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Topic Number Eleven
The Immune System
The Immune system
1. Innate Immunity: Nonspecific Defenses
 Defenses against any pathogen
 It does not confer long-lasting or protective
immunity to the host
2. Adaptive immunity: Specific Defenses
 Immunity, resistance to a specific pathogen.
Three Lines of Defense Against Infection
1. First Line of Defense: Non-specific natural
barriers which restrict entry of pathogen.
Examples: Skin and mucous membranes.
2. Second Line of Defense: Innate non-specific
immune defenses provide rapid local response
to pathogen after it has entered host.
Examples: Fever, phagocytes (macrophages
and neutrophils), inflammation, and interferon.
3. Third line of defense: Antigen-specific immune
responses, specifically target and attack
invaders that get past first two lines of defense.
Examples: Antibodies and lymphocytes.
Three Lines of Defense Against Infection
First Line of Defense:
1. Skin
Intact skin, keratin (waterproof), form physical
barriers that prevent the entry of microorganisms
and viruses
Secretions from the skin
 Sebum: Oily substance produced by sebaceous
glands that forms a protective layer over skin.
Contains unsaturated fatty acids which inhibit
growth of certain pathogenic bacteria and fungi
 Also include proteins such as lysozyme, an enzyme
that digests the cell walls of many bacteria
Infections are rare in intact skin. Exceptions:
 Hookworms can penetrate intact skin
 Dermatophytes: “Skin loving” fungi
Normal microbiota compete with pathogens.
2. Mucous membranes
Saliva: Washes microbes from teeth and mouth
mucous membranes.
 Mucus: Thick secretion that traps many microbes.
 Urination: Cleanses urethra.
 Vaginal Secretions: Remove microbes from
genital tract.
II. Second Line of Defense
1. Phagocytosis
 Phagocytosis is carried out by white blood cells:
macrophages, neutrophils, and occasionally
eosinophils.
 Wandering macrophages:
Originate from
monocytes that leave blood and enter infected
tissue, and develop into phagocytic cells.
 Fixed Macrophages (Histiocytes): Located in
liver, nervous system, lungs, lymph nodes, bone
marrow, and several other tissues.
Process of Phagocytosis
Antimicrobial Proteins
1. The complement system
 About 30 serum proteins activated in a cascade
Effects of Complement Activation
1.Opsonisation - enhancing phagocytosis of antigens
2.Chemotaxis neutrophils
attracting
macrophages
and
3.Cell Lysis - rupturing membranes of foreign cells
4.Clumping of antigen-bearing agents
Effects of Complement Activation
II. Interferons: Antiviral proteins that interfere
with viral multiplication.
–Have no effect on infected cells.
–Host specific, but not virus specific.
Interferon alpha and beta: Produced by virus
infected cells and diffuse to neighboring cells.
Cause uninfected cells to produce antiviral
proteins (AVPs).
Interferon gamma: Produced by lymphocytes.
Causes neutrophils to kill bacteria.
Interferons (IFNs)
Inflammatory Response
Promote changes in blood vessels that allow more
fluid, more phagocytes, and antimicrobial proteins to
enter the tissues
Functions of Inflammation
1. Destroy and remove pathogens
2. If destruction is not possible, to limit effects by
confining the pathogen and its products.
3. Repair and replace tissue damaged by pathogen
and its products.
Major events in the local inflammatory
response
Blood clot
Pin
Pathogen
Macrophage
Chemical signals
Phagocytic cells
Capillary
Blood
clotting
elements
Phagocytosis
Red blood cell
1
Chemical signals released
by activated macrophages
and mast cells at the injury
site cause nearby capillaries
to widen and become more
permeable.
2
Fluid, antimicrobial proteins,
and clotting elements move
from the blood to the site.
Clotting begins.
3
Chemokines released by various
kinds of cells attract more
phagocytic cells from the blood
to the injury site.
4 Neutrophils and macrophages
phagocytose pathogens and
cell debris at the site, and the
tissue heals.
