Inflammation

Question 1

What are the two main roles of inflammation

Answer 1

to remove damaged cells and clear cells such as infections and toxins

Question 2

What types of tissues and cells does it involve

Answer 2

any vascularised tissue, recruiting immune cells, fluid and molecular compartments

Question 3

What initiates inflammation

Answer 3

initiated when cellular damage leads to the release of damage associated molecular patterns (DAMPs) or the body detects pathogen associated molecular patterns (PAMPs)

Question 4

Characteristic pathology of inflammation

Answer 4

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.

Question 5

What happens to blood vessels during inflammation

Answer 5

thicken

Question 6

effects of chronic inflammation

Answer 6

repetitive rounds of inflammation so tissue damage and repair occurs leading to scarring and loss of tissue function

Question 7

what is inflammation

Answer 7

non specific response to cellular injury and it is designed to remove the cause and consequence of injury

Question 8

four main signs of inflammation

Answer 8

redness(rubor), heat(calor), pain(dolor), swelling (tumor), loss of function (functio laesa)

Question 9

what happens during acute inflammation

Answer 9

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

Question 10

what occurs when there is damage in a steady state

Answer 10

1. inflammatory signals are released as there is non-apaptopic cell death and there is detection of foreign material
2. vasodilators released by mast cells including histamine and nitric oxide
3. there are vascular changes including increased permeability, dilation, reduced flow and plasma leakage

Question 11

what benefits so increased vascular permeability and leakage bring

Answer 11

increased antibodies, increased proteins, increased leukocyte migration and increases barrier

Question 12

what does vasodilation do in acute inflammation

Answer 12

increases blood flow causing redness and warmth (rubor and calor)

Question 13

what does increased permeability do during acute inflammation

Answer 13

exudation of protein rich fluid to the extravasular space causing swelling (tumor)

Question 14

what does of fluid from vessels (reduced flow) lead to

Answer 14

concentration of red cells resulting in decreased velocity and stasis of blood flow

Question 15

what dos leukocyte rolling, adhesion and migration do

Answer 15

leads to accumulation of inflammatory cells

Question 16

look at table about the other soluble mediators released at an injury

Answer 16

look at the table about the other soluble mediators released at an injury

Question 17

what is exudate and its function

Answer 17

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

Question 18

how are immune cells recruited to site of injury

Answer 18

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

Question 19

example of chemokine.

Answer 19

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)

Question 20

Neutrophil extravasation

Answer 20

1. chemoattraction (chemokines released by mast cells stimulate upregulation of adhesion molecules called selectins on endothelial cells)
2. Rolling adhesion: carbohydrate ligands on low affinity state on neutrophils bind to selectins
3. Tight adhesion: change from rolling to tight adhesion to endothelial wall
4. migration through endothelium

Question 21

neutrophil function at the site of inflammation

Answer 21

1. pathogen recognition by use of TLR4 and CD14 to identify liposaccharides present in gram negative bacteria
2. pathogen clearance: phagocytosis, netosis
3. cytokine secretion which will recruit and activate other immune cells

Question 22

what is an immunogen

Answer 22

an antigen independently capable of driving an immune response in the absence of additional substances

Question 23

what is a hapten

Answer 23

a small molecule that alone does not act as an antigen but when bound to a lather molecule can create and antigen

Question 24

what is the difference between acute vs chronic and granular inflammation

Answer 24

acute doesnt need antigen (rheumatoid arthiritis, asthma, IBS, hepatitis). Chronic and granular does (crohns, tubercolosis, leprosy, tumour reaction, foreign body granuloma)

Question 25

hallmarks of chronic inflammation

Answer 25

persistent inflammatory stimuli and it a viscous cycle where inflammatory agent is not cleared and there is a concurrent repair process (fibrosis and angiogenesis)

Question 26

what are the bad effects of macrophages

Answer 26

• 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

Question 27

granulomatous formation

Answer 27

happens in chronic inflammation. aggregation of activated macrophages and is a barrier designed for clearance. Triggered by strong T-cell responses.

Question 28

wound healing

Answer 28

results in Extracellularmatrix (collagen) formation) which is difficult to remove and leads to scarring

Question 29

Look at table on acute vs chronic inflammation

Answer 29

look at table on acute vs chronic inflammation

Question 30

explain the molecular, cellular and physiological processes regarding rubor

Answer 30

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). 

Question 31

explain the molecular, cellular and physiological processes regarding calor

Answer 31

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. 

Question 32

explain the molecular, cellular and physiological processes regarding dolor

Answer 32

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.

Question 33

explain the molecular, cellular and physiological processes regarding loss of function

Answer 33

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.