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 Granulocytes Neutrophils Eosinophils Basophils Agranulocytes Monocytes/Macrophages T-lymphocytes B-lymphocytes Antibodies Cell mediated immunity: Adaptive immune response in which antigenspecific 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 Diversity Memory Clonal expansion Specialization Functional significance Ensures that distinct antigens elicit specific responses Enables immune system to respond to large variety of antigens Leads to enhanced responses to repeated exposures to the same antigens Increases number of antigen-specific lymphocytes to keep pace with microbes generates responses that are optimal for defense against different types of microbes Adaptive allows immune system to respond to newly encountered antigens Non-reactivity to self prevents injury to the host during responses to foreign antigens 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, 7 th edition, 2011

Types of T Cells

From: Immunobiology by Janeway The concept of clonal selection

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 Immunogenicity: measures the effectiveness by which an antigen elicits an immune response (a) Foreign human or animal cells Plant molecules

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 (T H ) cell Interleukin-1 is secreted by APC to activate T H cells Interleukin-2 is produced by T H cells to activate B and other T cells

The common pathway of specific immunity

Overview of specific immunity

Lysis of infected cell by activated T cytotoxic lymphocyte Granzymes and Perforins generated by CD8 T lymphocytes lyse the infected cell

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 Class II MHC found on some types of white blood cells From: Immunobiology by Janeway

MHC functions The function of MHC molecules on APCs 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 education 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) V Light chains Antigen binding sites C V C C V C V Y shaped arrangement ends of the forks formed by light and heavy chains contain a wide range of variable antigen binding sites C -S-S- C Disulfide bonds Heavy chains

B lymphocyte activation and antibody production Once B cells process the Ag, interact with T H cells, and are stimulated by growth and differentiation factors, they undergo 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 Fc binds to various cells and molecules of the immune system

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 (pentamer), 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 Abs Complement fixation Precipitation Cross-linked bacterial cells Lysing bacterial cells Antibodies aggregate antigen molecules

Primary response to Antigen 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 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 Natural Immunity acquired through the normal life experiences not induced through medical means. Active Immunity 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. 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 Heat or chemical Administer Vaccine stimulates immunity but pathogen cannot multiply Ags Dead. But, antigenicity is retained

Live attenuated cells or Viruses: Whole cell vaccines Process that substantially lessens or negates the virulence of viruses or bacteria eliminates virulence factors Ags Virulence is eliminated or reduced Ags Administer Live, attenuated cells or viruses 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 back-mutation 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

What is immunological memory?