Chapter 17
Specific Defenses of the Host:
The Immune Response
Specific Defenses of the Host: The Immune
Response
•Acquired immunity - Developed during an individual's lifetime
Distinct Cells in Adaptive Immune System
• Lymphocytes (B cells, T cells)
– Determining specificity of immunity
• Specialized epithelial and stromal cells
– Providing anatomic environment
• APC (antigen presenting cells) - antigen presentation –
mediation of immunologic functions
– Monocyte/macrophage
– Dendritic cells
– Natural killer cells and other members of myeloid cells
(leukocyte that is not lymphocyte)
Blood cells differentiation
Dual Nature of the Adaptive Immune System
• Red bone marrow stem cells produce
lymphocytes
1. B cells -Humoral immunity
–Some lymphocytes that mature in red
bone marrow become B cells.
– Antibody production
– Antibodies are found in serum and lymph.
2. T cells - Cell-mediated immunity
– Some lymphocytes migrate through the
thymus become T cells (T-lymphocytes)
– Activation of macrophages, natural killer
cells (NK)
– Antigen-specific cytotoxic T-lymphocytes
– Release of various cytokines in response to
an antigen.
Dual Nature of the Adaptive Immune System
Immune system
• The most important nature of immune system is
self/non-self recognition.
– Self/non-self recognition is achieved by having every cell of the body
displays an individual specific marker.
• Any cell not displaying this marker is treated as non-self and attacked.
• The process is so effective that undigested proteins are treated as
antigens.
Major Histocompatibility Complex (MHC)
• The major histocompatibility complex (MHC) is a set of cell
surface molecules (proteins) encoded by a large gene family in all
vertebrates.
• On the cell surface, each MHC molecule displays a molecular
fraction, called epitope, of a protein.
– The presented antigen can be either self or nonself.
– MHC population on the cell membrane gives information about the balance of
proteins within the cell.
• MHC molecules mediate interactions of leukocytes, with other
leukocytes or body cells.
• In humans, MHC is also called human leukocyte antigen (HLA).
•MHC proteins transfer information about proteins within a cell to the
cell surface
Humoral Immunity
• An antigen (Ag), or immunogen, is a chemical substance that
when introduced into the body stimulates the production of
specific antibodies (antibody generation)
• Antibody (Ab) – A protein produced by B cells in response to
recognition of an antigen
– Protein made in response to exposure to bacteria and other pathogens,
toxins, plant pollen and red blood cells that the body recognized as alien, or
non-self.
– Capable of combining specifically with that antigen.
• Highly specific recognition of foreign antigens (non-self)
– A vast universe of distinct antigenic specificities
• Mechanisms for elimination of microbes bearing such antigens
• Immunologic memory
• Tolerance of self-antigens
The Nature of Antigens
• As a rule, antigens are proteins or large polysaccharides.
– Only large molecules, infectious agents, or insoluble foreign matter can elicit an
immune response in the body.)
• A hapten is a small molecule that cannot cause the formation of
antibodies unless combined with a carrier molecule;
1. Can elicit an immune response only when attached to a large carrier such as a
protein.
• The carrier may be one that also does not elicit an immune response by itself.
2. Once the body has generated antibodies to a hapten-carrier, the
small-molecule hapten may also be able to bind to the antibody
independent of the carrier molecule.
The Nature of Antibodies
• Antibody is a large Y-shaped protein an immunoglobulin (Ig)
• They are secreted form of the B-cell receptor
• The antibody recognizes a unique part of the antigen - epitope ( a
portion of a molecule to which an antibody binds) or antigenic
determinants.
Figure 17.3
Antibody Structure
• The Ig monomer consists of four paired polypeptide chains connected by disulfide
bonds.
– Two identical heavy chains
– Two identical light chains
• Each chain has two domains: one constant domain (C) and one variable domain (V)
• The constant domains or C domains of the heavy and light chains make up the C
region
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The type of heavy chain present defines the class of antibody (IgA, IgD, IgE, IgG, and
IgM)
• The variable or V domains of the heavy and light chains together make up the V
region of the antibody and confer on it the ability to bind specific antigen
epitope.
Figure 17.5a-c
Ag-Ab Binding
• Antigen-antibody complex
– Affinity - the strength of the reaction between a single
antigenic determinant and a single antibody
– Specificity - Specificity refers to the ability of an
individual antibody combining site (V) to react with only
one antigenic determinant or the ability of a population of
antibody molecules to react with only one antigen.
Figure 17.9
IgG antibodies
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Monomer
80% of serum antibodies
Fix complement
In blood, lymph, intestine
Cross placenta
Enhance phagocytosis; neutralize
toxins & viruses; protects fetus &
newborn
• Half-life = 23 days
IgM antibodies
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Pentamer
5-10% of serum antibodies
Fix complement
In blood, lymph, on B cells
Agglutinates microbes; first
Ab produced in response to
infection
• Involved in response to ABO
blood group
• Half-life = 5 days
IgA antibodies
• Dimer
• 10-15% of serum antibodies
• In secretions, mucus, salvia, tears,
and breast milk
• Mucosal protection
• Half-life = 6 days
IgD antibodies
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Monomer
0.2% of serum antibodies
In blood, lymph, on B cells
On the surface of B cells,
initiate immune response
• Half-life = 3 days
IgE antibodies
• Monomer
• 0.002% of serum antibodies
• On mast cells and basophils,
in blood
• Allergic reactions; lysis of
parasitic worms
• Half-life = 2 days
Clonal Selection
• Hematopoietic stem cell differentiate to produce naive B
lymphocytes
– Each lymphocyte bears a single type of receptor with a unique specificity - can
recognizes only one type of antigen epitope
• Naive cells mature into inactive B lymphocytes.
