Chapter 15
Specific Immunities: The Adaptive
Line of Defense (1 of 2)
Third line of defense –
adaptive
or
acquired
immunity
•
Product of B and T lymphocytes dual system
– Immunocompetence: ability of the body to
interact with a wide spectrum of foreign substances
Specific Immunities: The Adaptive
Line of Defense (2 of 2)
•
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
Development of the Immune
Response System
• Cell receptors or markers confer specificity and
identity of a cell
• Major functions of receptors are:
– To perceive and attach to nonself or foreign molecules
– To promote the recognition of self molecules
– To receive and transmit chemical messages among other cells of the system
Major Histocompatibility Complex
(MHC)
• Set of cell surface proteins (receptors) essential
for the acquired immune system in the
recognition of self and in rejection of foreign molecules
• MHC molecules (receptors) are found on all cells except RBCs
• The MHC is also known as the human
leukocyte antigen (HLA) system
• The MHC gene family is divided in two main
Functions of MHC Groups (1 of 2)
•
Class I MHC
– genes code for markers that
display unique characteristics of self and allow
recognition of self molecules and regulation of
immune reactions
– Required for T lymphocytes to interact with
pathogens
•
Class II MHC
– genes code for immune
regulatory receptors found on
antigen-
Lymphocyte Receptors
•
The role lymphocytes play 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
•
Antigens are molecules, so their chemical
Origin of Diversity and Specificity in
the Immune Response
Lymphocytes use 500 genes to produce a
tremendous variety of specific receptors
•
Clonal Selection Theory
– Undifferentiated
lymphocytes in embryo and fetus undergo a
continuous series of divisions and genetic
Development of Lymphocytes (1 of 2)
•
In the bone marrow, lymphocytic stem cells
differentiate into either T or B cells
– B cells stay in the bone marrow while T cells
migrate to the thymus
– Both T and B cells migrate to secondary
lymphoid tissue
– Secondary lymphoid tissues will constantly be
Specific B-Cell Receptor:
Immunoglobulin (1 of 2)
•
Immunoglobulins
– large glycoproteins
that serve as specific receptors of B cells and
as antibodies
– Composed of 4 polypeptide chains in a
Y-shaped arrangement:
2 identical heavy chains (H)
2 identical light chains (L)
– Wide range of variable antigen binding sites
T-Cell Receptors for Antigen
• Formed by genetic recombination like B-cell
receptors, with variable and constant regions
• 2 parallel polypeptide chains
• Unlike B-cell receptors, T-cell receptors are small,
Specific Events in T-Cell Maturation
•
Maturation is directed by the thymus gland
and its hormones
•
Different classes of T-cell receptors termed
CD receptors
or
clusters of differentiation
– CD4 on T helper (TH) cells
– CD8 on T cytotoxic (Tc) cells
Specific Events in 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
B Cells versus T Cells
TABLE 15.1 Contrasting Properties of T Cells and B Cells Site of Maturation Immune surface Markers Circulation
in Blood Receptors for Antigen
Distribution in Lymphatic Organs Require Antigen Presented with MHC Product Antigenic Stimulation General Functions T
cells Thymus gland
T- cell receptor, CD molecules, MHC I receptors High
numbers T-cell receptor (TCR)
Paracortical sites (interior to the follicles) Yes Helper and cytotoxic T cells and memory cells Regulate immune functions, kill foreign and infected cells, synthesize cytokines B
cells Bone marrow
Immunoglo bulin MHC I and MHC II
receptors
Low
numbers Immunoglobulins D and M Cortex (in follicles) No
Characteristics of Antigens and
Immunogens
•
Antigen (Ag)
– substance that elicits
immune response in specific lymphocytes
– Antigenicity – property of behaving as an
antigen
Foreignness, size, shape, and accessibility
•
Antigens have many
antigenic
Functional Categories of Antigens
• Alloantigens – cell surface markers and molecules that occur in some members of the same species but not in others
– Determine blood group and major histocompatibility profile
