Adaptive immunity: an introduction

A/Prof Li Zhang

School of Biotechnology and

Biomolecular Sciences
Room 4106, E26
9385-2042
L.Zhang@unsw.edu.au

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 Learning outcomes
On successful completion of this learning activity, students will be
able to:

• Describe the features of adaptive immune responses.

• Describe the characteristics of antigens.
• Understand the key difference between B cell and T cell
receptors in recognizing antigens.
• Explain the importance of lymphocyte diversity through B cell
and T cell receptors.
• Explain the clonal selection theory and its significance in
adaptive immune responses.
• Explain antibody specificity, affinity and affinity maturation.
• Describe different types of epitopes.
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 Adaptive immunity

(Acquired immunity, specific immunity)

• Highly specific to the substance that has induced the response.

• It requires time to develop in the primary response.
• Immunological memory. A stronger and faster secondary
response.

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 Cells of the adaptive immune system

Neutrophils
Monocytes/macrophages
Eosinophils
Basophils
Dendritic cells
Lymphocytes

Lymphocytes: B cells, T cells, NK cells and ILC (innate lymphoid cells).

B cells and T cells are the cells of the adaptive immune system.

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 Adaptive immune responses
•B cells: producing antibodies (B-cell-mediated response or
humoral immune response). Different subsets of B cells. B1, B2,
marginal B cells.
•T cells: different subsets of T cells to perform different
functions (T-cell-mediated response)
•Naïve lymphocytes: those that have not yet been activated by
antigens.
•Effector lymphocytes: those that have been activated by
antigens and differentiated into fully functional lymphocytes.

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 Adaptive immune responses
• Antigen (Ag): a substance that can bind specifically to an antibody or a T
cell receptor. Proteins, peptides, polysaccharides or lipid. An antigen may
or may not be able to induce immune responses on their own.

• Immunogen: An immunogen is a substance that can induce adaptive

immune responses. An immunogen is also an antigen, an antigen may or
may not be an immunogen.

• A foreign substance with a large molecule size and complex structure

usually induces a better adaptive immune response. In general, proteins
are better in inducing adaptive immune responses than saccharides and
lipids.

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Adaptive immune responses occur in secondary lymphoid organs

B cells and T cells use their receptors (BCR and TCR) to recognize antigens.
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 Structure of B cell receptor/an antibody (immunoglobulin)
• Membrane bound Immunoglobulin (Ig): B-
cell receptor (BCR).
• Humans have five classes of antibodies.
Newly generated B cells have IgM and IgD
on their membrane. IgM recognizes antigen,
the function of IgD is not clear.
• Terminally differentiated B cells (plasma
cells) secret Ig of the same antigen
specificity.
• Antibodies have a Y shape
• Containing four protein chains (2 light
chains and 2 heavy chains), which are
connected by disulfide bonds
• Two types of light chains: lambda and
kappa. One antibody molecule uses only one
type of light chain.
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 Structure of an antibody (immunoglobulin) molecule
• Both the light and heavy chains have variable
regions (V) and constant regions (C).

• The V region of one light chain and one heavy chain

forms an antigen binding site. The specificity of an
antibody is determined by the V regions.

• One immunoglobulin molecule has two antigen

binding sites. The strength of the interaction
between a single antigen-binding site and its antigen
is called affinity. The total binding strength is called
avidity.

• The constant region defines how a specific antibody

contributes to an immune response.

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 Structure of an antibody (immunoglobulin) molecule

• Three regions within the variable

region of the light chain and heavy
chain have hypervariability in
amino acid sequence called
hypervariable regions or
complementarity determining
regions (CDRs)
• CDRs are crucial to the diversity of
antigen specificities of antibodies

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 B cell receptor complex

• A heterodimer Igα/Igβ (CD79) is

part of the B cell receptor complex
(co-receptor). They are the invariant
signaling proteins.
• Binding to antigen by B cell receptor
triggers the phosphorylation of
ITAM motifs in Igα/Igβ, initiating
the signaling pathway.
• ITAM (immunoreceptor tyrosine-
based activation motif).

