Antibody concepts - (Jun/09/2007 )
Just wondering when it says that antibodies help destry pathogens etc this can only happen if the body has been exposed to this same pathogen before right?...so say for example "strain A" enters my body, the immune response takes place with the final result being plasma/memory cells being produced...these plasma cells secrete the antibodies that will forever be in my system right? and the memory cells are incase "strain A" ever comes back into my body can help destroy this strain along with the antibodies right?...so once these antibodies hv been secreted via plasma cells does this mean that they destroy the rest of Strain A within me
if this is the case i just read that there are 3 main ways of destryong antigens...like neutralizaion, opsonization and complement...does this mean that in order for the antibodies to bind to these forign objects my system shld hv come across these bugs before???
one last thing...when a pathogen enters us are cells such as macrophages the 'first line of defense' ie meaning that antibodies will not be secreted due to the fact these macrophages/neutrophils can destroy it
can someone please help, i have an exam on friday and wanna make sure i have these concepts correct
The answer to all your questions are in all standard immunology text books. Let me try summarising some of them.
The immune system has many layers or steps of defense and with every step, immunity if more specific and strong. You must be aware of Innate and Acquired Immune systems. When an organism breeches the physical barriers and enters the human body, they are limited by inflammation that will involve not only the cellular components you mentioned (white blood cells) but also the humoral. Complement system is a part of innate immunity. You have also missed noting a very important part of our innate immunity - The Natural Antibodies. Perhaps that will answer all your doubts.
Natural Ab (NAb) are produced by a class of B-cells (B1 cells) without previous exposure to the organism. You must be aware of blood group Antibodies. Like them, we have other natural antibodies in innate system that are directed non-specifically to various antigens in the microbes playing an important role in immunity. So, even in innate immunity, when you have not ever come across an bug, there are antibodies that will play role in clearing the bugs.
The next question was what is innate immunity clears the bugs. Innate and Adaptive Immunity function together. Innate immunity just buys time for adaptive immunity also to come into action on the first encounter. The cellular components of innate immune system you have mentioned don't just clear the bugs but activate the adaptive immune system also. So, there is no way that the adaptive immune system stays quiet while the innate does all the work.
And, it is not always required for antibody production to be exposed to the same bug. Like, I mentioned about natural antibodies that are already there before you were exposed to the bug and another was you can have antibodies against a bug is through immunisation.
Yep I know they can be found in standard textbooks (I'm using Janeway online as thats the one we were told to read) but sometimes I wonder If the way I'm thinking about the stuff I read is wrong so just wanted to see if what I wrote was correct...
Ok..soo hmmm NAb...I actually haven't come across them/heard about them...maybe it was just something we should know..eeepp..ok so if we have NAb against a bug does this mean the humoral response still takes place creating memory cells and plasma cells which secrete MORE antibodies which are the exact same of the NAb?..is this what always happens...ok so say a bug does enter the system...as mentioned above say for eg: we talk about neutralization...do the NAb's come attack the antigen and macrophages digest them?...and this as you said buys time for the adaptive immune system to get working...so say after maybe 4 days 30% of bug is still remaining is this the time where dendritic cells present fragments on MHC molecules etc etc creating plasma cells/memory cells (this is the humoral response right??)...
say after 2yrs we are reinfected with this bug does that mean the antibodies that were produced first time round come attack and get rid of them via neutralization etc (does the humoral response take place again????) but in that case what are the point of the memory cells if we already have antibodies to fight them??
sorry for the questions..I know you have explained above...but I just wanna make sure the way I write something is understood by those who read it...
