nm1344: i shall pick up where i left off yesterday i was talking about 
localised infections and i gave one example which was rhi which was papilloma 
virus er which as you know causes warts so it's infection is localised to the 
skin infection of squamous epithelium what i'm going to talk about briefly now 
is rhinoviruses er er er er a small R-N-A virus which as you know i hope causes 
colds common colds inhalation of aerosols bearing this virus results in 
infection er and this infection occurs despite the mucus and stuff although one 
assumes that most most viruses that enter your upper respiratory tract are got 
rid of occasionally viruses will get through that mucus barrier and infect the 
underlying er underlying epithelial cells obviously if there are circumstances 
where the cilia are inhibited er which does happen if it gets very cold then o 
one might expect perhaps that the chances of infection are increased and this 
might be one possible explanation for why er colds seem to be more prevalent in 
cold weather simply because the cilia being cold are less efficient than in 
warm weather now i think i mentioned that the receptor for the rhinovirus a 
molecule called C-D-fifty-four is very widely expressed and a whole range of 
cells many cells in fact i believe all cells under certain circumstances 
express this molecule er so in principle rhinovirus can in infect any old cell 
or at least attach to and enter any cell in fact the infection is always 
restricted to the upper respiratory tract now the reason for that is supposed 
to be is quite simple because the virus is actually adapted to replicate best 
at lower temperatures obviously you understand your upper respiratory tract is 
cooler than the rest of your body so a virus that's best adapted to replicate 
at thirty seven point two degrees may be what replicates so well at that part 
of er the body whilst the virus which is er adapted to replicate at low 
temperatures will replicate well and in fact that's the case with rhinovirus it 
is its optimum replication temperature's about thirty two thirty three degrees 
it replicates rather less well at thirty seven degrees so that in fact this 
virus in effect is temperature sensitive so cold-adapted er and er temperature 
sensitivity of course really are the same thing so that's the reasonably 
reasonable and likely explanation for why rhinoviruses infections are 
restricted to the upper respiratory tract okay so that's a couple of examples 
of localised virus infections and as you well know many virus infections in 
travel through the whole body so we have to think about how viruses disseminate 
how they move around how their infections become systemic or systematic 
evidently the initial step will be some sort of local infection all viruses 
except those that are arbovirus transmitted are arthropod transmitted and so 
may enter directly into tissues all viruses obviously start somewhere an 
infection a localised infection starting somewhere so you get initial 
replication at the primary site of infection and then what we have is the 
progeny virus from that initial infection er enter the circulatory system okay 
get into the blood talk about how that happens in a moment getting into the 
blood obviously you'll have virus in the blood and that at this stage is 
described as the primary viraemia viraemia simply means virus V-I-R in the 
blood –aemia okay primary means it's the first time the virus is in the blood 
so initial er primary viraemia the consequence of this primary viraemia 
obviously is that the virus moves to other cells in the body so that there's a 
second wave of replication of the virus more progeny virus occurs and we get a 
secondary viraemia obviously in the secondary viraemia there's going to be much 
more virus in the circulatory system than in the primary viraemia it's a second 
wave if you like evidently the consequence of this secondary viraemia will be 
further widespread infection of other tissues through the body so it's quite 
simple to imagine and understand how how it disseminates how it how i this 
works classical example of this i'm not sure if i have slides about it later on 
is is measles measles is transmitted by er aerosol droplets so the initial site 
of infection is the lungs so the virus first of all replicates in the lungs the 
lung tissue the lung epithelium it then gets into the blood and passes through 
all sorts of other tissues in the body now how does this spread occur obviously 
the spread of the virus is essentially mechanical and the virus hasn't got legs 
so it can't walk around it hasn't got flagella like some bacteria er and it 
doesn't have invasive mechanisms think of clostridium for example which 
produces er enzymes collagenate which can digest the tissue so the bacterium 
can spread through the tissues actively as it were viruses inevitably can only 
be spread around inevitably mechanically now this can be either i haven't got 
this quite set out properly have i the virus can either spread as virus as 
virions sort of free virus and of course that happens or of course it can 
