Microbiology: A Systems Approach Chapter 15 Specific Immunity and Immunization PowerPoint to accompany Cowan/Talaro Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Mar 30, 2016
Microbiology: A Systems Approach
Chapter 15Specific Immunity and Immunization
PowerPoint to accompany
Cowan/Talaro
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
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Chapter 15 Topics
- Thirdline of Defense- B cells - T cells- Specific Immunities
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Thirdline of Defense• Specific immunity is a complex
interaction of immune cells (leukocytes) reacting against antigens– Stages– Self and nonself– Clonal selection– Antigens
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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
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An overview of the stages of lymphocyte development and function.
Fig. 15.1 Overview of the stages of lymphocyte development
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Self and nonself• Markers
– glycoprotein– located on the cell surface – Eg. Major histocompatibility complex
(MHC)
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Markers• Host cells receptors (ex. MHC)
confer specificity and identity• Role – detection, recognition, and
communication• Lymphocyte cells recognize the
host cell receptors as “self”• Lymphocyte cells recognize
microbe receptors as ‘nonself’
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Major histocompatibility complex (MHC)
• Self receptor• Glycoprotein• Found on all nucleated cells• In humans – Human leukocyte
antigen (HLA) is equivalent to the MHC
• Classes of MHC
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Classes of MHC• Each individual has a unique MHC
profile– Expression of a particular
combination of MHC genes • Class I – all nucleated cells• Class II – macrophages, dendritic
cells, B cells
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The Class I and II MHC for humans are surface receptors consisting of glycoproteins.
Fig. 15.2 The human major histocompatibility complex.
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Clonal selection• The synthesis of varied receptor types
– 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
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B cell clone• Application of immunology• Propagate a single clone in order
to synthesis monoclonal antibodies• Monoclonal antibody
– possess a single specificity for antigen
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The clonal selection theory of lymphocyte development and diversity.
Fig. 15.3 Overview of the clonal selection theory of lymphocytedevelopment and diversity.
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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.
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Receptors• Present on B and T cells
– Immunoglobulin molecule• Light chain• Heavy chain• Variable region• Constant region
• B cell receptors are secreted as antibodies
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The structure of a receptor for B cells.
Fig. 15.5 Simplified structure of an immunoglobulinmolecule on the surface of B cells.
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The structure of the receptor for T cells.
Fig. 15.6 Proposed structure of the T cell receptor for antigen.
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Antigens• Foreign material• Size and shape• Alloantigens• Superantigens
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Foreign material• Proteins and polypeptides
– enzymes, cell surface structures, hormones, exotoxins)
• Lipids – cell membranes
• Glycoproteins – blood cell markers
• Nucleoproteins – DNA complexed to proteins
• Polysaccharides – capsules, LPS)
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Size and shape• Immunogen
– Less than1000 daltons – no immune recognition– Greater than 1000 daltons – immune recognition– Proteins are better immunogens than
polysaccharides • Epitope
– portion of the antigen (ex. Amino acids) recognized by lymphocyte receptor
• Haptens – antigens that are too small to elicit an immune
response
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A hapten can complex with a larger carrier protein in order to stimulate an immune response.
Fig. 15.8 The hapten-carrier phenomenon.
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Alloantigens• Cell surface markers that occur in
some members of the same species– blood typing (transfusion) – MHC profile (organ grafting)
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Superantigen• Bacterial toxins• T cell activation much greater than
normal antigens• Large release of cytokines• Results in toxic shock syndrome
and some autoimmune diseases
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Examples of different antigens and their characteristics.
Fig. 15.7 Characteristics of antigens.
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B cells• Activation• Antibody• Antibody-antigen interaction• Response
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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
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The stages of B-cell activation and antibody synthesis.
Fig. 15.10 Events in B-cell activation and antibody synthesis.
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Antibody• Product of B cell (plasma cell)
activation– Immunoglobulin (Ig) or antibody
• Structure– Four polypeptides – Connected by disulfide bonds– Antigen binding fragment (Fabs)– Crystallizable fragment (Fc)
• Classes
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Fab• Variable (N-terminal of the heavy
and light chains)• Binds to the antigenic determinant • Swiveling enables more efficient • Held together by disulfide bonds
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Fc• Constant (C-terminal of heavy
chain)• Binds to macrophages• Anchors Ig to lymphocyte• Held together by disulfide bonds• Responsible for class identification
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The complete structure of an IgG antibody.
Fig. 15.11 Working models of antibody structure.
