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The Adaptive Immune
Response
B-cells
The innate immune system provides immediate protection.
The adaptive response takes time to develop and is antigen specific.
Activation of B and T lymphocytes
Naive
Naive
Plasma cells
ADAPTIVE IMMUNITY
The adaptive immune system consists of lymphocytes and their
products, including antibodies.
The receptors of lymphocytes are much more diverse than
those of the innate immune system, but lymphocytes are not
inherently specific for microbes, and they are capable of
recognizing a vast array of foreign substances.
http://www.pathologystudent.com/wpcontent/uploads/2010/07/normal-lymphs.jpg
There are two types of adaptive Immunity
Cellular immunity: mediated by T lymphocytes and is responsible
for defense against intracellular microbes.
http://yang-sheng.com/wp-content/uploads/2011/05/adoptive_immunity.gif
Humoral immunity: mediated by B lymphocytes and their
secreted products, antibodies (also called immunoglobulins, Ig)
that protects against extracellular microbes and their toxins.
Types of Adaptive Immune Reponses
Lymphocytes
Although lymphocytes appear morphologically unimpressive and similar to
one another, they are actually remarkably heterogeneous and specialized
in molecular properties and functions.
Lymphocytes and other cells involved in immune responses are not fixed in
particular tissues (as are cells in most of the organs of the body) but are
capable of migrating among lymphoid and other tissues and the vascular
and lymphatic circulations.
This feature permits lymphocytes to home to
any site of infection.
In lymphoid organs, different classes of
lymphocytes are anatomically segregated in such
a way that they interact with one another only
when stimulated to do so by encounter with
antigens and other stimuli.
http://www.nature.com/nri/journal/v12/n1/images/nri3128-f5.jpg
Mature lymphocytes that have not encountered the antigen for
which they are specific are said to be naive (immunologically
inexperienced).
http://www.nature.com/ni/journal/v5/n9/images/ni0904-873-F1.jpg
After they are activated by recognition of antigens and other
signals lymphocytes differentiate into:
effector cells, which perform the function of eliminating microbes.
memory cells, which live in a state of heightened awareness and
are better able to combat the microbe in case it returns.
http://www.nature.com/nri/journal/v7/n12/images/nri2204-f1.jpg
B Lymphocytes
B lymphocytes develop from precursors in the bone marrow.
Mature B cells constitute 10% to 20% of the circulating peripheral lymphocyte
population and are also present in peripheral lymphoid tissues such as lymph
nodes, spleen, and mucosa-associated lymphoid tissues.
B cells recognize antigen via the B-cell antigen receptor complex.
Membrane-bound antibodies called IgM and IgD, present on the surface of all
mature, naive B cells, are the antigen-binding component of the B-cell receptor
complex.
Each B-cell receptor has a unique antigen specificity, derived from RAGmediated rearrangements of Ig genes.
After stimulation by antigen and other signals, B cells develop into plasma
cells that secrete antibodies, the mediators of humoral immunity.
http://theadventuresofbecky.files.wordpress.com/
2010/03/plasma-cell-100x-website-arrow.jpg
http://cytochemistry.net/cellbiology/medical/06_016.jpg
http://www.nature.com/nri/journal/v5/n3/images/nri1572-f1.jpg
Immunoglobulins (cont.)
• Biologic properties of immunoglobulin
domains
 Ch3 - cytotrophic reactions involving:
•
•
•
•
macrophages and monocytes
heterologous mast cells
cytotoxic killer cells
B cells
 Ch2
• binding complement
• control of catabolic rate
 Vh/Vl
• antigen binding
B Lymphocytes
..
γ2
µ
δ
V
V
γ3
V
γ1
D
V
V
V
V
Ψε
D
D
α1
J
ε
Ψγ
J
µ
V
D J
J
µ
V
D J
J
D J
3' (DNA)
J
J
V
α2
Germline
D J
D
V
γ4
µ
µ
Rearranged
1° Transcript
µ-mRNA
44 Variable (V) gene segments,[2] plus 27 Diversity (D) gene segments and 6 Joining (J) gene
segments.[3] The light chains also possess 2 Constant (Cμ and Cδ) gene segments and numerous V
and J gene segments, but do not have D gene segments. DNA rearrangement causes one copy of
each type of gene segment to go in any given lymphocyte, generating an enormous antibody
repertoire; roughly 3×1011 combinations are possible, although some are removed due to self
reactivity. (https://en.wikipedia.org/wiki/V(D)J_recombination)
B Lymphocytes
.
Hind III
J
µ
VDJ
3'
Germline DNA
Allele A
µ
B cell leukemia
DJ
µ
Germline
Allele B
Leukemia Normal
B
A
J probe
http://4.bp.blogspot.com/IXXEpj_bFg8/T_QO506s1lI/AAAAAAAAAEc/pEUu2wprOhU/s1600/ig+ge
ne+in+b+cell+differentiation.png
http://www.nature.com/nri/journal/v2/n2/images/nri726-f1.gif
http://www.cellsignal.com/reference/pathway/images/B_Cell_Receptor.jpg
In addition to membrane Ig, the B-cell antigen receptor complex
contains a heterodimer of two invariant proteins called Igα and Igβ.