spread in cells that are infected and which migrate the best examples of 
migrating cells are of course leucocytes whose job is to move around the body 
they do that and if they happen to be infected and in the case of measles they 
are obviously they will carry the virus into the circulatory system and 
elsewhere now when i say circulatory system what we think of first of all is 
the blood circulation but we must never forget the lymphatic system which i 
shall be talking about later on when i talk about er way the immune response 
works so let's not go into detail about lymphatic system now what i have said 
here is this spread of virus is aided by the inflammation which occurs as a 
consequence of the infection now the inflammation is a subject which i shall 
take up later inflammation occurs whenever you have tissue damage consequence 
of inflammation means that the local blood vessels particularly capillaries and 
lymphatics become much more leaky the purpose of this leakiness is to allow 
things cells in particular to get into the tissues but a consequence obvious 
consequence of this leakiness of these vessels is that things in the tissues 
can get into the circulation so when you have the inflammation occurring if 
there are infectious things er at that site which there will be er they can 
find they find it much easier to mechanically mechanically to enter into the 
circulation because the circulatory system is more leaky and this is something 
we need to remember i have said that the local lymph nodes may be the first 
site of secondary replication i've talked about primary viraemia and a wave 
secondary wave of infection generating a secondary viraemia now the local lymph 
node is the place where tissue er fluids and cells first of all drain to and 
end up in or at it okay so anything that's in your tissues will go firstly to 
the local lymph node or may go directly into the circulation but it's more 
likely to go to the local lymph node okay so when we get a sore throat what 
happens you have an infection at the back of your pharynx virus particles move 
to the lymph nodes and the-there they start replicating and they're not just 
replicating but you get an immune response there and so that's why your lymph 
nodes here swell up and are very tender when you've got a sore throat we'll 
come back to that because that's actually a very important part of the 
pathogenesis of disease so the local lymph node is usually likely to be at any 
rate the first site of secondary replication lymph nodes and lymphatics and 
things like that we will come back to and talk about in more detail later right 
as i say measles is a good example primary infection is in the lungs spreads 
via lymphatics to the local lymph node thence to the blood and everywhere else 
now when i was talking to you the other day i mentioned there are basically 
three kinds of this er infection localised disseminated where it goes 
everywhere and disseminated where there are particularly target particular 
target tissues where er where they might be especially severely affected and 
the examples that i give here i've actually already given them er so i'll just 
say them again polio in the central nervous system polio targets the central 
nervous system consequence is paralysis H-I-V targets the lymphocytes and other 
cells but lymphocytes are our primary target consequence is er the immune 
suppression hepatitis virus targets the liver and doesn't actually infect any 
other tissue in the body okay so the two kinds of dissemination measles on the 
one hand nearly all the tissues are affected and these other viruses which tend 
to go to particular tissues that brings me onto this to the issue of the nature 
of the diseases that viruses cause it goes almost without saying that the 
symptoms of the infection the symptoms of the disease which is generated 
infected so we talk about syndromes now the word syndrome and you've heard it 
in the severe acute respiratory syndrome the word syndrome means a collection 
of signs and symptoms associated with damage to particular cells or tissues i 
don't know if i've given you any examples in there or not a couple of examples 
the obvious examples are oh respiratory syndromes where infection of the 
respiratory tract by almost any old pathogen will cause sneezing coughing 
shortage of breath and things like that so the symptoms are not due to the 
agent which is causing the disease not the the nature of the symptoms rather of 
course the symptoms are due to the agent but the nature of the symptoms is due 
to the cells which are infected likewise er with gastroenteritis er bowel 
syndrome syndromes common er er the common symptoms are diarrhoea and vomiting 
any old virus or bacteria which infects your bowel will cause diarrhoea and 
vomiting okay so the symptoms are due to the nature of the cells that are 
infected not the nature of the agent i shall talk much more later about the 
pathogenic process and how viruses actually cause disease cos in a way that's 
the central problem now we must keep contact with this idea that i'm talking 