Remember that B-cell have a receptor (B-cell receptor, BCR) that is basically cell surface antibody with the same antigen specificity as the antibodies which will be produced by this B cell. So you have a large pool of B cells all with different specificities. The specificities are determined by re-arrangement of the germline antibody (immunoglobulin) genes. Signals through the BCR are important for the B-cell in terms of survival, activation and proliferation. So when the naive B-cell is exposed to the antigen specific for it's BCR you get proliferation of this particular B-cell (clonal expansion) and production of effector B-cells (plasma cells ) and memory cells. The plasma cell won't be long-lived and will die of following the immune response and the memory cells will be more long-lived and remain in the circulation. They will undergo clonal expansion to the same antigen again the next time that particular pathogen causing an infection but the memory response is faster and more efficient (lower threshold for activation). Vaccination works on stimulating memory responses (B-cell or T-cells) so you have a better chance of fighting a paricular infection as if you'd already been infected before and developed immunity. Most forms of immunity aren't life-long so vaccinations require boosters.
Antibodies work by binding antigen on the surface of pathogens, not attacking them. The antigen is just a molecular structure within the pathogen. If the binding prevents infection the antibody is neutralising (I'd normally think of this in terms of viruses with antibodies binding their receptors necessary for infection of cells), targeting complement to the pathogen and targeting bacteria etc. for phagocytosis and killing by neutrophil or macrophages (opsonisation).
The BCR recognises antigen directly not through MHC Class I or II like the T-cell receptor (although TCR and T-cell memory involves similar processes to the B-cell clonal expansion and rearrangement of germline encoded receptors).
As Nabin says the infection triggers your inflammatory response and brings in innate cells (neutrophils first) and acquired cells later.
Hope that makes things clearer.
Your questions are so good. I cannot answer all of them.
What I meant my buying time is . . . a germ enters human body that body has not seen till now. The germ can cause illness rapidly unless it is limited or eliminated. For that the innate immune system comes into action. This has both the humoral and cellular systems. In the mean time, with the help of the innate system, the more specific adaptive immunity develops which may take some time. (not sure how much. . I think 3-4 days). Till that time, the innate system will have limited or, if it can, eliminated the germs. But, now we have the specific defense against the germ ready in our body. They remain as memory cells.
Next time the same germ enters the body, innate will also attack, but the adaptive defense is already there in the body and their response time is less. The B cells will mature into plasma cells and start producing Abs and also B cell population expands that will remain as memory cells. The Ab produced will specifically tag the germs. As adaptive immunity which is specific is also vigorous, the germs are eliminated faster.
I think I have not been able to answer you properly. I will attempt again later. Hope others too comment on this as your questions are very interesting and challenging and needs a good understanding of basics of Immunology. I definitly need to do some revision before I attempt again (before Friday, of course)
The point U were missing that I wanted to highlight were
- we need not come across the same germ before we have B cells producing Ab. There can be cross-reactive Abs because Abs are not against germs but epitopes and germs can have a common epitope. Similarly, vaccination can make Ab producing B cells.
- innate system always comes into action even when there is previous history of exposure to the germ. They are always the 'first line of defense'.
Thanks for the replies...very helpful .. I am reading over my notes again and think I have understood now..or so I hope ....one other thing....the T-cell receptors have a wide range that allows them to recognize peptide fragments right? this is the same for MHC molecules...seeing as these 2 receptors recognize the same antigen does this mean they have the same structure??
Umm .. . MHC Molecules are not receptors, are they? They are proteins that are anchored on the surface of cells (class I on infected or cancerous cells and II on APCs) that display antigens to T cells. As for example, a macrophage engulfs a germ then the germ is broken down into fragments and these fragments are linked to proteins from MHC and then these are transported to the cell surface and anchored such that MHC protein then displays the fragment.
T Cell Receptor (TCR) on other hand are receptor molecules present on surface of T cells. These recognise the MHC molecule bound antigens. Unlike B Cell Receptors, for T Cell receptor to recognise an antigen, MHC molecule has to present the Antigen.
I hope you got the difference. MHC Molecule is not receptor but a medium by which an antigen is presented to TCR.
PS - please post new thread for new topic. That will be more convenient and easy to follow.
