Inflammation Flashcards
What are the two types of inflammatory response?
Acute
Chronic
What is inflammation?
A non specific response to cellular injury
Designed to remove the cause and consequence of injury
What are the four main signs of inflammation?
Redness (Rubor)
Heat (calor)
Swelling (tumor)
Pain (dolor)
Why is it considered a universal process?
It is seen in all tissues
Obsorved in almost every disease
Caused by a huge range of different stimuli
Every cell in the body can be involved in the inflammatory process
What is the main feature af acute inflammation?
Quick
What happens in inflammation (simple), why does the area become red?
Change In local blood flow
Structural change in microcasvulature
Recruitment/accumulation of immune cells and proteins
What does a Tissue look like in the steady state?
Epithelium
Interstitial space - contains mast cells and macrophages
Vasculature - RBCs, leukocytes, neutrophils
This pretty much applies to all viable vascularised tissue
What happens to a tissue when it is damaged?
- A wound causes non apoptotic cell death and may introduce foreign (pathogens) material
This triggers the immune response
- Mast cells (and others) release vasodilators
Namely histamine and nitric oxide - Cause vascular changes. Increased permeability, dilation, reduces flow, plasma leakage
What benefits does increased vascular permeability and leakage bring?
More possibly specific antibodies that could killl the pathogen
More proteins for cell repair
Leukocyte migration
Provides a barrier
What are some of the main types of soluble mediators released at injury?
Histamine
Prostaglandins
Cytokines
Chemokines
Complement
What is the source of histamine and what does it do?
Comes from mast cells, basophils and platelets
Causes vasodilation, increased vascular permeability, endothelial activation and
What is the source of prostaglandins and what do they do?
Mast cells and leukocytes
Vasodilation, pain, fever
What is the source of cytokines and what do they do?
Eg TNF and IL-1
macrophages, endothelial cells, mast cells
Endothelial activation (adhesion molecules), fever, pain, anorexia, shock
What is the source of chemokines and what do they do?
Leukocytes, activated macrophages
Chemotaxis, leukocyte activation
What is the main source of complement and what do they do?
Eg C5a, C3a and C4a
Plasma
Leukocyte chemotaxis and activation, vasodilation (mast cell activation), opsonisation
What is the name of the fluid that seeps out of blood vessels?
Exudate
Contains proteins and cells (eg blood cells)
Provides a protective barrier against further spread of the cause of inflammation
What happens in immune cell recruitment?
Recruitment and activation signals (chemokines) at the site of damage are produced
These diffuse out to form a gradient
Leukocytes express receptors for these chemokines, allowing them to migrate to the source of the chemokines
What is one of the main chemokines involved in immune cell recruitment?
IL-8
Receptor: CXCR1 and 2 g coupled 7 transmembrane proteins
Secreted from : neutrophils, often the first cell type recruited to the site of inflammation
What are the 4 steps involved in neutrophil extravisation?
- Chemo attraction. Cytokines released by macrophages (IL-1, TNF) causes up regulation of neutrophil adhesion molecules in the endothelium (eg selectins)
- Rolling adhesion. Carbohydrate Luganda in a low affinity state on neutrophils bind to selectins
- Tight adhesion. Chemokines promote change to high affinity binding to Ligands
- Transmigration. Cytoskeletal rearrangement and extension of pseudopodia. Leads to the movement of neutrophils into the interstitia
What do neutrophils do at the site of inflammation?
- Pathogen recognition. Use of TLR4 and CD14 to identify lipopolysaccharides on gram negative bacteria
- Pathogen clearance. Phagocytosis
- Cytokines secretion. Recruitment and activation of other immune cells
If the neutrophil response Is enough, what happens in the resolution of acute inflammation?
- Neutrophils and immune cells kill the pathogen
- Neutrophils have a short half life and turnover of inflammatory mediators (eg histamine) are turned over very quickly
- Macrophages. These clear apoptotic cells, and produce anti inflammatory mediators
- The wound is repaired
What is the difference between acute inflammation and chronic and granulomatous inflammation with respect to antigens?
Acute doesn’t necessarily need an antigen
However chronic often results form prolonged presence of the antigen
What are some examples of diseases involving chronic inflammation?
Rheumatoid arthritis, asthma,
Inflammatory bowel, hepatitis, psoriasis, MS
What are some examples of diseases involving granulomatous inflammation?
TB, leprosy, some tumor reactions, sarcoidosis, crohns
What is different in chronic inflammation that acute?
Same initial start
However, there is a persistent inflammatory stimuli (eg prolonged infection, unclearable particultes, autoimmunity)
There is a distinct immune cell infiltrate. In interstitial space, inflammatory macrophages, T cells, antibody secreting cells (plasma)
Leads to a vicious cycle as the inflammatory agent is not removed. This can lead to bystander tissue destruction
What is the role of macrophages in chronic inflammation?
They are recruited as monocytes. But there are also tissue resident macrophages
GOOD:
Phagocytic, cytotoxic, anti inflammatory, wound repair
BAD:
Cytotoxic, inflammatory, profibrotic
What is the role of lunphocytes in prolonged inflammation
Innate and adaptive work together, can be specific
T CELLS:
Pro inflammatory, cytotoxic, regulatory (reconstruction of tissue)
B CELLS:
Cenrste plasma cells that secrete antibody, clear infection, inflammatory (can cause a viscious cycle and poor more inflammation), can operate locally or remotely
What is granulomatous inflammation?
Chronic inflammation with distinct pattern of granulomatous formation
Caused by the aggravation of activated macrophages, a barrier designed for clearance
Triggered by strong T cell responses. And resistant agents (mycobacterium, tumour)
What are some differences between chronic and acute inflammation?
ACUTE:
Immediate, short lasting, vasodilation, increased vascular permeability, leukocyte response, neutrophils predominate, histamine release, prominent necrosis, leads to completer resolution or chronic inflammation
CHRONIC:
Delayed onset, can last years, persistent inflammation, ongoing tissue injury, attempts at healing, monocytes/macrophages predominate, ongoing cytokines release, prominent scarring, leads to scarring g or loss of function
What are the outcomes (sequaele) of acute inflammation?
The inflammatory agent is cleared
Can lead to the formation of puss which may take longer to clear
Damaged cells are removed
Restoration of normal tissues function
What are the outcomes of acute inflammation?
Excess tissue damage and scarring
Loss of organ function —> organ failure
Wat are some consequences of inflammation and wound healing?
Can lead to collagen deposition forming a scar
In most cases this is fine, however in places such as the lungs it can cause broncho-pneumonia as the walls of the alveoli are no longer very thin
Can lead to loss of function (eg in the heart)