about 
that the the natural history the lifecycle of the virus on a macroscopic scale 
therefore i've said how viruses spread from one individual to another how they 
gain entry to the body how they move about the body and infect particular 
tissues and the last point that we want to summarise is how the virus gets out 
obviously in order to spread to other individuals they have to be shed from the 
infected host the viruses that are infecting the respiratory tract mouth bowel 
and so on it's perfectly obvious how the virus gets out with other viruses it's 
less obvious how they are shed particularly those viruses that replicate 
exclusively in internal organs hepatitis is one example it replicates only in 
the liver or cytomegalovirus is another example of a virus which is only 
infecting internal organs okay and so is not actually shed so it's less obvious 
how these viruses spread we'll come back to that later on er in the case of 
hepatitis virus and cytomegalovirus it's actually vertical transmission so 
that's a very unusual situation where blood is shed okay which i was saying the 
other day and so the infection is from mother to child not from one individual 
to another horizontally okay so that brings me to the end of that particular 
topic the virus has gone the full cycle it's entered its host replicated and 
got out of its host now as we well know yeah
sm1345: can we have some more of topic four please
nm1344: more handouts there is a bundle i thought i circulated them all can you 
pass them back could you pass them back pass them back as a bundle er i'll keep 
a few thank you very much actually these are the er i should say i've given out 
also the list of viruses which i mentioned the other day so there's a handout 
lecture notes topic four and the list of viruses which should be circulating 
okay i've star- started them at the back i started them at the front and left a 
pile down here so you will get it eventually so don't worry okay as i say the 
virus has gone full circle what about the host er a point that i frequently 
make is that the pathogen and its host are organisms which are co-evolving okay 
so the virus has developed these mechanisms of moving from host to host and 
replicating and so on the host at the same time of course has developed 
mechanisms evolved mechanisms i should say er for counteracting the deleterious 
effects of the virus and getting rid of the virus so the next topic er as you 
will have gathered by now i'm quite sure is going to be er the host response to 
the infection topic four okay so there we go the host response what i'm going 
to do in this lecture is describe how the host's immune system that is your 
immune system my immune system er respond to the virus infection with the aim 
of eliminating that virus that's the ideal but in fact that very often doesn't 
happen our immune system is far from perfect and very often our immune system 
cannot actually eliminate a pathogen and the consequence is that you get a 
chronic infection long term infection in that situation the job of the immune 
response the immune system is to contain the damage done by the virus and that 
is very often efficiently done although the virus cannot be got rid of the 
deleterious consequences of the infection are limited by the immune response 
okay now i know that you've had lectures from Miss Jones about the immune 
system er and i say in my notes at the beginning o on the website that i'm 
assuming that you have a basic grasp of immunology so that i don't have to 
define what an antibody is or what T Cells are and things like that or what 
complement is you know that already but i do appreciate that a lot of people 
find immunology quite a tough science because there's so much so may terms that 
you're not familiar with if you have problems then for goodness sake stop me 
and ask me to define er what i'm talking about i'm perfectly happy to do that 
okay i'm going to recapitulate some elements of immunity the immune system 
basically like all systems of the body all tissue systems is comprised of cells 
quite obviously i've listed here what i think of as the most important cells of 
the immune system and you need to get really quite familiar with the biology of 
these cells the first bunch of cells that we think about when we talk about 
immuno immunology is the lymphocytes there are two kinds of lymphocyte B and C 
the B Cell is called the B Cell cos it's from the bone marrow well all cells in 
the immune system are from the bone marrow but in distinction the T Cells have 
to go through the thymus T for thymus B for bone marrow okay these two types of 
lymphocytes which are distinct are both antigen-specific that is they are 
capable of responding er to stimulation with specific antigen by generating an 
immune response so lymphocytes are key to the adaptive response because they 
are immune er they are antigen specific another cell type which it is difficult 
to say is less important than the lymphocyte is the dendritic cell now i don't 
know whether er you have actually dealt much with the dendritic cells the job 
