15-Nov-17

Lecture PowerPoint to accompany

Foundations in
Microbiology
Ninth Edition

Talaro
Chapter 15
Adaptive, Specific
Immunity and
Immunization
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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Specific Immunity – Adaptive Line of Defense

Third line of defense – ACQUIRED
• Importance of acquired immunity?
– Children with genetic defect or AIDS
• Production of specific immunity
– Dual system of B and T lymphocytes in response to a foreign
Host Defenses molecule, called an antigen
• Immunocompetence: Ability of the body to react with a
wide spectrum of foreign substances begin to develop
• Starts during fetal development
– Child is born with a POTENTIAL to produce immunity against
millions of foreign

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• Completion: extending late puberty 4
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Specific Immunity – Adaptive Line of Defense

• Antigen:
– Any molecule that can stimulate a response by T and B cells
– Protein, polysaccharide and other components of cell/viruses
– Any exposed or released chemicals even from our own cells
• PAMPs Vs Antigens
– Both are part of microbe and can stimulate immune response
– PAMPs are shared by may types of microbes
– Antigens are unique molecules that stimulate specific immunity
• Two features that characterize specific immunity:
– SPECIFICITY – Abs 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 5 6

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Classifying Immunities
• Active immunity
– Results when a person is challenged with Ag that stimulates production of Abs
– Creates memory
– Takes time but is lasting
• Passive immunity
– Preformed antibodies are donated to an individual
– Does not create memory
– Acts immediately, but 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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Classifying Immunities Acquired

Immunity

• Natural active immunity – acquired upon

infection and recovery Natural Artificial
Immunity Immunity

• Natural passive immunity – acquired by a child

through placenta and breast milk Active Passive Active Passive
Immunity Immunity Immunity Immunity

• Artificial active immunity – acquired through

inoculation with a selected Ag

• Artificial passive immunity – administration of

immune serum or globulin
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Overview of Specific Immune Responses Development of the Immune Response System

Separate but related activities of the
specific immune response: Cell receptors or markers confer specificity and identity of a cell.
I. Development and differentiation • Major functions of receptors are:
II. Lymphocytes and antigens 1. To perceive and attach to non-self or foreign molecules
III. The challenge of B and T lymphocytes
2. To promote the recognition of self molecules
by antigens
IV. B lymphocytes and the production 3. To receive and transmit chemical messages among other cells of the
and activities of antibodies system

V. T lymphocyte responses 4. To aid in cellular development

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Major Histocompatibility Complex and its functions Lymphocyte Receptors

• Human leukocyte antigen (HLA) • Lymphocyte’s role in surveillance and recognition is a function
• Glycoprotein receptors found on all nucleated of their receptors.
cells • B-cell receptors – bind free antigens
• Plays a role in recognition of self and in rejection
Class I MHC • T-cell receptors – bind processed antigens
of foreign tissue
– Class I – markers that display unique characteristics of
self molecules and regulation of immune reactions
• required for T lymphocytes
– Class II – recognize and react with foreign antigens;
present on macrophages, dendritic and B cells (APCs) Class II MHC
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• involved in presenting antigen to T-cells 15 16
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Origin of Diversity and Specificity Origin of Diversity and Specificity

• Lymphocytes use 500 genes to produce a tremendous • In the bone marrow, lymphocytic stem cells
variety of specific receptors. differentiate into either T or B cells.

• B cells stay in the bone marrow.

• Undifferentiated lymphocytes undergo genetic mutations
and recombinations while they proliferate in the embryo. • T cells migrate to the thymus.

• Both T and B cells migrate to secondary

• Form a billion different clones with the ability to react with a
tremendous variety of antigens lymphoid tissue.

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Clonal Selection Theory Specific B-Cell Receptor: Immunoglobulin

• Lymphocyte specificity is
preprogrammed, before an antigen has Receptor genes of B cells govern immunoglobulin
(Ig) synthesis.
ever entered the system. • Large glycoproteins that serve as specific receptors
• Each genetically different type of of B cells
lymphocyte expresses a single specificity. • Composed of 4 polypeptide chains:
– 2 identical heavy chains (H)
• First introduction of each type of antigen – 2 identical light chains (L)
into the immune system selects a • Y shaped arrangement – ends of the forks formed
genetically distinct lymphocyte. by light and heavy chains contain a wide range of
variable antigen binding sites
• Causes it to expand into a clone of cells • Variable regions
that can react to that antigen • Constant regions
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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 21 22

receptor.

T-Cell Receptors for Antigen

• Formed by genetic
recombination, with variable and
constant regions

• 2 parallel polypeptide chains

• small, without humoral functions

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Contrasting Properties of B Cells and T Cells 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.