1. Most of them will never
encounter a matching foreign
antigen
2. Those that get in contact with
a matching antigen are activated
and produce many clones
of themselves – plasma cells that
produce antibodies
3. Some become memory cells
Figure 17.5 - Overview
Clonal deletion
• Body doesn't make Ab against self, self-tolerance
• Clonal deletion -the process of destroying B and T cells after they
have expressed receptors for self-antigens and before they develop
into fully immunocompetent lymphocytes
Activation of B cells to produce antibodies
• The first exposure to a microbe or an antigen, either by infection
or by vaccination, leads to the activation of B lymphocytes
plasma cells
antibody producing cells
1. T-dependent antigens
– Antigens which require
participation of T cells
for immune response
2. T independent antigens
Figure 17.4 - Overview
– Antigens that stimulate B cells without help of T cells
• Repeating subunits – polysaccharides or
lipopolysaccharides
• Can bind multiple receptors of the B-cell
Figure 17.6
Cell-Mediated Immunity
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Red bone marrow stem cells give rise to T cells
• mature in the thymus gland
• migrate to lymphoid tissues
• An antigen must be processed by an antigen-presenting
cell and positioned on the surface of the APC (antigen
presenting cell).
• T cells recognize antigens in association with MHC on
an APC
Antigen-Presenting Cells
APCs - B cells, Dendritic cells and Macrophages.
Figure 17.13
Figure 17.12
Classes of T Cells
• T cells are classified according to their functions and cell-surface
glycoproteins called CDs.
– Helper T Cells
– Cytotoxic T Cells
– Regulatory T Cells
Helper T Cells
• Helper T cells, or CD4 cells, are activated by MHC class II on
APCs.
• After binding an APC, CD4 cells secrete cytokines that activate
other T cells and B cells.
• TH1 cells activate cells involved in cellular immunity.
• TH2 cells are associated with allergic reactions and parasitic
infections.
Helper T Cells
Figure 17.13
Cytotoxic T Cells
• Cytotoxic T cells (TC), or CD8 cells, are activated by
endogenous antigens and MHC class I on a target cell and are
transformed into a CTL (cytotoxic T lymphocyte).
• CTLs lyse the target cell or induce apoptosis in the target cell.
Cell-mediated Cytotoxicity
Figure 17.10 - Overview
Figure 17.14
Apoptosis
• Programmed cell death
is also called apoptosis
• Cytotoxic T cells are
able to directly induce
apoptosis in cells
– opening up pores in the
target's membrane and
releasing chemicals
which bypass the normal
apoptotic pathway.
Regulatory T Cells
• Regulatory T cells (TR) are vital for keeping the immune system in
check, helping to avoid immune-mediated pathology and
unrestricted expansion of effector T cell
– Suppress other T cells when Ag no longer present
– Involved in the checkpoints to prevent immune responses to self.
T cells compete
for same antigen
T cells compete for
cytokine signals
Cytotoxic
T cell
Mature
dendritic
cell
Regulator
y T cell
Regulator
y T cells
Proliferation
Extracellular Killing by the Immune System
• Natural killer (NK) cells lyse virus-infected and tumor cells. They
are not immunologically specific.
Antibody-Dependent Cell-Mediated Cytotoxicity
• In ADCC, NK cells and macrophages lyse antibody-coated cells.
Cytokines: Chemical Messengers of Immunity Cells
• Cells of the immune system communicate with each other by
means of chemicals called cytokines.
– Interleukins (IL) are cytokines that serve as communicators
between leukocytes.
– Chemokines cause leukocytes to move to the site of infection.
– Gamma Interferon activates macrophages
Summary
Immunological Memory
• The amount of antibody in serum is called the antibody titer.
• The response of the body to the first contact with an antigen is
called the primary response. It is characterized by the appearance
of IgM followed by IgG.
• Subsequent contact with
the same antigen results in a
very high antibody titer and
is called the secondary,
anamnestic, or memory response.
– Memory B cells
– The antibodies are primarily IgG
Antiserum
• Serum containing antibodies is often called antiserum.
• When serum is separated by gel electrophoresis,
antibodies are found in the gamma fraction of the serum
and are termed immune serum globulin, or gamma
globulin
Figure 17.17
Types of adaptive Immunity
• Acquired active immunity;
– resulting from infection
– naturally this type of immunity may be long-lasting.
• Acquired passive immunity
– Antibodies transferred from a mother to a fetus (trans placental transfer)
or to a newborn in colostrum results in naturally in the newborn;
– can last up to a few months.
• Artificially acquired active immunity
– Immunity resulting from vaccination
– can be long-lasting.
• Artificially acquired passive immunity
– refers to humoral antibodies acquired by injection;
– can last for a few weeks.
Learning objectives
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Differentiate between humoral and cellular immunity.
Define antigen, epitope, and hapten.
Explain the function of antibodies and describe their structural and chemical
characteristics.
Name one function for each of the five classes of antibodies.
Compare and contrast T-dependent antigens and T-independent antigens.
Differentiate between plasma cell and memory cell.
Describe clonal selection.
Describe four outcomes of an antigen-antibody reaction. Differentiate between
helper T, cytotoxic T, and regulatory T cells.
Differentiate between TH1 and TH2 cells.
Define apoptosis.
Define antigen-presenting cell.
Describe the function of natural killer cells.
Describe the role of antibodies and natural killer cells in antibody-dependent
cell-mediated cytotoxicity.
Identify at least one function of each of the following: cytokines, interleukins,
interferons.
Distinguish a primary from a secondary immune response.
Contrast the four types of adaptive immunity.