3 - Antibodies

It is the Fc regions that create different classes of antibodies

(IgM, IgG, IgE, IgA and IgD). Each of these has specific functions as well a site of action. (Table 15.1)

IgD

- 0.2% in serum 1) Found primarily on surface of naive B cells as BCR for naive B cells. 2) Not secreted into serum.

IgA

- 10-15% in serum 1) Found in blood as monomer and found in secretions (saliva, sweat, mucus) as a dimer, joined by a J chain and a secretory piece. 2) Transmitted to newborns in breast milk and due to presence in all secretions as well as serum, it is the most abundant antibody in the overall body.

IgM

- 5-10% in serum 1) The only class of antibody that doesn't need T help to be produced. It is the default antibody produced by all naive B cells. It is the BCR for naïve B cells. 2) When secreted by plasma cell it is secreted as a pentamer, joined by J chain . 3) Fixes complement, e.g. activates the classical complement cascade. Because it is a pentamer, is very, very good at activating complement. 4) Neutralizes bacterial toxins. 5) Pentamer is too large to get out of circulation and is primarily found in the blood.

These constant regions (Fc)

- are the same in all humans. i. My antibodies look just like your antibodies. b. They are slightly different in different animals. This means that IgG from a mouse "looks" slightly different than what human IgG looks like.

IgE

- least abundant in serum (bound in tissues by mast cells) 1) Found in higher concentrations in allergic (ATOPIC) individuals 2) Mediates response to helminths and parasitic worms. 3) Is THE major antibody involved in ADCC against helminths. IgE binds to parasites. 4) Mast cells, basophils and eosinophils are the primary cells that act in this pathway because they have IgE via FcRs found on their surface.

IgG

-80% in serum 1) Is secreted by plasma cells in monomeric form, activates classical complement cascade when two IgG antibodies bind to the same antigen and C1 binds to the IgG Fc region. 2) Only antibody able to cross the placenta and confer immunity to a fetus (Fig. 16.7) due to an IgGR found on the placenta. 3) Protects against viral and bacterial infection. 4) IgG is the primary antibody against aberrant cells such as cancers cells. NK, cells play the primary role in ADCC against these type of antibody coated cells. The cells involved, bind via recognition of Fc receptors and lob toxic molecules at pathogen/aberrant cell to destroy it.

Antibody Function: Agglutination

1) Antibodies aggregate large particulate cells or molecules. 2) Allow phagocytes to ingest large amounts of bacteria or antigen easily.

Antibody Function: Neutralization

1) Antibody blocks pathogen attachment site (especially good for viruses). 2) Blocks toxin activity by binding it before it can attach to receptor on cell. 3) Any antibody can neutralize a pathogen/virus/toxin

Antibodies

1. The job of a B cell is to make antibodies against specific pathogens.

Antibody Function: What cant antibodies do?

Antibodies are not effective against intracellular pathogens, such as replicating viruses, or intracellular bacteria (those that hide out in macrophages.

Antibody Function: Opsonization

Coating bacteria with antibody (monomers work best for opsonization).

Antibody Function: Precipitation

Fig 18.57 1) Involves soluble antigens. 2) Antibodies bound to antigens precipitates them out of solution, but antigen to antibody ration critical for it to work effectively.

Antibody Function: Antibody-dependent cell-mediated cytotoxicity (ADCC)

Not all antibodies participate in ADCC Only IgE & IgG

Each Antibody

Starts as a monomer Figure 15.7

Class of Antibodies

Table 15.1 All antibodies have specific functions that they perform. Not all antibodies can perform every function.

What are antibodies?

They are proteins that are secreted into the body fluids that bind to identify and eliminate antigens/pathogens.

Default antibody

always secreted by initially by a naïve partially activated B cell is IgM. IgD is never secreted.

Function of antibodies

are neutralization, opsonization, complement activation, immobilization, ADCC, and agglutination (Fig. 15.8).

Antibody Function: Complement Activation

classical pathway (primarily IgG and IgM activate complement)

There are 3 possible changes

from mu ----> gamma, alpha, epsilon . These cassettes are responsible for making a different class of antibody (Fig. 15.15)

Each antibody monomer (cont)

has a variable region responsible for binding antigen (Fab). The variable region created by the combination of the light chain and heavy chain is unique to each B cell. There is a constant region (Fc) that allows antibodies to have specific functions.

The BCR on all NAÏVE B cells

is always both IgM and IgD

Each antibody monomer

is composed of two identical heavy chains and two identical light chains.

When a B cell switches Fc regions

the BCR on the clonal offspring will be the same as the antibody it secretes (secretes IgG, has IgG as its receptor)(Fig. 15.10).

On one B cell

the Fab region will be identical although the constant regions are transcripts/translations of either the delta or the (MU symbol) gene cassette.

When a B cell switches constant regions

the genetic cassettes used to create the variable region of both the heavy and light chains will remain the same.

The BCR on a B cell

will bind an identical antigen to what antibody is secreted by that B cell.