Transcript Specific Immunity and Immunization

Microbiology: A Systems
Approach, 2nd ed.
Chapter 15: Host Defenses IISpecific Immunity and Immunization
15.1 Specific Immunity: The Third and
Final Line of Defense
• Not innate, but adaptive
• Acquired only after an immunizing event such as an
infection
• Immunocompetence: the ability of the body to react
with myriad foreign substances
– Development of B and T lymphocytes
– The lymphocytes become specialized for reacting only to
one specific antigen or immunogen
• Antigens stimulate a response by T and B cells
• Two characterizing features of the third line of defense
– Specificity
– Memory
5 Main Stages of Immunologic
Development and Interaction
• Lymphocyte development and differentiation
• The presentation of antigens
• The challenge of B and T lymphocytes by
antigens
• B lymphocytes and the production and
activities of antibodies
• T lymphocyte responses
Figure 15.1
15.2 An Overview of Specific Immune
Responses
• Development of the Dual Lymphocyte System
– All lymphocytes arise from the same basic stem
cell type
– Final maturation of B cells occurs in specialized
bone marrow sites
– Maturation of T cells occurs in the thymus
– Both cell types then migrate to separate areas in
the lymphoid organs
Entrance and Presentation of Antigens
and Clonal Selection
• Foreign cells cross the first line of defense and
enter the tissue
• Phagocytes migrate to the site
• Macrophages ingest the pathogen and induce an
inflammatory response if appropriate
• Dendritic cells ingest the antigen and migrate to
the nearest lymphoid organ
– Process and present antigen to T lymphocytes
• Pieces of antigen drain into lymph nodes
– Activate B cells
Activation of Lymphocytes and Clonal
Expansion
• When challenged by antigen, B and T cells
proliferate and differentiate
• This creates a clone (group of genetically
identical cells)
• Some become memory cells
Products of B Lymphocytes: Antibody
Structure and Functions
• Progeny of dividing B-cell clone are called
plasma cells
• Programmed to synthesize and secrete
antibodies into tissue fluid and blood
• When antibodies attach to antigen, the
antigen is marked for destruction or
neutralization
• Humoral immunity
How T Cells Respond to Antigen: CellMediated Immunity (CMI)
• When activated by antigen, T cell gives rise to
one of three different types of progeny
– TH1 cells- activate macrophages and help activate
TC cells
– TH2 cells- assist B-cell processes
– TC cells- lead to the destruction of infected host
cells and other “foreign” cells
Receptors on Cell Surfaces Involved in
Recognition of Self and Nonself
• Major functions of immune system receptors:
– Attachment to nonself or foreign antigens
– Binding to cell surface receptors that indicate self,
such as MHC molecules
– Receiving and transmitting chemical messages to
coordinate the response
– Aiding in cellular development
Major Histocompatibility Complex
• Set of genes that codes for human cell receptors
• Gives rise to a series of glycoproteins (MHC molecules)
found on all cells except red blood cells
• Also known as human leukocyte antigen (HLA) system
• Three classes of MHC genes identified:
– Class I genes- code for markers that display unique
characteristics of self
– Class II genes- code for immune regulatory receptors found on
macrophages, dendritic cells, and B cells; and are involved in
presenting antigens to T cells during cooperative immune
reactions
– Class III genes- encode proteins involved with the complement
system
Figure 15.2
Lymphocyte Receptors and Specificity
to Antigen
• B cells have receptors that bind antigens
• T cells have receptors that bind processed
antigens plus MHC molecules on the cells that
present antigens to them
The Origin of Diversity and Specificity
of the Immune Response
• The Clonal Selection Theory and Lymphocyte
Development
– Early undifferentiated lymphocytes in the embryo,
fetus, and adult bone marrow undergo a
continuous series of divisions and genetic changes
– Generates hundreds of millions of different types
of B and T cells
Figure 15.3
Summary of the Mechanism
• Stem cells in bone marrow can become
granulocytes, monocytes, or lymphocytes
• Lymphocytic cells become either T cells or B cells
• Cells destined to become B cells stay in bone
marrow
• T cells migrate to the thymus where they build
their unique antigen receptor
• B and T cells then migrate to secondary lymphoid
tissues
Figure 15.4
Proliferative Stage of Development
• Does not require the actual presence of foreign
antigens
• By the time T and B cells reach the lymphoid
tissues, each one is equipped to respond to a
single unique antigen
• This diversity is generated by rearrangements of
the gene segments that code for the
proteinaceous antigen receptors on the T and B
cells
• Each genetically unique line of lymphocytes
arising from these recombinations
Clonal Selection and Expansion
• Second stage of development
• Requires stimulation by an antigen
• Antigen contact with a lymphocyte stimulates
the clone to undergo mitotic divisions
Two Important Generalities From the
Clonal Selection Theory