Adaptive Immunity: Specific Defenses of the Host
Third line of defense. Involves production of
antibodies and generation of specialized
lymphocytes against specific antigens
Terminology
Antigen (Ag):
is any foreign molecule That is
specifically recognized by lymphocytes and elicits a
response from them
 Antibody (Ab): Proteins made in response to an Ag;
can combine with that Ag.
 Complement: Serum proteins that bind to Ab in
an Ag–Ab reaction; cause cell lysis
Antigenic Determinants
Antibodies recognize and react with antigenic
determinants or epitopes on an antigen
Haptens
Haptens. A hapten is a molecule too small to
stimulate antibody formation by itself. However.
when the hapten is combined with a larger
carrier molecule. usually a serum protein. the
hapten and its carrier together form a conjugate
that can stimulate an immune response.
Antibody Structure
The five classes of immunoglobulins
Lymphocytes
The vertebrate body is populated by two main
types of lymphocytes: B lymphocytes (B cells)
and T lymphocytes (T cells)
The plasma membranes of both B cells
and T cells have about 100,000 antigen
receptor that all recognize the same epitope
Lymphocyte Development
 Arise from stem cells in the bone marrow
 But they later develop into B cells or T cells, depending on
where they continue their maturation
Bone marrow
Lymphoid
stem cell
Thymus
T cell
B cell
Blood, lymph, and lymphoid tissues
(lymph nodes, spleen, and others)
T Cell Receptors
 The antigen receptors on B cells are called B cell
receptors (or membrane immunoglobulins) and the
antigen receptors on T cells are called T cell
receptors
V
V
C
C
MHC
MHC molecules : Are encoded by a family of
genes called the major histocompatibility
complex and function in signaling between
lymphocytes and cells expressing antigen.
Infected cells produce MHC molecules which
bind to antigen fragments and then are
transported to the cell surface in a process
called antigen presentation
Class I MHC molecules, found on almost all
uncleated cells of the body
Display peptide antigens to cytotoxic T cells
Infected cell
Antigen
fragment
1
1 A fragment of
foreign protein
(antigen) inside the
cell associates with
an MHC molecule
and is transported
to the cell surface.
Class I MHC
molecule
2
T cell
receptor
(a) Cytotoxic T cell
2 The combination of
MHC molecule and
antigen is recognized
by a T cell, alerting it
to the infection.
Class II MHC molecules, located mainly on dendritic cells
(antigen-presenting cells), macrophages, and B cells
Display antigens to helper T cells
Antigenpresenting
cell
Microbe
1 A fragment of
foreign protein
(antigen) inside the
cell associates with
an MHC molecule
and is transported
to the cell surface.
Antigen
fragment
1
Class II MHC
molecule
2
2 The combination of
MHC molecule and
antigen is recognized
by a T cell, alerting it
to the infection.
(b)
T cell
receptor
Helper T cell
Clonal selection theory
 States that each lymphocyte has membrane-bound
immunoglobulin receptors specific for a particular
antigen and after the receptor is engaged, a clone of
antibody-producing cells (plasma cell) and memory cells
are produced. In the secondary immune response
memory cells facilitate a faster, more efficient response
Antibody concentration
(arbitrary units)
1 Day 1: First 2 Primary
3 Day 28:
Second exposure
exposure to
response to
to antigen A; first
antigen A
antigen A
exposure to
produces antiantigen B
bodies to A
104
4 Secondary response to antigen A produces antibodies
to A; primary response to antigen B produces antibodies to B
103
Antibodies
to A
102
Antibodies
to B
101
100
0
7
14
21
28
35
Time (days)
42
49
56
Clonal selection theory (Continued)
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).
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.
