Transcript Foundations in Microbiology

Lecture PowerPoint to accompany
Foundations in
Microbiology
Sixth Edition
Talaro
Chapter 15
Adaptive, Specific
Immunity and
Immunization
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Specific Immunity – Adaptive Line
of Defense
Third line of defense – acquired
• Production of specific antibodies by dual system of B
and T lymphocytes in response to an encounter with
a foreign molecule, called an antigen
• 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
2
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
3
• 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 immune serum or globulin
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5
Overview of Specific Immune
Responses
Separate but related activities of the specific immune
response:
• Development and differentiation of the immune
system
• Lymphocytes and antigens
• The challenge of B and T lymphocytes by antigens
• B lymphocytes and the production and activities of
antibodies
• T lymphocyte responses
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7
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
8
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 – receptors that recognize and react with
foreign antigens; located primarily on macrophages
and B cells
• involved in presenting antigen to T-cells
10
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
11
Clonal Selection Theory
• Lymphocytes use 500 genes to produce a
tremendous variety of specific receptors.
• Undifferentiated lymphocytes undergo
genetic mutations and recombinations while
they proliferate in the embryo.
• Form a billion different clones with the
ability to react with a tremendous variety of
antigens
12
• 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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• Lymphocyte specificity is preprogrammed,
existing in the genetic makeup before an antigen
has ever entered the system.
• Each genetically different type of lymphocyte
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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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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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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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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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
• Maturation is directed by the thymus gland
and its hormones.
• 7 classes of T-cell receptors termed CD cluster of differentiation
• Mature T cells migrate to lymphoid organs
and occupy specific sites.
24
Entrance and Processing of Antigens
and Clonal Selection
• Antigen (Ag) is a substance that provokes an
immune response in specific lymphocytes.
• Also called an immunogen
• Property of behaving as an antigen is
antigenicity
25
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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• Foreign molecules less than 1,000 MW,
called haptens
• Not antigenic unless attached to a larger
carrier
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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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Antigen Processing and Presentation
to Lymphocytes
• 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.
– 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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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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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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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 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.
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Classes of Immunoglobulins
5 classes of immunoglobulins (Ig):
1.
2.
3.
4.
5.
IgG
IgA
IgM
IgD
IgE
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Antibodies in Serum
• 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 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
• 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 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.
49
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 improving
opsonization; 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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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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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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Route of Administration ad 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 an nonimmunized person
will encounter the pathogen
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