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  • Despite being surrounded by harmful microorganisms, toxins, and the threat of our own cells turning

  • into tumor cells, humans manage to survive; largely thanks to our immune system.

  • The immune system is made up of organs, tissues, cells, and molecules that all work together

  • to generate an immune response that protects us from microorganisms, removes toxins, and

  • destroys tumor cells - hopefully not all at once!

  • The immune response can identify a threat, mount an attack, eliminate a pathogen, and

  • develop mechanisms to remember the offender in case you encounter it again - all within

  • 10 days.

  • In some cases, like if the pathogen is particularly stubborn or if the immune system starts attacking

  • something it shouldn't like your own tissue, it can last much longer, for months to years,

  • and that leads to chronic inflammation.

  • Your immune system is like the military - with two main branches, the innate immune response

  • and the adaptive immune response.

  • The innate immune response includes cells that are non-specific, meaning that although

  • they distinguish an invader from a human cell, they don't distinguish one invader from

  • another invader.

  • The innate response is also feverishly fast - working within minutes to hours.

  • Get it?

  • Feverishly” - that's cause it's responsible for causing fevers.

  • The trade off for that speed is that there's no memory associated with innate responses.

  • In other words, the innate response will respond to the same pathogen in the exact same way

  • no matter how many times it sees the pathogen.

  • The innate immune response includes things that you may not even think of as being part

  • of the immune system.

  • Things like chemical barriers, like lysozymes in the tears and a low pH in the stomach,

  • as well as physical barriers like the epithelium in the skin and gut, and the cilia that line

  • the airways to keep invaders out.

  • In contrast, the adaptive immune response is highly specific for each invader.

  • The cells of the adaptive immune response have receptors that differentiate one pathogen

  • from another by their unique parts - called antigens.

  • These receptors can distinguish between friendly bacteria and potentially deadly ones.

  • The trade off is that the adaptive response relies on cells being primed or activated,

  • so they can fully differentiate into the right kind of fighter to kill that pathogen, and

  • that can take a few weeks.

  • But the great advantage of the adaptive immune response is immunologic memory.

  • The cells that are activated in the adaptive immune response undergo clonal expansion which

  • means that they massively proliferate.

  • And each time the adaptive cells see that same pathogen, they massively proliferate

  • again, resulting in a stronger and faster response each time that pathogen comes around.

  • Once the pathogen is destroyed, most of the clonally expanded cells die off, that's

  • called clonal deletion.

  • But some of the clonally expanded cells live on as memory cells and they're ready to

  • expand once more if that pathogen ever resurfaces.

  • Now, it's time to meet the soldiers - which are the white blood cells or leukocytes.

  • Hematopoiesis is the process of forming white blood cells, as well as red blood cells, and

  • platelets and it takes place in the bone marrow.

  • Hematopoiesis starts with a multipotent hematopoietic stem cell which can develop into various cell

  • types - it's future is undecided.

  • Some become myeloid progenitor cells whereas others become lymphoid progenitor cells.

  • The myeloid progenitor cells develop into myeloid cells which include neutrophils, eosinophils,

  • basophils, mast cells, dendritic cells, macrophages, and monocytes, all of which are part of the

  • innate immune response and can be found in the blood as well as in the tissues.

  • The neutrophils, eosinophils, basophils, and mast cells are considered granulocytes, because

  • they contain granules in their cytoplasm, and the trio of neutrophils, eosinophils,

  • and basophils are also referred to as polymorphonuclear cells, or PMNs, because they're nuclei contain

  • multiple lobes instead of being round.

  • The mast cells, aren't considered PMNs because their nucleus is round.

  • During an immune response, the bone marrow produces lots of PMNs, most of which are neutrophils.

  • Neutrophils use a process called phagocytosis - that's where they get near a pathogen

  • and reach around it with their cytoplasm toswallowit whole, so that it ends up

  • in a phagosome.

  • From there, the neutrophils can destroy the pathogen using two methods - they can use

  • their cytoplasmic granules or oxidative burst.

  • First, the cytoplasmic granules fuse with the phagosome to form the phagolysosome.

  • The granules contain molecules that lower the pH of the phagolysosome, making it very

  • acidic, and that kills about 2% of the pathogens.

  • Now, the neutrophil doesn't stop there.

  • It keeps swallowing up more and more pathogens until it's full of pathogens, and at that

  • point, it unleashes the oxidative burst.

  • During an oxidative burst, the neutrophil produces lots of highly reactive oxygen molecules

  • like hydrogen peroxide.