As Nabin says MHC are cell surface proteins and present peptides generated from proteins either from taken up from outside the cell/exogenous antigen (MHC Class II) or endogenous antigens/produced within the cell (MHC Class I). The peptides bound are roughly 8/9 amino acids (MHC I) or slightly longer 13-18 aas (MHC II). There are particular amino acids within the peptide (anchor residues) which are important for binding so the particular MHC can bind alot of different peptides with these anchor residues (with different affinities) i.e. not specific to a peptide like a TCR but a broader range of peptides. The anchor residues are different for specific MHC molcules.
The particular different MHC alleles each person has is called the haplotype and this determines what different peptides are bound and is one part of the genetic basis for why people respond differently to different infections. Different populations may have different haplotypes because of different infections in their past history which may have allowed them to survive certain endemic diseases. This is a bit speculative but I'm sure there are quite a few studies about this out there.
The structure doesn't need to be the same as they're binding short amino acid stretches. A specific TCR binds a specifc peptide but the wide range of TCRs (as with antibodies/immunoglobulin) comes through the random combinations of the various TCR gene segments. So the possible diversity of in immunoglobulin is 10 to the power of 11 (through random joining of segments, junctional flexibility, nucleotide addition and somatic mutation) and 10 to the power 15 for the alpha/beta TCR (in the same way but without somatic mutation). Each rearrangement of the antibody/TCR genes to generate the binding specificity occurs once per cell and is irreversible so there's a large pool of different B-/T-cells with different specificities and any cells with receptors that don't react or react with self are eliminated (not always true and autoreactive cells are kept in check by regulatory T cells aswell),
Hope this helps. There will be more information in Janeway about all thes things.
hi there..thanks for the really detailed replies...
man i am so screwed for this exam..thought i knew stuff but i dont...eeekk..anyway back to it
so MHC are proteins--i see...i assumed they were recpetors as the'display' fragements to the T-cells and hence "receive" the fragment (get what i mean) but yep i get it now...
so ceri you talk about the diversity of the receptors on the T-cell/antibody...the receptor on the b-cell is the same right as the antibody they secrete? so if i was to describe how t-cell/antibody/b-cell diversity was prodced do i just talk about gene segments VDJ parts on a chromosome and say for antibodys/b-cell (cos they are the same thing right except for the constant region on an Y..do i just talk about the VJD regions the fact that there are this many and that many gene segments for light/heavy genes and for t-cell kinda say the same thing except that like you said don't undergo somatic mutation??
another thing..i accept that antigen binding sites are formed from various gene segments but then wats all this stuff about hypervariable loops etc and framework regions. or is it saying that each V domain is made up of a gene segment and each of these has hypervariable region loops on each heavy/light chain come together forming the ABSite?
Many thanks Nabin/Ceri for all your help...wish me luck!!
PS can i define a gene segement as like one long massive gene broken up into bits then randomly combining with outher segments which hence create the diveristy ie one V gene broken up into many little gene segments then one long J gene broken up into bits and then randomly combine...??
Good Luck for your eggjam. Don't worry. . . eggjams are supposed to be like that.
I have little knowledge in Immunology and tried answering your answers. Hope they helped. I still need to answer your queries about Antibodies but as you seem to have understood the concept, I didnt post further.
The questions you raised were brilliant and that requires lot of thinking. It is good that you are confused; that's the way to begin. Then only you will seek for answers and find new things. After your exam, when you have time, read about Antibody mediated immune regulations. You will most probably find your answers. I am also going through them. In short, the circulating antibodies can both enhance and suppress immune reaction depending upon many factors that have not been completely understood. So, can't say exactly what antibodies do when they encounter antigens.
An example of immune suppression by antibodies is well known. Anti-D Antibodies are given to suppress immune reaction against Rh antigen from developing in Rh Negative mother. That is IgG mediated immune suppression. The most likely mechanism is that the AntiD Antibodies given passively mask the D Antigens and so immune reaction does not develop. There are other explanations too but this is the most likely.
While IgM and IgG3 enhance immune activity and so does IgE.
But regarding your last question, I am sorry I am not able to answer those.
PS - Please post new questions unrelated to the topic as new thread. It is more likely to be spotted by everyone and answered.