of the dendritic cell and i'll give you whoops sorry about what's happened page 
up the thing about the dendritic cells their job er and i'll be talking about 
them a bit more later on their job is actually in activation of the lymphocytes 
lymphocytes don't just turn themselves when they interact with an antigen there 
have to be other cells involved and the key cell that's involved in the 
activation of the lymphocyte is the dendritic cell okay i want to emphasise 
that cos i don't think it's emphasised enough having said that i will slightly 
qualify it by saying er that er the role of the dendritic cell is much more 
important in a primary immune response that is the first time you encounter er 
a pathogen than in secondary immune responses the dendritic cell is the key to 
the development of the primary immune response macrophages they are important 
also in activating lymphocytes but probably important more important in 
secondary immune responses perhaps when you have when you encounter a pathogen 
for the second time subsequent time er the dendritic cells then are less 
important then the macrophages as it were kick in [?] the cell which is busily 
activating lymphocytes like many cells in the immune system macrophages 
actually have multiple functions and this is another thing that bothers people 
that come across immunology for the first time cos i talk about macrophages 
important in activating lymphocytes and then in brackets and for killing 
bacteria by the way so macrophages have these multiple functions that's not all 
their functions they kill bacteria as you probably know by gobbling them up and 
digesting them inside the phagolysosomes and all that and i put in brackets 
down at the bottom here another cell type which tends to be neglected er 
doesn't get talked about nearly enough and that is the granulocytes so called 
neutrophils and polymorphs and things like that i'm not going to talk about 
those because they're important for killing bacteria and not much else there is 
one other thing that they're important for that in in interaction with 
parasites and eliminating parasites things like worms okay and for reasons 
which again i'm not going to go into these cells or some of these cells are 
important in things like allergy but never mind that's by the way there are of 
course other cells er but these cells from a biological point of view 
lymphocytes dendritic cells and macrophages you need to know about now another 
thing that perhaps is never emphasised enough is that the immune system is not 
just a sort of fluid thing it is organised into tissues all body systems are 
organised into tissue the digestive system the central nervous system all that 
lot no less the immune system and we talk about two kinds of tissue primary 
lymphoid tissue and secondary now the primary tissue is the bone marrow and the 
thymus where cells develop as i've just mentioned bone marrow all cells of the 
immune system come form the bone marrow ultimately T Cells develop in the 
thymus and the process by which they develop they develop is referred to as 
hematopoiesis not that's a slightly long and difficult word which i will i'm de 
defining here but i tend to use it more or less continuously so if i suddenly 
say hematopoiesis or hematopoietic that refers to the development of cells of 
the immune system and blood generally actually the secondary lymphoid tissue 
now i've just now a little while ago mentioned lymph nodes and i have to also 
include the spleen okay and the secondary lymphoid tissue this is where the 
immune responses occur very much so the immune responses don't just occur sort 
of anywhere they occur in the lymphoid tissue secondary lymphoid tissue which 
is highly structured and highly developed in order to optimise the way in which 
the immune response to a pathogen occurs so as i was now just saying the first 
port of call as it were for an infecting virus is the lymph node so that's 
where its replication gets underway at the same time what's happening there is 
that the immune response is developing against that pathogen so a theme which 
perhaps er is implicit which i'll now said explicitly is that the immune 
response develops in concert with the development of the immune o o the virus 
infection so one has to think about how the virus infection develops and 
spreads through the body and in an equivalent way how does the immune response 
develop to counteract that infection okay they are not separate in separate 
compartments obviously they all both occur in the same compartments okay so the 
immune system is organised into tissues which are of course connected by the 
circulatory system lymphatic circulation and the blood circulation i've just 
just now mentioned okay we'll come back to the issue of circulation now again a 
point that i know Elizabeth has made is that if we divide the immune system 
into innate immunity and adaptive immunity now these this is a conceptual 
division the immune system isn't in two separate boxes one labelled innate the 
