Transcript Antibodies, structure. Classes of Immunoglobulines

Lector Tvorko M. S.
ANTIBODIES (IMMUNOGLOBULINS)
Antibodies are globulin proteins (immunoglobulins)
that react specifically with the antigen that stimulated their
production. They make up about 20% of the protein in
blood plasma.. There are five classes of antibodies: IgG,
IgM, IgA, IgD, and IgE.
IMMUNOGLOBULIN STRUCTURE
Immunoglobulins are glycoproteins made up of light (L)
and heavy (H) polypeptide chains. The terms "light" and
heavy" refer to molecular weight; The simplest antibody
molecule has a Y shape and consists of four polypeptide
chains: two H chains and two L chains. The four chains
are linked by disulfide bonds. An individual antibody
molecule always consists of identical H chains and
identical L chains.
The Immune system includes 5 classes of
Immunoglobulin (Ig)
Heavy (H)
polypeptide
chains
Class of
immunoglobulin

Ig G

Ig M

Ig A

Ig E

Ig D
Ig G - 22,,22
Ig M - (22)5, (22)5
Ig A - (22)n , (22)n,,
Ig E - 22, 22
IgD - 22, 22
If an antibody molecule is treated with a proteolytic enzyme such as
papain, peptide bonds in the "hinge" region are broken, producing two
identical Fab fragments, which carry the antigen-binding sites, and one Fc
fragment, which is involved in placenta! transfer, complement fixation,
attachment site for various cells, and other biologic activities
IMMUNOGLOBULIN CLASSES
IgG. Each IgG molecule consists of two L chains
and two H chains linked by disulfide bonds
(molecular formula H2L2). Because it has two
identical antigen-binding sites, it is said to be
divalent.
IgG is the predominant antibody in the
secondary-response
and
constitutes
an
important defense against bacteria and viruses.
IgG is the only antibody to cross the placenta
only its Fc portion binds to receptors on the
surface of placental cells. It is therefore the most
abundant
immunoglobulin
in
newborn.
IgG is one of the two immunoglobulins that can
activate
complement
and
opsonizes.
IgM is the main immunoglobulin produced early in the primary response. It is
present as a monomer on the surface of virtually all B cells, where it functions
as an antigen-binding receptor In serum, it is a pentamer composed of 5 H2L2
units plus one molecule of J (joining) chain. Because the pentamer has 10
antigen-binding sites, it is the most efficient immunoglobulin in agglutination,
complement fixation (activation), and other antibody reactions and is important
in defense against bacteria and viruses. It can be produced by the fetus in
certain infections. It has the highest avidity of the immunoglobulins; its
interaction with antigen can involve all 10 of its binding sites.
IgA is the main immunoglobulin in secretions such as
colostrum, saliva, tears, and respiratory, intestinal, and
genital tract secretions. It prevents attachment of bacteria
and viruses to mucous membranes. Each secretory IgA
molecule consists of two H2L2 units plus one molecule
each of J (joining) chain and secretory component. The
secretory component is a polypeptide synthesized by
epithelial cells that provides for IgA passage to the
mucosal surface. It also prelects IgA from being degraded
in the intestinal tract. In serum, some IgA exists as
monomericH2L2.
IgE is medically important for two
reasons: (1) it mediates immediate
(anaphylactic) hypersensitivity, and
(2) it participates in host defenses
against certain parasites, eg, helminths
(worms). The Fc region of IgE binds to
the surface of mast cells and basophils.
Although IgE is present in trace amounts
in
normal
serum
(approximately
0.004%), persons with allergic reactivity
have greatly increased amounts, and IgE
may appear in external secretions. IgE
does not fix complement and does not
cross the placenta.
IgD. This immunoglobulin has no
known antibody function but may
function as an antigen receptor; it
is present on the surface of many
B lymphocytes. It is present in
small amounts in serum.
Major Functions of Human Immunoglobulins
• Function IgM Main Ig during Primary Response (Early
antibody).
Fixes Complement (most effectively).
• IgG Main Ig during Secondary Response (late antibody).
Opsonization.
Fixes Complement.
Neutralizes Toxins, Viruses.
• IgA Secretory mucosal Ig
Prevents invasion from gut mucosa.
• IgE Immediate Hypersensitivity.
Mast cell and Basophil reactions.
Activates Eosinophils in helminth infection
• IgD Function Unknown.
