1885: Louis Pasteur and Pierre Paul Emile develop attenuated live virus vaccines for cholera and rabies.
1890: Emil von Behring and Shibasaburo Kitasato discover that serum from animals contains anti-toxic activity, giving short-term protection against diphtheria or tetanus - leading to the concept of ANTIBODIES.
1893: William Coley treats tumors with live bacteria and lysates.
1891: Robert Koch describes delayed-type hypersensitivity.
1896: Jules Bordet defines complement as a heat-labile active agent in the blood.
1901: Karl Landsteiner discovers blood groups.
1942: Jules Freund and Katherine McDermott discover adjuvants.
1945: Robin Coombs develops agglutination and the Coombs test.
Adaptive Immunity and Vaccination
Adaptive immunity adapts to the pathogen and efficiently resolves infection.
Vaccination exemplifies the adaptive immune system.
Immunization with a vaccine leads to immunological memory.
Evolution of Adaptive Immunity
All vertebrates possess an adaptive immune system.
Adaptive immune genes trace back to cartilaginous fish, from which our sophisticated system evolved.
Immune Cell Development
Lymphoid stem cells give rise to T cells, B cells, and NK cells.
Myeloid stem cells give rise to Monocytes, Megakaryocytes, Neutrophils, and Red blood cells.
T cells develop in the Thymus.
B cells develop in the Bone Marrow.
Historical Discoveries in Immunology (1946-2020)
1946: George Snell and Peter Gorer describe the Mouse major Histocompatibility Complex.
1951: Astrid Fagraeus discovers Plasma B cells make antibodies.
1956: Dick Van Bekkum gives an Experimental description of Graft vs Host disease.
1957: Frank MacFarlane Burnet proposes the Theory of clonal selection.
1959: James McGowan shows Lymphocytes are the immune cell and move through the body via the Lymphatic system.
1959-62: Gerald Engelman determines the Structure of antibodies.
1962: Jaques Miller discovers the thymus.
1973: Ralph Steinman identifies dendritic cells.
1974: Niels Jerne proposes the Immune network hypothesis.
1974: Rolf Zinkernagel and Peter Doherty describe T cell restriction to MHC.
1975: Georges Kohler and Cesaer Milstein discover monoclonal antibodies.
1975: Discovery of Natural killer cells Rolf Keissling, Eva Klein, Hans Wigzell.
1976: Susumu Tongewa discovers Somatic mutation In B cells.
1983: James Allison, Elis Reinhertz, Phillipa Marrack, John Kappler discover the TCR.
1986: Timothey Mossman describes T helper cell subsets.
1994: Polly Matzinger proposes the Danger Model of Immune tolerance.
1995: James Allison discovers CTLA4.
1995: Simon Sakauchi identifies Regulatory T cells.
1996: Toll like receptors identified.
2010: Immune checkpoint blockade approved by the FDA.
2017: Karl H June develops CAR T cells.
2020: mRNA Vaccines developed.
Immunological Dysfunction
HOST DEFENCE: Immune system protects against pathogens.
HOMEOSTASIS: Maintaining balance within the body.
HYPERSENSITIVITY: Inappropriate/too Much Immune Response.
TRANSPLANT REJECTION: Immune system attacks transplanted organs.
AUTOIMMUNITY: Immune system attacks the body's own tissues.
Immune response must be appropriate in type and magnitude.
AUTO-INFLAMMATION
CANCER
IMMUNODEFICIENCY: Too Little Immune Response.
Summary of Key Points
The immune system defends against pathogens.
Vertebrates have innate and adaptive immunity.
Innate responses are triggered by germline-encoded receptors.
Adaptive responses are adapted to their antigenic target.
Vaccines use the adaptive immune response for protection.
Immune system dysfunction can cause disease.
Recommended Reading
Janeway’s Immunobiology by Kenneth Murphy (9th Edition).
How the immune system works by Lauren Sompayrac.
Links: http://www.ncbi.nlm.nih.gov/books
Norton website: wwnorton.co.uk
30% off print textbooks (WN105)
15% off Ebooks (WN107)
Assessments
Immunology Problems – formative (available on Minerva, submission on March 6th).
Open book format.
Some information is in lectures, some requires research.
Practice MRQ sheet is available throughout the module.
End of semester MRQs summative (closed book, computer cluster).
Discussion Board in Minerva.
Immunology Careers
Destinations of PhD graduates:
UK: 66%
Rest of EU: 9%
USA: 10%
Australia: 2%
Canada: 2%
Other: 12%
Career sectors for PhD graduates:
Academia: 53.1%
Industry: 17.4%
Academia/Healthcare: 12.0%
Healthcare: 6.5%
Government: 3.2%
Non-profit: 1.7%
Publishing: 1.4%
Education: 1.2%
Science comms: 1.2%
Consultancy: 0.6%
Self employed: 0.6%
Aquaculture: 0.5%
Law: 0.5%
Career break: 0.2%
Research subjects for PhD graduates in academia/healthcare:
Animal health: 9.1%
Bioinformatics: 0.8%
Cardiovascular: 0.8%
Ecology: 1.0%
Gastroenterology: 1.3%
Genetics: 1.3%
Immune response: 15.0%
Infectious disease: 20.6%
Inflammation & autoimmune disease: 15.5%
Marine biology: 1.0%
Microbiology: 1.8%
Neurology: 2.0%
Oncology: 8.9%
Ophthalmology: 0.8%
Plant science: 1.0%
Public health: 0.8%
Sports science: 0.8%
Surgery: 0.8%
Therapeutics: 3.0%
Transplantation: 3.0%
Urology: 1.5%
Vaccines: 3.6%
Other: 5.8%
Career Pathways in Immunology
Academia: BSc -> Masters -> PhD -> Postdoc/Junior Research Scientist -> Research Fellow -> Lecturer -> Senior Lecturer -> Reader -> Senior Management / Principal Investigator -> Associate Professor -> Professor
Non-Academic: Examples include IP manager, flow cytometry specialist, healthcare advertising, patent attorney, laboratory manager, scientific publishing, business analyst, clinical trials manager, grant manager, secondary school teacher, sales manager, water microbiologist, government research, army officer, campaigns & policy officer, scientific marketing, bioinformaticist, science writer, operations manager, science communications, specialist nurse.
B Cells and B Cell Receptors (BCR)
B cells have a B cell receptor (BCR).
1 BCR recognizes 1 specific epitope on an antigen.
The Complementarity Determining Region is the part of the BCR that binds to the epitope.
BCRs are composed of Heavy and Light chains.
Epitopes and BCR Specificity
An epitope is the portion of the antigen that the antibody binds to.
There are millions of B cells, each expressing a single BCR with specificity to a single epitope.
The diversity of BCRs is created by shuffling genes together.
BCRs recognize the surface of whole antigens.
B Cell Differentiation
Circulating B cells each have different specificities.
Upon activation, B cells can differentiate into:
PLASMA cells (antibody-secreting cells)
MEMORY B cells
T Cells and T Cell Receptors (TCR)
T cells have a T cell receptor (TCR).
TCRs recognize short peptides/epitopes derived from whole protein antigens presented on MHC molecules.
TCR diversity is created by shuffling genes.
T Cell Subsets
T HELPER cells (TH1, TH2)
CYTOTOXIC T cells
MEMORY T cells
Antigens and Epitopes
An antigen is anything recognized by the immune system (protein, lipid, chemical).
Cells of the innate and adaptive immune system have receptors that recognize portions of antigens.
The recognized portion is called an epitope.
TCR vs. BCR
T cells have a TCR - 1 TCR recognizes 1 specific epitope from an antigen.
B cells have a BCR - 1 BCR recognizes 1 specific epitope on an antigen.
There are millions of different T and B cells, each expressing a single TCR or BCR to a single antigen.
Receptor Diversity and Selection
TCR and BCR diversity is created by shuffling genes.
Lymphocytes are 'tested' to ensure they don't recognize 'self' antigens (THYMIC EDUCATION and CLONAL SELECTION/DELETION).
Then travel around waiting to encounter their cognate antigen.
Antigen Presentation
BCRs recognize portions of whole proteins.
TCRs recognize portions of proteins presented to them on MHC.
Receptor Repertoire
The complete set of TCRs and BCRs is called the receptor repertoire, representing lymphocyte receptor diversity.The complete set of TCRs and BCRs is called the receptor repertoire, representing lymphocyte receptor diversity.