other labelled adaptive these two conceptual components of the immune response 
work together they are co-ordinated concerted together you don't have the one 
and then the other separately come together innate immunity as you know is 
something which is immediately available upon infection okay so it's al there 
all the time it is non-specific so it doesn't distinguish between corona 
viruses and rhinoviruses it works against any old virus and the essential 
another essential point about it is that it is do it is not adaptive in other 
words it has no memory okay in other words the innate immune response is no 
better the second third fourth time around than it was the first time around 
there's no memory the adaptive immune system by the way er on the other hand er 
is not immediately available it's relatively slow acting takes two or three or 
four days for it really to get underway on the other hand it's specific so that 
it recognises particular pathogens so it distinguishes between corona viruses 
and rhinoviruses and more importantly it adapts to the challenge of infecti an 
infection in the sense that there is memory okay the next slide's there now 
this issue of memory is really quite simple what it means is that the second 
response is different from the first response usually much stronger okay there 
are situations where actually a secondary response is less powerful than the 
primary response but obviously that's not much good er 
from our point of view the secondary response is usually much stronger much 
more powerful than the primary response because the adaptive immune system has 
adapted to the pathogen to give a better response the second time around now as 
i say i want to stress this point that these aren't two separate systems they 
are linked together and the same system they both are efficient for a necessary 
for efficient resistance to pathogens defects in either one or the other lead 
to severely increased susceptibility to disease so we cannot get along without 
either of them have to have both in order to cope best with pathogens that said 
it's interesting to notice er that you only get adaptive immunity in in 
vertebrates the the most primitive organisms that have adaptive immunity are 
the jawless fish agnatha no invertebrates have adaptive immunity er and yet 
they seem to get along perfectly well er in evolutionary terms er so why is 
adaptive immunity so very important i sometimes ask myself er you could argue 
that adaptive immunity is important for long life you can say okay insects and 
worms with their non-adaptive innate immunity can cope for a few weeks or a few 
months which is their lifetime but if they're expected to live for many decades 
as we do they wouldn't because they don't have an adaptive immune response that 
argument doesn't actually work because there are plenty of long-lived 
invertebrates I'm thinking of molluscs in particular i believe things like 
squids and octopuses can live for many years so we have the adaptive immunity 
we think it's wonderful but i wonder if it's absolutely that necessary okay so 
equally importantly to the point that that they they are overlapping systems 
one has to think one has to understand that the two parts though i am hesitate 
to say that the two chunks i i don't want to separate them really one has to 
you have to understand that they work together interactively they interact 
together er and what happens is that you very often find you find full stop er 
that cellular components of the innate system are activated by products of 
cells of the adaptive system so something produced by a lymphocyte responding 
to an antigen will turn on macrophages so that the macrophages do their job 
better okay likewise products of macrophages which are subject to infection by 
bacteria or whatever products of those cells can in turn activate lymphocytes 
and make lymphocytes work better at their job so the system overlaps and 
interacts and you must never think of innate immunity and adaptive immunity 
working in isolation so I've said enough about that i won't press that any more 
but there is this diagram here er innate immunity cross-talking with adaptive 
immunity powers up the pathogen okay so let's actually move on to talking about 
more specifically er the response to virus infection the generation of the anti-
viral immune response in any community let's go back a couple of steps I've 
said to you that with the exception of arthropod-borne er infections a virus 
infection always starts at a localised spot the innate immune system is 
everywhere present always available and obviously it is going to act locally 
where the virus is replicating okay it is activated now the word activated 
obviously means turned on er and I'll clarify what i mean by this a little 
little bit later on er so the point is that components of the innate immune 
system the cells of the innate im immune system are made more active by 
specific products of the pathogen okay now in the case of viruses er a 
component of the virus which tends to turn on very strongly some parts of the 