Mostly on the Surface of B cells.
Immunoglobulins
• Antibody-mediated mechanisms of antigen disposal
Binding of antibodies to antigens
inactivates antigens by
Viral neutralization
(blocks binding to host)
and opsonization (increases
phagocytosis)
Agglutination of
antigen-bearing particles,
such as microbes
Precipitation of
soluble antigens
Complement
proteins
Bacteria
Virus
Activation of complement system
and pore formation
MAC
Pore
Soluble
antigens
Bacterium
Enhances
Phagocytosis
Macrophage
Foreign cell
Leads to
Cell lysis
• Class II MHC molecules, located mainly on
dendritic cells, macrophages, and B cells
– Display antigens to helper T cells
Antigenpresenting
cell
Microbe
1 A fragment of
foreign protein
(antigen) inside the
cell associates with
an MHC molecule
and is transported
to the cell surface.
Antigen
fragment
1
Class II MHC
molecule
2
2 The combination of
MHC molecule and
antigen is recognized
by a T cell, alerting it
to the infection.
(b)
T cell
receptor
Helper T cell
• Class I MHC molecules, found on almost all
nucleated cells of the body
– Display peptide antigens to cytotoxic T cells
Infected cell
Antigen
fragment
1
1 A fragment of
foreign protein
(antigen) inside the
cell associates with
an MHC molecule
and is transported
to the cell surface.
Class I MHC
molecule
T cell
receptor
2
(a) Cytotoxic T cell
2 The combination of
MHC molecule and
antigen is recognized
by a T cell, alerting it
to the infection.
• The role of helper T cells in acquired
immunity
1 After a dendritic cell engulfs and degrades a bacterium, it displays
bacterial antigen fragments (peptides) complexed with a class II
MHC molecule on the cell surface. A specific helper T cell binds
to the displayed complex via its TCR with the aid of CD4. This
interaction promotes secretion of cytokines by the dendritic cell.
Cytotoxic T cell
Dendritic
cell
Bacterium
Peptide antigen
Class II MHC
molecule
Helper T cell
Cell-mediated
immunity
(attack on
infected cells)
TCR
2
3
1 CD4
Dendritic
cell
Cytokines
2 Proliferation of the T cell, stimulated
by cytokines from both the dendritic
cell and the T cell itself, gives rise to
a clone of activated helper T cells
(not shown), all with receptors for the
same MHC–antigen complex.
B cell
3 The cells in this clone
secrete other cytokines
that help activate B cells
and cytotoxic T cells.
Humoral
immunity
(secretion of
antibodies by
plasma cells)
1 After a macrophage engulfs and degrades
2
a bacterium, it displays a peptide antigen
complexed with a class II MHC molecule.
A helper T cell that recognizes the displayed
complex is activated with the aid of cytokines
secreted from the macrophage, forming a
clone of activated helper T cells (not shown).
A B cell that has taken up and degraded the
same bacterium displays class II MHC–peptide
antigen complexes. An activated helper T cell
bearing receptors specific for the displayed
antigen binds to the B cell. This interaction,
with the aid of cytokines from the T cell,
activates the B cell.
3 The activated B cell proliferates
and differentiates into memory
B cells and antibody-secreting
plasma cells. The secreted
antibodies are specific for the
same bacterial antigen that
initiated the response.
Bacterium
Macrophage
Peptide
antigen
Class II
MHC
molecule
B cell
2
1
TCR
3
Clone of plasma cells
Endoplasmic
reticulum of
plasma cell
CD4
Cytokines
Helper T cell
Secreted antibody
molecules
Activated
helper T cell
Clone of memory
B cells
Humoral Immune response
• The activated cytotoxic T cell
– Secretes proteins that destroy the infected target
cell
1 A specific cytotoxic T cell binds to a
class I MHC–antigen complex on a
target cell via its TCR with the aid of
CD8. This interaction, along with
cytokines from helper T cells, leads to
the activation of the cytotoxic cell.
2 The activated T cell releases perforin
molecules, which form pores in the
target cell membrane, and proteolytic
enzymes (granzymes), which enter the
target cell by endocytosis.
Cytotoxic T cell
3 The granzymes initiate apoptosis within the
target cells, leading to fragmentation of the
nucleus, release of small apoptotic bodies,
and eventual cell death. The released
cytotoxic T cell can attack other target cells.
Released
cytotoxic
T cell
Perforin
Cancer
cell
Granzymes
1
TCR
Class I MHC
molecule
Target
cell
3
CD8
2
Peptide
antigen
Apoptotic
target cell
Pore
Cytotoxic
T cell
Immune synapsis