Inflammation Flashcards
What is inflammation?
A non-specific immune response to cellular injury designed to remove the cause & consequences of injury
What are the conical features of inflammation?
Redness (Rubor) Heat (Calor) Swelling (Tumor) Pain (Dolor) Loss of function (Functio laesa)
What are the causes of inflammation?
Pathogens, allergens, autoantigens, physical damage, extreme temperatures, non-apoptotic cell death
What is acute inflammation?
Short term rapid response non-specific to cellular injury
Instantaneous changes to blood flow
recruitment of immune cells
What occurs to vasculature during acute inflammation?
Structural alterations to the microvasculature
Transient vasoconstriction of arterioles following vasodilation of arterioles and capillaries
Results in increased blood flow to the tissue, presenting rubor and callor
What cells are resident in the interstitium?
Resident macrophages, dendritic cells, mast cells
Where is the interstitium located?
The intermediate layer between the epithelium and the vascular endothelium
What generates inflammatory signals?
Non-apoptotic cell death (Damage-associated molecular patterns)
Pathogen-associated molecular patterns - lipopolysaccharides
Vasodilator release
Name the two main vasodilators:
Nitric oxide and histamine
How are vasodilators released from mast cells?
Mast cell degranulation
What is mast-cell degranulation?
The fusion of lysosomes and secretory vesicles to exocytose compounds
What effect does increased blood flow have in the local area of inflammation?
Locally raised temperature reduces the effectiveness of pathogen reproduction
What effect does histamine exert?
Increased permeability of vascular endothelium, resulting in an exudate forming within tissues,
Cells in walls withdraw from each other (diapedesis), leaky capillaries, the formation of tissue fluid
What is exudate?
Protein-rich fluid
What does exudation and increased blood flow result?
Stasis of circulation in area
Which cells release histamine?
Mast cells, basophils and platelets
What are the benefits of increased vascular permeability?
Increased antibody and leukocyte presence, increased availability of protein and formation of the barrier.
What is the cytokine network?
Interaction between macrophages and CD4 t cells
What inflammatory factor is released from macrophages?
Interleukin-1
GM-CSF
What is the function of IL-1?
Generates chemotactic signal of chemokines, activates T-cells
What is the role performed by IL-12?
Activates Th1, and NK cells
How is chemotaxis achieved?
Chemokines diffuse out to establish a chemical gradient, leukocytes expressing complimentary chemokine receptors migrate towards to chemokine source
What is CXCL8?
IL-8
Which cell secrete CXCL8?
Macrophages
What is the role of CXCL8?
Chemotactic attract for neutrophils , neutrophil migration to the site of infection
What receptors do CXCL8 bind to?
G-coupled 7-TM proteins (CXCR-1/2)
Which cells are the initial responders to inflammation?
Neutrophils
How do cytokines influence adhesion molecules?
Upregulates endothelial production of adhesion molecules
Which cell secretes chemoattract cytokines?
Macrophages
What is the main example of an adhesion molecule?
E and P-Selectins
What is the first step of neutrophil migration?
Rolling and adhesion
Describe the neutrophil binding with the endothelial cell surface:
Establishes reversible binding between selectins induced on the endothelial cell surface and carbohydrate ligands in a low-affinity state
Which ligand binds onto P and E-selectins?
PSGL-1 (Selectin-P ligand)
Which switch ensures that there is a tight adhesion to the endothelial surface?
Low to high-affinity switch in integrins
What are the two integrin ligands?
LFA-1, MAC-1 (high affinity)
Which factors promote the low-high affinity switch in neutrophil tight adhesion? (Selectin –> integrin-mediated)
IL-8
C5A
Leukotriens LTB4
Formylated peptides and platelet activating factor
Which molecule presented on the endothelial surface interacts with the neutrophil integrins, MAC-1, LFA-1?
ICAM-1/2
Which chemotaxin gradient do neutrophils migrate across?
IL-8
Which molecule secreted by endothelial cells stimulates diapedesis?
CD99
How do infiltrating neutrophils pass through the endothelial membrane?
Disrupts the interactions of junction adhesion molecules (JAM) and vascular endothelial cadherins (VE-cadherin)
How is the rearrangement of the cytoskeleton of pseudopodia caused during the neutrophil invasion?
PECAM interactions
Which cells release prostaglandins?
Mast cells, leukocytes
What action do prostaglandins exhibit?
Vasodilation, pain, fever
Which cells secrete TNF, and IL-1?
Macrophages, endothelial cells, mast cells
What is the role performed by TNF & IL-1?
Endothelial activation (adhesion molecules) fever, malaise, pain, and anorexia, shock
Which cells secrete chemokines?
Macrophages and leukocytes
What is the role performed by chemokines?
Chemotaxis
Leukocyte activation
Which receptors identify pathogen-associated molecular patterns (PAMPs)?
Toll-like receptors
CD14
Give an example of a PAMP?
Lipopolysaccharides present on gram-negative bacteria
Which enzymes are secreted by lysosomes?
Lysozyme and elastase
What is the role of reactive oxygen species & NADPH oxidase?
Secreted to interfere and disrupt microbial function
What is netosis?
Hint: NETs
Neutrophil extracellular traps (NETs) are networks of extracellular fibres composed of neutrophil DNA which bind pathogens
How long is the half-life of activated neutrophils?
Short half-life
What is the resolution of an acute inflammatory response??
Clearance of apoptotic cells and produce anti inflammatory mediators
Repair: ECM & granularof formation
What are the sensory stimulatory signals transmitted by nociceptor neurons?
PGEs and histamines
What is chronic inflammation?
Arises as a response to injury with associated
Fibrosis occurring over a prolonged period of time in comparison with acute inflammation
The formation of which structure characterizes chronic inflammation?
Granulomas
Why does chronic inflammation occur?
Persistent exposure to stimuli
What are the examples of persistent stimuli?
Infection (TB, Hepatitis)
Pollutants and allergens
Inclearable particulates
Auto-immunity
Which cells are involved in chronic inflammation?
Inflammatory macrophages
T cells
Plasma cells
What are the roles performed by macrophages?
Phagocytosis of pathogens & necrotic cells
Recognize and engulf apoptotic cells
Anti-inflammatory responses through cytokine release
Antigen-presenting cells
Promotes tissue repair through stimulating angiogenesis and fibrosis
Whare are regulatory T cells? (Treg)
Regulate the effector and activation stages of T-cells, secretes IL-10
Downregulates macrophages
What is granulomatous inflammation?
Chronic inflammation with a distinct pattern of granuloma formation
What are granulomas?
Aggregation of activated macrophages forms when the immune system attempts to form a clearance barrier, surrounding the pathogen
Prevents infection spread.
Compare the onset of acute and chronic inflammation:
Immediate onset (lasts few days) v Delayed onset (Last weeks, months, years)
Compare the immune cells present in both types of inflammation:
Neutrophils
V
Macrophages & Monocytes
What are the chemical releases in acute and chronic inflammation?
Histamine
v
Cytokine release
What are the outcomes of acute inflammation?
Complete resolution
Progression to chronic
What are the outcomes of chronic inflammation?
Scarring
Loss of function
