis
What is Hageman factor?
Where is it located?
What is it activated upon?
- Inactive proinflammatory protein produced in liver
- Activated upon exposure to subendothelial or tissue collagen
What can gram -ve organisms activate to cause DIC?
Hageman factor
What does Hageman factor activate?
- Coagulation and fibrinolytic systems
- Complement
- Kinin system - cleaves HMWK to bradykinin, which mediates vasodilation, increased vascular permeability and pain
What are the 2 main substances which mediate pain?
- PGE2
- Bradykinin
Sensitize sensory nerve endings
What 3 substances cause vasodilation and relaxation of arteriolar SM (causing rubor and calor?
- Histamine (primarily)
- PGs
- Bradykinin
What does swelling in inflammation come from?
Leakage of fluid from postcapillary venules into interstitial space
What 2 factors cause tumor?
Tissue damage and histamine
How does fever occur?
- Pyrogens cause macrophages to release IL-1 and TNF
- Increase COX activity in perivascular cells of hypothalamus
- Increased PGE2 raises temperature set point
