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: