Professional

Professional APCs are very efficient at internalizing antigens, either by phagocytosis or by receptor-mediated endocytosis, and then displaying a fragment of the antigen, bound to a class II MHC molecule, on their membrane. The T cell recognizes and interacts with the antigen-class II MHC molecule complex on the membrane of the antigen-presenting cell. An additional co-stimulatory signal is then produced by the antigen-presenting cell, leading to activation of the T cell. The expression of co-stimulatory molecules is a defining feature of professional APCs.

There are three main types of professional antigen-presenting cells:

• Dendritic cells (DCs), which have the broadest range of antigen presentation, and are probably the most important APC. Activated DCs are especially potent T_Hcell activators because, as part of their composition, they express co-stimulatory molecules such as B7. This B7 co-stimulator of mature interdigitating dendritic cell (IDC) interacts with surface CD28 of naïve T-cell.

• Macrophages

• Certain B-cells, which express (as B cell receptor) and secrete a specific antibody, can internalize the antigen, which bind to its BCR and present it incorporated to MHC II molecule, but are inefficient APC for most other antigens.

• Certain activated epithelial cells

Non-professional

A non-professional APC does not constitutively express the Major Histocompatibility Complex class II (MHC class II) proteins required for interaction with naive T cells; these are expressed only upon stimulation of the non-professional APC by certain cytokines such as IFN-γ. All nucleated cells express the Major Histocompatibility Complex class I necessary to be considered a non-professional APC. As erythrocytes do not have a nucleus, they are one of the few cells in the body that cannot display antigens.

4. Describe the factors influencing immunogenicity; Compare the structures of t-independent and t-dependent antigens;

FACTORS INFLUENCING IMMUNOGENICITY

Contribution of the Immunogen

Foreignness The immune system normally discriminates between self and non-self such that only foreign molecules are immunogenic.

Size There is not absolute size above which a substance will be immunogenic. However, in general, the larger the molecule the more immunogenic it is likely to be.

Chemical Composition In general, the more complex the substance is chemically the more immunogenic it will be. The antigenic determinants are created by the primary sequence of residues in the polymer and/or by the secondary, tertiary or quaternary structure of the molecule.

Physical form In general particulate antigens are more immunogenic than soluble ones and denatured antigens more immunogenic than the native form.

Degradability Antigens that are easily phagocytosed are generally more immunogenic. This is because for most antigens (T-dependant antigens, see below) the development of an immune response requires that the antigen be phagocytosed, processed and presented to helper T cells by an antigen presenting cell (APC).

Contribution of the Biological System

Genetic Factors Some substances are immunogenic in one species but not in another. Similarly, some substances are immunogenic in one individual but not in others (i.e. responders and non-responders). The species or individuals may lack or have altered genes that code for the receptors for antigen on B cells and T cells or they may not have the appropriate genes needed for the APC to present antigen to the helper T cells.

Age Age can also influence immunogenicity. Usually the very young and the very old have a diminished ability to mount and immune response in response to an immunogen.

Method of Administration

Dose The dose of administration of an immunogen can influence its immunogenicity. There is a dose of antigen above or below which the immune response will not be optimal.

Route Generally the subcutaneous route is better than the intravenous or intragastric routes. The route of antigen administration can also alter the nature of the response

Adjuvants Substances that can enhance the immune response to an immunogen are called adjuvants. The use of adjuvants, however, is often hampered by undesirable side effects such as fever and inflammation.

CHEMICAL NATURE OF IMMUNOGENS

Proteins The vast majority of immunogens are proteins. These may be pure proteins or they may be glycoproteins or lipoproteins. In general, proteins are usually very good immunogens.

Polysaccharides  Pure polysaccharides and lipopolysaccharides are good immunogens.

Nucleic Acids Nucleic acids are usually poorly immunogenic. However, they may become immunogenic when single stranded or when complexed with proteins.

Lipids In general lipids are non-immunogenic, although they may be haptens.

See figure 1a.

 TYPES OF ANTIGENS

T-independent Antigens T-independent antigens are antigens which can directly stimulate the B cells to produce antibody without the requirement for T cell help In general, polysaccharides are T-independent antigens. The responses to these antigens differ from the responses to other antigens.

Properties of T-independent antigens

Polymeric structure These antigens are characterized by the same antigenic determinant repeated many times as illustrated in Figure 1b.

Polyclonal activation of B cells Many of these antigens can activate B cell clones specific for other antigens (polyclonal activation). T-independent antigens can be subdivided into Type 1 and Type 2 based on their ability to polyclonally activate B cells. Type 1 T-independent antigens are polyclonal activators while Type 2 are not.

Resistance to degradation T-independent antigens are generally more resistant to degradation and thus they persist for longer periods of time and continue to stimulate the immune system.

T-dependent Antigens T-dependent antigens are those that do not directly stimulate the production of antibody without the help of T cells. Proteins are T-dependent antigens. Structurally these antigens are characterized by a few copies of many different antigenic determinants as illustrated in the Figure 2.