– Responsible for incompatibilities in blood transfusion or organ grafting
• Superantigens – potent T cell stimulators
– Toxic shock toxin (massive release of cytokines leading to cell death)
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
The Role of Antigen Processing and
Presentation (1 of 2)
•
T-cell dependent antigens must be processed
by phagocytes called
antigen-presenting
cells (APC)
before their contact with T cells
•
Three cell types can serve as APCs:
– Macrophages
– Dendritic cells (most common)
– B cells
•
APCs modify the antigen; then the antigen is
The Role of Antigen Processing and
Presentation (2 of 2)
•
Antigen presentation involves a direct
collaboration among an APC and a
T helper
cell (T
H)
– Interleukin-1 (IL-1) cytokine secreted by
APC to activate TH cells
– Interleukin-2 (IL-2) cytokine produced by TH
T-Cell Responses and Cell-Mediated
Immunity
• Cell-mediated immunity (CMI) requires the direct
involvement of T lymphocytes in the immune response
• T cells secrete cytokines that act directly on other cells
• Before T cells get activated, the antigen must be presented in association with an MHC complex on a APC, to ensure recognition of self
Types of T Cells (1 of 3)
TABLE 15.2 Characteristics of Subsets of T Cells
Types
Primary Receptors on
T Cell
Functions/Important Features
T helper cell 1 (TH1) CD4
Activates other CD4 and CD8 cells; secretes IL-2, tumor necrosis factor, and interferon gamma; responsible for delayed hypersensitivity; interacts with MHC-II receptors
T helper cell 2 (TH2) CD4 Drives B-cell proliferation; secretes IL-4, IL-5, IL-6, IL-10; can dampen T
H1activity
T regulatory cell (Treg) CD4, CD25
Involved in development of immune tolerance; suppression of pathological immune responses, inflammation, autoimmunity
T cytotoxic cell (TC) CD8
Types of T Cells (2 of 3)
•
T Helper (T
H) cells
(also called CD4 cells)
– They express CD4 receptors and are activated
by antigen/MHC II
– Most prevalent type of T cell in blood and
lymphoid organs
– Regulate immune reaction to antigens,
including other T and B cells
– Also involved in activating macrophages and
increasing phagocytosis
Types of T Cells (3 of 3)
•
Cytotoxic T (T
c) cells
(also called CD8 cells)
– They express CD8 receptors and are activated
by antigen/MHC I
– Destroy foreign or abnormal cells by secreting
perforins and granzymes
•
Natural killer (NK) cells
– Lack specificity; circulate through the spleen,
Cytotoxic T Cells
Natural Killer (NK) Cells
1) NK cell releases perforins, which polymerize and form a hole in the foreign cell membrane.
T Cells and Superantigens
•
Reaction has drastic consequences
•
Superantigens
are found orimarily in bacteria
and viruses, and are a form of virulence factor
– Enterotoxin from pathogenic staphylococci,
certain toxins of group A streptococci, and proteins of Epstein-Barr virus
•
Provoke overwhelming immune responses by
large numbers of T cells regardless of specificity
– Release of massive amount of cytokines
Events in 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
Antibody Structure and Functions
(1 of 2)
•
Immunoglobulins (Ig)
: molecule with 4
polypeptide chains connected by disulfide bonds
•
All antibodies have two functionally distinct
segments (
fragments
):
– Antigen binding fragments (Fabs) “arms”
with their amino-terminal end (variable regions of the heavy and light chains) as antigen-binding sites
Antigen-Antibody Binding (1 of 3)
• The Fab antigen-binding site is composed of
hypervariable regions with an extremely variable amino acid content
• The groove of this antigen binding site has a
specific three-dimensional fit for the antigen
• The specificity of the two Fab sites is identical for
each antigen
Antigen-Antibody Binding (2 of 3)
Antigen-Antibody Binding (3 of 3)
Antibody-Antigen Interactions
(1 of 3)
•
Principle activity of antibodies
: unite
with, immobilize, 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. Carried out by antibodies
called “opsonins”
– Neutralization – Antibodies fill the surface
Antibody-Antigen Interactions
(2 of 3)
