Inflammation Flashcards
What are the two main roles of inflammation
to remove damaged cells and clear cells such as infections and toxins
What types of tissues and cells does it involve
any vascularised tissue, recruiting immune cells, fluid and molecular compartments
What initiates inflammation
initiated when cellular damage leads to the release of damage associated molecular patterns (DAMPs) or the body detects pathogen associated molecular patterns (PAMPs)
Characteristic pathology of inflammation
The presence of increased fluid and leukocyte numbers as the damaged tissue secretes a range of signals that induces 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 happens to blood vessels during inflammation
thicken
effects of chronic inflammation
repetitive rounds of inflammation so tissue damage and repair occurs leading to scarring and loss of tissue function
what is inflammation
non specific response to cellular injury and it is designed to remove the cause and consequence of injury
four main signs of inflammation
redness(rubor), heat(calor), pain(dolor), swelling (tumor), loss of function (functio laesa)
what happens during acute inflammation
inflammation is a rapid response, non-specific response to cellular injury.
1) changes in local blood flow
2) structural changes in the microvasculature
3) recruitment/accumulation of immune cells and proteins
what occurs when there is damage in a steady state
- inflammatory signals are released as there is non-apaptopic cell death and there is detection of foreign material
- vasodilators released by mast cells including histamine and nitric oxide
- there are vascular changes including increased permeability, dilation, reduced flow and plasma leakage
what benefits so increased vascular permeability and leakage bring
increased antibodies, increased proteins, increased leukocyte migration and increases barrier
what does vasodilation do in acute inflammation
increases blood flow causing redness and warmth (rubor and calor)
what does increased permeability do during acute inflammation
exudation of protein rich fluid to the extravasular space causing swelling (tumor)
what does of fluid from vessels (reduced flow) lead to
concentration of red cells resulting in decreased velocity and stasis of blood flow
what dos leukocyte rolling, adhesion and migration do
leads to accumulation of inflammatory cells
look at table about the other soluble mediators released at an injury
look at the table about the other soluble mediators released at an injury
what is exudate and its function
it is formed when fluid, proteins and cells have seeped out of a blood vessel and forms a barrier between the inflammed tissue and the normal tissue limiting inflammatory stimuli and microbes from enetering normal tissue
how are immune cells recruited to site of injury
Chemokines/other inflammation signal are produced
Chemokines diffuse out to form a gradient (chemokines act on endothelial cells to promote cell recruitment)
Leukocytes expressing complementary chemokine receptors migrate towards chemokine source
example of chemokine.
CXCL8 or IL8. Binds to CXCR1 and CXCR2 g-coupled r7-transmembrane proteins. Attracts neutrophils(which are often the first cell type recruited to site of inflammation)
Neutrophil extravasation
- chemoattraction (chemokines released by mast cells stimulate upregulation of adhesion molecules called selectins on endothelial cells)
- Rolling adhesion: carbohydrate ligands on low affinity state on neutrophils bind to selectins
- Tight adhesion: change from rolling to tight adhesion to endothelial wall
- migration through endothelium
neutrophil function at the site of inflammation
- pathogen recognition by use of TLR4 and CD14 to identify liposaccharides present in gram negative bacteria
- pathogen clearance: phagocytosis, netosis
- cytokine secretion which will recruit and activate other immune cells
what is an immunogen
an antigen independently capable of driving an immune response in the absence of additional substances
what is a hapten
a small molecule that alone does not act as an antigen but when bound to a lather molecule can create and antigen
what is the difference between acute vs chronic and granular inflammation
acute doesnt need antigen (rheumatoid arthiritis, asthma, IBS, hepatitis). Chronic and granular does (crohns, tubercolosis, leprosy, tumour reaction, foreign body granuloma)
hallmarks of chronic inflammation
persistent inflammatory stimuli and it a viscous cycle where inflammatory agent is not cleared and there is a concurrent repair process (fibrosis and angiogenesis)
what are the bad effects of macrophages
- they are cytotoxic and so if you can’t clear the infection, they can cause damage to normal tissue
- inflammatory: will attract more T-cells to site of injurt
- profibrotic: excessive formation of collagen
granulomatous formation
happens in chronic inflammation. aggregation of activated macrophages and is a barrier designed for clearance. Triggered by strong T-cell responses.
wound healing
results in Extracellularmatrix (collagen) formation) which is difficult to remove and leads to scarring
Look at table on acute vs chronic inflammation
look at table on acute vs chronic inflammation
explain the molecular, cellular and physiological processes regarding rubor
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 - see E-module 5) and accumulation of blood contents including red blood cells (redness).
explain the molecular, cellular and physiological processes regarding calor
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.
explain the molecular, cellular and physiological processes regarding dolor
many of the same mediators that signal to endothelial cells and other immune cells during inflammation, also signal on local nerve cells. uring acute inflammation molecules such as histamine and the prostogladins (PGEs) released by mast cells and neutrophils drive pain sensitization in local nociceptor neurons. At later stages macrophages and lymphocytes can also contribute to this process releasing pro-inflammatory cytokines such as interleukin-6, tumour necrosis factor and interleukin-1beta.
explain the molecular, cellular and physiological processes regarding loss of 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.
