Antibody Structure/Activity & Autoantibodies

Antibody, also known as Immunoglobulin (Ig), is produced by active B-Cells called plasma cells. Antibodies have a variable region that recognizes specific characteristics on pathogens called epitopes or antigens. Each Plasma Cell makes antibodies that are directed against a single antigen. Antibody can be secreted as free floating antibody or be bound to the plasma cell membrane to act as the B-Cell Receptor.

 

Antibodies are the most important part of Humoral Immunity and act via multiple different mechanisms. Antibodies can have a direct effect on pathogens by coating the pathogen so that it cannot interact with cells. However, antibodies primary work via their interactions with other immunologic processes. Antibodies “tag” pathogens so that they can be more easily recognized by other immune processes. The variable region of the antibody binds to the pathogen while the constant portion of the antibody interacts with NK cells, macrophages, and complement. The Constant Region (Fc) can:

  • Bind to C1 and trigger the complement cascade.
  • Bind to Fc receptors on macrophages which in turn increases the phagocytosis and removal of the pathogen. This process is called Opsonization.
  • Interact with NK Cells which can cause direct damage to the pathogen via the release of perforins and granzymes.This is called Antibody-Dependent Cell-Mediated Cytotoxicity.

Antibody Function complement macrophage nk cell immunoglobulin

 

Antibody has a Y shape and is made up of 2 heavy chains and 2 light chains. Antibody is broken down into 2 main regions, the constant region and the variable region. The variable region (Fv) of the antibody is present at the “tip” of the antibody and has 2 separate places where antigen can bind.  The Fv is made up of part of the light chains and part of the heavy chains. The Constant Region (Fc) is the “stem” of the antibody and is primarily made up of the heavy chain. The Constant Region doesn’t vary much within isotype groups while the variable regions can have infinite variability. It needs to be able to “match” whatever antigen it is targeted against.

Antibody Structure Heavy Chain Light Variable Constant Region

 

There are 5 different types of heavy chain. Each type of heavy chain is consistent within a subgroup of antibodies called an isotype. The different isotype groups are IgA, IgE, IgM, IgG and IgD (which is low yield for step 1). Each isotype has unique characteristics and actions.

  • IgM = is the first type of antibody produced following the exposure to any antigen and can be thought of as “Basic” antibody. It’s activation is Helper T-Cell Independent and therefore can be triggered by exposure to peptide or carbohydrate antigens.
  • IgG = is the main antibody found in the blood. It requires interaction with Helper T-Cells (Helper T-Cell Dependent Activation) and therefore can only be formed in response to a peptide antigen in a host with functioning T-Cells (i.e. not in somebody with a severe T-Cell Immunodeficiency like AIDs or Hyper IgM Syndrome). IgG is the only isotype that can cross the placenta to the fetus.
  • IgA = forms Mucosal Immunity and protects the bodies orifices. Found in mucus, tears, saliva, and breast milk. Prevents the entry of pathogens into the GI, urogenital, and respiratory tracts.
  • IgE = Bound to the membrane of Mast Cells. Plays a role in acute inflammation and Type I Hypersensitivity (Anaphylaxis). When multiple membrane bound IgE molecules bind allergens and aggregate/cross-link, they cause the release of histamine.

Isotype Switching,or Class Switching, is the process by which plasma cells change the class/isotype of the antibody they produce. IgM is the first isotype of antibody that is created following the exposure to any antigen. Over time these IgM antibodies can switch classes to take advantage of the characteristics of other isotypes and be effective in a wider range of situations. Following this Isotype Switch the newly created antibodies will recognize the same antigen as before (and therefore have the same variable region), but they will have a different constant region. Primarily this switch occurs from IgM to the more potent IgG. Anytime the question isn’t specifically talking about Mucosal Immunity or Anaphylaxis it is safe to assume they are discussing IgM and/or IgG. IgM is the dominant antibody at the beginning of the humoral response and over the course of weeks IgG becomes the predominant immunoglobulin. You can apply this knowledge to determine what type of humoral immune response is taking place. If you see mostly IgM antibody you know there is an active or recent infection, while a mostly IgG driven response is likely the result of recurrent or past infection. In this way IgG is responsible for the immunologic memory present in humoral immunity. Remember that the presence of antibodies to a pathogen does not necessarily mean there is/has been an infection. Somebody that has received a vaccine against a pathogen may have high levels of IgG against that pathogen even if they have never had an infection. Hyper IgM Syndrome is a type of immunodeficiency where there is an inability to class switch that leads to very high levels of IgM and low levels of all other isotypes.

 

Antibodies are supposed to be directed at pathogens. When antibodies are directed at the body’s own cells, the antibody is called an Autoantibody and they cause autoimmune diseases. There are laboratory tests available to detect these autoantibodies and the results can be used to help diagnose these conditions.

Autoantibodies

* Anti-nuclear antibody (ANA) is a non-specific autoantibody present in many autoimmune diseases. Its presence is not diagnostic of any particular disorder, but can give evidence that an autoimmune process is occurring.

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