Immunoglobulin D (IgD) function

• Humans typically produce all five Ig isotypes but B cells produce and display only one heavy chain isotype, except for unstimulated B cells, which express both IgM and IgD.
• The variable Region recognizes the antigen.
• The remaining part of the protein contains heavy chain, constant regions, mu, Delta, Gamma, epsilon or alpha, representing different classes of IG molecules.

IgD Loss After Stimulation:

• IgD helps naïve B cells sense antigens in the early phase of immune response.
• Once a B cell is activated, IgD is no longer needed.

Primary Reason for IgD Expression:

• IgD is expressed with IgM in naïve B cells due to its functional and developmental role in the early immune response and its unique regulation.

Functional Role of IgD

• IgD acts as a secondary receptor alongside IgM on naïve B cells, helping in antigen recognition and immune tolerance.
• This dual expression allows the immune system to fine-tune responses, as IgD has a higher antigen-binding flexibility than IgM.
• Producing IgD is less resource-intensive than producing other isotypes like IgG or IgA, making it suitable for naïve B cells

IgG Molecule:

• IgG molecule is represented by the gamma heavy chain and can be located on the surface or secreted.
• There are four subclasses of IgG, collectively making up the greatest amount of IG molecules in the serum.

SLE

• Systemic lupus erythematosus (SLE) is a classic example of an immune complex-mediated disease, which occurs when antigen-antibody complexes (immune complexes) form in the circulation and deposit in tissues, triggering inflammation and tissue damage.
• IgG is the most abundant antibody in circulation and is highly involved in forming soluble immune complexes.
• IgG antibodies bind to self-antigens (autoantigens) to form immune complexes in diseases like SLE.
• Deposition of IgG-containing immune complexes activates the complement system, recruits immune cells, and leads to inflammation and tissue damage.
• IgA is important at mucosal surfaces and in secretions and does not typically play a central role in systemic immune complex-mediated diseases like SLE.
• IgD’s primary role is as a receptor on naïve B cells, and it has no significant involvement in immune complex diseases.
• IgE is associated with allergic reactions and type I hypersensitivity (e.g., asthma, anaphylaxis), not immune complex diseases.

IgM Molecule

• IgM is represented by the mu heavy chain.
• This large IG molecule can be found as a cell surface monomer or secreted pentamer.
• IgM is the first antibody to be formed during an initial immune response.

IgA Molecule

• IgA is represented by the Alpha heavy chain.
• IgA is found in a monomeric formation in the serum.
• The addition of a chain links to monomers, forming a dimer, and it is present in this formation at mucosal surfaces.

IgE Molecule

• IgE is represented by the epsilon heavy chain and is present at relatively low levels in the serum.
• IgE is predominantly found on the surface of mast cells and basophils that have isotype-specific receptors for recognition of IgE.

IgD Molecule

• IgD is represented by the Delta heavy chain and is almost exclusively found on the surface of B cells.

Antibody Function

• The effector functions of each IG class are important for the multifactorial disease treatment of the human condition.
• Effective functions result from interactions between heavy chain constant regions and other serum proteins or membrane receptors, not all antibody classes have the same functional properties.

Immunoglobulin Information

• Immunoglobulin A has an Alpha heavy chain, IgD has a delta heavy chain, IgE has an epsilon heavy chain, IgG has a gamma heavy chain, and IgM has a mu heavy chain.
• IgL, which exists in bird peptides and blood of lungfish, has an upsilon heavy chain.
• Light chains can either be kappa or lambda chains for all immunoglobulins.
• IgA is 10-15% of total immunoglobulin, IgD and IgE are only 1-2%, IgG is 75-80%, and IgM is about 5-10% of total immunoglobulin.
• IGA opposes in monomer and dimer form. The dimer form is also the normalized secretory form of IgA.
• IGT, IGE, and IgG oppose in monomer form only, whereas IgM mostly opposes in pentameric form or in monomer structures when expressed with plasma.
• IgA dimers have a J chain between the two monomers and a Secretary chain component.
• IgM has a J chain and an extra constant domain in its heavy chain, also present in IgE.
• Two monomers of IgA are linked by nht to form the dimer form of IGA, and the Secretary component wraps around the two monomers of IgA to encase the dimer.
• IgM has the same monomeric structure as IgE but opposes in the pantamonic structure and contains J chain in its structure.

The IGs:

• IGA is present in external secretions like breast milk, tears, etc., gastrointestinal, respiratory epithelium. It opposes in two forms, IGA one and IGA two and is present in mono Marie form.
• IGT is the membrane immunoglobulin expressed by MarieTV B cells. It plays a role in activation and differentiation of B cell moving towards IgG antibody. It mediates the hypersensitivity reactions, most specifically type one directions. It also binds not cells and provides immunity towards parasites.
• IgG is the most abundant immunoglobulin in serum and is the only immunoglobulin that can pass through the placenta toward the fetus, with four forms, 1234. It is used by plasma cells and is a major component of hemoral immunity. It also plays role in ADCC, immediate cluster pathway.
• IgM is present in membrane more B cells and activates the complement system, that is the classical pathway.