• Lymphocyte specificity is preprogrammed,
existing in the genetic makeup before an
antigen has ever entered the tissues
• Each genetically distinct lymphocyte expresses
only a single specificity and can react to only
one type of antigen
Preventing Reactions to Self
• Any clones that react to self are destroyed
during development through clonal deletion
• Autoimmune diseases are thought to be
caused by the loss of immune tolerance to self
The Specific B-Cell Receptor: An
Immunoglobulin Molecule
• The receptor genes that undergo recombination are
those governing immunoglobulin (Ig) synthesis
• Igs: large glycoprotein molecules that serve as the
antigen receptors of B cells and as antibodies when
secreted
• Y-shaped arrangement
• Ends of forks contain pockets called the antigen
binding sites
– Can be highly variable in shape to fit a wide range of
antigens
– Variable regions (V)
Figure 15.5
T-Cell Receptors
• Belongs to the same protein family as the Bcell receptor
• Relatively small and never secreted
Figure 15.6
15.3 The Lymphocyte Response
System in Depth
• Specific Events in B-Cell Maturation
– Bone marrow sites harbor stromal cells
– Stromal cells nurture the lymphocyte stem cells
and provide chemical signals that initiate B-cell
development
– B cells circulate through the blood, “homing” to
specific sites in lymph nodes, spleen, and GALT
– Adhere to specific binding molecules where they
come into contact with antigens
Specific Events in T-Cell Maturation
• Directed by the thymus gland and its hormones
• Mature T lymphocytes express either CD4 or CD8
coreceptors
– CD4 binds to MHC class II, expressed on T helper cells
– CD8 binds to MHC class I, found on cytotoxic T cells
• Constantly circulate between the lymphatic and
general circulatory system, migrating to specific
T-cell areas of the lymph nodes and spleen
Entrance and Processing of Antigens
and Clonal Selection
• Antigen (Ag): a substance that provokes an immune
response in specific lymphocytes
• Antigenicity: the property of behaving as an antigen
• Immonogen: another term for an antigen
• Characteristics of Antigens
– It is perceived as foreign
– Complex molecules are more immunogenic
– Categories
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Proteins and polypeptides
Lipoproteins
Glycoproteins
Nucleoproteins
Polysaccharides
Figure 15.7
Effects of Molecular Shape and Size
• Substance must be large enough to initiate an
immune response from the surveillance cells
• Lymphocyte recognizes and responds to only a
portion of the antigen molecule- the epitope
• Mosaic antigens- very complex with numerous
component parts, each of which elicit a separate
lymphocyte response
• Haptens: small foreign molecules that consist of
only a determinant group
– Too small to elicit an immune response on their own
– If linked to a larger carrier molecule, then the
combination develops immunogenicity
Figure 15.8
Other Types of Antigens
• Alloantigens: cell surface markers and
molecules that occur in some members of the
same species but not in others
• Superantigens: bacterial toxins, potent
stimuli for T cells
• Allergens: antigens that evoke allergic
reactions
15.4 Cooperation in Immune
Reactions to Antigens
• The Role of Antigen Processing and Presentation
– Antigen-presenting cells (APCs): cells that act upon
and formally present antigens to lymphocytes
• Macrophages
• B cells
• Dendritic cells
– Engulf the antigen and modify it so it is more immunogenic and
recognizable
– After processing, the antigen is bound to the MHC
receptor and moved to the surface of the APC so it is
accessible to T lymphocytes
Figure 15.9
Presentation of Antigen to the
Lymphocytes and Its Early
Consequence
• APCs activate CD4 T helper cells in the lymph
nodes
– This class of T cell has an antigen-specific T-cell
receptor
• Binds to MHC class II
• Binds to a piece of the antigen
• Binds to a piece of the CD4 molecule (which also binds to
MHC class II)
• Once identification has occurred, a molecule on
the APC activates the T helper cell
• TH produces interleukin-2 (IL-2)
• The T helper cells can now help activate B cells
15.5 B-Cell Response
• Activation of B Lymphocytes: Clonal
Expansion and Antibody Production
– Clonal selection and binding of antigen
– Antigen processing and presentation
– B-cell/T-cell recognition and cooperation
– B-cell activation
– Clonal expansion
– Antibody production and secretion
Figure 15.10
The Structure of Immunoglobulins
Figure 15.11
Antibody-Antigen Interactions and the
Function of the FAb
Figure 15.12
Principal Activity of an Antibody
Figure 15.13
Functions of the Fc Fragment
• Fc end contains an effector protein that can
bind to receptors on the membranes of cells
• The effect of this binding depends upon that
cell’s role
Classes of Immunoglobulins
Evidence of Antibodies in Serum
Figure 15.14
Monitoring Antibody Production over
Time: Primary and Secondary
Response to Antigens
Figure 15.15
15.6 T-Cell Response
• Cell-Mediated Immunity (CMI)
– Require the direct involvement of T lymphocytes
throughout the course of the reaction