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Classes• Isotypes – based on the Fc fragment• Immunoglobulin (Ig)
– IgG– IgA– IgM– IgD– IgE
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IgG• Monomer• Primary response• Memory cell response• Most prevalent in tissue fluid and
blood
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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
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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
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IgD• Monomer• Small amounts in the serum• Receptor for antigens on B cells
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IgE• Allergies• Parasite infections• Fc portion binds to mast cells and
basophils– release chemical mediators that aid
inflammation
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The characteristics of the different immunoglobulin classes.
Table 15.2 Characteristics of the immunoglobulin classes.
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Antibody-antigen interactions
• Opsonization• Agglutination• Neutralization• Complement fixation
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A complementary fit between an antibody and antigen involves hydrogen bonds and electrostatic attractions.
Fig. 15.12 Antigen-antibody binding
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Opsonization• Microbes or particles coated with
antibodies• Enables macrophages to recognize
and phagocytize microbe
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Agglutination• Antibodies cross-link cells or
particles into clumps• Renders microbes immobile• Enhances phagocytosis• Principle for certain immune tests
(RBC typing)
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Neutralization• Antibody binds to
– The microbe or virus receptor– Antigenic site of a molecule (Eg.
Exotoxin)• Prevents further binding of
microbe or toxin
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Complement fixation• Antibodies interaction with
complement proteins (Eg. Classical pathway)
• Lysis of microbial cell
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The different functions of antibodies.
Fig. 15.13 Summary of antibody functions
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Response• Primary• Secondary
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Primary• First exposure
– Latent period• Lack of antibodies synthesis
– Synthesis of antibodies • Level of synthesis (titer)• IgM first• Followed by IgG, and some IgA and IgM
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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
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The stages of primary and secondary responses to antigens.
Fig. 15.15 Primary and secondary responses to antigens.
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T cell• Activation• Types
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Activation• Cell-mediated immunity• Antigen presenting cells • Transformation
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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)
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Antigen presenting cells (APC)
• Macrophages and dendritic cells– Process and present antigen in
association with MHC II– T cell CD receptor recognize
antigen/MHC II
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Transformation• Activated T cells prepare for
mitosis• Effectors cells or types (TH, TC) are
produced• Memory cells are produced
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Types• Helper T cells (TH)• Cytotoxic T cells (TC)
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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
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TC
• Binds and lyses cells (apoptosis) – 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
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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.
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Characteristics of the different subsets of T cells.
Table 15.3 Characteristic of subsets of T cells.
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An example of a cytotoxic T cell destroying a cancer cell.
Fig. 15.17 A cytotoxic T cell has mounted a successfulattack on a tumor cell.
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Specific Immunities• Active• Passive• Natural• Artificial• Vaccines
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Active• Natural or artificial• Antigen activates B and T cells• Memory cells• Long-term protection
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Passive• Natural or artificial• Receive antibodies from another
individual or animal• No memory cells• No antibody production • Short-term protection
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Natural• Immunity produced by normal
biological experiences, no medical intervention– Natural active
• Eg. Infection– Natural passive
• Eg. Mother to child
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Artificial• Immune protection through
medical procedures or intervention– Artificial active
• Eg. vaccination– Artificial passive
• Eg. immunotherapy
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Summary of the different acquired immunities.
Fig. 15.18 Categories of acquired immunities
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Vaccines• Types
– Killed whole cell or inactivated viruses– Live, attenuated cells or viruses– Antigenic molecules from bacteria or
viruses– Genetically engineered microbes or
microbial antigens
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Example of how different types of vaccines are designed.
Fig. 15.19 Strategies in vaccine design.
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New vaccines• DNA vaccines
– Insert microbial DNA into plasmid– Inoculate recipient with plasmid– Host cell expresses microbial DNA– Immune system reacts to microbial
antigen expressed on the host cell surface
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Benefits of vaccinations• Long-lasting immunity• Herd immunity
– Indirect protection of nonimmune– Prevents epidemics
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In the U.S., there is a recommended childhood and adolescent immunization schedule.
Table 15.6 Recommended childhood and adolescent Immunization schedule.i
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In the U.S., there is a recommended adult immunization schedule.
Table 15.7 Recommended adult immunization schedule.
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In the U.S., there is a recommended adult immunization schedule.
Table 15.7 Recommended adult immunization schedule.
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The steps associated with the preparation of DNA vaccines.
Fig. 15.20 DNA vaccine preparation