Inflammation Flashcards
What are the ten reasons why inflammation is important?
- Pathogenic basis of many diseases
- Roles in triggering immunity
- A set of processes that keeps us alive
- Most AI drugs work by preventing formation or actions of mediators
- Works on a daily basis
- Deficiency in a segment of inflammation can cause severe diseases
- Complex relationship inflammation/cancer
- Dysregulation of inflammation: lethal or chronic, debilitating diseases
- Problems caused by AI drugs (iatrogenic)
- Angiogenesis (ageing, tissue remodeling)
What is the ultimate goal after an injury?
Stabilization of the tissue
Describe the general pathway for what happens when you are exposed to microorganisms
Microorganism may pass epithelial or secretion barriers
Innate immune cells are ready to target anything foreign and will eliminate what they can really quickly
Macrophages may be activated for phagocytosis
The antigen may drain to the lymph node which may cause further exposure to NK cells and macrophages
Adaptive immunity will then kick in later
Define inflammation and list its two categories
“Inflammation is the reaction of vascularized living tissues to local injury or infection, characterized by the movement of fluid and leukocytes from the blood into the affected tissue”
2 main categories:
1. Acute
2. Chronic
A coordinated set of processes through which the host attempts to localize and eliminate micro-organisms, damaged cells, inanimate foreign particles, or antigens
List three roles of inflammation
Defence against microorganisms
Initiation of the healing process
Elimination of damaged cells, inanimate foreign particles
Acute inflammation has a ____ onset, relatively ____- lived, stereotypic response to injury or infection, characterized by the _______ out of the ____ and into the ____
Rapid onset Short-lived Movement of fluid and neutrophils Blood Affected tissue
T/F:
Often an acute inflammatory response evolves into a chronic one
False
Rarely becomes chronic
Main aim is to fix the problem and not let it get worse
What are some negative aspects about inflammation?
• Acute inflammation: o Appendicitis (possibility of perforation due to excessive pus formation) o Meningitis (intra-cranial pressure)
• Chronic inflammation:
o Tuberculosis (impairment of lung function)
o Arthritis (incapacitation)
o Initiation of cancer?
List some cells involved in inflammation
Neutrophils
Endothelial cells
Macrophages
Fibroblasts
Select the wrong answer:
Neutrophils kill microorganisms
Endothelial cells regulate movement of protein from blood into the tissue
Macrophages degrade fibrin/debris, kill microorganisms and secrete cytokines (regulatory molecules)
Fibroblasts secrete collagen and express adhesion molecules
Fibroblasts secrete collagen BUT DON’T EXPRESS ADHESION MOLECULES
Endothelial cells express adhesion molecules to assist neutrophils to pass into cells
Exudate has ___ protein content
High
T/F:
Pus occurs all the time
False
Occurs sometimes
List the 4 cardinal signs of inflammation
Redness
Heat
Swelling
Pain
T/F:
The heat and redness associated with inflammation occurs because of fluid movement from blood into the tissue (exudation)
False
Heat and redness occurs due to increased blood flow (hyperaemia or erythema)
Swelling is caused by fluid movement from blood into tissues
Define pus
inflammatory exudate containing viable and dead neutrophils, cell debris, viable and dead micro-organisms, protein, lipid, DNA etc
What is supparation?
The formation of pus
What is purulent?
Consisting/containing/secreting pus
_____ causes heat and redness
Hyperaemia
passage of larger than normal volumes of blood through a tissue
T/F:
Hyperaemia is specific to inflammation
False
Hyperaemia is needed for the formation of ____
exudate
Explain the role of vasodilation during hyperaemia
Vasoactive mediators act on the smooth muscle cells of arterioles
Smooth muscle cells relax and the arterioles dilate= vasodilation
Capillaries that were ‘dormant’ now start to carry blood
More blood is now flowing through the microvascular bed and thus the tissue
For exudation to occur, there must be increased _______
Vascular permeability
T/F:
Fluid moving from blood into the affected tissue during exudation results in faster blood flow
False
Slower blood flow
During mild/moderate acute inflammation, how does exudate move into the tissue?
Through inter-endothelial gaps in post-capillary venules only (contraction of endothelial cells)
(immediate/transient AND delayed/prolonged)
During more severe inflammation, how does exudate move into the tissue?
