Microbiology: A Systems Approach PowerPoint to accompany Microbiology: A Systems Approach Cowan/Talaro Chapter 15 Specific Immunity and Immunization Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Chapter 15 Topics - Thirdline of Defense - B cells - T cells - Specific Immunities

Thirdline of Defense Specific immunity is a complex interaction of immune cells (leukocytes) reacting against antigens Specific Self and nonself (foreign) Antigens Antibodies & specialized lymphocytes

Self and nonself Markers glycoproteins located on the cell surface Eg. Major histocompatibility complex (MHC)

Markers Host cells proteins (ex. MHC) confer specificity and identity Role – detection, recognition, and communication Lymphocyte cells recognize the host cell markers as “self” Lymphocyte cells recognize microbe markers as ‘nonself’

Major histocompatibility complex (MHC) Self receptor Glycoprotein Found on all nucleated cells In humans – Human leukocyte antigen (HLA) is equivalent to the MHC Different Classes of MHC

Specific Acquired Immunities Active Passive Natural Artificial Vaccines

Active Antigen activates B and T cells Memory cells Long-term protection Natural or artificial

Passive Receive pre-formed antibodies from another individual or animal No memory cells No antibody production Short-term protection Natural or artificial

Natural Immunity produced by normal biological experiences, no medical intervention Natural active Eg. Infection Natural passive Eg. Mother to child – across the placenta, via breast milk

Artificial Immune protection through medical procedures or intervention Artificial active Eg. vaccination Artificial passive Eg. Injection of preformed antibodies (antiserum) Immediate but short-lived protection

Summary of the different acquired immunities. Fig. 15.18 Categories of acquired immunities

Duality of the Immune System Humoral Immunity B-lymphocytes produce antibodies Antibodies in fluids ( blood, lymph, etc.) Defense against Bacteria Toxins Circulating viruses

Duality of the Immune System Cell-Mediated Immunity T-cells (lymphocytes) Acts against foreign tissues or organisms Regulates the activity of other immune system cells

Cell-Mediated Immunity Defends against Bacteria or viruses that are within the host cells Fungi, protozoa and helminths Transplanted tissue cancer

Mature T and B cells migrate to the lymphoid tissue, where they encounter antigens. Fig. 15.4 Major stages in the development of B and T cells.

Stages Dual lymphocyte development and differentiation Presentation of antigens Challenge of B and T lymphocytes by antigens Production of antibodies by B cells (plasma cell) T lymphocyte responses

An overview of the stages of lymphocyte development and function. Fig. 15.1 Overview of the stages of lymphocyte development

Receptors Present on B and T cells Immunoglobulin molecule Light chain Heavy chain Variable region Constant region B cell receptors are secreted as antibodies

The structure of a receptor for B cells. Fig. 15.5 Simplified structure of an immunoglobulin molecule on the surface of B cells.

The structure of the receptor for T cells. Fig. 15.6 Proposed structure of the T cell receptor for antigen.

Antigens Foreign material Size and shape are important

Antigens Microbial products Non-microbial products Capsules, cell walls Flagella Fimbria Bacterial toxins Viral protein coats Other surface molecules Non-microbial products Pollen Egg white Blood cell surface markers Serum proteins from other individuals Transplanted tissues

Foreign material Antigenic Proteins and polypeptides enzymes, cell surface structures, hormones, exotoxins) – usu. Glycoproteins - blood cell markers Large Polysaccharides - capsules, LPS) Not very Antigenic Lipids & cell membranes Nucleic acids (DNA)

Size and shape Size affects antigenicity Haptens Too small – no immune recognition Large – immune recognition Proteins are better immunogens than polysaccharides because of their complex shape Haptens antigens that are too small to elicit an immune response

A hapten can complex with a larger carrier protein in order to stimulate an immune response. Fig. 15.8 The hapten-carrier phenomenon.

Superantigen Bacterial toxins T cell activation much greater than normal antigens Large release of cytokines Results in toxic shock syndrome and some autoimmune diseases

Examples of different antigens and their characteristics. Fig. 15.7 Characteristics of antigens.

Antibody Product of B cell activation Structure Immunoglobulin (Ig) family of proteins Produced in response to an antigen Structure Highly specific for the antigen that stimulated the production of the antibody Antigen –binding site on the antibody specifically binds the antigen Has at least two antigen-binding sites

Antibody Structure 2 identical heavy chains 2 identical light chains Linked by disulfide bridges Variable region binds antigen Constant region determines the class of the antibody Fc – stem region binds complement or allow antibody to be attached to the surface of a cell.

The complete structure of an IgG antibody. Fig. 15.11 Working models of antibody structure.

