Chapter 4

Humoral Immune System

Melisa Intan Barliana

 Innate Immune Response
v Internal defence :
§  Celullar responses :
v Phagocytosis
v Natural Killer cells
v Inflammation
v Fever
- Humoral responses :
•  Complement system
•  Interferon
•  Cytokines
 Adaptive Immune Response
•  Cell responses :
§  T lymphocytes
§  B lymphocytes
v Humoral responses :
§  Cytokines
§  Antibodies : IgM, IgG, IgA, IgE, IgD
Class I MHC Proteins

Figure 21.15a
 The activated
cytotoxic T cell

1 A specific cytotoxic T cell binds to a 2 The activated T cell releases perforin 3 The granzymes initiate apoptosis within the
class I MHC–antigen complex on a molecules, which form pores in the target cells, leading to fragmentation of the
target cell via its TCR with the aid of target cell membrane, and proteolytic nucleus, release of small apoptotic bodies,
CD8. This interaction, along with enzymes (granzymes), which enter the and eventual cell death. The released
cytokines from helper T cells, leads to target cell by endocytosis. cytotoxic T cell can attack other target cells.
the activation of the cytotoxic cell.

Cytotoxic T cell Released

cytotoxic
Perforin T cell
Cancer
cell
Granzymes
Apoptotic
1 TCR CD8 3
target cell
Class I MHC 2
Pore
molecule

Target
cell Peptide
antigen Cytotoxic
T cell
Class II MHC Proteins

Figure 21.15b
 Class II MHC molecules

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 Peptide antigen
cell Helper T cell Cell-mediated
Class II MHC
Bacterium molecule immunity
(attack on
TCR infected cells)

2 3
Humoral
1 CD4 immunity
(secretion of
Dendritic Cytokines antibodies by
B cell
cell plasma cells)
2 Proliferation of the T cell, stimulated 3 The cells in this clone
by cytokines from both the dendritic secrete other cytokines
cell and the T cell itself, gives rise to that help activate B cells
a clone of activated helper T cells and cytotoxic T cells.
(not shown), all with receptors for the
same MHC–antigen complex.
Development
of Th1
Development
of Th2
Development
of Th17
 B-lymphocytes
v  Antigen-presenting cell
§  Presents antigen to T
cells
v  B cell receptors Antigen- Antigen-
binding binding site
§  Bind to specific, intact site Disulfide
bridge
antigens Light Variable
chain regions

§  Are often called Constant

C C
membrane antibodies regions
Transmembrane
or membrane region

immunoglobulins
Plasma
v  Expresses only a single Heavy chains
membrane

specific antibody B cell Cytoplasm of B cell

(a) A B cell receptor consists of two identical heavy

chains and two identical light chains linked by
Figure 43.8a several disulfide bridges.
 B-Cell Activation
Two required steps
v Binding of antigen to surface immunoglobulin
v Secretion of B cell growth factors by activated CD4+
cells
Plasma cells
•  Produce large amounts of antibody
Memory cells
•  Respond to subsequent pathogen encounters
•  Quicker, more vigorous response
 The humoral immune response
§  Generates a clone of short-lived activated effector
cells and a clone of long-lived memory cells
Antigen molecules
Antigen molecules bind to the antigen
B cells that receptors of only one
differ in of the three B cells
antigen shown.
specificity Antigen
receptor

The selected B cell

proliferates, forming
a clone of identical
cells bearing
receptors for the
selecting antigen.

Some proliferating cells Some proliferating

develop into long-lived cells develop into
memory cells that can Antibody short-lived plasma
respond rapidly upon molecules cells that secrete
subsequent exposure antibodies specific
to the same antigen. for the antigen.
Clone of memory cells
Clone of plasma cells
 B Cells: A Response to Extracellular
Pathogens
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).
Bacterium
Macrophage
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.

Peptide
antigen

Class II B cell
MHC
molecule 2 Secreted antibody
3 Clone of plasma cells
1 molecules
TCR CD4 Endoplasmic
reticulum of
plasma cell
Cytokines

Helper T cell Activated

helper T cell Clone of memory
B cells
Phases of the humoral immune response
Stage of B cell Maturation
B lymphocyte development
B lymphocyte development (2)
Immunoglobulin
gene
rearrangement
Distinct B cell subsets mediate different types
of antibody response
 Immunoglobulins (Ig)

v Also known as antibodies

§  Neutralize and opsonize pathogens
§  Found in human serum
v Found in the gamma globulin class of plasma
proteins, produced by B cells
v Different Ig have different structures and specific
functions
v Bind to antigen
 Ig Production
v Activated B cell transforms into plasma cell
v Plasma cell synthesizes Ig (2000/sec)
v Synthesis of Ig:
§  Packed in endoplasmic reticulum
§  Channeled through Golgi apparatus
§  Glycosylated
§  Transported to surface for secretion
 Synthesis,
assembly and
secretion of
immunoglobulins
 Blood Proteins
Serum Electrophoresis

v Albumin - most abundant, carries hormones, metals

etc.
v Globulins – α, β, γ
v Gamma globulins - immunity- antibodies.
v Antibody - Ab half life about 3 weeks.
Structure of an Antibody Molecule
 Antibody Structure

v  4 polypeptide chains
§  2 light chains
§  2 heavy chains
v  Fab region
§  Fab = fragment antigen binding
§  Specific binding site for antigen
v  Fc region
Fc = fragment crystalline
Interacts with Fc receptor
v  Hinge region
Flexibility for Ag binding
 Antibody
Domain Function
v  V domain (VL - VH)
§  Antigen binding
v  C1 domain (CL - CH1)
§  Coupling of L and H
chains
v  CH2
§  Interacts with complement
v  CH3
§  Attaches to Fc receptors
§  Activates
•  Macrophages
•  PMN
•  Platelets
 Ig Isotypes
IgM First Ig class produced after initial exposure to
(pentamer) antigen; then its concentration in the blood declines

