Characteristics Innate immune system Adaptive immune system

Specificity Not specific Very specific

Diversity Limited; germline encoded Very large; receptors are produced by

somatic recombination of gene
segments
Memory None Yes
Nonreactivity to Yes Yes
self
Components
Cellular and Skin, mucosal epithelia; Lymphocytes in epithelia; antibodies
chemical antimicrobial molecules secreted at epithelial surfaces
barriers
Blood proteins Complement, others Antibodies

Cells Phagocytes (macrophages, Lymphocytes

neutrophils), natural killer cells,
innate lymphoid cells

Adaptive immunity is not independent of innate immunity

 Adaptive Immunity
Adaptive immunity displays four characteristic attributes:
• Antigenic specificity:
– Permits it to distinguish subtle differences among antigens.
– Antibodies can distinguish between two protein molecules that differ in
only a single amino acid.
• Diversity:
– The immune system is capable of generating tremendous diversity in its
recognition molecules, allowing it to recognize billions of unique
structures on foreign antigens.
• Immunologic memory:
– Once the immune system has recognized and responded to an antigen, it
exhibits immunologic memory; that is, a second encounter with the same
antigen induces a heightened state of immune reactivity. Because of this
attribute, the immune system can confer life-long immunity to many
infectious agents after an initial encounter
• Self/nonself Recognition:
– The ability of the immune system to distinguish self from nonself and
respond only to nonself molecules is essential
 Clonal selection
first proposed in the 1950s by Macfarlane Burnet to explain why
antibodies, which can be induced in response to virtually any
antigen, are produced in each individual only to those antigens
to which he or she is exposed.
-that proposed the existence of a large number of antibody-
forming cells, each of which is genetically preprogrammed to
produce a unique antibody specificity.
-Clonal selection is a process proposed to explain how a single B
or T cell that recognizes an antigen that enters the body is
selected from the pre-existing cell pool of differing antigen
specificities and then reproduced to generate a clonal cell
population that eliminates the antigen.
 Clonal selection continue….
-Clonal selection of lymphocytes
is the central principle of adaptive
immunity.
-The specificity of these receptors
is determined by a unique genetic
mechanism that operates during
lymphocyte development in the
bone marrow and thymus to
generate millions of different
variants of the genes encoding
the receptor molecules.
-During a person's lifetime these
lymphocytes undergo a process
akin to natural selection; only
those lymphocytes that encounter
an antigen to which their receptor
binds will be activated to
proliferate and differentiate into
effector cells.

identical progeny, known as a clone

 Antibodies
Antibodies belong to the class of proteins called globulins, so named for their
globular structure. Collectively, antibodies are known as immunoglobulins
(abbreviated Ig).