B cells also express several other molecules that are essential for their
responses. These include complement receptors, Fc receptors, and
CD40.
Upon activation, B lymphocytes proliferate and then differentiate into
plasma cells that secrete different classes of antibodies with distinct
functions (Fig. 6-12).
Upon activation, B lymphocytes proliferate and then differentiate into
plasma cells that secrete different classes of antibodies with distinct
functions (Fig. 6-12).
Many polysaccharide and lipid antigens have multiple identical
antigenic determinants (epitopes) that are able to engage many antigen
receptor molecules on each B cell and initiate the process of B-cell
activation.
Typical globular protein antigens are not able to bind to many antigen
receptors, and the full response of B cells to protein antigens requires
help from CD4+ T cells.
B cells ingest protein antigens into
vesicles, degrade them, and display
peptides bound to MHC molecules
for recognition by helper T cells.
The helper T cells express CD40L
and secrete cytokines, which work
together to activate the B cells.
http://upload.wikimedia.org/wikipedia/commons/thumb/f/f7/B_cell_activation.png/300px-B_cell_activation.png
Immunoglobulins
• IgG, IgM and IgA constitute 95% of serum
immunoglobulins
• IgE trace, IgD B cell membrane associated
• Monomeric IgM on B cell surface
constitutes B cell receptor
• B cell antigen receptor complex contains
nonpolymorphic transmembrane proteins
like the CD3 proteins of TCR, Igα and Igβ
Each plasma cell secretes antibodies that have the same antigen binding
site as the cell surface antibodies (B-cell receptors) that first recognized
the antigen.
Polysaccharides and lipids stimulate secretion mainly of IgM antibody.
Protein antigens, by virtue of CD40L- and cytokine-mediated helper T-cell
actions, induce the production of antibodies of different classes, or
isotypes (IgG, IgA, IgE).
Cytokines that induce isotype switching include IFN-γ and IL-4.
Helper T cells also
stimulate the production of
antibodies with high
affinities for the antigen.
This process, called affinity
maturation, improves the
quality of the humoral
immune response.
Isotype switching and
affinity maturation occur
mainly in germinal centers,
which are formed by
proliferating B cells,
especially in helper T celldependent responses to
protein antigens.
http://www.cs.unm.edu/~immsec/html-imm/AFF-MAT1.JPG
Helper T cells are required for efficient isotype switching, affinity
maturation and generation of long lived memory B cells
Signal 1
Signal 2
Antibodies bind to microbes and prevent them from infecting cells,
thus “neutralizing” the microbes. IgG antibodies coat (“opsonize”)
microbes and target them for phagocytosis, since phagocytes
(neutrophils and macrophages) express receptors for the Fc tails of
IgG. IgG and IgM activate the complement system by the classical
pathway, and complement products promote phagocytosis and
destruction of microbes.
The production of most
opsonizing and
complement-fixing IgG
antibodies is stimulated
by TH1 helper cells,
which respond to many
bacteria and viruses;
thus, the protective
response to most
bacteria and viruses is
driven by TH1 cells.
http://classconnection.s3.amazonaws.com/817/flashcards/995817/jpg/formation_of_secretory_iga1323598120594.jpg
http://classconnection.s3.amazonaws.com/799/flashcards/1565799/png/capture1337446126520.png
http://faculty.ccbcmd.edu/courses/bio141/lecguide/unit5/intro/gensteps/images/u3fg18b.jpg
Some antibodies serve special roles at particular anatomic sites.
IgA is secreted from mucosal epithelia and neutralizes microbes
in the lumens of the respiratory and gastrointestinal tracts (and
other mucosal tissues).
IgG is actively transported across the placenta and protects the
newborn until the immune system becomes mature.
IgE and eosinophils
cooperate to kill parasites,
mainly by release of
eosinophil granule contents
that are toxic to the worms.
TH2 cells secrete cytokines
that stimulate the
production of IgE and
activate eosinophils, and
thus the response to
helminths is orchestrated by
TH2 cells.
http://faculty.ccbcmd.edu/courses/bio141/lecguide/unit5/humoral/5classes/images/u3fig2t.jpg
Most circulating IgG antibodies have half-lives of about 3 weeks.
Some antibody-secreting plasma cells migrate to the bone marrow and
live for years, continuing to produce low levels of antibodies.
The majority of effector lymphocytes induced by an infectious
pathogen die by apoptosis after the microbe is eliminated, thus
returning the immune system to its basal resting state, called
homeostasis.
The initial activation of lymphocytes also generates long-lived memory
cells, which may survive for years after the infection.
Memory cells are an expanded pool of antigen-specific lymphocytes
(more numerous than the naive cells specific for any antigen that are
present before encounter with that antigen), and that respond faster
and more effectively when re-exposed to the antigen than do naive
cells. This is why the generation of memory cells is an important goal
of vaccination.
http://www.nature.com/nri/journal/v3/n10/images/nri1201-i1.jpg
http://course1.winona.edu/kbates/Immunology/images/figure_06_20.jpg
http://legacy.owensboro.kctcs.edu/gcaplan/anat2/notes/Secondary-lymph-follicle-.jpg