Classes
•  Immunoglobulin M (IgM)
(monomer)
•  Immunoglobulin G (IgG)
•  Immunoglobulin A (IgA)
J chain
Promotes neutralization and agglutination of
antigens; very effective in complement activation
(see Figure 43.19)
IgG Most abundant Ig class in blood; also present in
tissue fluids
Only Ig class that crosses placenta, thus conferring
passive immunity on fetus
Promotes opsonization, neutralization, and agglutination
of antigens; less effective in complement activation than
IgM (see Figure 43.19)

IgA Present in secretions such as tears, saliva, mucus,

(dimer) and breast milk
•  Immunoglobulin D (IgD) Provides localized defense of mucous membranes by
Secretory J chain
component agglutination and neutralization of antigens (see
•  Immunoglobulin E (IgE) Figure 43.19)

Presence in breast milk confers passive immunity on

nursing infant
IgE
Triggers release from mast cells and basophils of
(monomer)
histamine and other chemicals that cause allergic
reactions (see Figure 43.20)

IgD Present primarily on surface of naive B cells that have

(monomer) not been exposed to antigens

Acts as antigen receptor in antigen-stimulated

Transmembrane proliferation and differentiation of B cells (clonal
region selection)
 IgM

v Found on B-cell surface

v Pentamer (5 monomers)
§  No Fc portions exposed
§  Phagocytic cells can not bind
pathogens opsonized by IgM
v Excellent activator of
complement cascade
§  Classic pathway
v Produced during first
exposure to antigen
 IgG
v Most prevalent
antibody
(80% serum antibody)
v Four subclasses
§  IgG1 and IgG3
•  Primarily recognize
protein antigens
§  IgG2 and IgG4
•  Bind carbohydrate antigens
v Only antibody that
crosses placenta
v Produced on second
antigen exposure
Primary
and
secondary
humoral
immune
response
 IgA

v Found in fluid secretions

§  Tears
§  Saliva
§  Nasal solution
§  GI mucus
v Dimeric form
§  Linked with secretory component
v Secreted in breast milk
 IgD

v Function not fully

understood
v Found on B-cell
surface during
different stages of
maturation
v Possible involvement
in cell differentiation
 IgE
v Least common serum
isotype
v Most IgE bound to IgE Fc
receptor on mast cells
v Antigen binding to IgE
releases inflammatory
substances
§  Histamine
§  Pathogenesis of hay
fever, allergic asthma
Classes of Antibodies or
Immunoglobulins
Ig Expression During B Lymphocyte Maturation
v IgM 5monomers on a chain, agglutination
and complement
v IgG serum, passive immunity, neutralize,
precipitate, opsonize
v IgA monomer in serum, dimmers in
mucus, protects outer surfaces.
v IgD antigen receptors on B cells
v IgE antigen receptors on mast cells and
basophiles.
 B Cell Activation
Pathway of antigen to follicular B cells
 B Cell Activation

In all these cases, the antigen that is presented to

B cells is generally in its intact, native conformation
and is not processed by antigen-presenting cells.
This, of course, is one of the important distinctions
between the forms of antigens recognized by B and
T lymphocytes
Functional responses of B cells to antigens
Antigen
presentation on
B cells to helper
T cells
Helper T cell-dependent antibody responses to
protein antigens
Mechanism of helper T
cell-mediated B cell
activation
 Results of
antigen
binding
Functions of Activated
B cells :
v  Neutralize
v  Opsonization
v  Agglutination
v  Fixing complement
v  Precipitation
Neutralization of microbes and toxins by antibodies
Antibody-mediated Opsonization and Phagocytosis
of Microbes
 Cytokines

v Mediators involved in cellular immunity,

including hormone like glycoproteins
released by activated T cells and
macrophages
v Some are co-stimulators of T cells and T cell
proliferation
v Interleukin 1 (IL-1) released by macrophages
co-stimulates bound T cells to:
§  Release interleukin 2 (IL-2)
§  Synthesize more IL-2 receptors
Cytokines

Figure 21.17a
 Cytokines
v IL-2 is a key growth factor, which sets up a positive
feedback cycle that encourages activated T cells to
divide
§  It is used therapeutically to enhance the body’s
defenses against cancer
v Other cytokines amplify and regulate immune and
nonspecific responses
v Examples include:
§  Perforin and lymphotoxin – cell toxins
§  Gamma interferon – enhances the killing power of
macrophages
§  Inflammatory factors
 Humoral
Immunity
Monoclonal
Antibodies
1.  Inject mouse with
antigen.
2.  Sacrifice mouse
remove spleen and
mix with myeloma
cells.
3.  Some cells fuse to
form hybridoma cells.
4. Hybridomas produce
MAbs. Each clone’s
Ab targets same
antigenic determinant.
The roles of the major participants in the
acquired immune response
Humoral immune response Cell-mediated immune response

First exposure to antigen

Antigens engulfed and Antigens displayed

Intact antigens displayed by dendritic cells by infected cells

Activate Activate Activate

Secreted
cytokines
B cell activate
Helper Cytotoxic
T cell T cell

Gives rise to Gives rise to Gives rise to

Active and Memory

Plasma Memory Active
memory cytotoxic
cells B cells cytotoxic
helper T cells T cells
T cells

Secrete antibodies that defend against Defend against infected cells, cancer
pathogens and toxins in extracellular fluid cells, and transplanted tissues
Immunity - Dual Systems