IgG Antibody Functions and Characteristics

Antibody Functions

• Antibodies are good at agglutinating pathogens, immobilizing them, and allowing for phagocytosis
• Antibody classes:
  • IgG: most common antibody found in serum, has various subclasses (IgG1, IgG2, IgG3, IgG4), secreted as a monomer, produced later in humoral response
  • Functions: opsonization, activating complement, and triggering antibody-mediated cytotoxicity by Natural Killer cells
  • IgA: predominantly found as a dimer, secreted into tears, saliva, breastmilk, and mucus, functions in neutralizing and agglutinating pathogens
  • Can also be found in blood as a monomer with similar functions to IgG

B-Cell Development

• B cells develop from common lymphoid precursors into Pre-pro B cells in the bone marrow
• B cells become irreversibly committed to the B-cell lineage at the pro-B cell stage, where immunoglobulin gene recombination begins
• As B cells mature, their surface markers change, allowing for communication with stromal cells in the bone marrow
• The B-cell receptor (BCR) is a membrane-bound antibody that associates with a disulfide-linked heterodimer (Ig-α & Ig-β)

B-Cell Activation

• Antigen binds to the BCR with the help of a B-cell co-receptor (CD21) and initiates a downstream signaling cascade promoting B-cell survival and proliferation
• The antigen is presented to the B cell, which increases its expression of co-stimulatory molecules (CD80/86, iCOSL, CD40)
• The B cell presents the antigen to a T-helper cell within germinal centers of a lymphoid follicle, leading to the formation of an immunologic synapse

Antibody Production

• After interaction with a Tfh cell, some B-cells differentiate into plasma cells for antibody secretion
• Some B-cells move into germinal centers of lymphoid follicles, where they undergo antibody class switching, somatic hypermutation, and production of high-affinity antibodies

Antibody Classes and Functions

• There are 5 main classes of antibodies: IgM, IgG, IgD, IgE, and IgA
• General antibody functions include:
  • Neutralization: inactivating pathogens and preventing binding to cells
  • Agglutination: preventing pathogen binding to cells and promoting clearance
  • Opsonization: promoting phagocytosis
  • Complement activation: initiating the classical pathway and promoting phagocytosis
  • Antibody-dependent cell-mediated cytotoxicity: activating Natural Killer cells and inducing apoptosis of infected cells
  • Degranulation: activating Fc granulocytes and triggering degranulation

Antibody Classes

• IgG: most common antibody found in serum, secreted as a monomer, produced later in the humoral response
  • Functions: opsonization, binding to Fc receptor on phagocytes to enhance phagocytosis, IgG1 and IgG3 activate complement, IgG2alpha triggers antibody-mediated cytotoxicity by Natural Killer cells
• IgA: predominantly found as a dimer, secreted into tears, saliva, breastmilk, and mucus
  • Functions: neutralizing pathogens, agglutinating pathogens, inducing degranulation of granulocytes
• IgE: secreted as a monomer in small quantities, binds to cells with Fc receptor for IgE triggering degranulation of granulocytes (eosinophils, basophils, mast cells)
• IgD: secreted as a monomer in very small quantities, most prevalent in secretions of the upper respiratory tract, binds to basophils and mast cells

B-Cell Development and Activation

• B-cell development stages in bone marrow:
  • Stages: pro-B, large pre-B, small pre-B, immature B, mature B
• Two checkpoints in bone marrow:
  • Checkpoint 1: after pro-B stage, ensures proper rearrangement of heavy chain genes
  • Checkpoint 2: after small pre-B stage, ensures proper rearrangement of light chain genes
• B-cell development after bone marrow:
  • Immature B cells migrate to spleen, where they express CD21 and IgD, and are considered mature but naive
  • Mature naive B cells enter general circulation, then migrate to lymph nodes
• B-cell activation:
  • Naive B cells encounter antigen in lymph node through one of two ways:
    • Antigen flows into lymph node through afferent lymphatics and binds to BCR
    • Macrophages or dendritic cells encounter antigen in periphery and bring it to lymph node
  • Antigen recognition leads to B-cell activation, which requires three signals:
    • Signal 1: antigen binding to BCR
    • Signal 2: co-stimulation by CD40 and CD40L
    • Signal 3: cytokine stimulation by Tfh cells

Lymph Node Structure and Function

• Lymph nodes are bean-shape structures with three main regions:
  • Cortex: contains lymphocytes, macrophages, and follicular dendritic cells, arranged into primary follicles that enlarge into secondary follicles with germinal centers after antigen exposure
  • Paracortex: contains mostly T-lymphocytes and dendritic cells, which present antigens to T-helper cells
  • Medulla: more sparsely populated with lymphoid-linage cells, often plasma cells actively secreting antibody molecules

B-Cell Activation and Differentiation

• B-cell activation leads to differentiation into plasma cells or memory B cells
• Plasma cells:
  • No longer have BCR, secrete large numbers of antibody molecules
• Memory B cells:
  • Circulate in periphery, continue to express BCR, longer-lived than naive B-cells
  • Differentiation into memory B cells is unclear

Antibody Structure and Function

• Antibody structure: protein molecules with two heavy chains and two light chains
  • Heavy chain: constant region (Fc) and variable region (Fab)
  • Light chain: variable region and antigen-binding portion
• Antibody functions: six categories:
  • Neutralizing pathogens
  • Agglutinating pathogens
  • Opsonization
  • Complement activation
  • Antibody-mediated cytotoxicity
  • Inducing degranulation of granulocytes