Introduction to the immune system

despite being surrounded by harmful

organisms toxins and the threat of our

own cells turning into tumor cells

humans manage to survive thanks largely

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 though

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 cuz 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 might not even

think of as being part of the immune

system things like chemical barriers

like Lymes 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 cyia that line the Airways to

keep Invaders out in contrast the

Adaptive immune response is highly

specific for for each Invader the cells

of the Adaptive immune response have

receptors that differentiate one

pathogen from another by their unique

Parts called

antigens adaptive immunity is also

diverse meaning it can recognize almost

an infinite number of specific antigens

and mount a specific response against

each of them 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 that

pathogen is destroyed most of the

clonally expanded cells die off and

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 the pathogen ever

resurfaces now it's time to meet the

soldiers which are the white blood cells

or lucaites

hematopoesis is the process of forming

white blood cells as well as red blood

cells and platelets and it primarily

takes place in the bone marrow

hematopoesis starts with a multi- potent

hematopoetic stem cell which can develop

into various cell types its future is

undecided some become myoid progenitor

cells whereas others become lymphoid

progenitor

cells the myoid progenitor cells develop

into myoid cells which include

neutrophils eosinophils basophils masted

cells dendritic cells macroasia 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 and

basophils are considered granulocytes

because they contain granules in their

cytoplasm and neutrophils in particular

are also referred to as

polymorphonuclear cells or pmns because

their nuclei contain multiple loes

instead of being

round during an immune response the bone

marrow produces lots of cells many of

which are nutrifil neutrophils use a

process called phagocytosis that's where

they get near pathogen and reach around

it with their cytoplasm to swallow it

whole so that it ends up in a fagone

from there the neutrophils can destroy

the pathogen using two methods they can

use their cytoplasmic granules or

oxidative burst first the cytoplasmic

granules Fus with a phagosome to form

the fago liome the granules contain

molecules that lower the pH of the fagal

liome making it very acidic and that

kills about 2% of the

pathogens now the neutr fill doesn't

stop there it keeps swallowing up more

and more path pathogens until it's full

of pathogens and at that point it

unleashes the oxidative burst during an

oxidative burst the neutr produces lots

of highly reactive oxygen species like

hydrogen peroxide these molecules start

to destroy nearby proteins and nucleic

acids within the phagolysosomes which

are the components of the pathogen that

has been ingested the net result is that

the pathogen is

eliminated now in comparison to

neutrophils eosinophils and basophils

are far less common they both contain

granules that contain histamine and

other pro-inflammatory molecules

eosinophils stained pink with the D

eosin which is where they get their name

they are aiic cells even though it's

not their primary mechanism of attack

they are best known for fighting large

and unwieldy helic parasites or worms by

releasing molecules that can poke holes

in the outer layer of helmets these

cells are also involved in allergic

reactions such as atopic dermatitis and

allergic rinitis also known as hay fever

when involved in allergic reactions

eosinophils degranulate meaning they

release various enzymes and proteins

within their granules and this causes an

inflammatory

reaction next you have basophils and

they stain blue with the di hematoxylin

and unlike neutrophils basophils are

non- aidic on the flip side they

have granules that contain histamine and

other pro-inflammatory molecules

therefore they are important in

initiating allergic

responses finally there are the masted

cells which live in tissues not in the

blood and they're very similar to

basophils they are also non- aiic

and are involved in allergic

responses next up are the monocytes

macrofagos and dendritic cells which are

also aiic cells they gobble up

pathogens present antigens and release

cyto which are tiny molecules that

attract other immune cells to to the

area monocytes only circulate in the

blood some monocytes migrate into

tissues and differentiate into macras

which remain in tissues and aren't found

in the blood dendritic cells are the

prototypical antigen presenting cell

dendritic cells are usually found in

sites that are in contact with most

external antigens like the skin

epithelium or the gastrointestinal

mucosa when dendritic cells are young

and immature they're excellent at

phagocytosis constantly eating large of

protein found in the intial fluid but

when a dendritic cell phagocytose is a

pathogen it's a life-changing Coming of

Age moment mature dendritic cells will

destroy the pathogen and break up its

protein into short amino acid

chains dendritic cells will then move

through the lymph to the nearest lymph

node and they'll perform an antigen

presentation which is where they present

those amino acid chains which are

antigens to te- cells antigen

presentation is what connects the Nate

and adaptive immune systems antigen

presentation is something that can be

done by dendritic cells macrofagos as

well as monocytes which is why all of

these cells are referred to as antigen

presenting cells dendritic cells are the

best of this process because they are

the only cells that live where pathogens

enter through the epithelia like skin

gut and Airways and they are the only

cells that can traffic from these

tissues to lymph nodes where te- cells

circulate now only tea cells with

receptor that can bind to the specific

shape of the antigen will be activated

and 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 te- 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 hysto

