Antibody Function

Immunoglobulins

IgG – most prevalent in blood (serum) – secondary response

very long serum half-life: IgG > 20 days (G₃ is less; drugs last minutes to hours) – attaching proteins to F_c region prolongs halflife
only antibody involved in placental transfer

IgA – most prevalent in mucosal secretions

IgM – 1^st in antibody response – primary response

IgD – cell surfacebased (small amounts)

IgE – small core bound in tissue (allergies, asthma, etc.)

IgA and IgM exist as multimers and have J chains holding them together

all types can exist on surface of B-lymphocytes as monomers

classical complement: IgM, IgG; IgA~ non compliment mech.

Mechanisms of Antibody-Mediated Immunity

Antibody alone

Neutralization of virus
Inactivation of virus, toxin and enzymes secreted by pathogens
Signal transduction by binding to cell surface receptor ( either on host or pathogen)
(immunity almost always comes from neutralization of virus or toxins)

Antibody + effector molecules

Complement cascade activation

Activation of Fc receptor-bearing cells

Primarily phagocytic but also most basophils, lymphocytes etc.Þ cells more pathogenically destructive

Physical Mechanisms Responsible for the Functional Effects of Antibody

Interference with accessibility to a site: direct, indirect (steric), allosteric binding to pathogen

Introduction of a conformational change (stabilizing non-optimal conformation)

Possible Mechanisms of Virus Neutralization by Antibody

prevention of attachment to host cell (thus preventing vesicle uptake of virion and its dumping in cell at lower pH)
disruption of cell penetration (preventing envelope virus from fusing membranes after attachment)
interference with virion uncoating preventing release of genetic material
preventing release of nucleic acid after attachment and penetration
abrogation of post-uncoating events (prevents transcription of gene products)- little evidence but some

Antibodies and Viruses

subset of antibody to virion surface proteins can mediate neutralization (some need a few antibodies, others need thousands)

neutralization in vitro does not correlate perfectly with protection in vivo (immunity = 3-way reaction between cell, viron and antibody)
non-neutralizing antibodies can contribute to protection in vivo (often with addition of complement)

Antibodies and Bacteria

Effector Function Mediated by Other Molecules (complement) or Cells

Classical compliment Pathway (CCP)

There are subclass-related differences in complement activation – these differences arise at multiple steps of the complement pathway

there is no absolute ranking of the IgG subclasses for complement activation

no absolute ranking of IgG complement activation or correlation between flexibility and ability to activate complement

variety of consequences exist:

(1) creation of opsonization sites

Receptors for Fc Region (ie Fcg R₁, Fcg R₂, Fcg R₃) (R_{1 and}R₂)_{intrinsic affinity} < (R₃)_{intrinsic affinity} – binds immune complex

In both CCP and FcR dependent pathways, multivalency of Fc region (functional affinity) plays critical role