inflam Flashcards
what is inflammation
Inflammation is a protective biological process designed to remove damaged cells and clear threats such as infections and toxins.
non-specific response to cellular injury
how is it 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)
what to those cause
This causes the cells in the damaged tissue to secrete a range of signals designed to induce inflammation including molecules that alter the structure of nearby blood vessels and chemokines that promote the recruitment of immune cells to the site of injury
what is the function of the immune cells
The aim of immune cell recruitment is to clear the source of the initial inflammatory signal, and eventual resolution and repair of the inflamed tissue. As a result inflammation has a characteristic pathology associated with the presence of increased fluid and leukocyte numbers.
what happens to the blood vessels
thickening of the blood vessels.
what happens if the acute inflammation can’t remove the inflammatory stimuli
adaptive immune cells are recruited and a state of chronic inflammation can occur.
harmful effects of chronic inflammation
chronic inflammation can lead to repetitive rounds of inflammation, tissue damage and repair, resulting in scarring and loss of tissue function.
what are the 5 canonical cardinal features of inflammation
redness
heat
pain
swelling
what are some causes of inflammation
pathogens
allergy
extreme temp
describe acute inflammation
Inflammation is a rapid response non-specific response to cellular injury
why is there swelling
Change in local blood flow
Structural changes in the microvasculature
Recruitment/accumulation of immune cells and proteins
what happens when you get a break in the skin
non-apoptotic cell death- release signals that cause immune response
Detection of foreign material
which cells release vasodilators
mast cells degranulate releasing vasodilators causing increased blood flow which results in the classic warmth (calor) and redness (rubor) seen in inflammation.
what are the vasodilators
Histamine
Nitric Oxide
What are the vascular changes following vasodilator release
Increased permeability
Dilation
Reduced flow
plasma leakage
what does the increase in permeability do
allows movement of proteins and immune cells from the blood into the tissue as well as causing movement and build up of fluid into the affected tissues leading to another classical sign of inflammation, swelling (tumor)
benefits of increase permability
more protiens
more antibodies
leukocytes
form barrier
histamine production and action
mast cells, basophil, platelets
vasodialtion, i^ vascular permeability, endothelial activation
prosatgalndin action and source
Mast cells, leukocytes
Vasodilation, pain, fever
what is exudate
luid, proteins and cells that have seeped out of a blood vessel
acts as a barrier between inflammation and healthy tissue
how are immune cells recruited
chemokines produce inflammational signal
diffuse to form a gradient
leukocytes with complementary receptors
migrate towards the chemokine source
what are the stages to acute inflammation
steady state
damage
immune cell requirement
neutrophil Extravasation
what are the 4 steps to neutrophil Extravasation
chemo attraction
rolling adhesion
tight adhesion
transmigration
describe chemo attraction
secretion of chemokine act on endothelial layer cause upregulation of adhesion molecules e.g. selectins
describe rolling adhesion
Carbohydrate ligands in a low affinity state on neutrophils bind selectins
describe tight adhesion
Chemokines promote low to high affinity switch in integrins
what is mac 1
enhance binding to ligands
enhance binding of nuetrophil to endothelial walls
what is transmigration
Cytoskeletal re-arrangement and extension of pseudopodia
what is it mediated by
pecam on both cells
function of nuetrophil in inflammation
Pathogen recognition
Pathogen clearance
Cytokine secretion
phagocytosis
pathogen recognition describe
identify lipopolysaccharides (LPS) present in gram-negative bacteria
what are the 2 types of pathogen clearance
Phagocytosis
Netosis
what does cyotokine secreation do
Recruitment and activation of other immune cells
describe pahgocytosis mechanism
Large particles engulfed into membrane bound vesicles (phagosomes)
Phagosome fuses with lysosome (vesicles containing enzymes e.g. elastase and lysozyme) -> phagolysosome
Ractive oxygen species (ROS) – phagocyte NADPH oxidase
Antimicrobial peptides – e.g. defensins.
how is acute inflammation resolved
pathogen can be recognised as the source of the inflammation signal and treated
the nuetrophills then are rapidly dying as they have short half lives as are inflammatory mediaters like hiatmines and prostoglandin
what is macrophages role in the resolution
clear apoptotic cells
produce anti inflammatory mediaters
last step
wound is healed
what is an antigen
a molecule or molecular structure that can be recognised by an antibody
any substance to which your immune system can mount an antibody or adaptive immune response
what is a foriegn antigen
Foreign antigen: an antigen derived from molecules not found in the body
Self antigen:
Self antigen: an antigen derived from molecules produced by our bodies
Immunogen:
an antigen independently capable of driving an immune response in the absence of additional substances
Hapten
a small molecule that alone does not act as an antigen but when bound to a larger molecule can create an antigen
chronic inflammation initial
have the same initial phase with acute
difference between chrinuc and acute
persistent inflammatory
e.g. our own antigen
disctinct immune cell inflitrate
you would have inflammatory macrophage and t cells as well as plasma
a cycle
no clearnce of inflammatory agent
tisuue destruction
macrophages in inflammaton are recruited as whatg
monocytes
why are they good
PHAGOCYTIC
ANTI INFLAMMTORY
WOUND REPAIR
cytoxic
bad
cytotoxic - if they can’t remove infection they damage surrounding tissue
inflammatory-more neutrophils t cells at sight of infection if left unchecked
pro fibrotic- they promote of collegen for repair but caan get excess
what is granulomatous inflammation
Chronic inflammation with distinct pattern of granuloma formation
what is granuloma formation
disruption of surrounding tissue with clear distinc scaring
function
Aggregation of activated macrophages. A barrier designed for clearance.
what are they triggered by
Triggered by strong T cell responses.
form against what
Resistant agents
DIFFERENCE BETWEEN ACUTE AND CHRONIC INFLAM
acute is Immediate onset; lasts a few days Vasodilation, increased vascular permeability, leukocyte response Neutrophils predominate Histamine release Prominent necrosis Outcomes include: Complete resolution Progression to Chronic Inflammation
CHRONIC IS WHAT
Delayed onset; may last weeks, months or years Persistent inflammation, ongoing tissue injury, attempts at healing Monocytes / Macrophages predominate Ongoing cytokine release Prominent scarring Outcomes include: Scarring Loss of function
what is the outcome of inflammation linked to
site
type
length
positive outcome of inflammation
clear inflam agent
remove damage cell
restore normal function
negative
excess tissue damage
scarring
loss of organ function
so organ failure
what is the scar
unremoved collagen deposition
bad when in the thin epithial cells are replaced by collagen not allowing gas exchange
what causes teh sweling
vasodilation as a result of signalling by mast cell derived histamine and nitric oxide on the vascular endothelium leading to a breakdown in tight junctions. Vascular leakage increases blood flow into the inflamed tissue, leading to fluid build-up (swelling
redness
ccumulation of blood contents including red blood cells (redness
HEAT
Heat results from the increased presence of fluid at core body temperature at a site that would otherwise have a limited exposure to this. During inflammation infiltrating immune cells are also highly metabolically active, which may also contribute to the generation of heat as a by-product.
loss in function
fluid build-up and immune cell infiltration often result in the inability of that area of tissue to carry out its primary function. Take for example, inflammation of the lung parenchyma during respiratory infection, if immune cells and fluid build-up in the alveoli. a barrier is created which prevents efficient gas exchange between the capillaries and the air we inhale.
pain
many of the same mediators that signal to endothelial cells and other immune cells during inflammation, also signal on local nerve cells.
