Inflammation Flashcards
What is inflammation?
- Inflammation is non-specific response to cellular injury
- Designed to remove the cause and conseuqnce of injury
- Complex tightly regulated process
What are the causes of inflammation?
- Pathogens
- Allergents
- Autoantigens
- Physcial damage
- Extreme temperature
- Non-apoptotic cell death
What are disease causing inflammation?
- Infection
- Autoimminity
- Hyoersensitivity
- Trauma
- Fibrotic disease
- Cancer
What are the cell types in inflammation?
- Epithelial cells
- Endothelial cells
- Neutrophils
- Macrophages
- Lymphocytes
- Eoisingphils
- Mast cells
What is acute inflammation?
- Inflmmation is rapid response non-specific response to cellular injury
- Change in local blood flow - structural changes in microvasculature - recruitment/accumulation of immune cells and proteins
1. Steady state
2. Damage
What is damage in acute inflammation?
- Inflammatory signals: nonapoptoic cell death, detection of forge in in material
- Vasodilators rebased: histmaine, nitric chide
- Vascular changes: increased permeability, dilation, reduced flow, plasma leakage
What are examples of soluble mediators?
- Histamine
- Prostaglandins
- Cytokines (TNF, IL-1)
- Chemokines
- Complement (C5a, C3a, C4a)
Describe histamine
Principle Source: mast cells, basophils, platelets
Actions: vasodilation, increased vascular permeability, endothelial activation
Describe prostaglandins
Principle Source: mast cells, leukocytes
Actions: vasodilation, pain, fever
Describe cytokines (TNF, IL-1)
Principle Source: macrophages endothelial cells, mast cells
Actions: endothelial activation (adhesion meoclules), fever, malaise, pain, anorexia, shock
Describe chemokines
Principle Source: leukocytes, activated macrophages
Actions: chemotaxis, leukocytes activation
Describe complement (C5a, C3a, C4a)
Principle Source: plasma (produced in the liver)
Actions: leukocytes chemotaxis and activation vasodilation (mast cell stimulation), opsonisation
What is exudate?
Fluid proteins cells that have seemed out of a blood vessel
What is immune cell recruitment?
-Recruitment and inflammation signals at the site of manage e.g. chorines produced
-Chemokines diffuse out to form a gradient
-Leukocyytes expressing complementary chemokine receptors receptors migrate toward the chemokine source
E.G. Chemokine: CXCL8 otherwise known as IL-8
Receptors: CXCR1 and CXCR2, g-coupled 7-transmembrane proteins
Cell type: Neutrophils. Often the first cell type recruited to the site of inflammation
What happens during neutrophil extravasation?
- Chemoattraction: cytokines - endothelial upregualtion of adhesion molecules e.g. selections
- Rolling adgension: carbohydrate ligands in a low affinity state on neutrophils bind selectness e.g. PSGL1 (selectin P ligand) binds P and E-selectins
- Tight adhesion: chemokine promote low to high affinity switch in integrins LFA-1, Mac-1 – enhance binding to ligands e.g. ICAM-1/2
- Transmigration: - Cytoskeletal re-arrangement and extension of pseudopodia. Mediated by PECAM interactions on both cells.
What is the function of a neutrophil at sight of inflammation?
- Pathogen recognition: e.g. use of TLR4 and CD14 to identify lipopolysaccharides (LPS) present in gram-negative bacteria
- Pathogen clearance: phagocytosis, netosis
- Cytokine secretion: recruitment and activation of other immune cells
- Phagocytosis: -Large particles engulfed into membrane bound vesicles (phagosomes)-Phagosome fuses with lysosome (vesicles containing enzymes e.g. elastase and lysozyme) -> phagolysosome -Ractive oxygen species (ROS) – phagocyte NADPH oxidase -Antimicrobial peptides – e.g. defensins.
What is the resolution of acute inflammation?
- Pathogen recognition: Immune cells (e.g. neutrophils) and antimicrobials (e.g. antibodies) will infections or particulates.
- Short half life: -Neutrophils (especially activated) have a rapid half-life-inflammatory mediators are turned over rapidly
- Macrophages: -Clear apoptotic cells -Produce anti-inflammatory mediators
- Repair/wound healing: -Covered in the after online material (seals any gaps in membrane)
What are the reasons for chronic inflammation?
