Download Chapter 15 Adaptive, Specific Immunity and Immunization

Chapter 15
Adaptive, Specific Immunity and Immunization
Adaptive Immunity: The third line of defense
Third line of defense – acquired and specific.
• Dual System of B and T lymphocytes- Immunocompetence
• Antigen – Molecules that stimulate a response by T and B cells
• Two characteristic features of specific immunity:
•Specificity – antibody made to one specific antigen will not bind to other antigens
•Memory – lymphocytes are programmed to “recall” their first encounter with an antigen
and respond rapidly to subsequent encounters
Overview of the acquired immunity
(Adaptive) Acquired immunity
Cell mediated immunity
Humoral immunity
B-lymphocytes
Granulocytes
Neutrophils
Eosinophils
Basophils
Agranulocytes
Monocytes/Macrophages
T-lymphocytes
Antibodies
Cell mediated immunity: Adaptive immune response in which antigen-specific T-lymphocytes
have main role
Humoral immunity: Antibody mediated specific immunity where B- lymphocytes have main role
Innate and adaptive immunity
Innate immunity: always present (ready to attack)
Adaptive immunity: stimulated by exposure to microbe; more potent
Overview of specific immune responses
Properties of adaptive immune responses
Feature
Specificity
Functional significance
Ensures that distinct antigens elicit specific responses
Diversity
Enables immune system to respond to large variety of antigens
Memory
Leads to enhanced responses to repeated exposures to the same antigens
Clonal
expansion
Increases number of antigen-specific lymphocytes to keep pace with microbes
Specialization
generates responses that are optimal for defense against different types of
microbes
Adaptive
allows immune system to respond to newly encountered antigens
Non-reactivity
prevents injury to the host during responses to foreign antigens
to self
The two features that best distinguish adaptive and innate immunity are specificity and
memory
Primary and secondary immune responses illustrate specificity and memory in
adaptive immunity
From : Basic Immunology by Abbas & Litchman
• Humoral Immunity provides protection against extracellular pathogens
• Cell-mediated Immunity provides protection against intracellular pathogens
• Humoral and cell mediated immunity work in concert to eliminate an infecting pathogen
Antibodies generated by
a B cell-mediated
response are key in
eliminating free,
circulating viruses
T cell-mediated immunity is key
for destroying a virus once it is
within a cell
From: Immunobiology by Janeway
Development of B and T lymphocytes
From : Basic Immunology by Abbas & Litchman
B- lymphocytes maturation and antigens
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
T- lymphocyte maturation and antigens
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
B Cells and T Cells
Molecular Biology of the Cell. 4th edition.
Alberts B, Johnson A, Lewis J, et al. 2002
Lymphocyte classes
From: Abbas, Lichtman and Pillai. Cellular and Molecular Immunology, 7th edition, 2011
Types of T Cells
The concept of clonal selection
From: Immunobiology by Janeway
Antigens
• Antigen (Ag) is a substance that provokes an immune response in specific lymphocytes
• Antigenicity: ability of a peptide to react specifically with the functional binding site of a
complementary antibody
• Foreignness, size, shape, and accessibility
• Proteins are the most effective antigens
Microbial cells,
viruses
Foreign human
or animal cells
Plant molecules
(a)
•
•Immunogenicity: measures the effectiveness by which an antigen elicits an immune response
Antigen characteristics
• Perceived as foreign, not a normal constituent of the body
• Foreign cells and large complex molecules over 10,000 MW are most antigenic
• Epitope (Antigenic determinant) – small molecular group (site) on antigen that is recognized
by lymphocytes
• Antigen has many antigenic determinants
Haptens
• 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
(a)
Hapten
(b) Hapten bound to
carrier molecule
Insert Fig 15.8
No antibody
Antibody formed in
response to hapten &
to carrier
How haptens can elicit antibody production
Examples of carrier molecules:
1) Keyhole limpet hemocyanin (KLH)
2) Bovine serum albumin (BSA)
Special categories of Antigens
• Alloantigens – cell surface markers and molecules that occur in some members of the same
species but not in others e.g. Blood group antigens
• Superantigens – potent T cell stimulators; provoke an overwhelming response e.g. S. aureus
exotoxins
• Allergen – antigen that evokes allergic reactions
• Autoantigens – an antigen that despite being a normal tissue constituent is the target of a
humoral or cell-mediated immune response, as in autoimmune disease
e.g. Histone proteins in SLE (systemic lupus erythematosus)
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
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 (TH ) cell
• Interleukin-1 is secreted by APC to activate TH cells
• Interleukin-2 is produced by TH cells to activate B and other T cells
The common pathway of specific immunity
Overview of specific immunity
Lymphocyte activation and differentiation
T-Cell Activation and differentiation
TM
Memory CD4 T cell
IL-2,
One division forms
CD4 cell
APC
Produces IL-4 and other Bcell growth factors
TH 2
Ag
MHC-II
IL-4
Activated B cell
Production of tumor necrosis
factor and interferon gamma
(a) Reaction with CD4 cell
TH 1
Stimulate macrophages
(also delayed hypersensitivity)
Ag enters with APC and
activates CD4 or CD8 cell
TH 1
TM
Memory CD8 T cell
IL-2
Granzymes
Perforins
MHC-I
Ag
(b) Reaction with CD8 cell
CD8 cell
Activated
CD8 cell
TC
TC cell
recognizes
infected self
Destroyed
host cell
Ag
CD8
molecule
MHC-I
Infected host
cell
Lysis of infected cell by activated T – cytotoxic lymphocyte
Cellular immunity
Docking, then
activation by
interleukins
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
Class I MHC molecule
found on all nucleated
human cells
From: Immunobiology by Janeway
Class II MHC
found on some types of
white blood cells
MHC functions
The function of MHC molecules is to bind peptide fragments derived from pathogens and
display them on the cell surface for recognition by the appropriate T cells.
