Hi guys so lets pick up right where we left
off in the last video, where we examined how
the innate immune cells recognize foreign
antigen & then the subsequent secretion of
chemokines by macrophages once they've detected
an intruder
So now lets add another layer to the picture,
& begin exploring what happens once the phagocyte
detects a microbe or a cell that is expressing
a foreign antigen, & how it comes to deal
with terminating that foreign invader in the
process of phagocytosis which in itself is
really quite fascinating when u remember how
diverse and adapted all the cells in our body
really are especially when u consider that
there are billions & billions of cells in
our body all workin together in harmony
Now the steps of phagocytosis are particularly
important to know, because as we'll see later
on, defects in the process of intracellular
killing post-phagocytosis can leave hosts
particularly susceptible to severe & persistent
infections as in the case of chronic granulomatous
disease
So we have our phagocytic cell,for example
in this case, the macrophage, which is standing
guard, assisting our innate immune defenses
by using its pathogen recognition receptors
it detects the foreign antigen of microbes,
in this case a bacterial cell
what happens next?
well a number of things
1. as we saw in the previous video, the macrophage
becomes activated & begins to secretes chemokines
and acute phase proteins, such as your interleukins
and tumor necrosis factor which not only activate
the rest of our immune cells, both innate
& adaptive immmune cells, they also have effects
on the body as a whole, for example effecting
the endothelium as well as causing fever,
and therefore generally making the bodys environement
more hostile to invaders
So
Next, lets see how our phagocyte phagocytoses
the bacteria & then digests it with enzymes
intracelluarly...
the first step in phagocytosis... is the extension
of pseudopodia from the phagocyte to wrap
around & engulf the bacteria
then the pseudopodia fuse together to trap
the bacteria inside the phagocyte in whats
called a phagosome
now in this case our macrophage, which remember
has lots of digestive ezymes contained within
lysosomes, as do our other phagocytes, now
these lysosomes fuse with the trapped bacteria
in the phagosome, to form a phagolysosome
& this exposes the bacteria to the enzymes
contained within & subsequently kills the
bacteria
Now this intracellular killing within macrophages
happens by two different methods,
the first method is by Oxygen-independant
killing, and this form of killing, as the
name states, doesnt require oxygen & is performed
by enzymes such as lysozyme - which digests
bacterial cell walls by cleaving peptidoglycan,
defensins which form pores through bacterial
cell membranes, & then you have things like
lactoferrin which chelate iron & also some
other hydrolytic enzymes ... but the main
thing to remember here with these enzymes
is that their methods of killing are carried
out without oxygen, and these are grouped
collectively as oxygen-independant killing
mechanisms, lysozyme, lactoferrin, defensins
and hydrolytic enzymes
the other mechanism of intracellular killing
does requires oxygen, and is thus oxygen -dependent
and you may have heard this being referred
to as the respirartory burst, as its only
know
now this category of oxygen dependant killing
further divides into 2 different killing methods,
with both being centred around the generation
of oxygen-free-radicals
the first of our oxygen-dependant killing
mechanisms is by an ezyme, NADPH oxidase which
reduces oxygen to superoxide anion, which
then generates hydroxl radicals & hydrogen
peroxide which are both toxic & deadly to
microbes, so it basically generates lots of
oxygen free radicals
the second oxygen dependant method is by another
enzyme, myeloperoxidase, which combines chloride
ions with some of the hydrogen peroxide formed
by NADPH oxidase to produce hypocholrite,
which interestingly enough is actually the
same active ingredient that you'll find in
a bottle of household bleach under your sink
So those are your various intracellular killing
methods that happen after phagocytosis, and
the main thing really to remember is that
they divide into oxygen-dependant & oxygen-independant
killing mechanisms & the more important one
is actually the one that requires oxygen - the
oxygen dependant killing method, the respiratory
burst, which is quick and effectove
And therefore defects in the oxygen-dependant
killing within phagocytes actually has an
important clinical correlation & that is in
the development of chronic granulamatous disease,
where patients suffer from chronic severe
and persistent bacterial and fungal infections,
specifically from catalase positive organisms
and this is actually due to an inherited deficiency
or defect of NADPH oxidase - so the phagocyte
struggles to produce the oxygen free radicals
which are needed to destroy the catalase positive
organisms
now why is it only catalase positive organisms
and not catalase negative? Well the function
of catalase is to break down hydrogen peroxide
into 
water and oxygen, preventing it from used
by myeloperoxidase to form hypocholorites
ions to destroy any would be microbes
So far, we've examined anitgen detection & phaocytosis,
but theres another key feature to examine...
anitgen presentation, and thats what we'll
be having a look at in the next video
