The Humoral
Immune Response
Dr. Enas Al-khlifeh
[email protected]Faculty of Science
➢ B-cell activation
Outline
➢ The distribution and functions
of immunoglobulin isotypes.
➢ The destruction of
antibody-coated pathogens
via Fc receptors
➢ Antibodies produced by B cells cause the destruction of
extracellular microorganisms and prevent the spread of
intracellular infections.
➢ The activation of B cells and their differentiation into
antibody-secreting plasma cells is triggered by antigen
and usually requires helper T cells.
➢ The term ‘helper T cell’ is often used to mean a cell from
the TH2 class of CD4 T cells
B cells activation
➢ The roles of the surface
immunoglobulin
➢ Serves as the B-cell antigen
receptor (BCR)
1- Like the antigen receptor on T cells, it
transmits signals directly to the cell's interior
when it binds antigen.
2- The B-cell antigen receptor delivers the
antigen to intracellular sites where it is
degraded and returned to the B-cell surface
as peptides bound to MHC class II molecules.
➢ The humoral immune response is initiated
when B cells that bind antigen are signaled
by:
➢ Helper T cells
➢ Microbial antigens alone
★ The peptide- MHC II
complex can be
recognized by
antigen-specific helper
T cells.
★ T cells stimulated make
proteins that, in turn,
cause the B cell to
proliferate and its
progeny to differentiate
into antibody-secreting
cells.
Some microbial antigens (e.g., bacterial
polysaccharides) can activate B cells
directly in the absence of T-cell help
(T cell Independent activation)
★ The ability of B cells to respond directly
to these antigens provides a rapid
response to many important bacterial
pathogens.
★ Somatic hypermutation
and switching to certain
immunoglobulin isotypes
depend on the
interaction of
antigen-stimulated B
cells with helper T cells.
★ Antibodies induced by
microbial antigens alone
are less variable and
less functionally
versatile than those
induced with T-cell help.
Different
cytokines
induce
switching to
different
isotypes
When an armed helper T cell
encounters an antigen-binding B
cell, it becomes polarized and
secretes IL-4 and other cytokines
at the point of cell-cell contact
B cells and helper T cells must recognize
epitopes of the same molecular complex in order
to interact (linked recognition)
E.g., An epitope on a viral coat protein is
recognized by the surface immunoglobulin on a B
cell and the virus is internalized and degraded.
Peptides derived from viral proteins, including
internal proteins, are returned to the B-cell surface
bound to MHC class II molecules. Here, these
complexes are recognized by helper T cells, which
help to activate the B cells to produce antibody
against the coat protein.
Antigen-binding B cells are trapped in the T-cell
zone of secondary lymphoid tissues and are
activated by encounter with armed helper T cells
Immunological memory
memory
➢ The ability of the immune system to quickly and
specifically recognize an antigen that the body
has previously encountered and initiate a
corresponding immune response.
➢ Provides secondary, tertiary and other
subsequent immune responses to the same
antigen.
Lymphoid follicle: Germinal
Centers
● Are formed when activated B
cells enter lymphoid follicles
and proliferate
– Somatic hypermutation
– Affinity maturation
– Isotype switching of Ab class.
● Selected B cells will mature to
plasma cells or become
memory cells
The Clonal Expansion
➢ After B cell activation, the B cells clone
themselves through clonal expansion (Mitosis).
➢ During each cellular division, random mutations
occur that gradually increase the binding affinity
for B cell-produced antibodies to antigens.
Class switching:
➢ Occurs after activation of a mature B cell via
its membrane-bound antibody molecule (or B
cell receptor) to generate the different classes
of antibody,
➢ all with the same variable domains as the
original antibody generated in the immature B
cell during the process of V(D)J
recombination, but possessing distinct
constant domains in their heavy chains.
Immunoglobulin for
Treating Infections: One
More Mechanism of
Action