Module 0: B cells and antibodies
Humoral immunity refers to the production of antibody/immunoglobulins molecules in response to
an antigen
Antigens
Antigen: substance that is recognized by receptors on B- or T-lymphocytes or by soluble antibodies
Immunogen: an antigen that is recognized by the body as non-self and that induces an adaptive
immune response
Epitopes
Epitopes: The actual parts or fragments of an antigen that react with receptors on B- or T-
lymphocytes, or with free circulating antibody molecules
Polysaccharides have many of the same epitope
Proteins, usually have several epitopes of different specificity
Antibodies may recognize conformational or linear epitopes (determinants)
Conformational determinants depend on folding of the antigen
o Parts of protein fold to form epitope
o When protein denatures, conformation is lost and won’t be recognized by antibody
Linear epitopes can still be recognized after denaturation of the protein
B-lymphocytes, plasma cells and memory cells
B-cells:
circulate in the body
primary function is to recognize antigens
has surface receptors specific for a certain antigen BCR
o membrane bound immunoglobulin
o when antigen binds to BCR, B-cell gets activated
plus co-stimulatory signal B-cell will proliferate and develop plasma cell
plasma cell produces secreted antibodies
some B cells become memory cells
Primary humoral immune response: naive B cells are stimulated by an antigen, become activated and
differentiate into antibody-secreting cells that produce antibodies specific for the eliciting antigen
Secondary humoral immune response: elicited when the same antigen stimulates memory B cells,
leading to the production of greater quantities of specific antibody, than are produced in the primary
response
Antibodies
Antibodies:
major soluble effector molecule of the adaptive immune system
glycoproteins secreted by plasma cells
same specificity as the B cell receptor from which the plasma cell was originally derived
consist out of:
o two identical heavy
o two identical light chains
connected by disulfide (S-S) bonds and non-covalent bonds
o y-shaped
tips of the “Y”: variable regions that form the antigen binding sites that
recognize the epitopes Fab portions
1
, Bottom of the "Y": formed by the C terminal region of the two heavy chains,
is called the constant region Fc portion
Fc portion defines class and subclass
Fc region determines what happens with the antigen by binding to
special Fc receptor on macrophages and other phagocytes
Antibody classes
Name Types Function Structure
IgA 2 Secreted antibody found in mucosa, such as the gut,
respiratory tract, urogenital tract and in saliva, tears
and breast milk. It prevents colonization by
pathogens.
IgD 1 Immunoglobulin that functions mainly as an antigen
receptor on B cells (BCR) that have not been
exposed to antigens.
IgE 1 Secreted antibody that protects against parasitic
worms by coupling eosinophils to these pathogens
and by inducing the degranulation of these
eosinophils. IgE binds to allergens and triggers
histamine release from mast cells and basophils, and
is therefore involved in allergy.
IgG 4 Human IgG comes in four forms, that together
provide the majority of antibody-based immunity
against invading pathogens. IgG is the only secreted
antibody capable of crossing the placenta to give
passive immunity to the fetus in mammals.
IgM 1 Expressed on the surface of activated B cells
(monomer) and in a secreted form (pentamer). It has
generally low affinity, but due to its pentameric form
high avidity. IgM eliminates pathogens in the early
stages of B cell-mediated primary (humoral)
immunity before there is sufficient (higher affinity)
IgG.
Affinity: is determined by the binding strength to an epitope
Avidity: the accumulated strength of multiple individual non-covalent binding interactions
Selection and activation of B cells; Clonal selection and expansion
B-cells are genetically programmed to make an antibody with unique antigen-binding site (Fab
region) through a series of somatic recombinations
These antibodies form BCR on membrane
Variation of antigens is huge, but BCRs on single B cell are identical
Clonal selection: antigen binds to BCR that fits and activates the B cell
Clonal expansion: cytokines from activated T-helper cells activate B-cell to proliferate
Activation of B cells by T cell-dependent antigens
Antibody responses against most proteins are dependent on the action of T helper cells
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