Damage to endothelial cells in all microvesels
immediate/prolonged
What are the two forms of pressure acting on the microcirculation?
Colloid osmotic pressure= fluid is moving from the interstitial space into the capillary because there is high concentrations of proteins within the capillaries in comparison to the interstitial space
Hydrostatic pressure= blood in arterioles meeds high resistance of capillaries, drives fluid across the endothelial wall from inside to out
T/F:
During normal conditions, there is generally greater hydrostatic pressure in comparison to colloid osmotic pressure
False
They are both fairly equal
During acute inflammation there is an imbalance between the two pressures which causes the movement of fluid/protein from the blood into the tissue
List three reasons for exudation
The fluid dilutes the toxins and increases the flow into lymphatics
More plasma proteins are brought into the affected area: antibodies, complement system proteins, fibrin system proteins
Brings in more neutrophils which can destroy micro-organisms
Increased blood flow _____ hydrostatic pressure and can result in ______
Increases
Exudate (swelling)
Chemotactic mediators results in the _______ which causes ____ or ______
results in the recruitment and stimulation of inflammatory cells
Results in acute or chronic inflammation
Vasoactive mediators causes ______ which results in _____
Causes increased blood flow and vascular permeability to proteins
Results in exudate
Where does histamine come from and what is its role
Comes from mast cells in tissue and platelets in blood
It is a vasoactive mediator (increases vasodilation in arterioles and vascular permeability to post capillary venules)
List two lipid-derived mediators that are pro-inflammatory mediators acting on blood vessels
Prostanoids
Leukotrienes
A2 acts on ____ to form ______
acts on the membrane phospholipid to form arachidonic acid
____ and ____ act on arachidonic acid to form ___ and ____. This will induce inflammation by acting on blood vessels.
Cyclooxygenases and lipoxygenases
Prostanoids and Leukotrienes
How do corticosteroids inhibit inflammation?
Inhibit A2 from acting on the phospholipid membrane thus prevents the inflammation pathway
What do NSAIDs and Zileuton do?
Non-steroidal anti-inflammatory drugs inhibit cyclyoxygenases
Zileuton inhibits lipoxygenases
List 3 vasoactive mediators involved in inflammation
Histamine
Lipid-derived mediators (prostanoides and leukotrines)
Plasma derived mediators (complement fragments and kinins)
List four vasoactive mediators that result in vasodilation (act on arterioles)
Histamine
Kinins
Prostaglandin E2
Prostaglandin I2
List four vasoactive mediators that result in increased vascular permeability of post capillary venules
Histamine
Kinins
C3a, C5a
Leukotrines B4 and C4
_____ can increase your sensitivity to pain
Prostaglandins
What are the two main roles of neutrophils?
Kill microorganisms
Release chemotactins to attract other neutrophils and macrophages
Where are neutrophils produced?
Bone marrow
T/F:
Neutrophils reside in tissues
False
They are in the blood
They enter tissues when they have been signalled to do so
In what order do these reach their maximum?
Oedema, monocytes/macrophages, neutrophils
First oedema
Then neutrophils
Then macrophages/monocytes
List the main neutrophil events
Margination in small vessels Emigration from vessel into tissue Phagocytosis of micro-organisms Killing of microorganisms Death of the neutrophil
In what stage does rolling, adhesion and emigration occur for neutrophils
First stage
Margination in small vessels- adherence to the endothelium
How do neutrophils adhere to the endothelium
Both neutrophils and endothelial cells express integrins
How do neutrophils emigrate from the vessel into the tissue?
Follow a chemogradient towards the target tissue
How do neutrophils kill microorganisms?
Form a phagosome
Phagosome fuses with granulues to form phagolysosome
Granulues released in phagolysosome to kill microorganism
ROS can be directed into phagolysosome
OR
as neutrophils die they release a NET (neutrophil extracellular trap)
- This consists of DNA and anti-microbial proteins attached
- Kills the microorganism
T/F:
Neutrophils don’t have ER or ribosomes
False
they don’t have ER and golgi apparatus
T/F:
Neutrophils are incapable of proliferation
True
T/F:
Neutrophils are a long lived cell
False
Short-lived
What are the general roles of macrophages?
Kill microrgansisms
Phagocytose debris/microorganisms
Regulate other cells by producing cytokines
Where do monocytes originate from?
