The Humoral Adaptive Immunity Susanna Hilda Hutajulu Basic Immunology Course Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta April, 24, 2012 [email protected]
Sep 15, 2015
The Humoral Adaptive Immunity
Susanna Hilda Hutajulu
Basic Immunology Course
Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta
April, 24, 2012
Antibody-mediated Immunity
Toxin-induce disease Viral infectionBacterial infection
Definition of humoral adaptive immunity
Humori (Latin) = fluid.
adoptively transferred by serum
mediated by soluble antibody molecules that float
in biological fluids.
Soldiers of the battle in
human immune response:
B cells
Antibodies
B cell maturation takes place in bone marrow, B cell activation takes place in secondary lymphoid organs.
Antibody structure
Fab fragment
Fc fragment
Antibody contributes to immunity in 3 ways:
- neutralization- opsonization- complement activation
Topic outlines
1. B cell activation induce antibody secretion
2. The distribution and functions of immunoglobulin classes
3. The destruction of antibody-coated pathogens via Fc receptor
1. B cell activationThe initiation of humoral immune response
Generally requires antigen-specific T cell help.
Help from Th cell will come after antigen processing.
Link recognition.
Second signal is always required for B cell activation
Thymus-dependent antigen (T helper cell activation)- 1st signal: crosslinking of BCR- 2nd signal come from T helper cell
Thymus-independent antigen- 1st signal: crosslinking of BCR- 2nd signal: direct binding of antigen to
innate receptor or massive crosslinking of IgM membrane by polimeric antigen
Helper T cells activate B cells that recognize the same antigen (= link recognition).
The humoral immune response is initiated when B cells that bind antigen are signaled by helper T cells
Activation of TH cell:1. Expression of CD40-L2. Membrane-bound 3. Synthesis and secretion of cytokines
B cell activation takes place in secondarylymphoid organs.
Activated B cells migrate into follicles and proliferate to form germinal centers (GCs).
GC B cells undergo:
Proliferation Somatic hypermutation of V region
(improved affinity for antigens) Selection for high affinity BCR Isotype switching Differentiation into plasma cells and
memory cells
B cell activation results in high-affinity antibody-secreting plasma cells and high affinity memory B cells.
GC B cells undergo class switching
Every B cell begins by expressing IgM as its cell receptor, the first antibody produced in immune response is always IgM.
In isotype switching, immune response may express IgG, IgA or IgE.
Class switching is stimulated by cytokines (released by T cells) or mitogenic signal (from pathogen).
Characteristics of Ig isotypes
The number and location of interchain disulfide bonds
The number of attached oligosaccharide moieties.
The number of C domain
The length of hinge region.
Fc fragment
Fab fragment
H= heavy chainL= light chain
GC B cells undergo class switching, preceded by
transcriptional activation of heavy chain region genes.
Class switching is directed by cytokines.
Thymus-independent antigens
Bacterial antigens which have ability to activate B cells, do not require T cell help.
Special properties of some bacterial polysaccarides, polimeric proteins, and lypopolysaccarides enable them to stimulate B cells.
Two classes: TI type 1 intrinsic activity (+) TI type 2 intrinsic activity (-)
TI-1 antigens can directly induce B cell division without T cell help (= B cell mitogen, induces cells to
undergo mitosis).
B cell class switching by TI-2 is enhanced by cytokines.
DC may be able to bind innate receptor, secrete TNF fam cytokine and activate class switching.
Example of different classes of antigen that elicit
antibody responses.
2. Distribution and function of immunoglobulin classes
Extracellular pathogens are in most sites in the body antibodies must be equally widely distributed to combat them.
Distribution is determined by their isotypes.
IgG: extracelluler fluid, fetus (by transplacental transport)
IgM: >> plasma
IgA:monomeric: extracelluler fluid dimeric: in secretion across epithelia
IgE is beneath epithelial surface(respiratory, gastrointestinal, skin)
Brain is normally devoid of Ig.
Antibodies of different classes operate in
distinct places and have distinct effector functions.
Functions of Ig isotypes
Function of antibody
Neutralization= High-affinity IgG and IgA antibodies can neutralize bacterial toxins
Neutralization= High-affinity IgG and IgA antibodies can inhibit the infectivity of viruses.
Antibodies blocks adherence
of some bacteria.
Antibody:antigen complexes activate the classical pathway of complement
enhance opsonization and lyse some bacteria.
3. The destruction of antibody-coated pathogens via Fc receptors
Many pathogens do not bind to neutralizing targets on pathogen surface
need to be linked to
Fc receptor.
Cells bearing Fc receptor:
Phagocytic cells (neutropil, macrophage)
Non-phagocytic secrete mediator when their FcRare engaged NK cells
eosinophil
basophil
mast cells
The Fc receptors are signaling receptors specific for
immunoglobulins of different classes.
Fc receptors activate NK cells to destroy
antibody-coated targets in antibody-dependent cell-mediated cytotoxicity (ADCC).
Mast cells and basophils bind IgE antibody via the high-affinity Fc receptor.
Fc receptors on phagocytes facilitate phagocytosis
to ingest and destroy pathogens.
Clearance of immune complex from circulation
Summary
Human immune response involves antibody production the binding of antibody-pathogen elimination by phagocytic cells and other molecules
The antibody production usually requires Th cells help but certain pathogen can stimulate B cells independently.
Roles of antibody include neutralization, opsonization and complement activation.
Thank you