innate immune response is double sided R-N-A now this is where one has to start 
actually thinking a little bit about virus replication and the molecular 
biology of viruses you know from Andrew that many viruses have R-N-A genomes 
some of them have double-stranded R-N-A genomes those that have single-stranded 
R-N-A genomes very often have to have a replicative intermediate which is a 
double-sided R-N-A molecule so double-sided R-N-A molecules are associated with 
viruses they are not associated with cells our cells do not contain double-
sided R-N-A so the presence of a double-sided R-N-A molecule obviously is 
indicative of infection by a virus okay so any virus that generates or has 
double-sided R-N-A will turn on components of the innate immune system so 
unusual components of the pathogen turn on the innate immune system just as a 
quick aside to bacteria in the case of bacteria the components that turn on the 
innate immune response there are things like like the lypopolysaccharide coat 
of bacteria our cells don't have lypopolysaccharides in them so that's another 
unusual pathogenic component and also er bacterial D-N-A can turn on innate 
immune reponses because bacterial D-N-A is methylated in a different from human 
D-N-A so again is distinguishable from human D-N-A so our immune response our 
innate immune response has evolved means of recognising pathogens which okay 
are non-specific in the sense they don't distinguish one pathogen from another 
but they do recognise that this is an unusual organism a virus which should not 
be there okay now i said that innate immunity tends to be thought as local 
acting adaptive immunity occurs both locally and systemically okay so at the 
site of infection you get the immune response also in other parts of the body 
particularly the secondary lymphoid tissue you get the immune response 
generated generated now as you know the adaptive immune response is activated 
by protein antigens not usually protein antigens usually proteins can be other 
things but almost always proteins which interact with the lymphocytes and the 
lymphocytes interact with the antigens because they bear receptors specific for 
those antigens okay now this recognition phase where the lymphocytes are 
recognising an antigen er as something which is foreign to the self is 
sometimes spoken of as the cognitive phase the learning phase okay cos these 
lymphocytes are learning that there is a protein there that should not be there 
obviously a very specific situation now again you will have learned from 
Elizabeth that an individual lymphocyte one lymphocyte bears only one specific 
receptor okay so one lymphocyte can interact only with a particular antigen 
this is spoken of is called kernel distribution of receptors so clone as you 
recolle recollect the real definition of a clone is the descendants of a single 
cell okay so a clone of cells will all have the same receptors so that's not 
quite what i just said a single cell has a single receptor a clone of cells all 
have the same receptor confusing i know but just the important point is that a 
particular lymphocyte will have only one receptor for a particular antigen now 
i haven't got time to go into sort of theoretical background issues about the 
nature of the receptors but what is important to grasp is that our immune 
system can actually respond to almost anything any protein i should say er you 
take protein from mice and inject it into a rabbit that rabbit will generate an 
immune response to that protein from mice the point is we have to be able to 
respond to anything that challenges us now that means that given that we a 
particular lymphocyte has only one receptor and we can respond to almost any 
antigen there are few individual lymphocytes sorry there are few lymphocytes er 
specific for a particular antigen in a naﶥ individual the naﶥ individual is 
one that hasn't encountered the antigen before sometimes well i won't go into 
what it sometimes called but the point is er that what happens as a consequence 
of this interaction of the rare lymphocyte with the antigen is that the 
lymphocytes divide and proliferate and grow okay and this amplifies and can 
amplify enormously the number of cells with the receptors to that particular 
pathogen and this is spoken of usually very often as the activation phase okay 
so the er lymphocyte recognises the antigen in the cognitive phase there aren't 
many of that lymphocyte but it starts to divide having recognised and we go 
into this activation phase the last step and of course the essential step is 
that these activated cells these activated lymphocytes differentiate to 
generate cells which can eliminate the pathogen and that is called the effector 
phase so there's cognitive phase activation phase and the effector phase the 
effector phase is where your activated lymphocytes and other cells helping them 
are getting rid of the pathogen okay so we speak of effector cells the nature 
of the effector cells i shall be going into presently obviously these effector 
cells there are many of them at the height of the immune response working away 
