Foundations in
Microbiology Seventh Edition
Chapter 15
Adaptive, Specific Immunity and Immunization
Lecture PowerPoint to accompany
Talaro
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15.1 Specific Immunity – Adaptive
Line of Defense
Third line of defense – acquired
• Dual System of B and T lymphocytes
– Immunocompetence
• Antigen – Molecules that stimulate a response by T and B cells
• Two features that characterize specific immunity:
– Specificity – antibodies produced, function only against the antigen that they were produced in response to
– Memory – lymphocytes are programmed to “recall” their first encounter with an antigen and respond rapidly to subsequent encounters
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Classifying Immunities
• Active immunity – results when a person is
challenged with antigen that stimulates production of
antibodies; creates memory, takes time, and is lasting
• Passive immunity – preformed antibodies are
donated to an individual; does not create memory, acts
immediately, and is short term
• Natural immunity – acquired as part of normal life
experiences
• Artificial immunity – acquired through a medical
procedure such as a vaccine
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• Natural active immunity – acquired upon
infection and recovery
• Natural passive immunity – acquired by a child
through placenta and breast milk
• Artificial active immunity – acquired through
inoculation with a selected Ag
• Artificial passive immunity – administration of a
preparation containing specific antibodies
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Figure 15.1
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Overview of Specific Immune
Responses
Separate but related activities of the specific immune response:
• Development and differentiation of the immune system
• Lymphocytes and antigen processing
• The cooperation between lymphocytes during antigen presentation
• B lymphocytes and the production and actions of antibodies
• T lymphocyte responses
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Figure 15.2 (I)
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Figure 15.2 (II-V)
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15.2 Development of the Immune
Response System
Cell receptors or markers confer specificity and identity of a cell
• Major functions of receptors are:
1. To perceive and attach to nonself or foreign molecules
2. To promote the recognition of self molecules
3. To receive and transmit chemical messages among other cells of the system
4. To aid in cellular development
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Major Histocompatibility Complex (MHC)
• Receptors found on all cells except RBCs
• Also known as human leukocyte antigen
(HLA)
• Plays a role in recognition of self by the
immune system and in rejection of foreign
tissue
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Functions of MHC
• Genes for MHC clustered in a multigene
complex:
– Class I – markers that display unique characteristics
of self molecules and regulation of immune
reactions
• Required for T lymphocytes
– Class II – regulatory receptors found on
macrophages, dendritic cells, and B cells
• Involved in presenting antigen to T-cells
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Figure 15.3
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Lymphocyte Receptors
• Lymphocyte’s role in surveillance and
recognition is a function of their receptors
• B-cell receptors – bind free antigens
• T-cell receptors – bind processed antigens
together with the MHC molecules on the
cells that present antigens to them
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Clonal Selection Theory
• Lymphocytes use 500 genes to produce a tremendous variety of specific receptors
• Undifferentiated lymphocytes undergo a continuous series of divisions and genetic changes that generate millions of different cell types
• Each cell has a particular/unique receptor specificity
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• In the bone marrow, lymphocytic stem cells
differentiate into either T or B cells
• B cells stay in the bone marrow
• T cells migrate to the thymus
• Both T and B cells migrate to secondary
lymphoid tissue
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Figure 15.4
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• Lymphocyte specificity is preprogrammed, existing in the genetic makeup before an antigen has ever entered the system
• Each genetically different type of lymphocyte (clone) expresses a single specificity
• First introduction of each type of antigen into the immune system selects a genetically distinct lymphocyte
• Causes it to expand into a clone of cells that can react to that antigen
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Figure 15.5
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Specific B-Cell Receptor:
Immunoglobulin
Receptor genes of B cells govern immunoglobulin (Ig) synthesis
• Large glycoproteins that serve as specific receptors of B cells
• Composed of 4 polypeptide chains: – 2 identical heavy chains (H)
– 2 identical light chains (L)
• Y shaped arrangement – ends of the forks formed by light and heavy chains contain a wide range of variable antigen binding sites
• Variable regions
• Constant regions
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Figure 15.6 (a)
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Development of Receptors
• Immunoglobulin genes lie on 3 different chromosomes
• Undifferentiated lymphocyte has 150 different genes
for the variable region of light chains and 250 for the
variable region and diversity region of the heavy chain
• During development, recombination causes only the
selected V and D genes to be active in the mature cell
• Once synthesized, immunoglobulin is transported to
cell membrane and inserted there to act as a receptor
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Figure 15.6 (b)
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T-Cell Receptors for Antigen
• Formed by genetic recombination, with
variable and constant regions
• 2 parallel polypeptide chains
• Small, not secreted
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Figure 15.7 Proposed structure of the T-cell receptor
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15.3 Lymphocyte Responses and
Antigens
• B-cell maturation
– Directed by bone marrow sites that harbor stromal cells,
which nurture the lymphocyte stem cells and provide
hormonal signals
– Millions of distinct B cells develop and “home” to
specific sites in the lymph nodes, spleen, and GALT
– Come into contact with antigens throughout life
– Have immunoglobulin as surface receptors for antigens
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Lymphocyte Responses and
Antigens
• T-cell maturation
– Maturation is directed by the thymus gland and
its hormones
– Different classes of T-cell receptors termed CD
- Cluster of differentiation
• CD4 and CD8
– Mature T cells migrate to lymphoid organs
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Entrance and Processing of Antigens
and Clonal Selection
• Antigen (Ag) is a substance that provokes an
immune response in specific lymphocytes
• Property of behaving as an antigen is
antigenicity
– Foreignness, size, shape, and accessibility
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Characteristics of Antigens
• Perceived as foreign, not a normal constituent of the body
• Foreign cells and large complex molecules over 10,000 MW are most antigenic
• Antigenic determinant, epitope – small molecular group that is recognized by lymphocytes
• Antigen has many antigenic determinants
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Figure 15.8
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• Haptens – small foreign molecules that
consist only of a determinant group
– Not antigenic unless attached to a larger carrier
• Carrier group contributes to the size of the complex
and enhances the orientation of the antigen
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Figure 15.9 The hapten-carrier phenomenon
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Special Categories of Antigens
• Alloantigens – cell surface markers and
molecules that occur in some members of the
same species but not in others
• Superantigens – potent T cell stimulators;
provoke an overwhelming response
• Allergen – antigen that evokes allergic
reactions
• Autoantigens – molecules on self tissues for
which tolerance is inadequate
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15.4 Cooperation in Immune
Reactions to Antigens
• The basis for most immune responses is the
encounter between antigens and white blood
cells
• Lymph nodes and spleen concentrate the
antigens and circulate them so they will
come into contact with lymphocytes
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Antigen Processing and Presentation
to Lymphocytes
• T-cell dependent antigens must be processed by
phagocytes called antigen presenting cells (APC)
• APCs modify the antigen; then the Ag is moved to the
APC surface and bound to MHC receptor
• Antigen presentation involves a direct collaboration
among an APC, and a T helper cell
– Interleukin-1 is secreted by APC to activate TH cells
– Interleukin-2 is produced by TH to activate B and other T
cells
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Figure 15.10
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15.5 B Cell Responses
• B-cell activation and antibody production
– Once B cells process the Ag, interact with TH
cells, and are stimulated by growth and
differentiation factors, they enter the cell cycle
in preparation for mitosis and clonal expansion
– Divisions give rise to plasma cells that secrete
antibodies and memory cells that can react to
the same antigen later
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Figure 15.11
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Antibody Structure and Functions
• Immunoglobulins
• Large Y-shaped protein
• Consist of 4 polypeptide chains
• Contains 2 identical fragments (Fab) with
ends that bind to specific antigen
• Fc binds to various cells and molecules of
the immune system
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Figure 15.12
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Figure 15.13
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Antibody-Antigen Interactions
Principle antibody activity is to unite with the Ag, to call attention to, or neutralize the Ag for which it was formed
• Opsonization – process of coating microorganisms or other particles with specific antibodies so they are more readily recognized by phagocytes
• Agglutination – Ab aggregation; cross-linking cells or particles into large clumps
• Neutralization – Abs fill the surface receptors on a virus or the active site on a microbial enzyme to prevent it from attaching – Antitoxins are a special type of Ab that neutralize bacterial
exotoxins
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Figure 15.14
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Functions of the Fc Fragment
• Fc fragment binds to cells – macrophages,
neutrophils, eosinophils, mast cells,
basophils, and lymphocytes
• Certain antibodies have regions on the Fc
portion for fixing complement
– Binding of Fc may cause release of cytokines
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Classes of Immunoglobulins 5 classes of immunoglobulins (Ig):
1. IgG – monomer, produced by plasma cells (primary response) and memory cells (secondary), most prevalent
2. IgA – monomer circulates in blood, dimer in mucous and serous secretions
3. IgM – five monomers, first class synthesized following Ag encounter
4. IgD – monomer, serves as a receptor for antigen on B cells
5. IgE – Involved in allergic responses and parasitic worm infections
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Antibodies in Serum
• If separated by electrophoresis, globulin
separates into 4 bands:
– Alpha-1 (α1), alpha-2 (α2), beta (β), and gamma
(γ)
• Most are antibodies
• γ is composed primarily of IgG; β and α2
are a mixture of IgG, IgA, and IgM
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Figure 15.15 Pattern of human serum after electrophoresis
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Primary and Secondary
Responses to Antigens
• Primary response – after first exposure to an
Ag immune system produces IgM and a gradual
