Inflammation

Definitions & Key takeaways

Inflammation is a natural response that our body has to injury or infection. It helps protect us from potential harm and promotes healing. Inflammation involves blood vessels dilating and becoming more permeable, and attracting more immune cells and fluid into local tissue. The classical signs of inflammation are heat, pain, redness, swelling and they can lead to a loss of function. The inflammatory response ends with wound repair and resolution, either restoring the initial tissue integrity, or leaving a fibrous scar.

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Introduction0:00–1:12

Inflammation classically describes four key signs. Each of which have a latin derivation, calor or heat dolar or pain, rubor or redness and tumor or swelling.
Sometimes these four signs combine to cause 1/5 sign which is fun Lysa or temporary loss of function due to pain or swelling.
All right. So, inflammation usually starts with some stimuli like a pathogen.
Now, even though pathogens are a common cause of infection, which can lead to inflammation. Inflammation can be caused by other things as well like toxins and trauma.
For example, after an intense workout, your muscles might feel sore that's due to inflammation trying to repair your overused muscle fibers.
Ultimately, the goal of inflammation is to respond to the stimuli and restore balance. Oftentimes that includes eliminating the cause of tissue injury, clearing out necrotic or dead cells and starting tissue repair.
Broadly speaking, inflammation can be triggered by external and internal factors. External factors can be nonmicrobial or microbial.

External triggers of inflammation1:12–2:10

Nonmicrobial factors include allergens, irritants and toxic compounds. Now, the two main microbial factors that trigger inflammation are virulence factors in pathogen associated molecular patterns or pamps.
Virulence factors are molecules that help pathogens, colonize tissues and cause infection. Pamps are small molecules with conserved patterns that are shared across many different pathogens, including bacterial wall components, like peptidoglycan, lipopolysaccharide or LPS, and lipoteichoic acid and fungal wall components like mannan for intracellular pathogens like viruses.
Pamps might include the viral RNA or DNA. Our immune system recognizes violence factors and pamps as foreign substances and can trigger an inflammatory response against them.

Internal triggers of inflammation2:10–3:11

Now, in terms of internal factors, it turns out that there's an endogenous equivalent to pamps called damage associated molecular patterns or damps.
Damps are intracellular proteins that get released when a cell's plasma membrane is injured or when a cell dies. So, damps are a signal that there's serious cell damage and they trigger inflammation.
Now, pamps and damps are recognized by pattern recognition receptors or P RRS, which are cell surface receptors on various leukocytes that help to activate those cells and spark the inflammatory response, which can be thought of as the innate immune system.
Key features are that this response is nonspecific, meaning that P RRS don't distinguish one specific pathogen from another.
Although they can distinguish between broad categories like viruses from bacteria. Also, the response is super fast occurring within minutes to hours.
And finally, there's no memory associated with innate responses. Generally speaking, there are two main types of leukocytes, granulocytes which include neutrophils, eosinophils, basophils and mast cells and a granulocytes which include lymphocytes and monocytes which can differentiate into macrophages or dendritic cells, the inflammatory process usually starts with either macrophages or mast cells, both of which are found in the tissues.

Inflammatory response3:11–6:52

When there's tissue damage. These cells respond to the pamps or damps.
Mast cells have Granules containing different inflammatory mediators like histamine serotonin cytokines and icosanoids like prostaglandins and leukotrienes.
These inflammatory mediators act on the endothelial cells surrounding the capillaries nearby, causing them to separate from each other.
In addition, macrophages which are the garbage truck of the body start to eat up invading pathogens. The release of cytokines causes capillaries to get larger and increase vascular permeability, allowing plasma proteins and fluids to leave the circulation.
Endothelial cells also help spur on this process by releasing nitric oxide which helps vasodilate the capillaries and makes them more permeable.
In addition, endothelial cells express more adhesion proteins to help leukocytes that are floating by in the blood to attach and roll along the vessel wall until they reach the injured site.
In particular, neutrophils get attracted to the site of infection by the chemokines and microbial products. The neutrophil then starts to squeeze through the gaps between two endothelial cells until it reaches the other side.
And this is called extravasation. It's kind of like squeezing between two fence poles to sneak into an amusement park rather than paying admission.
But that's not to say you should do that. Now, next, the leukocyte follows the gradient of inflammatory mediators to get to the site of inflammation.
Neutrophils are the first leukocytes recruited during the acute inflammatory process. And they're like hungry athletes, they immediately start phagocytosis or eating pathogens and damaged cells.
Neutrophils take a lot of pathogens quickly kind of like a vacuum and then undergo apoptosis, destroying themselves. And all of the pathogens they've taken in now, while this is all happening, there's also a family of soluble proteins called the complement system.
The complement proteins most often get activated in the presence of antibodies bound to pathogens or by molecules on the pathogens.
Once these complement proteins are active, they help attract leukocytes and help with opsonization. Meaning that they can bind to microbes so that leukocytes can more easily phagocytose them kind of like sticking a fork in a meatball so that it doesn't slip away.
Some of the complement proteins also kill pathogens by directly forming a channel in their membrane, literally punching a hole in it all the.
While dendritic cells continue to phagocytose pathogens and present bits of them to t lymphocytes. This activates the adaptive immune system which kicks in after a few days.
If the stimulus for all of this inflammation was a cut or a scrape, then platelets and clotting factors from the plasma reached the area and clot the wound.
This helps stop the bleeding as well as prevents pathogens from entering the bloodstream and provides a framework for tissue repair.
In summary, all of these factors contribute to the heat pain, redness and swelling. That's classic for inflammation.

Tissue Repair6:52–7:39

Now, the inflammatory response ends with tissue repair. Macrophages are recruited to eat up dead and dying cells so that when tissue can make room for new cells, this is followed by angiogenesis which is the formation of new blood vessels and that's triggered by growth factors released by macrophages.
These newly formed blood vessels are temporary, meaning that once the wound is healed, these new vessels regress. Finally, there are fibroblasts which come into the area of inflammation and synthesize collagen to help with wound healing.
Overall, if there's only mild damage, then the tissue regenerates back to its normal healthy state. But if there's severe damage, then the damaged cells get replaced by a nonfunctional fibrous scar.
All right. As a quick recap, inflammation is a complex response to harmful stimuli which could be from a pathogen, but it also could be from trauma or toxins.

Review7:39–8:13

The response involves blood vessels dilating and becoming more permeable and attracting more immune cells and fluid into the local tissue.
The classical signs of inflammation are heat, pain, redness and swelling. And these can lead to a loss of function.
The inflammatory response ends with wound repair and resolution, either restoring the initial tissue integrity or leaving a fibrous scar.