like mad and as I've sa- as they're all descended from cells they are clonal 
[?] clones they are all descended from cells bearing specific receptors thence 
these effector cells are themselves antigen specific okay so broadly we think 
of cognitive phase activation phase which is divison then differentiation into 
the effector phase and the effector cells are descended from the original 
lymphocytes bearing the receptor so they will obviously be specific for the 
particular pathogen which has turned the whole business on right so all being 
well the immune response will be terminated er by elimination of the pathogen 
having eliminated the pathogen there's no further stimulus for the immune 
response and a peculiar thing well not a peculiar thing a very important thing 
about cells lymphocytes is when they are no longer being stimulated they tend 
to die okay they do die there's no tendency about it they die one can't tend to 
die it's an all or none thing er so most effector cells at the end of the 
immune response disappear and are eliminated er some will survive okay some do 
survive they retain their specificity the important point about that is it 
means that at the end of the infection there are many more cells specific for 
that pathogen than there are in the naﶥ individual before the infection so 
the second response secondary response to the same pathogen is enhanced because 
there are more cells there able to respond to the infecting pathogen and that 
is the basis of infe 
er basis of immune memory quite simple okay now I've said and I'm going to 
stress this point er that the immune system is an organised tissue system and 
I'm going to stress the point again that the main site where the immune 
response occurs is the secondary lymphoid tissue particularly the lymph nodes 
okay initially antigen transferred or is transferred by cells to the local 
lymph node as I've been saying through the lymphatics where most specific cells 
are the specific cells the lymphocytes of the immune system are largely 
concentrated in the lymph nodes those little knots of tissue which i shall be 
showing you presently the vast bulk of the immune system is in the lymph nodes 
not circulating or in the tissues and this transfer is often i use the word 
often because one can't actually make hard and fast statements about this but i 
would say always in fact in primary infections this transfer is via the 
specialised dendritic cells okay right so a word about the dendritic cells er 
the they're called dendritic cells because under the microscope they've called 
all sorts of processes sticking out er dendrites like tree roots think of a 
mass of tree roots dendritic cells look that that and the purpose of all these 
dendrites is actually to trap and take up antigen from fluid okay now you have 
dendritic cells in say the skin in all er epithelial layers or more accurately 
you get them in the spa in in the connective tissue underneath the epithelium 
and when they're in in that that connective tissue they have a different name 
which is confusing Langerhans cells but don't worry about that because i think 
the term Langerhans call has more or less been dropped by now but if you come 
across the term Langerhans cell that's a dendritic cell which is in the tissue 
okay now it's well known that the dendritic cells are highly mo mi migratory 
and you can do ex a sim a very simple experiment er do it with mice if you take 
a mouse and paints its ear er with a fluorescent compound called fluorescene 
that penetrates the tissue and is take up by dendritic cells okay so the 
dendritic cells become fluorescent within m almost minutes certainly within an 
hour or two those fluorescent dendritic cell are in the mouse's are in the 
lymph node that drains the mouse's ear so the dendritic cells are moving from 
the tissues to the lymph nodes carrying foreign compounds in this case 
flourescene if it's a virus infection it'll be bits of virus or s whatever so 
the dendritic cell moves the antigen around and that's its job that's why it's 
so important okay now let's move on to think about the lymph node a little bit 
I'll talk about the structure in a bit more detail in a moment but it's a 
specialised organ the lymph node is a specialised organ where basically what's 
happening is that fluid from the tissues is being filtered through a dense 
network of leucocytes basically it's a bag of leucocytes through which fluids 
from the tissues are filtered okay that's where the antigen reactive lym 
lymphocytes are localised and so this filtration optimises the probability of 
lymphocytes interacting with er the antigen usually in the context of a 
dendritic cell what one has to understand is this filtration of course is 
facilitated er by cells being able to move across move from tissues and the 
circulation by crossing the walls of the lymphatic vessels and the capillary 
vessels i'll show you some diagrams in a moment the main means of exchange 
between the tissues and the circulatory system has to be across the walls of 
