The Nature of the Immunogen Contributes to Immunogenicity

Immunogenicity is determined, in part, by four properties of the immunogen: its foreignness, molecular size, chemical composition and complexity, and ability to be processed and presented with an MHC molecule on the surface of an antigen- presenting cell or altered self-cell.
FOREIGNNESS MOLECULAR SIZE CHEMICAL COMPOSITION AND HETEROGENEITY LIPIDS AS ANTIGENS

Properties of the immunogen contribute to immunogenicity

Immunogenicity is determined in part by four properties of the immunogen: its foreignness, molecular size, chemical composition and complexity, and ability to be processed and presented with an MHC molecule on the surface of an antigenpresenting cell or altered self cell. The biological system contributes to immunogenicity.

Properties of the immunogen Foreignness

Central tolerance during lymphocyte maturation. Cells that recognize self components during this process are inactivated. So when an antigen is introduced into an organism, the degree of its immunogenicity depends on the degree of its foreignness. There are some exceptions.

Some macromolecules (e.g., collagen and cytochrome c) have been highly conserved throughout evolution and therefore display very little immunogenicity across diverse species lines. Conversely, some self components (e.g., corneal tissue and sperm) are effectively sequestered from the immune system, so that if these tissues are injected even into the animal from which they originated, they will function as immunogens.

Molecular Size
The most active immunogens tend to have a molecular mass of >100,000 daltons (Da). Generally, substances with a molecular mass less than 5000 to 10,000 Da are poor immunogens.

Chemical Composition and Heterogeneity

Heteropolymers are usually more immunogenic than homopolymers. All four levels of protein organizationprimary, secondary, tertiary, and quaternarycontribute to the structural complexity of a protein and hence affect its immunogenicity. Appropriately presented lipid antigens can induce B-cell responses.For example, lipids can serve as haptens attached to suitable carrier molecules, such as the proteins keyhole limpet hemocyanin (KLH) or bovine serum albumin (BSA).

Susceptibility to Antigen Processing and Presentation

Large, insoluble, or aggregated macromolecules generally are more immunogenic than small, soluble ones because the larger molecules are more readily phagocytosed and processed. Macromolecules that cannot be degraded and presented with MHC molecules are poor immunogens.

3.

4.
Whereas a small part of the V region on an antibody determines the antigen specificity, single domains in the C region of heavy chains determine the effector functions. Biologic activities of antibodies divide intothree general areas: (1) protection, (2) placental transfer, and (3) cytophilic (literally, cell-loving) properties. Although antibody binding blocks the attachment of toxins or viruses (called neutralization), antibodies alone cannot directly destroy a foreign organism. Instead, antibodies mark them for destruction by other defense systems. When IgM or IgG (except IgG4) binds to antigen, the complement system is activated and promotes bacterial lysis or accelerated phagocytic uptake. IgM or IgG molecules that have not reacted with antigen do not activate complement. IgM also mediates agglutination reactions. The coating (opsonization) of organisms with primarily IgG antibodies leads to enhanced phagocytosis by macrophages and neutrophils. Antibodies allow for the interaction of several cell types with antigenantibody complexes through the cells Fc receptors. Three groups of human Fc receptors for IgG have been described (Table 4 -2). Because of their characteristic immunoglobulin-like extracellular domains, Fc receptors belong to the immunoglobulin gene superfamily (see Figure 9-4 in Chapter 9). Multiple biologic functions can be triggered through the crosslinking of any of the three Fc receptor classes. Macrophages have enhanced engulfment of antigen antibody complexes through Fc receptors. Bcell Fc receptor engagement by antigen antibody complexes regulates B-cell activation. Other cell types expressing Fc receptors (CD16) can use antibody-dependent cell-mediated cytotoxicity (ADCC), to lyse target cells coated with IgG. Certain antibodies, like IgA, can be localized to the lumens of mucosalined organs to provide mucosal immunity. The second area of biologic activity associated with the antibodies is the movement of maternal antibody across the placenta to the fetus. The human fetus and newborns have limited immune responses. Mechanisms of acquired immunity are not at full strength until some time after birth. Most of the protection for a fetus or newborn comes from maternal IgG that crosses the placenta during pregnancy. Only IgG can cross the placenta because only the g-chain CH 1 andCH 3 domains can bind to placental cells. Intact IgG or Fc fragments from IgG can cross the placenta, but Fab or F(ab9) 2 cannot. Maternal IgA, secreted in breast milk, neutralizes pathogens in the infants gut

http://www.wiley.com/legacy/products/subject/life/elgert/CH04.pdf

Immunology: Understanding The Immune System - Klaus D. Elgert

=Dear, wala pa ako nasearch sa number 2.. <3