  • These molecules start to destroy nearby proteins and nucleic acids - a bit like the neutrophil

  • dumping bleach on itself and then lighting itself on fire.

  • This process kills the neutrophil - a bit of a suicide mission - but each neutrophil

  • takes out a lot of pathogens with it.

  • Now, in comparison to neutrophils, eosinophils and basophils are far less common.

  • They both contain granules that contain histamine and other proinflammatory molecules.

  • Eosinophils stain pink with the dye eosin - which is where they get their name.

  • Eosinophils are also phagocytic, and they're best known for fighting large and unwieldy

  • parasites because eosinophils are much larger than neutrophils and have receptors that are

  • specific for parasites.

  • Unlike neutrophils and eosinophils, basophils are non-phagocytic.

  • They stain blue with the dye hematoxylin, and like eosinophils they can be helpful at

  • combating large parasites but also cause inflammation in asthma and allergy responses.

  • Finally, there are the mast cells which are also non-phagocytic and they're involved

  • in asthma and allergic responses.

  • Next up are the monocytes, macrophages, and dendritic cells, which are phagocytic cells

  • - they gobble up pathogens, present antigens, and release cytokines - tiny molecules that

  • help attract other immune cells to the area.

  • Monocytes only circulate in the blood.

  • Some monocytes migrate into tissues and differentiate into macrophages, which remain in tissues

  • and aren't found in the blood.

  • Other monocytes differentiate into dendritic cells, the prototypical antigen presenting

  • cell, which roam around in the lymph, blood, and tissue.

  • When dendritic cells are young and immature they're excellent at phagocytosis, constantly

  • eating large amounts of protein found in the interstitial fluid.

  • But when a dendritic cell phagocytoses a pathogen for the first time - it's a life-changing,

  • coming of age moment.

  • Mature dendritic cells will destroy the pathogen and break up it's proteins into short amino

  • acid chains.

  • Dendritic cells will then move through the lymph to the nearest lymph node and they'll

  • perform antigen presentation which is where they present those amino acid chains - which

  • are antigens - to T cells.

  • Antigen presentation is what connects the innate and adaptive immune systems.

  • Antigen presentation is something that can be done by dendritic cells, macrophages residing

  • in the lymph node, and monocytes which can travel to a lymph node after phagocytosing

  • a bloodborne pathogen - which is why all of these cells are referred to as antigen presenting

  • cells.

  • Now, only T cells with a receptor that can bind to the specific shape of the antigen

  • will get activated - that's called priming.

  • It's similar to how a lock will only snap open when a key with a very specific shape

  • goes in.

  • However, T cells can only see their antigen if it is presented to them on a silver platter

  • - and on a molecular level that platter is the Major Histocompatibility complex or MHC

  • for short.

  • So the antigen presenting cell will load the antigen onto an MHC molecule and display it

  • to T cells - and when the right T cell comes along - it binds!

  • Now the other group - the lymphoid progenitor cells - become lymphoid cells which are the

  • B cells, natural killer cells -quite a name huh?, and the T cells, which we've already

  • talked a little about.

  • B and T cells make up the adaptive immune system, while NK cells are part of the innate

  • immune system.

  • B cells and NK cells complete their development where they started - in the bone marrow, whereas

  • some lymphoid progenitor cells migrate to the thymus where they develop into T cells.

  • All of the lymphocytes are able to travel in and out of tissue and the bloodstream.

  • NK cells are large lymphocytes with granules and they target cells infected with intracellular

  • organisms, like viruses, as well as cells that pose a threat like cancer cells.

  • NK cells kill their target cells by releasing cytotoxic granules in their cytoplasm directly

  • into the target cell.

  • These granules contain some molecules that cause target cells to undergo apoptosis which

  • is a programmed cell death and some that punch holes in the target cell's membrane by binding

  • directly to the phospholipids and creating pores.

  • B cells, like T cells, also have a receptor on their surface that allows them to only

  • bind to an antigen that has a very specific shape.

  • The main difference is that B cells don't need antigen to be presented to them on an

  • MHC molecule, they can simply bind an antigen directly.

  • When a B cell binds to an antigen that's on the surface of a pathogen, it is capable

  • of phagocytosis and antigen presentation - so technically, they're also antigen presenting

  • cells as well.

  • Like other antigen presenting cells, the B cell will load the antigen onto an MHC molecule

  • called MHC II, and display it to T cells.