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 Activation of B cells leads to production of antibodies

Activation of B cells:

• Changes in metabolism
• Changes in gene expression
• Changes in the organization of the cell cytoskeleton

Proliferation (expansion), differentiation to plasm cells which secrete

antibodies and memory cells.
Plasma cells secreted antibodies and the original B cell receptors have
the same antigen specificity, although the antibody classes may be
different.
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 Why does antibody production help us?
• Neutralization: antibody
binding to pathogens or their
toxins to block their binding
to host cells
• Opsonization: the binding of
antibodies to antigens
increases the efficiency of
phagocytosis
• Antibody/antigen immune
complex activates the
complement system
• Antibody–dependent cell-
mediated cytotoxicity
(ADCC).
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 Epitopes
Epitope: An epitope (antigenic
determinant) is the part of antigen
that is recognized by antibodies or T
cell receptors.

Linear epitopes: formed by a

continuous sequence of amino acids
from the antigen. Linear epitopes for
antibodies are 5-12 amino acids.

Conformational epitopes: formed by

discontinuous parts of the antigen’s
amino acid sequence.
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 T cells

1. Generated in the bone marrow.

2. Becoming mature in the thymus.

Thymocytes: immature T cells in the thymus

3. T cell receptors recognize antigens presented by

antigen-presenting cells.

4. T cells are activated by an antigen and

differentiate to different subsets of T cells to
perform their functions.

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 T cells
• Cytotoxic T cells (Tc) (CD8+): killing
• Helper T cells (Th) (CD4+): secreting cytokines
Th1 helps CD8+
Th2 helps B cells to produce antibody (T-cell dependent
antibody production)
Regulatory T cells
• Memory T cells (either CD4+ or CD8+)

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 Structure of T cell receptor
•A T cell receptor contains two chains, most of T
cells have alpha and beta chains.
•Each chain has a variable region (V) and a
constant region (C).
•Structure is similar to Fab fragment of an
immunoglobulin.
•A T-cell receptor has only one antigen-binding site.
•T cell receptors are never secreted.
•T cell receptors only recognize peptides presented
by MHC molecules on antigen presenting cells.

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 T cell receptor complex

• CD3 is a protein complex, consisting

of four protein chains.

• Present on all types of T cells.

• Co-receptor of the T-cell receptor.

• Containing ITAM (immunoreceptor

tyrosine-based activation motif).

• Associated with T-cell receptors and

involved in generating activating
signals on recognition of antigen by
T-cell receptors.
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 MHC-restricted antigen presentation (MHC restriction)

T cells only recognize

antigens presented by
some self-MHC
molecules.

MHC: Major Histocompatibility Complex

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Dendritic cells form the bridge between innate
and adaptive immune responses

Which cell presents antigen to naïve T cell?

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 “The miracle of immunology”

……an individual, from the moment of birth, has

the ability to make antibodies against molecules
never before seen in the universe

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How could this be so?

The Clonal Selection Hypothesis

was from an Australian

SIR FRANK MACFARLANE

BURNET (1899-1985)

Shared 1960 Nobel Prize for

Physiology and Medicine with Peter
Medawar
 Clonal Selection Theory
• Each individual has MILLIONS of DIFFERENT B cells and T
cells.

• Each B cell or T cell has just ONE specificity, which is generated

by V(D)J recombination during the development of B and T cells
that is generated randomly at the ‘birth’ of the cell (specificities
arise PRIOR to antigen exposure).

• Around 250,000 antibody molecules are expressed on the surface

of each B cell surface and about 20,000 T cell receptor molecules
on each T cell, acting as ‘antigen receptors’.

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 Clonal Selection Theory
• These naive B and T cells circulate in the body until
they encounter an antigen.

• Antigen SELECTS a specific B cell or T cell by

binding to B or T cell receptor.

• The selected B or T cell is activated. The activated

B cell divides and differentiate into plasma cells
that are able to secrete “free antibodies” and
memory cells. The activated T cell divides and
differentiate into different subsets of T cells.
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Primary response: the response of the immune system to a first-time
encountered antigen. Secondary responses are faster and stronger (Why?)
Antibodies with high affinities are produced.
 Affinity maturation

Antibodies produced by B cells show increased

affinities during the course of an immune
response.

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 Somatic hypermutation (SHM)

1. During an immune response, mutations occur in genes

encoding for antigen-binding regions (the CDR regions) of
the antibodies. These mutations have an extremely high
rate, 105-106 fold greater than the normal rate of mutation
across the genome.

2. The mutations alter binding affinities and binding

specificities of the antibodies.

3. B cells with high affinities and specificities survive. Over

several rounds of selection, the antibodies secreted by B
cells have increased affinities in binding to the antigen.
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Adaptive and innate immunity

Vaccination
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Not all immune responses are protective

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