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Host Response

B cells
ll
Lecture #2

Ralph Feuer
Medical Microbiology (BIOL 584)
Spring 2012

Time Course of a Viral Infection

B Cells

White blood cell (lymphocyte)

Humoral immunity

Generate antibodies

B stands for Bursa of


Fabricius

Humours (body fluids)


Secreted antibodies

organ in birds in which avian B


cells mature

Professional Antigen Presenting


Cells

Features of Primary and Secondary


A tib d R
Antibody
Responses
Primary
y and secondary
y
responses differ
y response
p
Secondary
Much quicker
Produce larger amounts of
antibody
y
Higher average affinity

Antibody-secreting
y
g plasma
p m B
cells survive in the bone
marrow for long periods

The Basic Structure of an Immunoglobin

Antibodies are serum proteins

Two fold symmetrical structures

Fragmentation with proteases

Immunoglobulins
Immuno lobulins

Two identical heavy chains


Two
T identical
id ti l li
light
ht chains
h i

Fragments that retain antigenbindin capacity


binding
p it
Monovalent F(ab) fragments
Papain

Bivalent F(ab)2 fragments


Pepsin

Fc fragment

Unable to bind antigen


Has other important functions

Structures of IgG, IgA, and IgM


Antigenic binding site
Recognize the target
p p
epitope

Fc region
Responsible for
complement activation
Mediates binding to
phagocyte receptors
during opsonization

Somatic Gene Rearrangement in


mm
g
DNA
Immunoglobulin

Somatic Gene Rearrangement in


mm
g
DNA
Immunoglobulin
Two gene recombinant events
D-J joining, followed by VDJ joining
Loss of intervening
g gene
g
sequences

Transcription
p
of
f the
recombined gene
RNA processing (splicing)
Translation of heavy chain
protein

Mechanisms of Diversity in
A ti
R
t
Antigen
Receptors
Diversity is increased by
Different Ig heavy and light
chains

Although the upper limit of


t t l potential
total
t ti l repertoire
t i
is shown, only a fraction of
the p
potential repertoire
p
may actually be expressed
Positive/negative selection

Clonal Selection Theory of B cell


E
Expansion
i

B cell Maturation Into Plasma B cells

B cells are produced in the bone marrow

IgM+ transitional B cell migrate to the


spleen

Mature into B lymphocytes

B cells recognizing self-antigen during


maturation

Anergy
Ap pt sis
Apoptosis

Plasma B cells

Memory B cells

Have been exposed to antigen


Produce and secrete large quantities of
antibodies

Live for a long time


Respond quickly to second exposure of the
same antigen
ant gen

Immunoglobulin Isotypes

Different classes of
immunoglobulins

Two light chains

Five heavy chains

Each isotype defines a class of


immunoglobulin

and

, , , ,

Based on the identity of the


heavy chain

IgG
I
G
IgE
IgD (not show)
IgM (pentamers)
IgA
g (dimers)
( m rs)

Functions of IgG, IgA, and IgM

IgA

IgD

IgE

IgM

IgG

Dimer
Mucosal immunity
Neonatal passive immunity

N B cell
Nave
ll antigen
ti
receptor
t

Mast cell activation


Immediate hypersensitivity
Allergies (pollen, dander, certain foods)

Pentamer
Nave B cell antigen receptor
Complement Activation

O s i ti
Opsonization
Complement Activation
Ab-dependent cell-mediated cytoxicity
Neonatal immunity
Feedback inhibition of B cells

Isotype
yp Switching
g

Biological mechanism that changes an antibody from one class to another

Nave mature B cells produce both IgM and IgD

B cells are activated via their CD40 and IL-4 receptors (both modulated by
T helper cells)

undergo antibody class switching to produce IgG, IgA or IgE antibodies

Protective Roles of Serum Antibodies IgG


and
d IgM
I M

Presentation of Opsonized Antigen by


Ph
Phagocytic
ti Cells
C ll
Enhanced uptake of
bacterium by
ph
phagocytes
c t s
immobilization

Without opsonization,
phagocytes have
diffi lt iingesting
difficulty
ti a
bacterium
Like a slippery
pp y fish

Complement Proteins
Have a role in both non-specific
p f and specific
p f defenses
f

T-Independent
T
Independent Production of Antibodies

Leukocyte Rolling - Extravasation

Occurs mainly in post-capillary venules

Chemoattraction

Selectins

Integrins

Hemodynamic shear forces are minimized


Chemokines

Activated endothelial cells


Rolling leukocytes

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