inflammation Flashcards
- What is inflammation?
- What initiates inflammation?
Protective biological process that helps to remove damaged cells and clear toxins and infections
Non-specific response to cellular injury
Initiated when cellular damage (non-apoptotic cell death) leads to the release of damage associated molecular patterns (DAMPs) or the body detects pathogen associated molecular patterns (PAMPs)
causes cells in tissue to release a range of signals designed to induce inflammation
- What can chronic inflammation lead to?
- What is acute inflammation characterised by?
- How does Chronic inflammation occur?
Scarring and loss of tissue function due to repetitive rounds of inflammation
Rapid onset, and recruitment of innate immune cells, particularly neutrophils.
When acute inflammation cannot get rid of the inflammatory signal
adaptive immune cells recruited
- What are the 4 main signs of acute inflammation?
Redness (rubor)
Heat (calor) Swelling (tumour) Pain (dolor)
- List causes of inflammation
Pathogens
Allergens Auto-antigens Physical damage Extreme temperatures Non-apoptotic cell death
- What does the body release when there is damage done (e.g. wound in skin) ?
- What is the purpose of these chemicals?
Vasodilators (Histamine and nitric oxide)
Vascular changes:
Increased permeability
Dilation
Reduced flow
Plasma leakage into inflamed site
- What benefits do increased leakage and vascular permeability have?
Increases antibodies to site
increased proteins (inc activation of immune cells and provides proteins for tissue repair)
physical barrier
increased leukocyte migration
- What are the principle sources of Histamines and what are its actions?
- What are the principle sources of Prostaglandins and what are its actions?
Mast cells, basophils and platelets
Vasodilation, increased vascular permeability, endothelial activation
Mast cells & leukocytes Vasodilation, pain, fever
- What are the principle sources of Cytokines and what are its actions?
- What are the principle sources of Chemokines and what are its actions?
Macrophages, endothelial cells, mast cells
Endothelial activation, fever, malaise, pain, anorexia, shock
Leukocytes & activated macrophages Chemotaxis & leukocyte activation
- What are the principle sources of Complement and what are its actions?
- What is Exudate and what is it’s purpose?
Plasma (in liver)
Leukocyte chemotaxis & activation, opsonisation
Fluid containing proteins and cells that have seeped out of a blood vessel during inflammation acts as barrier and prevents leakage of inflammatory stimuli and harmful pathogens to surrounding tissue
- Outline the process of immune cell recruitment?
At the site of damage, inflammation and recruitment signals (e.g. chemokines) are produced, which diffuse out to form a gradient.
Leukocytes that have complementary chemokine receptors move to the chemokine source
- What is CXCL8 also known as?
- What receptors bind to the chemokine CXCL8?
- Which cell type most prominently expresses these receptors that bind to CXCL8?
Interleukin-8 (IL-8)
CXCR1, CXCR2, These are g-coupled transmembrane proteins Neutrophils This is why they are often the first cell type to be recruited to the site of inflammation
- List and explain the 4 steps of neutrophil extravastion?
- Chemo-attraction - production of cytokines and chemokines at the site of inflammation → endothelial up-regulation of adhesion molecules
- Rolling adhesion - Neutrophils have carbohydrate ligands in a low affinity state which bind to selectins (E.g. PSG1 - selectin P ligand)
- Tight adhesion - chemokines promote low→ high affinity switch integrins - enhances binding of neutrophil to endothelial wall
- Transmigration through endothelial wall → cytoskeletal rearrangement and extension of pseudopodia
- What is the last step of neutrophil extravasation mediated by?
- What 3 main things do neutrophils do at the site of inflammation?
PECAM interactions on both endothelial side and neutrophil side
1. Pathogen recognition e.g. - use of TLR4 & CD14 to identify lipopolysaccharides present in gram-negative bacteria 2. Pathogen clearance - phagocytosis and netosis 3. Cytokine secretion - Recruitment and activation of other immune cells
what is the process of phagocytosis?
what else do phagocytes have that help with killing cells?
large particles are engulfed into a vesicle (phagosome)
phagosome fuses with a lysosome (vesicle containing elastase and lysozymes)
forms a phagolysosome
reactive oxygen species- phagocyte NADPH oxidase
antimicrobial peptides - eg defensin
- What is the function of macrophages in the resolution of acute inflammation?
Clear apoptotic cells
Produce anti-inflammatory mediators
- What is a hapten?
- What is the antigen type which independently can be capable of driving an immune response in the absence of additional substances?
Small molecule that alone does not act as an antigen but when bound to a larger molecule can create an antigen
Immunogen
- What is the difference between acute and chronic inflammation?
- What makes chronic inflammation a vicious cycle?
- what is the distinct immune cell infiltrate from chronic inflammation
Chronic is a persistent inflammation → prolonged infection → persistent toxic stimuli
No clearance of inflammatory agent Bystander tissue destruction Concurrent repair processes (fibrosis and angiogenesis)
inflammatory macrophages
T cells
plasma cells
what are examples of persistent inflammatory stimuli?
unclearable particulates eg silicon
allergens/ pollutants
persistent/ prolonged infection
autoimmunity
What are examples of chronic inflammation?
Multiple sclerosis Hepatitis rheumatoid arthritis inflammatory bowel disease asthma psoriasis glomerulonephritis
- What form are macrophages recruited as in the site of inflammation?
- List some advantageous things about macrophages
monocytes
Phagocytic - good at clearing apototic cell bodies and foreign materials
Cytotoxic - can clear infection
Anti-inflammatory - suppress immune response
Wound repair
- List some disadvantageous things about macrophages
Cytotoxic - if can’t clear infection they damage tissue
Inflammatory Pro-fibrotic - excessive formation of collagen → fibroblast proliferation
- What can T cells do in inflammation?
Pro-inflammatory (eg TNF, IL-17, IFN gamma)
Regulatory (TGF- beta) Cytotoxic (e.g. granzymes, perforin)
- What do T cells allow in an immune response to inflammation?
- What do B cells do in inflammation?
Specificity to occur, (can also guide macrophages)
Generate plasma cells → antibodies Protective - clearing infection Also pro-inflammatory
- What is granulomatous inflammation?
- What is a granuloma?
Chronic inflammation with distinct pattern of granuloma formation
Aggregation of activated macrophages → barrier designed for clearance
- What triggers granulomatous inflammation?
- What are examples of granulomatous inflammation?
Strong T cell responses
Resistive agents (e.g. mycobacterium, tumour)
tumour formation Crohns disease Leprosy TB Sarcoidosis Foreign body granuloma
- Compare the outcomes of acute and chronic inflammation?
- What are released in acute and chronic inflammations respectively?
- What leukocyte is dominant in each inflammation?
Acute - Complete resolution or Progression to Chronic Inflammation
Chronic - Scarring & Loss of function
Acute - histamine release Chronic - ongoing cytokine release
Acute- neutrophil
Chronic- monocyte/ macrophage
- List some positives outcomes of acute and chronic inflammation
- List some negatives outcomes of acute and chronic inflammation
Clear inflammatory agent
Remove damaged cells
Restore normal function
Excess tissue damage Scarring Loss of organ function → organ failure
- What is the major cause of these negatives of inflammation?
- What does wound healing lead to?
The inflammatory agent not being removed
Extracellular matrix (collagen) deposition