• 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, B cells
•Involved in presenting antigen to T-cells
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
Specific B-Cell Receptor: Immunoglobulin (Ig)
• Immunoglobulins are large glycoproteins that serve as specific receptors of B cells
• All antibodies are immunoglobulins
• Composed of 4 polypeptide chains:
• 2 identical heavy chains (H)
• 2 identical light chains (L)
Light chains
Antigen binding sites
V
V
V
V
C
C
C
• Y shaped arrangement – ends of the forks
formed by light and heavy chains contain a
wide range of variable antigen binding sites
• Variable regions and Constant regions
C
-S-S-
C
C
Heavy chains
Disulfide
bonds
B – lymphocyte 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
Antibody structure and functions
• Immunoglobulins
• Large Y-shaped protein
• Consist of 4 polypeptide chains
Fab
Fab
• Contain 2 identical fragments (Fab) with ends
that bind to a specific antigen
• Fc binds to various cells and molecules of the
immune system
Fc
Immunoglobulin classes
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
Immunoglobulin classes
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
• Neutralization – Abs fill the surface receptors on a virus or the active site on a microbial
enzyme to prevent it from attaching
Bacterial cell “tagged”
with Abs
Opsonization
Neutralization
Antibodies
block binding
Viruses
Opsonized bacteria engulfed
more readily
Antibody-Antigen interactions
• 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
• Precipitation - Aggregation of particulate antigen
Agglutination
Complement fixation
Precipitation
Abs
Antibodies aggregate
antigen molecules
Cross-linked
bacterial cells
Lysing bacterial
cells
Primary response to Antigen
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 from memory cells
Secondary response to Antigen
Secondary response – after second contact with the same Ag, immune system produces a
more rapid, stronger response due to memory cells
• Anamnestic response
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
Using monoclonal antibodies for treatment
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
Categories of acquired immunities
Acquired Immunity
Natural Immunity
acquired through the normal life experiences
not induced through medical means.
Active Immunity
Passive Immunity
is the consequence of a
is the consequence of
person developing his own one person receiving
immune response to a
preformed immunity
microbe.
made by another person.
Artificial immunity
produced purposefully through
medical procedures (also called immunization).
Active Immunity (same as
vaccination) is the
consequence of a person
developing his own
immune response to a
microbe.
Passive Immunity
is the consequence of
one person receiving
preformed immunity
made by another person.
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
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
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
Qualities of an effective Vaccine
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
Ags
Administer
Heat or
chemical
Ags
Dead . But ,
antigenicity is
retained
Vaccine stimulates immunity but
pathogen cannot multiply
Live attenuated cells or Viruses: Whole cell vaccines
Process that substantially lessens or negates the virulence of viruses or bacteria – eliminates
virulence factors
Ags
Ags
Viulence is eliminated
or reduced
Live, attenuated cells or
viruses
Administer
Alive. With same antigenicity
Vaccine microbes can multiply
and boost immune stimulation.
Attenuated vs 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 other people, can conceivably mutate back
to virulent strain
Antigenic molecules (Vaccines from microbe parts)
• 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
Antigens stimulate immunity
but no pathogen is
present
Subunit vaccine (virus)
Acellular vaccine (bacteria)
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 backmutation to a virulent strain, neurological effects
Herd Immunity
• Immune individuals will not harbor it, reducing the occurrence of pathogens – herd immunity
• Less likely that a non-immunized person will encounter the pathogen
Credit: NIAID
Cytokines in cancer pathogenesis and cancer therapy Glenn Dranoff Nature Reviews Cancer 4, 11-22 (January 2004)
Innate immunity
Immune response
https://www.youtube.com/watch?v=skPtWocTKdU#t=19
https://www.youtube.com/watch?v=Bf2t8n1ibwQ
What is immunological memory?