Antibodies and Their Functions

Antibodies

• Antibodies are glycoproteins found in vertebrates.
• They are produced in response to foreign structures called antigens.
• Antigens are substances that trigger the production of antibodies.
• Antibodies recognize and bind to specific antigens.

Detection of Antibodies in Human Serum

• Serum Protein Electrophoresis (SPE) is a lab technique.
• It separates serum proteins based on size and charge.
• SPE helps diagnose conditions by analyzing protein patterns.
• Antibodies are typically found in the gamma globulin fraction of serum.

Production of Antibody

• B cells differentiate into plasma cells after stimulation.
• Plasma cells secrete antibodies, which are also called immunoglobulins.
• Immunoglobulins mediate humoral immunity.
• The process involves binding to antigen, chemical signals from helper T cells, becoming plasma cells and releasing antibodies.

Antibody

• Gamma globulin proteins react with antigens.
• These antigens stimulated their production.
• Antibodies make up 20% of plasma protein.
• Five classes of antibodies exist: IgG, IgM, IgA, IgD, and IgE.
• These classes differ based on heavy chain differences.

Structure of Antibody

• Antibodies have a Y-shaped structure.
• They consist of four polypeptide chains: two heavy chains and two light chains.
• The chains are linked by disulfide bonds for stability.
• Variable regions of the Y bind to specific antigens.
• The constant region determines the antibody class and its function in the immune response.

Definitions of Fc and Fab Regions

• The antigen binding fragment (Fab) recognizes antigens.
• The crystallizable fragment (Fc) interacts with immune system components.

Antibody-Binding Site

• Within the variable domains, there are three regions with extreme variability.
• These highly variable regions are called hypervariable regions.
• These regions contact antigens directly.
• They form the antigen binding site.
• The regions are also referred to as complementarity-determining regions or CDRs.

Variable Regions of Antibodies (Complementarity Determining Regions - CDRs)

• CDR's in light and heavy chains of antibodies are highly variable.
• These are essential for antigen binding.

Binding of an Antigen by an Antibody

• Antibodies bind to antigens using their CDRs.
• This binding involves precise interactions between antibody and antigen structures.

Flexibility of Antibody Molecules Via Hinge Region

• Antibodies have flexibility via the hinge region.
• This flexibility allows for the antibody to bind to antigens in different orientations.

Enzymatic Digestion of Antibodies

• Enzymes like papain and pepsin can digest antibodies.
• Papain cleaves antibodies into Fab fragments and Fc fragments.
• Pepsin cleaves antibodies into F(ab')2 fragments.

Membrane-bound and Secreted Antibodies

• Membrane-bound antibodies are critical for B cell activation.
• B cells are activated when membrane-bound antibodies bind to specific antigens.
• This interaction triggers B cell proliferation and differentiation.

Types of Heavy and Light Chains in Antibodies

• Antibodies have various types of heavy chains (gamma, alpha, mu, epsilon, delta).
• Antibodies also have kappa and lambda light chains.

Classes and Subclasses of Immunoglobulins

• IgG, IgM, IgA, IgD, and IgE are the major classes of immunoglobulins.
• Subclasses of immunoglobulins differ based on the heavy chain's structure.

Immunoglobulin G (IgG)

• IgG is the most abundant antibody in serum.
• It’s important in secondary immune responses.
• It provides long-term immunity.
• Most subclasses can cross the placenta; important in maternal immunity to the newborn.
• IgG participates in complement fixation, precipitation, and neutralization of viruses and toxins.

IgG Subclasses

• IgG has four subclasses with differences in half-life, concentration, binding to antigens, transfer across the placenta, Fc binding and complement fixation.

Immunoglobulin M (IgM)

• IgM is the first antibody secreted in an immune response.
• It's crucial in primary immune responses, serving as a critical early immune response.
• IgM is the most important cell surface antibody.
• IgM is not transported across the placenta.
• High IgM levels in newborns raise concerns for intrauterine infections.

Immunoglobulin A (IgA)

• IgA is more abundant than other antibody classes.
• It's major in mucosal areas and secretions.
• IgA provides crucial mucosal immunity.
• IgA exists in dimeric form, with important secretory components enabling transport through mucosal surfaces.

Immunoglobulin E (IgE)

• IgE is involved in allergic reactions and defense against parasitic infections.
• Low levels of IgE in serum, present on surfaces of mast cells and basophils, enabling these cells to release inflammatory mediators during allergic responses.

Immunoglobulin D (IgD)

• IgD functions mainly as a B cell receptor.
• IgD has a transmembrane region.

Fc Receptors

• Fc receptors are proteins on various cell surfaces that bind to the Fc portion of antibodies.
• These receptors' activation triggers various cellular functions and regulates the immune response.

Functions of Antibodies

• Antibodies neutralize toxins and viruses.
• Antibodies opsonize microbes, facilitating phagocytosis.
• Antibody-dependent cell-mediated cytotoxicity (ADCC) eliminates target cells.
• Antibodies activate complement to prevent microbes from attaching to mucosal surfaces.
• Antibodies mediate complement-dependent cytotoxicity (CDC).