– Agglutination – Ab aggregation; cross-linking cells or particles into large clumps – Complement fixation – Activation of the
classical complement pathway can result in the specific rupturing of cells and some
viruses
Functions of the Fc Fragment (1 of 2)
•
Fc fragment binds to cell membranes
– macrophages, neutrophils, eosinophils, mast
cells, basophils, lymphocytes
•
Regions on the Fc portion in certain
antibodies fix complements
Classes of Immunoglobulins
• 5 functional classes (isotopes) of
immunoglobulins (Ig):
– IgG – monomer, produced by plasma cells
(primary response) and memory cells (secondary), most prevalent
– IgA – monomer circulates in blood, dimer in mucous and serous secretions
– IgM – five monomers, first class synthesized following Ag encounter
– IgD – monomer, serves as a receptor for antigen on B cells
TABLE 15.3 Characteristics of
Antibodies in Serum
• Regardless of the site where antibodies are first
secreted, a large quantity eventually ends up in the blood
– Antiserum: serum containing specific antibodies
• If separated by electrophoresis, globulins in
antiserum separate into 4 bands:
– Alpha-1 (α1), alpha-2 (α2), beta (β), and gamma (γ)
• Most are antibodies
• Gamma globulin (γ) is composed primarily of IgG
Immunity Categories by Mode of
Acquisition
• 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
Examples of Origins of Immunity
(1 of 2)
1. Natural Active immunity: Getting and infection
– After recovering from infectious disease, a person may be actively resistant to reinfection (period varies according to the disease)
2. Natural Passive Immunity: Mother to Child
– IgG antibodies bodies from the maternal
bloodstream can pass or be actively transported across the placenta to the fetus
Examples of Origins of Immunity
(2 of 2)
3. Artificial Active Immunization: Vaccination
– Microbial (antigenic) stimulus, which triggers the immune system to produce antibodies and memory cells
4. Artificial Passive Immunization:
Immunotherapy
Categories of Acquired Immunities
(1 of 6)
The figure of “Categories of Acquired Immunities.”
•
Acquired Immunity
Categories of Acquired Immunities
(2 of 6)
The figure of “Categories of Acquired Immunities” continues on this slide.
Active Immunity results when a person
Categories of Acquired Immunities
(3 of 6)
The figure of “Categories of Acquired Immunities” continues on this slide.
Passive Immunity results when a person is
Categories of Acquired Immunities
(4 of 6)
The figure of “Categories of Acquired Immunities” continues on this slide.
– Artificial Immunity produced purposefully through medical procedures (also called
Categories of Acquired Immunities
(5 of 6)
The figure of “Categories of Acquired Immunities” continues on this slide.
Active Immunity (Same as vaccination)
Categories of Acquired Immunities
(6 of 6)
The figure of “Categories of Acquired Immunities” continues on this slide.
Passive Immunity results when a person is
Principles of Vaccine Preparation
(1 of 2)
•
Most vaccines are prepared from:
– Killed whole cells or inactivated viruses
– Live, attenuated cells or viruses
– Antigenic molecules derived from bacterial
cells or viruses
– Genetically engineered microbes or microbial
Principles of Vaccine Preparation
(2 of 2)
TABLE 15.4 Checklist of Requirements for an Effective Vaccine
• It should have a low level of adverse side effects or toxicity and not cause serious harm.
• It should protect against exposure to natural, wild forms of pathogen.
• It should stimulate both antibody (B-cell) response and cell-mediated (T-cell) response.
• It should have long-term, lasting effects (produce memory cells).
Attenuated versus Killed Vaccines
•
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
Strategies in Vaccine Design (1 of 5)
Strategies in Vaccine Design (2 of 5)
Strategies in Vaccine Design (3 of 5)
• 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
Strategies in Vaccine Design (4 of 5)
Strategies in Vaccine Design (5 of 5)
• Insert genes for pathogen’s antigen into plasmid
vector, and clone them in an appropriate host
– Stimulated 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