Bacterium
Macrophage
Peptide
antigen
Class II
MHC
molecule
B cell
2
3
1
TCR
Clone of plasma cells
Endoplasmic
reticulum of
plasma cell
CD4
Cytokines
Helper T cell
Secreted antibody
molecules
Activated
helper T cell
Figure 43.17
Clone of memory
B cells
Humoral and cell-mediated immunity
 The humoral immune
response involves the
activation and clonal
selection of B cells,
resulting
in
the
production of secreted
antibodies
 The
cell-mediated
immune
response
involves the activation
and clonal selection of
cytotoxic T cells
Cell-mediated immune response
Humoral immune response
First exposure to antigen
Intact antigens
Antigens engulfed and
displayed by dendritic cells
Antigens displayed
by infected cells
Activate
Activate
Activate
B cell
Gives rise to
Plasma
cells
Memory
B cells
Secreted
cytokines
activate
Helper
T cell
Gives rise to
Active and
memory
helper
T cells
Secrete antibodies that defend against
pathogens and toxins in extracellular fluid
Cytotoxic
T cell
Gives rise to
Memory
cytotoxic
T cells
Active
cytotoxic
T cells
Defend against infected cells, cancer
cells, and transplanted tissues
The role of helper T cells in acquired immunity
Helper T cells produce CD4, a surface protein
that enhances their binding to class II MHC
molecule–antigen complexes on antigenpresenting cells
Activation of the helper T cell then occurs
Activated helper T cells secrete several different
cytokines that stimulate other lymphocytes
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
Peptide antigen
Dendritic
cell
Helper T cell
Cell-mediated
immunity
(attack on
infected cells)
Class II MHC
molecule
Bacterium
TCR
2
3
1 CD4
Dendritic
cell
Cytokines
2
Proliferation of the T cell, stimulated
by cytokines from both the dendritic
cell and the T cell itself, gives rise to
a clone of activated helper T cells
(not shown), all with receptors for the
same MHC–antigen complex.
B cell
3
The cells in this clone
secrete other cytokines
that help activate B cells
and cytotoxic T cells.
Humoral
immunity
(secretion of
antibodies by
plasma cells)
Cytotoxic T cells
 Bind to infected cells, cancer cells, and
transplanted tissues
Binding to a class I MHC complex on an
infected body cell
 Activates a cytotoxic T cell and differentiates it
into an active killer
1
A specific cytotoxic T cell binds to a
class I MHC–antigen complex on a
target cell via its TCR with the aid of
CD8. This interaction, along with
cytokines from helper T cells, leads to
the activation of the cytotoxic cell.
2
The activated T cell releases perforin
molecules, which form pores in the
target cell membrane, and proteolytic
enzymes (granzymes), which enter the
target cell by endocytosis.
Cytotoxic T cell
3
The granzymes initiate apoptosis within the
target cells, leading to fragmentation of the
nucleus, release of small apoptotic bodies,
and eventual cell death. The released
cytotoxic T cell can attack other target cells.
Released
cytotoxic
T cell
Perforin
Cancer
cell
Granzymes
1 TCR
2
Class I MHC
molecule
Target
cell
3
CD8
Peptide
antigen
Apoptotic
target cell
Pore
Cytotoxic
T cell
The Results of Ag-Ab Binding
Binding of antibodies to antigens
inactivates antigens by
Viral neutralization
(blocks binding to host)
and opsonization (increases
phagocytosis)
Agglutination of
antigen-bearing particles,
such as microbes
Precipitation of
soluble antigens
Complement
proteins
Bacteria
Virus
Activation of complement system
and pore formation
MAC
Pore
Soluble
antigens
Bacterium
Foreign cell
Enhances
Leads to
Phagocytosis
Cell lysis
Macrophage
Active and Passive Immunization
Active immunity: Develops naturally in response to
an infection
Can also develop following immunization, also called
vaccination
Passive immunity: Provides immediate, short-term
protection
Is conferred naturally when IgG crosses the placenta
from mother to fetus or when IgA passes from
mother to infant in breast milk
Can be conferred artificially by injecting antibodies
into a nonimmune person
The allergic response
IgE
Allergen
Histamine
1
3
2
Granule
Mast cell
1 IgE antibodies produced in 2 On subsequent exposure to the 3
Degranulation of the cell,
response to initial exposure
same allergen, IgE molecules
triggered by cross-linking of
to an allergen bind to
attached to a mast cell recogadjacent IgE molecules,
receptors or mast cells.
nize and bind the allergen.
releases histamine and other
chemicals, leading to allergy
symptoms.