V-region Variable (N-terminal of the heavy and light chains) Binds to the antigen Swiveling enables more efficient binding Held together by disulfide bonds

Fc Constant (C-terminal of heavy chain) Binds to macrophages Anchors Ig to lymphocyte Held together by disulfide bonds Responsible for class identification

Classes based on the Fc fragment Immunoglobulin (Ig) IgG IgA IgM IgD IgE

IgG Monomer Primary response Memory cell response Most prevalent in tissue fluid and blood

IgM Five monomers Held together by a J chain First to be synthesized during primary immune response Associated with complement fixation Receptor for antigens on B cells Circulates in the blood

IgA Monomer or dimer (secretory IgA) Dimer – held together by a J chain Secretory IgA (mucous and serous secretions) Local immunity Salivary glands, intestine, nasal membrane, breast, lung, genitourinary tract Protection for newborns

IgD Monomer Small amounts in the serum Receptor for antigens on B cells

IgE Allergies Parasite infections Fc portion binds to mast cells and basophils release chemical mediators that aid inflammation

The characteristics of the different immunoglobulin classes. Table 15.2 Characteristics of the immunoglobulin classes.

B cells Activation Antibody Antibody-antigen interaction Response

Activation Clonal selection and binding of antigen Instruction by chemical mediators Transmission of signal to the nucleus B cell changes into a plasma cells and begins mitosis Clonal expansion and memory cell formation Antibody production and secretion

Clonal selection The synthesis of varied receptor types Clone approximately 500 genes undergo rearrangement eventually one clone recognizes an antigen and expands (proliferates) Clone each mature lymphocyte possesses a single combination or receptor specificity Expansion a single cell is stimulated by antigen recognition Clonal deletion cells that recognize self are removed

The clonal selection theory of lymphocyte development and diversity. Fig. 15.3 Overview of the clonal selection theory of lymphocyte development and diversity.

The stages of B-cell activation and antibody synthesis. Fig. 15.10 Events in B-cell activation and antibody synthesis.

Antibody-antigen interactions Opsonization Agglutination Neutralization Complement fixation

A complementary fit between an antibody and antigen involves hydrogen bonds and electrostatic attractions. Fig. 15.12 Antigen-antibody binding

The different functions of antibodies. Fig. 15.13 Summary of antibody functions

Agglutination Antibodies cross-link cells or particles into clumps Renders microbes immobile Enhances phagocytosis Principle for certain immune tests (RBC typing)

Opsonization Microbes or particles coated with antibodies Enables macrophages to recognize and phagocytize microbe

Neutralization Antibody binds to The microbe or virus receptor Antigenic site of a molecule (Eg. Exotoxin) Prevents further binding of microbe or toxin

Complement fixation Antibodies interaction with complement proteins (Eg. Classical pathway) Lysis of microbial cell

Response Primary Secondary

Primary First exposure Latent period Synthesis of antibodies Lack of antibodies synthesis Synthesis of antibodies Level of synthesis (titer) IgM first Followed by IgG, and some IgA and IgM

Secondary Re-exposure to the same immunogen (Anamnestic response) Antibody synthesis, titer, and length of antibody persistence is rapid and amplified Primarily due to memory cells

The stages of primary and secondary responses to antigens. Fig. 15.15 Primary and secondary responses to antigens.

Apoptosis Programmed cell death Genetic program that is turned on and stimulates the cell to digest itself Debris is cleared away by macrophages without stimulating inflammation The way the body gets rid of unneeded or worn out cells

T cell Activation Types

Activation Cell-mediated immunity Cytokines Antigen presenting cells Interleukins – IL-1, IL-2 Gamma interferon Tumor Necrosis Factor ( TNF) Antigen presenting cells Activated macrophages

Cell-mediated immunity Direct involvement of T cells Produce and react to cytokines Activated simultaneously with B cell activation Subset of T cells have unique CD receptors (CD4, CD8)

Antigen presenting cells (APC) Macrophages and dendritic cells Process and present antigen in association with MHC T cell CD receptor recognize antigen/MHC

Transformation Activated T cells prepare for mitosis Effectors cells or types (TH, TC) are produced Memory cells are produced

Types Helper T cells (TH) Cytotoxic T cells (TC)

TH Regulate immune reactions to antigens by releasing cytokines CD4 receptor Type of cytokine will determine subset of TH TH1 (activate other T cells, delayed type hypersensitivity) TH2 (B cell differentiation) Cytokines also activate macrophages Most prevalent in the blood Insert animation .0083 T helper cell dependent antigen

TC Binds and lyses cells (apoptosis) CD8 receptor microbe, viral infected cells, foreign cells, cancer cells CD8 receptor Perforins – punch holes in the membrane Granzymes – degrade proteins Natural killer (NK) cells related to TC attack virus infected cells and cancer cells Insert animation .0034 Cytotoxic T cell

An example of helper and cytotoxic T cell activation and differentiation. Fig. 15.16 Overall scheme of T-cell activation and differentiation into different types of T cells.

Characteristics of the different subsets of T cells. Table 15.3 Characteristic of subsets of T cells.

Relationship between Cell-Mediated and Humoral Immunity T- independent antigens Can stimulate B-cells directly Antibodies will be produced without the need for T-helper cells T-dependent antigens Most antigens are not sufficient to stimulate the B-cells directly A T-helper cell has to recognize the antigen and assist the B-cell Most antigens are T-dependent

An example of a cytotoxic T cell destroying a cancer cell. Fig. 15.17 A cytotoxic T cell has mounted a successful attack on a tumor cell.