Antigens, Antibodies, and Epitopes

• Antigens and antibodies are key components of the immune system

Antigen or Immunogen

• The terms antigenic determinant, epitope, and hapten are related to antigens
• Antigens are recognized by the body as foreign
• This recognition causes the body to produce an antibody that reacts specifically with the antigen
• Antigens include toxins, bacteria, foreign blood cells, and the cells of transplanted organs

Epitopes

• Pathogens possess many antigens that can stimulate antibody production
• Antigenic determinants are also known as epitopes
• Epitopes elicit different antibodies, leading to a polyclonal response
• Monoclonal antibodies are created by expanding a single clone

Hapten

• A hapten on its own is not immunogenic
• A carrier molecule is needed for a hapten to cross-link the B-cell receptor
• Haptens have a binding site for antibodies and can neutralize them

Factors Affecting Antigenicity

• Degree of foreignness: The more different something is, the more immunogenic it is
• Size and complexity: Larger and more complex substances tend to be more antigenic
• Dose of antigen: A larger dose typically leads to a bigger response
• Genetic makeup of the host: Genetic differences affect the ability to produce antibodies

Antibodies

• Antibodies are also called immunoglobulins, referring to their globular structure
• Antibodies are also called gamma globulins due to their electrophoretic mobility
• There are five classes/isotypes of antibodies: IgG, IgM, IgA, IgD, and IgE
• Classes are based on the type of heavy chains (γ, μ, α, δ, ε)
• Antibodies are produced by plasma cells

Antibody Structure

• Composed of two heavy and two light chains
• Heavy chains are identical (2γ, 2δ, 2α, 2μ, or 2ε)
• Light chains are identical (2κ or 2λ)
• There are 5 isotypes of antibodies

IgM

• It is produced early in response to an acute infection
• IgM is a pentamer with 10 binding sites and acts as an agglutinin
• It does not cross the placenta
• IgM activates the complement system
• Naturally occurring antibodies are of the IgM type
• Functions best in cold temperatures (4°C)
• Naïve B-cell antigen receptor

IgG

• It is involved in a long-term response to infection
• IgG is a monomer with 2 binding sites
• It can cross the placenta, which can sometimes lead to miscarriage
• IgG activates the complement system
• IgG does not agglutinate, but it does opsonize
• They are immune antibodies, not naturally occurring
• Functions best in warm temperatures (37°C)
• Feedback inhibition of B-cells

IgE

• IgE is a monomer
• It mediates allergic reactions such as itching and asthma
• IgE provides defense against helminthic infections

IgA

• IgA is present in secretions and mucosal surfaces
• It protects against infections in the urinary, GI, and respiratory tracts
• IgA deficiency can lead to infections in these organs/surfaces

IgD

• Naïve B-cell receptor

Antibody Effector Functions

• Blocking: Prevents a soluble ligand from binding to its membrane receptor.
• CDC (Complement-Dependent Cytotoxicity): Leads to cell lysis via complement activation.
• ADCC (Antibody-Dependent Cell-Mediated Cytotoxicity): Activates effector cells to release cytotoxins, killing infected cells.
• Opsonization and phagocytosis: Enhances phagocytosis of pathogens.

EBV Serologies

• IgM against EBV VCA indicates acute infection
• IgG against EBNA indicates prior infection
• Sensitivity is 85-90% and specificity is >95%