• are glycoproteins that consist of

two identical heavy polypeptide
chains and two identical light
polypeptide chains.
• -tetramer
• Each heavy chain is joined with a
light chain by disulfide bonds, and
additional disulfide bonds hold
the two pairs together.
• The amino-terminal ends of the
pairs of heavy and light chains
form a cleft within which antigen
binds.
• a single plasma cell can secrete
more than 2000 molecules of
antibody per second.
Antibodies are the secreted form of the B-cell
receptor.
Antibody molecules are roughly Y-shaped
molecules.
 General features of antibodies
four polypeptide chains.
-2 heavy (H) chains
-2 light (L) chains
Each chain is synthesized separately and is encoded by different genes.
Each chain is divided into two regions
-constant (C)regions- C-terminal (carboxyl terminal)
-variable (V) regions-N-terminal (amino terminal)
The variable and constant regions of both the light and the heavy chains
are structurally folded into functional units called domains.
L-chain has one V (VL) and one C (CL) domain
H-chain has
one variable domain (VH )
three or four constant domains (CH1, CH2, CH3, CH4)
The variability in sequence is limited to approximately the first 110
amino acids.
-All the H-chain constant domains except CH1 determines the fate
of the antigen once it becomes bound to the antibody.
 The hinge region
-Is a short stretch of amino acids on the heavy chain
located between the chain’s CH1 and CH2 regions.
-It provides the molecule with flexibility, which is very
useful in binding antigens.
-This flexibility can actually improve the efficiency with
which an antigen binds to the antibody.
-It can also help in cross-linking antigens into a large
lattice of antigen-antibody complexes, which are easily
identified and destroyed by macrophages.
 The antibody molecule can readily be cleaved into
functionally distinct fragments
Limited digestion with the protease papain cleaves antibody
molecules into three fragments.
- The Fab fragments; Two fragments are identical and contain
the antigen-binding activity.
(Fragment antigen binding)
-The Fab fragments correspond to the two identical arms of the
antibody molecule, which contain the complete light chains
paired with the VH and CH1 domains of the heavy chains.
-The other fragment contains no antigen-binding activity but
was originally observed to crystallize readily, and for this reason
was named the Fc fragment (Fragment crystallizable).
-it is the part of the antibody molecule that interacts with
effector molecules and cells.
Classes of Immunoglobulins
Five different classes of Immunoglobulins
IgM
IgD
IgG
IgA
IgE
Are classified based on the C regions.
 IgG
• IgG is the most common class of immunoglobulin.
• It is present in the largest amounts in blood and tissue fluids.
• Each IgG molecule consists of the basic four-chain
immunoglobulin structure—two identical H chains and two
identical L chains (either kappa or lambda)—and thus carries
two identical antigen-binding sites.
• There are four subclasses of IgG, each with minor differences in
its H chains but with distinct biological properties.
• IgG is the only class of immunoglobulin capable of crossing
the placenta; consequently, it provides some degree of immune
protection to the developing fetus.
• These molecules also are secreted into the mother’s milk and,
once they have been ingested by an infant, can be transported
into the blood, where they confer immunity.
 IgM
• IgM is the first class of
immunoglobulin made by B cells as
they mature,
• it is the form most commonly present
as the antigen receptor on the B-cell
surface.
• When IgM is secreted from the cells,
five of the basic Y-shaped units
become joined together to make a
large pentamer molecule with 10
antigen-binding sites.
• This large antibody molecule is
particularly effective at attaching to
antigenic determinants present on
the outer coats of bacteria.
• When this IgM attachment occurs, it
causes microorganisms to gglutinate,
or clump together.
 IgA
• IgA is the main class of antibody found in
many body secretions, including tears, saliva,
respiratory and intestinal secretions, and
colostrum (the first milk produced by
lactating mothers).
• Very little IgA is present in the serum.
• IgA is produced by B cells located in the
mucous membranes of the body.
• Two molecules of IgA are joined together and
associated with a special protein that
enables the newly formed IgA molecule to be
secreted across epithelial cells that line
various ducts and organs.
• Although IgG is the most common class of
immunoglobulin, more IgA is synthesized by
the body daily than any other class of
antibody. However, IgA is not as stable as
IgG, and therefore it is present in lower
amounts at any given time.
 IgD
• IgD molecules are present on the surface of
most, but not all, B cells early in their
development, but little IgD is ever released into
the circulation.
• It is not clear what function IgD performs, though
it may play a role in determining whether
antigens activate the B cells.
 IgE
• IgE is made by a small proportion of B cells and is
present in the blood in low concentrations.
• Each molecule of IgE consists of one four-chain unit and
so has two antigen-binding sites, like the IgG molecule;
however, each of its H chains has an extra constant
domain (CH4), which confers on IgE the special property
of binding to the surface of basophils and mast cells.
• When antigens bind to these attached IgE molecules,
the cell is stimulated to release chemicals, such as
histamines, that are involved in allergic reactions.
• IgE antibodies also help protect against parasitic
infections.
 IgG
Are large molecules, having a molecular weight of
approximately 150 kDa,
composed of two different kinds of polypeptide
chain.
One, of approximately 50 kDa, is termed
the heavy or H chain, and
the other, of 25 kDa, is termed the light or L
chain
- IgG is by far the most abundant immunoglobulin
and has several subclasses
 Types of light chain
• lambda (λ)
• kappa (κ)

• A given immunoglobulin either has κ chains or λ chains,

never one of each. No functional difference has been
found between antibodies having λ or κ light chains, and
either type of light chain may be found in antibodies of
any of the five major classes.
• The ratio of the two types of light chain varies from
species to species. In mice, the average κ to λ ratio is 20:1,
whereas in humans it is 2:1 and in cattle it is 1:20
 Types of heavy chains
Heavy chain defines the class, and thus the
effector function, of an antibody.
five main heavy-chain classes or isotypes.
-some of which have several subtypes, and these determine the
functional activity of an antibody molecule.
-heavy chains are denoted by the corresponding lower-case Greek
letter μ (IgM), δ (IgD), γ (IgG), α (IgA), and ε (IgE).
 Diversity of antibodies
The specific immune system (in other words, the
sum total of all the lymphocytes) can recognize
virtually any complex molecule that nature or
science has devised.
How is it that the body has such an
incredible diversity of receptors that are always
ready to respond to invading molecules?