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SM1001 Blood and Immunology Notes (1º)
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THEME 4- BLOOD AND IMMUNITY, LECTURE I- Immunology
1-Disease-causing organisms:
We do not care about virus and bacteria because of our immune system.
There are many millions of bacteria, fungi and viruses but relatively few are pathogenic, because relatively few can evade
our immune system and cause disease. Mostly our immune system reacts so quickly we are not aware of the attack.
We need our immune system to protect us from microscopic organisms like bacteria, virus, fungi, parasites and out own
maligned cells (cancer). So, it needs different mechanisms to adapt to these different types of threats.
2-Detecting Pathogens
How does our immune system decide whether an organism is a pathogen we have to respond to?
Immune cells stationed to detect microbial invasion are equipped with Pattern Recognition Receptors (PRR) that can detect
pathogens.
These cells are part of the rapid response - the innate immune system- which can come into action within minutes of
detecting one of these pathogens.
These receptors are picking up Pathogen Associated Molecular Patterns (PAMPS)
3-PRR and PAMPs
PRR: less than 100 different invariant receptors able to recognize around 1000 molecular patterns (pathogens).
PAMPs, this patters that can be recognised, are characteristic of common microbes, and the things that these microbes can get
rid of are really fundamental to how those microbes act:
Bacterial and fungal cell wall components, thigs like the fugela
Viral and bacterial RNA and DNA
These are the king of thigs our immune system can respond to.
Innate immune cells with PRR that will rapidly respond (part of our innate immune response), include:
Phagocytes such as neutrophils and macrophages
Dendritic cells
Liposaccharide (Lps) and peptidoglycan in bacterial cell wall are
common PAMPs, we can make them trigger these pattern recognition
receptors really quickly.!!
A good example of a PAMP
4-Destroying pathogens
4.1-Phagocytosis
After detecting these pathogens, we also need to be able to destroy them. One of the main ways of doing this is this process
called phagocytosis.
Cells capable of phagocytosis are called phagocytes.
, When bacteria are round macrophages, they can move its membrane up round that
bacteria, close over the top and seal (sellar) it into what we call phagosome. And
straight away that vacuum becomes more acidic, activates enzymes and start todestroy
that bacteria.
But we also have lysosome that contain lots of toxic enzymes and proteins. They fuse
with that phagosome, became phagolysosome and all the toxic products destroy that
bacteria really efficiently.
Phagocytosis.
4.2-Neutrophils mechanisms
But we also have neutrophils, also important phagocytes:
Largest circulating white blood cell population. White blood cells are all cells of
the immune system that can respond also known as leucocytes.
Bone marrow produces trillions each day
First line of defence against invading microbial pathogens (they come sooner
than macrophages).
They die within 1-2 days, the pus we see in for example wounds is made of dead neutrophils and dead pathogen.
They phagocytose pathogens (phagocytosis) and have other killing mechanisms:
Toxic products of the phagocytosis also damage the host, so if you get a severe threat and the neutrophil cannot phagocytose
very well or there are a lot of bacteria, it can degranulate these toxins to the outside.
Another mechanism consists on expelling the DNA to the outside if they are very activated. In this last mechanism, the
neutrophil develops an extracellular trap (NET or neutrophil extracellular trap) made of DNA and the toxic products, which
contract these bacteria and destroy it.
“Neutrophils can eliminate pathogens by multiple means, both intra- and extracellular. When neutrophils encounter
microorganisms, they phagocytose them. After they are encapsulated in phagosomes, the cells kill the pathogens using toxic
enzymes and proteins. The antibacterial proteins are released from the neutrophil granules either into phagosomes or into
the extracellular milieu, thus acting on either intra- or extracellular pathogens, respectively. Highly activated neutrophils
can eliminate extracellular microorganisms by releasing neutrophil extracellular traps (NETs).
NETs are composed of a core DNA element to which histones, proteins and enzymes that are released from neutrophil
granules are attached. NETs immobilize pathogens, thus preventing them from spreading but also facilitating subsequent
phagocytosis of trapped microorganisms. They are also thought to directly kill pathogens by means of antimicrobial histones
and proteases”.
4.3-Exocytosis
Mechanism used by eosinophils to kill larger pathogens like parasitic organisms (Helminth
worms).
Eosinophils externalise lysosomal vesicles containing these toxic proteins and enzymes to
destroy the pathogen that is to big to be phagocytosed.
These toxic proteins, very well designed for the function, cannot damage the host tissue because
they are being expelled to the outside. They are also so clever that can trigger healing
mechanisms that can try to repair that damage as well.
5- The adaptative immune system
Innate immune system is rapid and can be effective but…
Only recognizes 1000 patterns
Has no memory, so each time it sees the same pathogen gives the same response, do not get any better.
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