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T-Cell Maturation Characteristics of Antigen and Immunogen

• Antigen (Ag) is a substance that provokes an immune
• Maturation is directed by the thymus gland response in specific lymphocytes.
and its hormones. • Property of behaving as an antigen is antigenicity
• 7 classes of T-cell receptors termed CD - - • An immunogen is a type of antigen that actually does induce
cluster of differentiation an immune response upon introduction
• Immunogenicity
• Mature T cells migrate to lymphoid organs • Some molecules may be antigenic but no immunogenic
and occupy specific sites.
• Proteins and polypeptides, hormones, exotoxins, lipoproteins,
glycoproteins, nucleoproteins, polysaccharides
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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
• An antigen may has many antigenic
determinants.
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Special Categories of Antigens
• Alloantigens – cell surface markers of one individual that
are antigens to another of that same species
• Superantigens – potent T cell stimulators; provoke an
overwhelming response
• Allergen – antigen that provokes allergy
• Autoantigens – molecules on self tissues for which
tolerance is inadequate
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Haptens
• Foreign molecules less than 1,000 MW, called HAPTENS
• Not antigenic unless attached to a larger carrier
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Antigen Processing and Presentation
• T-cell dependent antigens must be processed by
phagocytes called antigen presenting cells (APC).
• APCs modify the antigen so it is more
immunogenic and recognizable; then the Ag is
moved to the APC surface and bound to MHC
receptor.
• Antigen presentation involves a direct
collaboration among an APC, a T helper cell and an
antigen-specific B or T cell.
– IL-1 is secreted by APC to activate TH cells.
– IL-2 is produced by TH to activate B and other T cells. 32
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B-cell Activation and Antibody Production

1. Clonal selection and binding of antigen
2. Instruction by chemical mediators
3. Signal is transmitted internally to the B-cell nucleus
4. B cells enter the cell cycle in preparation for mitosis and
clonal expansion.
5. & 6. Clonal Expansion (Memory cells and plasma cells)
7. Antibody production and secretion (2000 Abs / sec)
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Antibody Structure and Functions

• Immunoglobulins
• Large Y-shaped protein
• Consist of 4 polypeptide chains
• Contains 2 identical fragments (Fabs) with ends that bind to
specific antigen
• Fc (Crystallizable fragment) binds to various cells and
molecules of the immune system.
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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 (opsonins) 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 a bacterial exotoxin.

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Functions of the Fc Fragment

• Fc fragment binds to cells – macrophages, neutrophils,

eosinophils, mast cells, basophils, and lymphocytes.
• Fabs to antigen and Fc to phagocytes
• Fc region of allergy antibody (IgE) binds to basophils and mast
cells that leads to release of allergic mediators
• Accessory molecules on Igs:
– J chain (IgA and IgM)
– secretory component (IgA)
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Classes of Immunoglobulins
5 classes / isotopes of immunoglobulins (Ig):
1. IgG (Gamma)

2. IgA (Alpha)

3. IgM (Mu)

4. IgD (Delta)

5. IgE (Epsilon)

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Antibodies in Serum

• Serum containing specific antibodies ANTISERUM

• If separated by electrophoresis, globulin separates into 4
bands:
• Alpha-1 (α-1), alpha-2 (α-2), beta (β), and gamma (γ)
• Most are antibodies.
• γ is composed primarily of IgG; β and α-2 are a mixture of
IgG, IgA, and IgM.
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Primary and Secondary Responses to Antigens 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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Monoclonal Antibodies

• Antiserum: Polyclonal antibodies

• 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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T Cells & Cell Mediated Immunity

• Cell mediated immunity requires 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.

• T cell action vs B cell action

• Sensitized T cells proliferate into long-lasting memory T cells.

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Types of T cells

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Active immunity Vs Passive Immunity Acquired

Immunity

• Active immunity:
i. An essential attribute of an immunocompetent individual Natural Artificial
Immunity Immunity
ii. It creates a memory
iii. It requires several days to develop
iv. It can last for a relatively long Active Passive Active Passive
Immunity Immunity Immunity Immunity
• Passive immunity:
i. Lack of memory for the original antigen
ii. No production of new antibodies against that disease
iii. Immediate onset of protection
iv. Short-term effectiveness

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Immunization: Manipulating Immunity Vaccination

• 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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• 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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Live Attenuated Cells or Viruses

Killed or Inactivated Vaccines • Process that substantially lessens or negates the virulence of viruses or
bacteria – eliminates virulence factors
• Cultivate the desired strain, treat it with formalin or • Attenuation methods include
some other agent that kills the agent but does not – long-term cultivation, selection of mutant strains that grow at colder temperatures
(cold mutants), passage of the microbe through unnatural hosts or tissue culture, and
destroy its antigenicity. removal of virulence genes.
• Advantages of live preparations are:
• Often require a larger dose and more boosters to be – organisms can multiply and produce infection (but not disease) like the natural
organism
effective
– They confer long-lasting protection.
– usually require fewer doses and boosters
• Disadvantages include:
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– require special storage, can be transmitted to other people, can conceivably mutate 62
back to virulent strain

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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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, using vaccinia virus as carrier

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Genetically Engineered Vaccines 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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Route of Administration ad Side Effects Herd Immunity

• Most administered by injection; few oral, nasal • Immune individuals will not harbor it, reducing the
• Some vaccines require adjuvant to enhance immunogenicity and
occurrence of pathogens – herd immunity.
prolong retention of antigen.
• Less likely that an unimmunized person will encounter the
• Stringent requirements for development of vaccines
pathogen
• More benefit than risk

• Possible side effects include local reaction at injection site, fever, • Indirect protection of unimmunized individuals
allergies; rarely back-mutation to a virulent strain, neurological effects.

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