Inflammation Flashcards
(36 cards)
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