Chronic inflammation: e.g. rheumatoid arthritis, asthma, glomerulonephritis, hepatitis, psoriases, MS, IBS
- Persistent inflammatory stimuli: persistent/prolonger infection e.g. YB, hepatitis B/C, persistent toxic simuli e.g. allergens, pollutes, unclear able particulates e.g. silica, autoimmunity e.g. self antigens
- Distinct immune cell infiltrate: inflammatory macropages, T cells and other lymphocytes, plasma (antibody secreting) cells
- Viscous cycle: no clearance of inflammatory agent, bystander tissue destruction, concurrent repair processes (fibrosisi and abiogenesis)
What are the good and bad parts of macrophages?
- Can recruited as monocytes to the site of inflammation but ALSO tissue resident
- GOOD: phagocytic, cytotoxic, anti-inflammatory (e.g. TGF-beta, IL-10), wound repair
- BAD: cytotoxic, inflammatory, pro-fibrotic
What are T cell lymphocytes?
- Innate and adaptive immune cells work together
- T cells in inflammation
- pro-inflammatory (e.g. TNF, IL-17, IFN-γ)
- Cytotoxic (e.g. granzymes, perforin)
- Regulatory (e.g. TGF-β)
What are B cell lymphocytes?
- Generate plasma cells that secrete antibody.
- Protective, clearing infection
- Inflammatory, driving reactions against self
- Can either be local to inflammatory site, or operate remotely
What is part of granulomatous inflammation?
- Granulomatous inflammation: e.g. TB, leprosy, foreign body granuloma, tumour reactions, sarcoidosis, Crohn’s disease
- Chronic inflammation with distinct pattern of granuloma formed
- Aggregation of activated macrophages and a barrier designed for clearance
- Triggered by strong T cell responses
- Resistant agents (e.g. mycobacterium tumour)
- Granuloma: ball of activated lymphocytes and macrophages
- Giant cells: fused macrophages with horseshoe-shaped nuclei
What are the features of acute inflammation?
- Immediate onset; lasts a few days
- Vasodilation, increased vascular permeability, leukocyte response
- Neutrophil predominate
- Histamine release
- Prominent necrosis
- Outcomes include: complete resolution / progression to chronic inflammation
What are the features of chronic inflammation?
- Delayed onset: may last weeks, months or years
- Persistent inflammation, ongoing tissue injury, attempts at healing
- Monocytes/macrophages predominate
- Ongoing cytokine release
- Prominent scarring
- Outcomes include: scarring / loss of function
What are the possible positive outcomes of acute and chronic inflammation?
clear inflammatory agent, removed damaged cells, restore normal tissue function
What are the possible negative outcomes of acute and chronic inflammation?
excess tissue damage, scarring, loss of organ function-organ failure
What does wound healing lead to?
Leads to extracellular matrix (e.g. collagen) deposition
What are the consequences of inflammation?
- Broncho-pneumonia
- Scarring
- Wound healing in sensitive tissue
What are key features of chronic inflammation?
- cytokines
- caused by persistent damage (e.g. persistent infection, autoimmunity)
- form Granulation tissue
What are the histology of chronic inflammation?
Lots of macrophages, lymphocytes and plasma cells
What is the difference between chronic and acute inflammation with onset?
Acute:
-Immediate onset; lasts a few days
Chronic:
-Delayed onset; may last weeks, months or years
What is the difference between chronic and acute inflammation with vascular?
Acute:
-Vasodilation, increased vascular permeability, leukocyte response
Chronic:
-Persistent inflammation, ongoing tissue injury, attempts at healing
What is the difference between chronic and acute inflammation with histology?
Actue:
-neutrophils predominate
Chronic:
-Monocytes/macrophages predominate
What is the difference between chronic and acute inflammation with release?
Acute:
-Histamine release
Chronic:
-Ongoing cytokine release
What is the difference between chronic and acute inflammation with prominence?
Acute:
-Prominent necrosis
Chronic:
-Prominent scarring
What is the difference between chronic and acute inflammation with outcome?
Acute: -Complete resolution -Progression to chronic inflammation Chronic: -Scarring -Loss of function
