Page 110 - Clinical Immunology_ Principles and Practice ( PDFDrive )

94 Part one Principles of Immune Response

Antigen-binding
Antigen-binding
Antibody sitesite
N
CH 3
N
Protein carrier
with CD4 T-cell Epitope
A A Haplen B-cell epitope epitopes Antigen

O O
Hapten N

O
Epitope
N
O O

Carrier
Glyconjugate Carbohydrate Protein T-cell
A B vaccine B-cell epitope carrier epitope
FIG 6.2 Haptens can modify the epitope of the antigen that is
recognized by immunoglobulin, while the T-cell epitope remains
unchanged.
Helper
CD4 Trinitrophenol Urushiol Penicillin
Tcell
(Picric acid) (poison ivy)
R=aliphatic chain
B-cell O OH O OH H
CD4 T-cell epitope N + N + OH R N S
presented by host – – N
A C MHC proteins O O O O
FIG 6.1 Hapten, Carriers, and Two Kinds of Antigens. The R OH
antigen-binding site of an antibody binds an antigen through + O
the latter’s epitope: this is the biochemical sense of antigen – N
used in ELISA, flow-cytometry and western blot analysis. Haptens O O
are self-conjugating antigen moieties that can modify epitopes FIG 6.3 Examples of small chemical haptens that can be rec-
and provide new binding specificities. Haptens and many antigens ognized by antigen specific immunoglobulins in the host, which
by themselves are not immunogens, the second sense of are produced B cells.
“antigen”. Immunogens (complete antigens) are processed by
antigen presenting cells to reveal T-cell epitopes presented by similarities, the nature of recognition by B cells and T cells is
MHC molecules. MHC, Major histocompatibility complex. quite distinct. Immunoglobulins (Igs) tend to recognize solvent-
exposed regions on a conformationally intact molecule (e.g., a
This memory state allows for a more rapid response to a later viral glycoprotein or a bacterial toxin). In contrast, TCRs typically
confrontation with the same or related antigen or pathogen. recognize peptide fragments of protein antigens presented by
This is the basis of induced immunological memory, which is host cell-surface molecules. In the case of TCRαβ, major histo-
the goal of many vaccines. compatibility complex (MHC) class I or II molecules are the
presenters and lead to MHC-restricted recognition of antigen.
THE NATURE OF ANTIGEN RECOGNITION Antigens for B Cells
BY IMMUNOGLOBULIN AND T-CELL Vaccines can be used to target toxin binding and neutralization.
RECEPTOR DIFFERS For example, when ingested, Vibrio cholerae produces the secreted
3,4
cholera toxin (CT) that can cause life-threatening diarrhea. Both
The receptors for B cells and T cells share similarities in develop- inactivated or attenuated forms of V. cholerae and recombinant
ment, structural organization, and function (Chapter 4). Both forms of the cholera toxin B subunit protein have been used
are derived from gene rearrangement events during development, as vaccines. When introduced orally, these vaccines can elicit
and both combine variable and constant regions within their antibodies that neutralize the activity of the toxin within the gut.
protein structure. Both are heterodimers that can be expressed In contrast, protective antibodies elicited by viruses and virus-
at the cell surface of their respective lymphocytes and convey derived vaccines most often act by preventing binding and entry
signals via partner chains within the transmembrane and of the virus into host cells. Typically, vaccination strategies for
intracytoplasmic segments that ultimately promote activation these types of pathogens, such as human immunodeficiency virus
and proliferation of the responding lymphocyte. Despite these (HIV) or influenza virus, employ semipurified or recombinant