dr. paul c. montgomery july 31, 2001 page 1 (of 5 ... · ontogeny of the immune response complex...
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Dr. Paul C. Montgomery July 31, 2001 Page 1 (of 5)
ANTIBODY STRUCTURE I (Lecture 2) Benjamini: Chapters 3, 4
I. Nature of Antigens (Ag)
Operational definition - any substance that stimulatesan immune response - antigen = immunogen
A. organs, tissues and cells may be antigenic - antigenicityor immunogenicity is related to a molecular configurationon the cell surface - eg. histocompatibility antigens -responsible for tissue rejection
B. microbial agents - bacteria and viruses can be antigenic -again usually readily accessible surface components
C. cell products - toxins and enzymesevident that antigens must be discussed at molecular level:
polysaccharides - glucose/glucuronic acid (Strep pneumoniae III) great natural antigen
proteins, polypeptides - serum proteins, enzymes, virus coats good antigens
combinations - lipoproteins lipopolysaccharides
nucleic acids - usually poor antigens
Concept of an antigenic determinantconsider serum albumin Mw 66-68,000inject into different speciesgenerate many Abs that react with serum albumineach Ab reacts with a different determinant on albumin molecule
- multiple antigenic determinants on a molecule like albumin - size of determinant related to size of cell surface receptor
II. Phylogeny of the Immune System
The immune system is first noted in the vertebrates - cyclostomes.The hagfish displays graft rejection (CMI) and the sea lampreyshows both CMI and antibody production. Its appearance coincidesthe appearance of lymphoid organs, with the antibody mediatedsystem apparently being a more recent evolutionary event.
III. Ontogeny of the Immune Response
Complex subject, species differences - but in general ontogeny recapitulates phylogeny.
Fetal (human) weeks ~ 6/7 thymus~ 8 lymphoid cells in thymus~ 7/8 pre B-cells~ 10/12 surface immunoglobulin (Ig)
lymphocytes past this timefetal contribution to circulating Ig begins
} vary
Dr. Paul C. Montgomery July 31, 2001 Page 2 (of 5)
ANTIBODY STRUCTURE I (Lecture 2) Benjamini: Chapters 3, 4
Neonatal (human)
- neonatal thymectomy has a profound effect on development of T cell compartment- limited capacity to mount B-cell response; compensation by two mechanisms:
1. Transplacental passage of maternal IgG (natural passive immunity) - systemic protection
2. Suckling - sIgA in mother's colostrum and milk introduced into infant's GI tract (natural passive immunity) - local protection.
- follow B cell compartment by looking at circulating immunoglobulin levels in the neonate.
Active vs Passive Immunity
Active - immunization directly carried out in host (long-lived)Passive - immune components (Ab or cells) transferred into
host (generally transient protection)
IV. Nature of Antibodies
A. Antibody (Ab) vs Immunoglobulin (Ig)Ig - general termAb - term used when specificity for antigen is defined
B. Nature of Immunoglobulin/Antibodies- glycoproteins with standard protein structural features- basic unit - 2 light and 2 heavy chains- found in: serum
secretions fixed to cell surfaces
Dr. Paul C. Montgomery July 31, 2001 Page 3 (of 5)
ANTIBODY STRUCTURE I (Lecture 2) Benjamini: Chapters 3, 4
Visualization - free boundary electrophoresis
A. Carrier membrane spotted with serum
B. Electrical current separates
serum components based on
charge differences.
C. Protein stain applied.
Intensity is traced with a densitometer.
D. Abs found in γ region.
Marked elevations in γ region
can be seen in myeloma patients.
Immunoglobulin Abnormalities in Various Diseases
Cellulose acetate patterns Densitometer tracing
Dr. Paul C. Montgomery July 31, 2001 Page 4 (of 5)
ANTIBODY STRUCTURE I (Lecture 2) Benjamini: Chapters 3, 4
Cerebrospinal Fluid
Dr. Paul C. Montgomery July 31, 2001 Page 5 (of 5)
ANTIBODY STRUCTURE (Lecture 2) Benjamini: Chapters 3, 4
Urine
V. Biochemical and Biological Features of Immunoglobulin Classes
Summarized below: