inflammation Flashcards
What is inflammation?
A complex and tightly regulated process which = Non specific response to cellular injury designed to remove the cause and consequence of that injury
What would happen without inflammation?
We would struggle to heal wounds, fail to fight infection and be susceptible to cellular injury
What are the canonical cardinal signs/features of inflammation? (Acute)
Redness (RUBOR)
Heat (CALOR)
Swelling (TUMOUR)
Pain (DOLOR)
What are the causes of inflammation?
Pathogens, Allergens, Auto-antigens, physical damage, extreme temperatures Non-apoptotic cell death
What cells in our body undergo inflammation?
ALL
When can inflammation occur?
some examples are Infection Autoimmunity Hypersensitivity Trauma Fibrotic disease Cancer
What is acute inflammation?
Short term rapid response non-specific to cellular injury
Instantaneous changes to blood flow
recruitment of immune cells
Why is there a change in blood flow in acute inflammation and what is the sign?
Bc of structural changes that occur in the microvasculature of tissue
Redness on skin
What does the structural change in microvasculature result in ?
(Change in blood flow) &
Accumulation of proteins and fluid and recruitment of immune cells to site of inflammation (swollen)
Where is the interstitium / interstitial layer located?
The intermediate layer between the epithelium and the vascular endothelium
What cells are resident in the interstitium?
Immune cells: Resident macrophages, mast cells
Dendritic cells?
What’s cells are present in the vasculature ?
White blood cells (prominently neutrophils)
Lymphocytes
Plasma and protein contents
What causes the release of signals activating the immune response after damage?
Non-apoptotic cell death ( in tissue and vasculature )
Detection of forgeign
What releases vasodilators ?
Immune cells esp Mast cells (but also basophils and platelets) release them rapidly upon activation/recognition of damage or recognition patterns
What are the 2 main vasodilators?
Histamine, nitric oxide
What vascular changes occur during inflammation?
Increased permeability
Dilation of bv (wider)
Reduced flow
Plasma leakage into interstitial membrane
What are the benefits of increased vascular permeability and leakage?
Increases:
Antibodies
Protein
What vascular changes are caused by vasodilators?
increased permeability
dilation of bv (wider)
reduced blood flow
plasma leakage into the interstitium
In what order do the events occur when there is cellular damage?
- inflammatory signals produced
- vasodilators released
- vascular changes occur
what benefits does increased vascular permeability and leakage bring?
increases:
- amount of ab to site, if specific then may be able to kill patho etc.
- protein in tissue site which allows increased activation of immune cells and source of protein for tissue repair to occur
- physical barrier
- leukocyte migration
What are some soluble mediators released at an injury?
histamine prostaglandins cytokines (TNF, IL-1) chemokines recruitment and production of complement (C5a, C3a, C4a)
What is the primary sources of histamine and what are its actions?
- Mast cells, basophils, platelets
- vasodilation, increased vascular permeability, endothelial activation
What are prostaglandins produced by and what actions do they carry out?
- Mast cells, leukocytes
- vasodilation, PAIN AND FEVER
What are cytokines produced by and what are their functions?
(TNF, IL-1)
- MACROPHAGES, endothelial cells, mast cells
- endothelial activation (Adhesion molecules), fever, malaise, pain, anorexia - lethargy, shock
What are chemokines released by and what are their functions?
- Leukocytes, activated macrophages
- chemotaxis, leukocyte activation
Where is complement produced and what is the function?
prod in the liver but the principle source is plasma
-Leukocyte chemotaxis and activation, vasodilation mast cell stimulation), opsonisation
What is exudate?
fluid, proteins and cells that have seeped out of bv into inflamed tissue as a result of the endothelium becoming more permeable
What does exudate form and why is this beneficial?
forms a separation between inflamed and healthy tissue:
acts as a physical barrier between site of inflammation and healthy tissue:
limits patho + inf stimuli from migrating into healthy tissue + causing further damage
what causes immune cell recruitment?
happens as a result of the inflammatory signals produced by immune cells and stromal cells at the site of inflammation
chemokines produced
what do chemokines do to recruit immune cells?
diffuse into the nearby vasculature and create a gradient
also act on endothelial cells themselves to promote this
How do leukocytes in the vasculature migrate to chemokines source?
they have complimentary chemokine receptors which allow them to migrate towards the source
What is an example of a chemokine?
IL-8
receptors of it most prominently expressed by neutrophils which are often the first cell type recruited to site of inflammation
How do neutrophils migrate from bv to interstitium and site of inflammation?
neutrophil extravasation which is rapid
First step of neutrophil extravasation
- chemo-attraction: cytokines and chemokines produced at site of inflammation which act on the endothelial layer to promote upregulation of adhesion molecules such as selectins
Second step
2.rolling adhesion: carbohydrate ligands in a low-affinity state on neutrophils bind selectins - neutrophils recognise the selectins and they start to interact w the endothelium and undergo rolling adhesion (gently interact w endothelial layer whilst migrating along bv)
Third
- tight adhesion - chemokines promote low to high-affinity switch in integrins which enhances binding of neutrophil binding to the endothelial wall
Fourth
Transmigration of neutrophil through the endotheial wall
-involves cytoskeletal rearrangement of np & extension of membrane pseudopodia through the endothelial wall
mediated by PECAM molecules on both sides (endothelial and neutrophil)
What are the functions of neutrophils at the site of inflammation?
Pathogen recognition
Pathogen clearance
cytokine secretion
phagocytosis
