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Transcript
TORTORA  FUNKE  CASE
ninth edition
MICROBIOLOGY
an introduction
18
Part A
Practical
Applications of
Immunology
PowerPoint® Lecture Slide Presentation prepared by Christine L. Case
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Vaccine History
 Variolation: Inoculation of smallpox into skin
(18th century).
 Vaccination: Inoculation of cowpox into skin.
 Herd immunity results when most of a population
is immune to a disease.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Principal Vaccines Used in the United States
to Prevent Bacterial Diseases in Humans
 DtaP
 Diphtheria: Purified diphtheria toxoid
 Pertussis: Acellular fragments of B. pertussis
 Tetanus: Purified tetanus toxoid
 Meningococcal meningitis: Purified polysaccharide from
N. meningitidis
 Haemophilus influenzae type b meningitis:
Polysaccharides conjugated with protein
 Pneumococcal conjugate vaccine: S. pneumoniae
antigens conjugated with protein
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Principal Vaccines Used in the United States
to Prevent Viral Diseases in Humans
 Smallpox: Live vaccinia virus
 Poliomyelitis: Inactivated virus
 Rabies: Inactivated virus
 Hepatitis A: Inactivated virus
 Influenza: Inactivated or attenuated virus
 Measles: Attenuated virus
 Mumps: Attenuated virus
 Rubella: Attenuated virus
 Chickenpox: Attenuated virus
 Hepatitis B: Antigenic fragments (recombinant vaccine)
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Monoclonal Antibodies (Mabs)
 Alemtuzumab: For leukemia
 Infliximab: For Crohn’s disease
 Rituximab: For non-Hodgkin’s lymphoma
 Trastuzumab: Herceptin for breast cancer
 Basiliximab and daclizumab: Block IL–2,
immunosuppresives for transplants
 Palivizumab: Treatment of RSV
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Monoclonal Antibodies
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 18.2
Monoclonal Antibodies
 Immunotoxins: Mabs conjugated with a toxin to target
cancer cells.
 Chimeric mabs: Genetically modified mice that produce
Ab with a human constant region.
 Humanized mabs: Mabs that are mostly human, except
for mouse antigen-binding.
 Fully human antibodies: Mabs produced from a human
gene on a mouse.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Precipitation Reactions
 Involve soluble
antigens with
antibodies.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 18.4
Agglutination Reactions
 Involve particulate
antigens and
antibodies.
 Antigens may be
 On a cell (direct
agglutination).
 Attached to latex
spheres (indirect or
passive
agglutination).
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 18.5
Antibody Titer
 Is the concentration of
antibodies against a
particular antigen.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 18.6
Viral Hemagglutination
 Hemagglutination involves agglutination of RBCs.
 Some viruses agglutinate RBCs in vitro.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 18.8
Viral Hemagglutination-Inhibition
 Hemagglutination involves agglutination of RBCs.
 Some viruses agglutinate RBCs in vitro.
 Antibodies prevent hemagglutination.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 18.9b
Neutralization Reactions
 Eliminate the harmful effect of a virus or exotoxin.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 18.9b
Complement Fixation Test
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Figure 18.10 (1 of 2)
Complement Fixation Test
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Figure 18.10 (2 of 2)
Fluorescent Antibody Techniques (Direct)
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 18.11a
Fluorescent Antibody Techniques (Indirect)
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Figures 18.11b, 3.6b
Enzyme-Linked Immunosorbent Assay
(Direct ELISA)
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Figure 18.14a
Enzyme-Linked Immunosorbent Assay
(Indirect ELISA)
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Figure 18.14b
Serological Tests
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Figure 18.13
Serological Tests
 Direct tests detect antigens (from patient sample).
 Indirect tests detect antibodies (in patient′s serum).
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Serological Tests
 Agglutination: Particulate antigens
 Hemagglutination: Agglutination of RBCs
 Precipitation: Soluble antigens
 Fluorescent-antibody technique: Antibodies linked
to fluorescent dye.
 Complement fixation: RBCs are indicator.
 Neutralization: Inactivates toxin or virus.
 ELISA: Peroxidase enzyme is the indicator.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Question 1
 Patient’s serum, influenza virus, sheep RBCs, and
anti-sheep RBCs are mixed in a tube.
