Inflammation Flashcards
What does Inflammation consist of?
Started at non-apoptotic cell death leading to DAMPS and PAMPS
Can be Acute, and involves recruitment of neutrophils to vascularised tissue.
Can become Chronic if response cannot remove the inflammatory stimuli.
What are the four main signs of acute inflammation?
Redness
Swelling
Heat
Pain
What Benefits does increased vascular permeability during inflammation bring?
Causes leakage: Increases antibodies Increases proteins ( tissue repair ) Increases barrier ( physical ) Increases leukocyte migration
Which 2 Vasodilators are released when inflammatory signals are released by non-apoptotic death/foreign material
Histamine
Nitric Oxide
Where are TNF, IL-1 cytokines released from and what do they do?
By Macrophages, endothelial cells and mast cells
causes : endothelial activation, fever, pain, anorexia, shock, malaise
Where are Chemokines released from and what do they do?
From Leukocytes and activated macrophages
Cause: chemotaxis and leukocyte activation
What Complement components are released and what do they do in response to injury?
Found in plasma, made in the liver
Cause: Leukocyte chemotaxis and activation
Vasodilation, Mast cell stimulation, Opsonisation.
Where are Prostaglandins released from and what do they do?
From Mast cells and Leukocytes
Cause : Vasodilation, pain, fever
Where is Histamine released from and what does it cause?
From Mast cells, Basophils and Platelets
Cause : Vasodilation, increased vascular permeability, endothelial activation
What is Exudate?
An exudate is any fluid, proteins and cells that filters from the circulatory system into lesions or areas of inflammation. Seeped out of blood vessel
Forms a barrier
How are cell recruited to site of damage?
Chemokines diffuse creating a gradient to which the leukocytes with the complementary receptors migrate towards.
How is Chemokine CXCR8 / IL-8 used for cell recruitment?
Gradients towards receptors:
CXCR1/CXCR2 g coupled receptors
Neutrophils recruited
Describe Neutrophil extravasation in 4 steps?
- Chemo-attraction (endothelial creates adhesion molecules)
- Rolling Adhesion (ligands on neutrophils bind to the selectins - adhesion molecule)
- Tight Adhesion (low affinity binding in step 2 becomes high affinity due to chemokines)
- Transmigration (pseudopedia extension from cytoskeleton- mediated by PECAM interactions)
How to neutrophils recognise pathogens?
TLR4 ( transmembrane protein )
CDI4 ( receptor )
These identify Lipopolysaccharides ( LPS ) present in gran negative bacteria
What three roles can Neutrophils play at the site of inflammation?
Pathogen clearance: Phagocytosis and Netosis
Cytokine secretion: Recruitment and activation of other immune cells
Phagocytosis: Engulfed into phagosomes. Fuse with lysosome to form phagolysosome. Reactive oxygen species phagocyte NADPH oxidase
How is Acute inflammation resolved?
Cells recruited have short half lives
Macriphages can clear apoptotic cells and produce anti-inflammatory mediators
Repair/wound healing
What is an Antigen?
Molecule recognised by antibody
What is an Immunogen?
Antigen independently capable of causing immune response without additional substances
What is a Hapten?
Small molecule which when bound to a larger can create an antigen
Examples of Chronic inflammation diseases?
Rheumatoid arthiritis Asthma IBS Hepititis Multiple sclerosis
What diseases are associated with granulomatous inflammation?
TB
Leprosy
Crohns disease
What are the distinct immune cell infiltrates for Chronic Inflammation?
Inflammatory macrophages
T cells
Plasma cells
- it is a cycle with not clearance of inflammatory agent
Bystander tissue is destroyed
Concurrent repair process
What Good macrophages are there?
Phagocytic
Cytotoxic
Anti-Inflammatory - TGF-beta, IL-10
Wound repair
What bad macrophages are there?
IF these are not cleared away e.g. chronic inflammation, can cause damage
Cytotoxic
Inflammatory
Pro-fibrotic
Which T cells can be found involved with inflammation?
Pro-inflammatory: TNI, IL-17, IFN-gamma
Cytotoxic: Granzymes, perforin
Regulatory: TGF-beta
How are B cells involved with inflammation?
Create Plasma cells for antibodies
Clear infection
Could drive reaction against self
Can be local to site or operate remotely
What are the characteristics of Granulomatous inflammation?
Triggered by strong T cell responses and resistent agents causing Chronic inflammation with granuloma formation
Aggregation of activated macrophages
A barrier is designed for clearance
What are some differences between Chronic inflammation?
Acute vs Chronic
quick onset - delayed onset
neutrophils - macrophages
necrosis - scarring
resolution - scarring/loss of function
How are wounds healed?
Fibrosis : ECM - Collagen deposition = scars
Angiogenesis
- Scars can cause loss of function e.g. broncho pneumonia