– T cells require some type of MHC recognition
before they can be activated
– T cells stimulate other T cells, B cells, and
phagocytes
The Activation of T Cells and Their
Differentiation into Subsets
• Mature T cells in lymphoid organs are primed to react
with antigens that have been processed and presented
to them by dendritic cells and macrophages
• Recognize an antigen only when it is presented in
association with an MHC carrier
• CD4 receptors recognize endocytosed peptides on
MHC-II
• CD8 receptors recognize peptides on MHC-I
• T cell is sensitized when an antigen/MHC complex is
bound to its receptors
• The activated T cells then transform in preparation for
mitotic divisions and differentiate into one of the
subsets
T Helper (TH) Cells
• Play a central role in regulating immune reactions to
antigens
• Also involved in activating macrophages
– Directly by receptor contact
– Indirectly by releasing cytokines like interferon gamma
• Secrete interleukin-2
– Stimulates the primary growth and activation of many
types of T cells
• Some secrete interleukins-4, -5, and -6
– Stimulate various activities of B cells
• When stimulated by antigen/MCH complex,
differentiate into either TH1 or TH2 cells
Cytotoxic T (TC) Cells: Cells that Kill
Other Cells
• Cytotoxicity: the capacity of certain T cells to kill a
specific target cell
• CD8 killer T cell becomes activated when it recognizes
a foreign peptide complexed with self MHC-I presented
to it
• After activation the TC cell severely injures the target
cell
– This involves the secretion of perforins and granzymes
• Target cells that TC cells can destroy include:
– Virally infected cells
– Cancer cells
– Cells from other animals and humans
Figure 15.16
Figure 15.17
Other Types of Killer Cells
• Natural killer (NK) cells
– Related to T cells
– Lack specificity for antigens
– Circulate through the spleen, blood, and lungs
– Probably the first killer cells to attack cancer cells
and virus-infected cells
15.7 A Practical Scheme for Classifying
Specific Immunities
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Active Immunity
Passive Immunity
Natural Immunity
Artificial Immunity
Figure 15.18
15.8 Immunization: Methods of
Manipulating Immunity for
Therapeutic Purposes
• Passive Immunization
– Immune serum globulin
– Specific immune globulin
– Antisera and antitoxins of animal origin
• Artificial Active Immunity: Vaccination
Immune Serum Globulin (ISG), aka
Gamma Globulin
• Contains immunoglobulin extracted from the
pooled blood of at least 1,000 human donors
• Processing concentrates the antibodies to
increase potency and eliminates potential
pathogens
• Method of choice for preventing measles and
hepatitis A and in replacing antibodies in
immunodeficient patients
• Injected intramuscularly
• Protection lasts 2-3 months
Specific Immune Globulin (ISG)
• Derived from a more defined group of donors
• Serum is obtained from patients who are in a
hyperimmune state after infections (ex.
pertussis, tetanus, chickenpox, hepatitis B)
• Contain higher titers of specific antibodies
from a smaller pool of patients than ISG
Antisera and Antitoxins of Animal
Origin
• Can be used when a human immune globulin
is not available
• Example: sera produced in horses for
diphtheria, botulism, and spider and snake
bites
Artificial Active Immunity: Vaccination
• Vaccination: exposing a person to material
that is antigenic but not pathogenic
• Stimulate a primary and secondary
anamnestic response to prime the immune
system for future exposure to a virulent
pathogen
Principles of Vaccine Preparation
Figure 15.19
Development of New Vaccines
• Difficult to design vaccines for latent or persistent
viral infections
– Host’s natural immunity can’t clear the infection
– Artificial immunity must then outperform the host’s
response to a natural infection
• Difficult to choose vaccine antigens that are safe
and that properly stimulate immunity
• Research focused on newer strategies for vaccine
preparation using antigen synthesis, recombinant
DNA, and gene cloning technology
Genetically Engineered Vaccines
• Recombinant DNA technology
• Trojan horse vaccine
– Genetic material from an infectious agent is inserted
into a live carrier microbe that is nonpathogenic
– The recombinant microbe multiplies and expresses
the foreign genes
– The vaccine recipient will be immunized against the
microbial antigens
• DNA vaccines
Figure 15.20
Route of Administration and Side
Effects of Vaccines
• Most vaccines are injected by subcutaneous,
intramuscular, or intradermal routes
• Only a few oral vaccines available, even though
they have advantages
• Some vaccines required the addition of an
adjuvant
• Common side effects
– Local reactions at the injection site
– Fever
– Allergies
• Some patients experience reactions to the
medium rather than the antigens
To Vaccinate: Why, Whom, and
When?
• Not only confers protection to the individual
receiving the vaccine, but it also protects
public heath
• Herd immunity
– Collective immunity through mass immunization
confers indirect protection on the nonimmune
members
– Important force in preventing epidemics