 Influenza virus agglutinates RBCs.
 What happens if the patient has antibodies against
influenza virus?
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Question 2
 Patient’s serum, Chlamydia, guinea pig complement,
sheep RBCs, and anti-sheep RBCs are mixed in a
tube.
 What happens if the patient has antibodies against
Chlamydia?
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Disorders Associated with the Immune System
 Harmful immune responses
 Allergies
 Transplant rejection
 Autoimmunity
 Superantigens cause release of cytokines that cause
adverse host responses.
 Immunodeficiencies
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
TORTORA  FUNKE  CASE
ninth edition
MICROBIOLOGY
an introduction
19
Part A
Disorders Associated
with the Immune
System
PowerPoint® Lecture Slide Presentation prepared by Christine L. Case
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Hypersensitivity Reactions
 Response to antigens (allergens) leading to damage.
 Require sensitizing dose(s).
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Type I (Anaphylactic) Reactions
 Involve IgE
antibodies.
 Localized: Hives or
asthma from contact
or inhaled antigens.
 Systemic: Shock
from ingested or
injected antigens.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 19.1a
Type I (Anaphylactic) Reactions
 Skin testing
 Desensitization
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 19.3
Type II (Cytotoxic) Reactions
 Involve IgG or IgM antibodies and complement.
 Complement activation causes cell lysis or damage by
macrophages.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
ABO Blood Group System
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Table 19.2
Hemolytic Disease of the Newborn
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Figure 19.4
Drug-induced Thrombocytopenic Purpura
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Figure 19.5
Type III (Immune Complex) Reactions
 IgG antibodies and antigens form complexes that lodge
in basement membranes.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 19.6
Type IV (Cell-Mediated) Reactions
 Delayed-type
hypersensitivities due
to TD cells.
 Cytokines attract
macrophages and
initiate tissue damage.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 19.8
Autoimmune Diseases
 Clonal deletion during fetal development ensures
self-tolerance.
 Autoimmunity is loss of self-tolerance.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Autoimmune Diseases
 Type I — Due to antibodies against pathogens.
 Type II — Antibodies react with cell-surface antigens.
 Type III (Immune Complex) — IgM, IgG, complement
immune complexes deposit in tissues.
 Type IV — Mediated by T cells.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Reactions Related to the Human Leukocyte
Antigen (HLA) Complex
 Histocompatibility antigens: Self antigens on cell
surfaces.
 Major histocompatibility complex (MHC): Genes
encoding histocompatibility antigens
 Human leukocyte antigen (HLA) complex: MHC genes
in humans
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Diseases Related to Specific HLAs
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Table 19.3
HLA Typing
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Figure 19.9
Reactions to Transplantation
 Transplants may be attacked by T cells, macrophages,
and complement-fixing antibodies.
 Transplants to privileged sites do not cause an immune
response.
 Stem cells may allow therapeutic cloning to avoid
rejection.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Grafts
 Autograft: Use of one's own tissue.
 Isograft: Use of identical twin's tissue.
 Allograft: Use of tissue from another person.
 Xenotransplantation product: Use of non-human tissue.
 Graft-versus-host disease can result from transplanted
bone marrow that contains immunocompetent cells.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Immunosuppression Prevents an Immune
Response to Transplanted Tissues
 Cyclosporine suppresses IL-2.
 Mycophenolate mofetil inhibits T cell and B cell
reproduction.
 Sirolimus blocks IL-2.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
The Immune System and Cancer
 Cancer cells possess tumor-specific antigens.
 TC cells recognize and lyse cancer cells.
 Cancer cells may lack tumor antigens or kill TC cells.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 19.10
Immunotherapy
 Treatment of cancer using immunologic methods.
 Tumor necrosis factor, IL-2, and interferons may kill
cancer cells.
 Immunotoxins link poisons with an monoclonal antibody
directed at a tumor antigen.
 Vaccines contain tumor-specific antigens.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Immune Deficiencies
 Congenital: Due to defective or missing genes
 Selective IgA immunodeficiency
 Severe combined immunodeficiency
 Acquired: Develop during an individual's life, due to
drugs, cancers, and infections.
 Artificial: Immunosuppression drugs.
 Natural: HIV infections.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings