This home page has been set up for Part II Pathology, Immunology Students, by Mike Clark.
My intended purpose in providing these pages is to offer an easy way for you access some of the information and images which can be used as an additional supplement to the Part II Immunology Lecture Course. By following the links which have been set up here you will be able to retrieve the text and images in various ways chosen by you.
Choose from the following menus by clicking on the highlighted text. Please note that some of the items might only be available from limited locations eg Cambridge University or the UK. Also it is worth book-marking this page because many of the resources below are shared with pages referring to my research interests but by returning here you will be able to see which ones I recommend from the point of view of my undergraduate teaching. On the other hand please feel free to browse and wander!
Immunology has essentially two important questions
The study of immunoglobulins and T-cell receptors and their gene structure can provide an enormous insight into the mechanism for generation of diversity (GoD) but unfortunately this also raises more questions about the concept of "Self Tolerance" than are answered.
Immunoglobulin molecules have been studied extensively for some time and much is known about their structure and function. The primary sequence at the gene and amino acid levels are known for immunoglobulins in the species man, mouse and rat as well as other species (see for example the online IMGT databases). In recent years a number of important crystal structures of immunoglobulins have been solved. We have very many structures solved for antibody Fab and Fv fragments, either alone or complexed with their antigens or anti-idiotypes. We also have structures solved for antibodies interacting with important Fc ligands such as Protein A, FcRn and FcgRIII. These structures together with mutational studies, on the antibodies, on their antigens, and on their receptors, are providing new insights into mechanisms of action of antibodies in the normal immune response in health and disease, as well as providing important strategies for therapeutic intervention.
The first complete structure of an immunoglobulin to have been solved was of a mouse IgG2a and was published by Harris et al Nature 360; 369 (1992). This structure has been deposited in the databanks with reference 1IGT. However structures for many other isotypes and subclasses have been modelled by assuming homology with the solved structures.
Our understanding of immunoglobulin genes needs to explain several observations of the humoral immune response (ie the production of antibody) to an antigen.
The T-cell antigen receptor and its genes pose similar questions and can be studied by analogy with the B-cell antigen receptor, immunoglobulin.
The following resources contain a collection of images illustrating immunoglobulin structure and function. [NB: To follow a similar sequence to the lectures visit each link in the list below in turn and then return to this page to find the next link]
Images of immunoglobulin molecules.
Basic IgG structure.
Mouse IgG2a
A structure of a complete IgG antibody.
Some models of human IgG1.
Differences in human IgG isotype and allotype.
IgG functions.
Functional sites on the IgG molecule (complement and Fc receptor).
Mike's Animated molecules.
I have made some animations from the model structures.
Some PDB format structure files to download.
Some of the model structures are provided in PDB format for use with suitable viewing applications.
About the Images
Please remember to bookmark this page before leaving so that you can return to it more easily later.
Also please note you may come across contradictions in factual content! Scientists and lecturers often make generalizations or simplifications of detail in order to teach principles. It is well to remember though that new research can change the facts or lead to a reinterpretation of old data and sometimes to completely new hypotheses!
Downloadable copies of Mike Clark's undergraduate immunology lecture notes
A review lecture on Fc Receptors and antibody effector functions in e-format commercially available. Clark, M.,
in Waldmann, H. (ed.), Monoclonal Antibodies as Therapeutic Agents:
Fundamentals, Therapeutic Applications and Latest Advances, The
Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (2007)
"Fc Receptors and Antibody Effector Functions"
(online at http://www.hstalks.com/?t=BL0471316-Clark)
A review lecture on antibody engineering in e-format commercially available. Clark, M.,
in Waldmann, H. (ed.), Monoclonal Antibodies as Therapeutic Agents: Fundamentals, Therapeutic Applications and Latest Advances, The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (2007) "Antibody Engineering of Fc Effector Functions"
(online at http://www.hstalks.com/?t=BL0471360-Clark)
A review lecture on Generation of Diversity in e-format commercially available.
Neuberger, M. (2007), "The Generation of Diversity in Antibody Genes", in Waldmann, H. (ed.), Monoclonal Antibodies as Therapeutic Agents: Fundamentals, Therapeutic Applications and Latest Advances, The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (online at http://hstalks.com/bio)
SRSWWW at EMBL-EBI, Hinxton, Cambridge, UK
This is the Sequence Retrieval System, an integrated collection of databases
containing sequence and structure information.
ImMunoGeneTics database 1st page (Montpellier France).
A very useful research database of sequences of Immunoglobulins, T-cell
receptors and MHC. This is now the preeminent resource for immunoglobulin
and T-cell receptor sequence and structure analysis.
Molecular Visualisation Freeware and RasMol Classic site:
For information on the top freeware applications which can be used to
look at three dimensional structures of molecules.
Rotating Molecular Models:
Including an Ig domain
The WWW Virtual Library.:
Biosciences index
Go to the Part II Pathology Home Page
Go to the Immunology Division Home Page
Go to the Pathology Department's Home Page
Go to this servers Home Page
These web pages are meant as an academic resource and as such I would like them to remain accessible and useful to the widest number of individuals. I have therefor deliberately avoided the current trend to introduce a whole host of unique and non-standard features which require specific web browsers to be used to access the pages. So until features such as frames are written into the HTML standards I am deliberately avoiding their use on this website. Hopefully users will agree that what is important is the information provided within the site rather than a specific mode of presentation.
Mike Clark.