the vessels of the circulatory system it goes without saying and really the 
only vessels which are involved here are the lymphatics and the capillaries 
because their walls are a single call thick you cannot imagine anything moving 
across er the wall of the aorta for example which is a very powerful er piece 
of tissue with lots of muscle and stuff in it nothing crosses the aorta wall if 
you're healthy er but things can easily cross into the capillaries and into the 
lymphocytes because the walls of those vessels is a single cell thick okay so 
it's actually really rather hard to find a good diagram that you can pinch of 
lymph nodes they're either too complicated or too simple what I've tried to do 
here I've drawn this myself I'm not terribly proud of it but i think i it 
describes er what the structure of the lymph node is at the sort of level of 
detail you need to know now this coloured bar here actually refers to the next 
diagram er which describes the cells in this particular parts let's go back in 
case you were wondering what that coloured bar was we'll come back to that in a 
moment now this ve this organ is typically er about the size of a lentil or 
something like that bean-shaped it's literally bean-shaped it's that sort of 
shape er and it's a has a capsule around like many little organs like the 
kidney whatever it has a capsule around it of quite tough connective tissue 
it's a thin capsule so in fact er lym lymph nodes can be quite easily ruptured 
as can the spleen and other suchlike tissues so it's a a capsulated organ now 
there are lymphatics associated with the lymph node and there are two sets of 
lymphatics lymphatics i should i have said are just little little little er 
blood-vessel-like little vessels which carry lymph from the tissue er so the 
afferent lymphatics are those lymphatics that go to the lymph node they are 
very fine vessels and they have er valves in them one-way valves that I've 
represented by these lines so stuff fluid that gets into them can only go one 
way there is no pump to drive through it through the lymphatics but as you move 
around obviously the lymphatics will be compressed and released and since the 
fluid can only go one way because of the because of the valve it eventually 
gets into er the lymph node now let me stress the point that these lines here 
are the the walls of the lymphatic vessels within the lymph node but what's 
happening is there is intense traffic across those walls of cells okay so cells 
in the lymph coming from the tissues via the afferent lymphatics is crossing 
these walls er these these vessel walls and entering the body of the lymph node 
which comprises leucocytes a great mass of leucocytes with these capillaries 
these lymphatics moving through eventually they collect here and then they move 
out from the lymph node by the efferent lymphatics efferent means from okay now 
what happens these collect together in ever bigger vessels and eventually go 
into what's called the thoracic duct which enters into the vena cavae which is 
the main ar main vein leading into the heart so material from fluid cells from 
the tissues enters the afferent lymphatics goes to the lymph nodes filters 
through the lymph nodes is gathered together in the efferent lymphatics goes to 
the thoracic duct thus into the blood circulation via the vena cavae okay a 
very nice system likewise blood goes into the er lymph node we have an artery 
entering in and a vein leaving obviously all these particular bits all these 
parts all these compartments of the lymph node all right it's not just this 
compartment that has this system they all have it and in this part of the lymph 
node the outer part as it were you have a capillary bed where the artery 
divides into these fine capillaries which are collected together into the vein 
these are spoken as high endothelial venules oh i don't know why er and here 
again because these capillaries are very fine-walled things you get intense 
exchange of cells across that wall into the tissue of the lymph node okay so 
you can see how the lymph node is a means of exchange a site for exchange 
rather between the two circulation systems exchange of cells and other theories 
er i don't want to talk about this in any details because er frankly i don't 
really understand er the cellular structure of lymph nodes and i'm not unique 
in that er but we find that the various components of the lymph nodes just go 
back from the outside of this cortex paracortex amygdala outside in cortex 
paracortex amygdale and the cortex is mostly B Cells apparently and the 
paracortex mostly T-cells but in the mygdala you get this big mixture B and T 
cells macrophages dendritic cells dendritic cells again they will have come 
that way lymphocytes and stuff will have come that way so you can see that as 
they move through there's all sorts of possibilities of interaction between B 
cells T cells and the whole lot the whole caboodle together so that's enough 
really about lymph nodes just want to emphasise that is the site where the 
immune response develops and we'll pick pick it up again later on okay