  • When a T cell gets activated it helps the B cell mature into a plasma cell, and a plasma

  • cell can secrete lots and lots of antibodies.

  • Typically, it takes a few weeks for antibody levels to peak.

  • The antibodies, or immunoglobulins, have the exact same antigen specificity as the B cell

  • they come from.

  • Antibodies, are just the B cell receptor in a secreted form, so they can circulate in

  • serum, which is the non-cellular part of blood - attaching to pathogens and tagging them

  • for destruction.

  • Because antibodies aren't bound to cells and float freely in the blood, this is considered

  • humoral immunity - a throwback to the termhumorswhich refers to body fluids.

  • Now the final type of lymphoid cell is the T cell and its in charge of cell mediated

  • immunity.

  • T cells are antigen specific, but they can't secrete their antigen receptor.

  • A naive T cell can be activated or primed to allow it to turn into a mature T cell by

  • any of the antigen presenting cells, but most often it's done by a dendritic cell.

  • Now, there are two main types of T cells, CD4 T cells and CD8 T cells - whereCD

  • stands for cluster of differentiation.

  • There are hundreds of CD markers in the immune system, and these CD markers are useful in

  • telling them apart.

  • For example, all T cells are CD3+, because CD3 is part of the T cell receptor.

  • So, CD4+ T cells, are actually CD3+CD4+, and these cells are called helper cells because

  • they're like generals on the battlefield, they secrete cytokines that help coordinate

  • the efforts of macrophages, B cells, and NK cells.

  • Helper T cells can only see their antigen if it is presented on an MHC II molecule.

  • CD8+ T cells are CD3+CD8+, and they're called cytotoxic T cells because they kill target

  • cells, really similarly to how NK cells do it with one major difference.

  • CD8+ T cells only kill cells that present a specific antigen on an MHC I molecule - which

  • is structurally similar to the MHC II molecule, whereas NK cells aren't nearly as specific

  • in who they kill.

  • So now let's go through a complete immune response with a bacterial pathogen in the

  • lungs.

  • To start, the bacteria will have to get breathed in, slip by your nose hairs, past the cilia

  • in the airways, and will then have to penetrate past the epithelium layer of the lungs.

  • Once it's in the lung tissue, the bacteria will start to divide and might encounter a

  • resident macrophage in the lung tissue which will ingest the bacteria and start releasing

  • cytokines.

  • Those cytokines start the inflammatory process by making blood vessels leaky and attracting

  • nearby eosinophils, basophils, and mast cells, which release their own cytokines and granules

  • amplifying the inflammation.

  • Neutrophils from the blood as well as fresh new ones from the bone marrow dive into the

  • tissue and join the battle.

  • If the pathogen was a virus, NK cells would help destroy the infected cells at this point.

  • This is all part of the innate immune response.

  • Around this point in the infection, immature dendritic cells digest the pathogens and move

  • from the lung tissue over to a nearby lymph node where they present the processed antigen

  • on an MHC II protein to a naive T cell.

  • The dendritic cell, which is part of the innate immune system, bridges the innate and adaptive

  • immune responses when it presents the antigen to the T cell - part of the adaptive immune

  • system.

  • Sometimes, if the infection is spreading, bacteria might find its own way to a lymph

  • node without the help of the dendritic cell.

  • In this case, B cells - part of the adaptive immune system - might directly phagocytose

  • the bacteria and present it to a naive T CD4+ cell.

  • Either way, if the antigen is the rightfitfor the T cell it will begin to differentiate

  • and undergo clonal expansion.

  • Differentiated CD4+ T cells will release cytokines that will induce B cells to differentiate

  • into plasma cells which secrete antibodies that will go into the lymph and then the bloodstream.

  • The antibodies will tag pathogens making it easier for phagocytes to eat them.

  • Once again, at this point, if the pathogen was a virus, the CD8+ T cells would kill any

  • infected cells that express the viral antigen on an MHC I.

  • Over time, as the invading pathogen dies off, most of the B and T cells die of neglect,

  • but a few turn into memory B cells and memory T cells, which linger for years in case their

  • needed in the future.

  • So, to recap - the immune system has innate and adaptive response.

  • The innate immune response is immediate, but non-specific, and lacks memory, whereas the

  • adaptive immune response is highly specific and remembers everything, but it takes several

  • days to get started and almost two weeks to peak.

Learning medicine is hard work!

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B2 US antigen immune pathogen immune response dendritic innate

Introduction to the immune system

  • 41 2
    Yu Chyi posted on 2020/01/14
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