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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.
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Valon Krasniqi

Chapter 15 Specific Immunity and Immunization Cowan/Talaro PowerPoint to accompany Copyright The McGraw­Hill Companies, Inc. Permission required for reproduction or display. Topics - Thirdline of Defense - B cells - T cells - Specific Immunities 2 • Specific immunity is a complex interaction of immune cells (leukocytes) reacting against antigens – Stages – Self and nonself – Clonal selection – Antigens 3
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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