increase in Ab titer (concentration of antibodies)
with the production of IgG
• Secondary response – after second contact with
the same Ag, immune system produces a more
rapid, stronger response due to memory cells
– Anamnestic response
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Figure 15.16
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Monoclonal Antibodies
• Originate from a single clone and have a
single specificity for antigen
• Pure preparation of antibody
• Single specificity antibodies formed by
fusing a mouse B cell with a cancer cell
• Used in diagnosis of disease, identification
of microbes and therapy
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Insight 15.2
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Insight 15.2
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15.6 T Cells & Cell-Mediated
Immunity
• Cell-mediated immunity requires the direct
involvement of T lymphocytes
• T cells act directly against Ag and foreign cells
when presented in association with an MHC
carrier
• T cells secrete cytokines that act on other cells
• Sensitized T cells proliferate into long-lasting
memory T cells
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Types of T Cells
1. T helper cells (CD4 or TH) most prevalent type of T cell; regulate immune reaction to antigens, including other T and B cells; also involved in activating macrophages and increasing phagocytosis; differentiate into T helper 1 (TH1) cells or T helper 2 (TH2) cells
2. Cytotoxic T cells (CD8 or TC) destroy foreign or abnormal cells by secreting perforins that lyse cells
3. Natural killer cells – lack specificity; circulate through the spleen, blood, and lungs
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Figure 15.17
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T Cells and Superantigens
• Reaction has drastic consequences
• Superantigens are a form of a virulence factor
• Provoke overwhelming immune responses by
large numbers of T cells
– Release of cytokines
– Blood vessel damage
– Toxic shock
– Multiorgan damage
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15.7 Immunization: Manipulating
Immunity
• Passive immunity – immune serum globulin
(ISG), gamma globulin, contains immunoglobulin
extracted from pooled blood; immunotherapy
• Treatment of choice in preventing measles and
hepatitis A and in replacing antibodies in
immunodeficient patients
• Sera produced in horses are available for
diphtheria, botulism, and spider and snake bites
• Acts immediately; protection lasts 2-3 months
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Vaccination
• Artificial active immunity – deliberately
exposing a person to material that is
antigenic but not pathogenic
• Principle is to stimulate a primary and
secondary anamnestic response to prepare
the immune system for future exposure to a
virulent pathogen
• Response to a future exposure will be
immediate, powerful, and sustained
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Vaccine Preparation
Most vaccines are prepared from:
1. Killed whole cells or inactivated viruses
2. Live, attenuated cells or viruses
3. Antigenic molecules derived from bacterial
cells or viruses
4. Genetically engineered microbes or microbial
agents
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Killed or Inactivated Vaccines
• Cultivate the desired strain, treat it with
formalin or some other agent that kills the
agent but does not destroy its antigenicity
• Often require a larger dose and more
boosters to be effective
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Live Attenuated Cells or Viruses
• Process that substantially lessens or negates the
virulence of viruses or bacteria – eliminates virulence
factors
• Advantages of live preparations are:
– Organisms can multiply and produce infection (but not
disease) like the natural organism
– They confer long-lasting protection
– Usually require fewer doses and boosters
• Disadvantages include:
– Require special storage, can be transmitted to other people,
can conceivably mutate back to virulent strain
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Antigenic Molecules
• Acellular or subcellular vaccines (subunit –
if a virus)
• Exact antigenic determinants can be used when
known:
– Capsules – pneumococcus, meningococcus
– Surface protein – anthrax, hepatitis B
– Exotoxins – diphtheria, tetanus
• Antigen can be taken from cultures, produced
by genetic engineering, or synthesized
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Figure 15.19
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Genetically Engineered Vaccines
• Insert genes for pathogen’s antigen into plasmid vector, and clone them in an appropriate host
– Stimulated the clone host to synthesize and secrete a protein product (antigen), harvest and purify the protein – hepatitis
• “Trojan horse” vaccine – genetic material from a pathogen is inserted into a live carrier nonpathogen; the recombinant expresses the foreign genes
– Experimental vaccines for AIDS, herpes simplex 2, leprosy, tuberculosis
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Genetically Engineered Vaccines
• DNA vaccines – create recombination by inserting
microbial DNA into plasmid vector
• Human cells will pick up the plasmid and express
the microbial DNA as proteins causing B and T
cells to respond, be sensitized, and form memory
cells
– Experimental vaccines for Lyme disease, hepatitis C,
herpes simplex, influenza, tuberculosis, malaria
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Figure 15.20
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Route of Administration and
Side Effects
• Most administered by injection; few oral, nasal
• Some vaccines require adjuvant to enhance
immunogenicity and prolong retention of antigen
• Stringent requirements for development of vaccines
• More benefit than risk
• Possible side effects include local reaction at injection
site, fever, allergies; rarely back-mutation to a
virulent strain, neurological effects
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Herd Immunity
• Immune individuals will not harbor it,
reducing the occurrence of pathogens –
herd immunity
• Less likely that a nonimmunized person will
encounter the pathogen