compatibility complex or MHC for short

so the antigen presenting cell will load

the antigen on an MHC molecule and

display it to t- cells

and when the right t- cell comes along

it

binds the final group of blood cells the

lymphocytes includes B cells t- cells

and natural killer cells B and t- cells

make up the Adaptive immune response

while natural killer cells are part of

the innate immune system B cells and

natural killer cells complete their

development where they started in the

bone marrow whereas some lymphoid

progenitor cells migrate to the thymus

where they develop into tea cells

all of the lymphocytes are able to

travel in and out of tissue and the

bloodstream natural killer 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

natural killer cells kill their target

cells by releasing cytotoxic granules

these granules contain molecules that

punch holes in the Target cell membrane

by binding directly to the phospholipids

and and creating pores and release some

molecules that get inside the cell and

cause target cells to undergo apoptosis

which is a type of program cell

death 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 do not need

antigens to be presented to them on an

MHC molecule they can simply bind to an

antigen directly when a B cell binds to

a protein antigen that's on the surface

of a pathogen it's capable of

internalizing that antigen degrading it

and presenting it to te- cells so

technically they're also antigen

presenting cells as well like other

antigen presenting cells the B cell

loads the antigen onto an MHC molecule

called mhc2 and displays it to t-

cells when a T Cell gets activated it

helps the B cell mature into a plasma

cell and a plas 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 came from antibodies are just

the B cell receptor in a secreted form

so they can circulate in the plasma

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 Ed

humoral immunity a throwback to the term

humors which refers to body

fluids now the final type of lymphoid

cell is the te- cell and it's in charge

of cell mediated immunity te- cells are

antigen specific but they cannot secrete

their antigen receptor a naive te- cell

can be activated or primed to allow it

to turn into a mature te- 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 where CD stands

for cluster of differentiation there are

hundreds of CD markers in the immune

system and these CD markers are useful

in telling different cells apart for

example all T cells are CD3 positive

because CD3 is part of the T Cell

antigen receptor so CD4 positive t-

cells are actually CD3 positive CD4

positive and these cells are called

helper cells because they're like

minerals on the battlefield they secrete

cyto kindes that help coordinate the

efforts of macroasia and B cells helper

T cells can only see their antigen if

it's presented on an mhc2 molecule cd8

positive t- cells are CD3 positive cd8

positive and they're called cytotoxic

te- cells because they kill target cells

really similarly to how natural killer

cells do it with one major difference

cd8 positive T cells only kill cells

that present a specific antigen on an

MHC c 1 molecule which is structurally

similar to the mhc2 molecule whereas

natural killer cells aren't nearly as

specific in who they

kill so now let's go through a complete

immune response with the bacterial

pathogen in the

lungs to start the bacteria will have to

get breathed in slip by your nose hairs

past the Celia 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

resonant macras in the lung tissue which

will ingest the bacteria and start

releasing cyto kindes those cyto kindes

start the inflammatory process by making

blood vessels leaky and attracting

nearby eosinophils basophils and masted

cells which release their own cyto

kindes and granules amplifying the

inflammation nutrifil 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

natural killer cells would 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

residing under the epithelium digest the

pathogens and move from the lung tissue

over to a nearby lymph node where they

present the processed antigen on an mhc2

protein to a naive tea cell the

dendritic cell which is part of the

innate immune response Bridges the

innate and the Adaptive immune responses

when it presents the antigen to the te-

cell which is part of the Adaptive

immune

response sometimes if the infection is

spreading bacteria might find its way to

a lymph node without the help of a

dendritic cell in this case b cells part

of the Adaptive immune response might

directly phagocytose the bacteria and

present it to a naive CD4 positive t-

cell either way if the antigen is the

right fit for the te- cell the te- cell

will begin to differentiate and undergo

clonal expansion differentiated CD4

positive t- cells will release cyto

kindes that will induce B cells to

differentiate into plasma cells which

secrete antibodies that will go into the

lymph and then into the bloodstream the

antibodies will tag pathogens making it

easier for the fago sites to eat them

some cyto kindes will activate macras to

kill bacteria that have been but

cannot be killed by the maccrage alone

unless it gets help from its friends the

tea cells of course if the pathogen was

a virus living and replicating in the

cyop plasma of the infected cells the

cd8 positive T cells would kill any

infected cells that Express the viral

antigen on an

mhc1 over time as the invading pathogen

dies off most of the BNT cells die of

neglect but a few turn into memory B

cells and memory t- cells which linger

for years in case they're needed in the

future all right as a quick recap the

immune system has an innate and an

Adaptive response the innate immune

response is immediate iate 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 helping current and future

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