Soluble Immune Complexes:

• Formed in circulation when antibodies bind to antigens, typically involving IgG antibodies.
• Remain soluble in blood and other bodily fluids, circulating freely in the bloodstream.
• Can deposit in tissues, leading to inflammation and tissue damage, examples include systemic lupus erythematosus (SLE) and serum sickness.

Insoluble Immune Complexes:

• Involve larger antigen-antibody complexes, often with IgM involvement.
• Insoluble or poorly soluble in blood and other bodily fluids.
• Tend to deposit in tissues, more prone to deposit in blood vessel walls or other tissues, leading to localized inflammation and damage, examples include immune complex glomerulonephritis.

Immune Complex Diseases Mediated by IgG:

Systemic Lupus Erythematosus (SLE)

• Predominantly IgG is involved.
• Soluble immune complexes of IgG and self-antigens can deposit in various tissues, contributing to inflammation and damage.
• Clinical Features: Joint pain, skin rashes, kidney involvement, and other systemic manifestations.

Rheumatoid Arthritis:

• Predominantly IgG is involved, including rheumatoid factor (IgM or IgA antibodies against IgG).
• Immune complexes deposit in joints, leading to chronic inflammation and joint damage.
• Clinical Features: Joint pain, swelling, and deformities.

Bacterial infection found in damp and moldy environments:

• Predominantly IgG is involved.
• Immune complexes are deposited in the lungs.

Immune Complex Diseases Mediated by IgM:

Post-Streptococcal Glomerulonephritis:

• Predominantly IgM and IgG are involved.
• Insoluble immune complexes deposit in the glomeruli of the kidneys, leading to inflammation and impaired renal function.
• Clinical Features: Hematuria, proteinuria, and hypertension.

Serum Sickness:

• Mainly IgM and IgG are involved.
• Soluble immune complexes deposit in various tissues, leading to systemic symptoms.
• Clinical Features: Fever, rash, joint pain, and other systemic manifestations.

Major Classes and Subclasses of Immunoglobulins (Ig) and Roles in Host Defenses:

IgM

• Pentameric structure in its secreted form and monomeric structure on the surface of B cells
• First antibody produced during the primary immune response
• Efficient at agglutination (clumping) of microbes and activates the complement system
• Secreted form is a pentamer of the basic H2L2 unit
• Present on the surface of immature B cells and plays an important role in immediate hypersensitivity
• Present on the surface of mature, unprimed B cells

IgD

• Monomeric structure
• Found mainly on the surface of mature B cells
• Functions as a membrane receptor for antigen recognition and in B cell activation and differentiation

IgG

• Monomeric structure
• Most abundant antibody in circulation
• Crosses the placenta, providing passive immunity to the fetus
• Opsonization of pathogens for phagocytosis, activates the complement system, and provides long-term immunity (secondary immune response)
• Plays an important role in immediate hypersensitivity

IgA

• Monomeric structure in circulation
• Multimeric forms may contain a secretory component
• Dimeric structure (joined by a J chain) in secretions like saliva and mucosal surfaces
• Provides mucosal immunity in areas like the respiratory and gastrointestinal tracts
• Prevents the attachment of pathogens to mucosal surfaces
• Found in tears, saliva, colostrum, and other secretions
• Multimeric forms have a J chain

IgE

• Monomeric structure
• Involved in allergic reactions and hypersensitivity
• Binds to mast cells, basophils, eosinophils, triggering the release of histamine
• Defends against parasitic infections
• Binds to Fc receptors on mast cells
• Plays an important role in immediate hypersensitivity
• Least abundant isotype in serum

Roles of Immunoglobulins in Host Defenses:

• Neutralization: Antibodies can neutralize toxins and viruses by binding to their active sites, preventing them from interacting with host cells.
• Opsonization: Antibodies enhance phagocytosis by binding to pathogens and marking them for engulfment by phagocytic cells.
• Complement Activation: Antibodies can activate the complement system, leading to the lysis of pathogens and the recruitment of immune cells.
• Agglutination: Antibodies promote the clumping of microbes, making it easier for phagocytes to capture and eliminate them.
• Mucosal Immunity: IgA provides protection at mucosal surfaces, preventing the attachment and invasion of pathogens.
• Allergic Reactions: IgE mediates allergic responses by triggering the release of histamine and other inflammatory mediators from mast cells and basophils.
• Passive immunity: IgG can cross the placenta, providing temporary immunity to newborns. Additionally, antibodies transferred through breast milk offer protection to infants.