Originate in bone marrow
Become macrophages later
T/F:
macrophages are long lived
True
can remain in tissues for months or years
T/F:
macrophages have a multi lobed nucleus
False
Single lobed
T/F:
macrophages are incapable of proliferating and differnetiating
False
What are the three types of cytokine actions?
Autocrine
Paracrine
Systemic (endocrine)
What is the role of cytokines?
Regulating other cells/pathways
Modify activities of cells
Stimulate or inhibit cellular functions
THEY ARE PROTEINS
What is the major source of Interleukin 1 and tumour necrosis factor?
Macrophages
What is over produced when you have arthritis?
TNF and IL-1
What are some general roles of TNF and IL-1
Make T cells proliferate
Make the hypothalamus give you a fever
Increase the expression of adhesion molecules
Cause stem cells to differentiate into leukocytes
What does PAMPs and PRRs stand for?
Pathogen Associated Molecular Patterns
Pattern Recognition Receptors
What do PRRs recognise?
PAMPs:
microbial origin
Lipids, carbohydrates, nucleic acids, proteins
DAMPs:
- Damage associated molecular patterns
- Released from damaged cells
- E.g. ATP, RNA, DNA
What is the role of PRRs
Activate the adaptive immune response
Detect microbial infection
Trigger anti-microbial host defences
T/F:
PRRs are part of the adaptive immune response
False
Part of the innate immune response
Toll-like receptors are a form of ______
pattern recognition receptors (PRRs)
What are the 5 possible forms of progression of acute inflammation?
Resolution Organisation Suppuration Chronic Inflammation Longer Term Healing
A granuloma is a nodular inflammatory lesion containing mostly -_____
macrophages, lymphocytes, fibroblasts
What is fibrinogen?
Glycoprotein made by the liver
Converted into fibrin by thrombin during coagulation
Describe what must happen for outcome 1 to occur- resolution
Mild stimulus no tissue damage Little or no fibrin deposition Fluid drains away through lymphatics Tissue stabilized quite rapidly
Describe acute healing by fibrosis
Copious amounts of fibrin are deposited
Macrophages/capillaries/fibroblasts migrate to the area and form granulation tissue
macrophages will then break down the fibrin
Fibroblasts will deposit collagen
T/F:
and abcess is superficial and an ulcer is deep
False
Ulcer= superficial
Abcess= deep
What can be found in pus?
Living/dead neutrophils, fluid, plasma proteins, living/dead microorganisms, cell debris, nucleic acids, myeloperoxidase
T/F:
Suppuration is almost always a response to viral infection
False
Bacterial infection
T/F:
Chronic inflammation is inflammation of prolonged duration (weeks to years) in which active inflammation, tissue destruction and tissue repair are proceeding simulatenously
True
What are the three major types of chronic inflammation?
Suppuration (chronic abcess)
Mixed (rheumatoid arthritis)
Granulomatous (tuberculosis)
T/F:
Suppuration occurs during chronic granulomatous inflammation
False
What are some characteristics of chronic inflammatory lesions?
Persistent
Cellular infiltration
Destruction of normal tissue
Formation of fibrous connective tissue
Describe chronic suppurative inflammation
Characterised by neutrophils
Inolves pus
Describe an abcess and what is it an example of
An example of chronic suppurative inflammation
Collection of pus within a solid tissue
What are the three types of chronic granulomatous inflammation
Foreign body granuloma
Chronic granulomatous inflammation of unknown origin
Immune type
Giant cells, epithelioid cells and difuse fibrosis are characteristics of _____
foreign body chronic granulomatous inflammation
Epithelioid cells and langhands giant cells are characteristic of _____
unknown origin chronic granulomatous inflammation
What is the role of a granuloma?
To contain a microorganism/irritant in order to prevent its dissemination
Focuses the immune response against the initiating factor
What happens when mice are injected with anti-TNF?
No granulomas form
Bacteria persist
Mouse death
Briefly describe how granulomas form
Chemokines recruit monocytes into an area
Cytokines cause monocytes to differentiate into macrophages or epithelioid cells
Cytokines cause epithelioid cells to fuse together to form giant cells
Growth factors recruit fibroblasts and they form fibrous tissue
What are some negative aspects of inflammation?
Complications of acute inflammation
Chronic inflammation
Systemic inflammation
