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MICROBIOLOGY
Chapter 19
Disorders Associated with the
Immune System
Dr. Abdelraouf A. Elmanama
Ph. D Microbiology
Medical Technology Department, Faculty of Science, Islamic University-Gaza
2008
Disorders Associated with the
Immune System
• Infection and immunosuppression are failures
of the immune system.
• Superantigens cause release of cytokines that
cause adverse host responses.
• Allergies and transplant rejection are harmful
immune reactions
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Hypersensitivity Reactions
• Response to antigens (allergens) leading to damage
• Require sensitizing dose(s)
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Type I (Anaphylactic) Reactions
• Involve IgE
antibodies
• Localized: Hives
or asthma from
contact or inhaled
antigens
• Systemic: Shock
from ingested or
injected antigens
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Figure 19.1a
Type I (Anaphylactic) Reactions
• Skin testing
• Desensitization
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Figure 19.3
Type II (Cytotoxic) Reactions
• Involve IgG or IgM antibodies and complement
• Complement activation causes cell lysis or damage by
macrophages
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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.
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Figure 19.6
Type IV (Cell-Mediated) Reactions
• Delayed-type
hypersensitivities due
to TD cells
• Cytokines attract
macrophages and
initiate tissue damage
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Figure 19.8
Autoimmune Diseases
• Clonal deletion during fetal development ensures selftolerance
• Autoimmunity is loss of self-tolerance
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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
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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
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Diseases Related to Specific HLAs
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Table 19.3
HLA Typing
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Figure 19.1
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.
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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
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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
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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, infections
• Artificial: Immunosuppression drugs
• Natural: HIV infections
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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
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Figure 19.11
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
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Acquired Immunodeficiency
Syndrome (AIDS)
2008
• 1981
In U.S., cluster of Pneumocystis and
Kaposi's sarcoma in young
homosexual men discovered. The
men showed loss of immune
function.
• 1983
Discovery of virus causing loss of
immune function.
Acquired Immunodeficiency Syndrome (AIDS)
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Figure 19.12a
The Origin of AIDS
• Crossed the species barrier into humans in Africa in
the 1930s
• Patient who died in 1959 in Congo is the oldest known
case
• Spread in Africa as a result of urbanization
• Spread in world through modern transportation and
unsafe sexual practices
• Norwegian sailor who died in 1976 is the first known
case in Western world
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HIV Infection
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Figure 19.12b
HIV Infection
Capsid
Reverse
transcriptase
DNA
Virus
Two identical + stands of RNA
1 Retrovirus penetrates
host cell.
Host
cell
DNA of one of the host
cell’s chromosomes
5 Mature
retrovirus
leaves host
cell, acquiring
an envelope as
it buds out.
Reverse
transcriptase
Viral RNA
Identical
strands of
RNA
2 Virion penetrates
cell and its DNA is
uncoated
4 Transcription of the
Viral proteins
RNA
provirus may also occur,
producing RNA for new
retrovirus genomes and
RNA that codes for the
retrovirus capsid and
envelope proteins.
Provirus
2008
3 The new viral DNA is
tranported into the host cell’s
nucleus and integrated as a
provirus. The provirus may
divide indefinitely with the
host cell DNA.
Figure 13.19
HIV Infection
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Figure 19.13
HIV Infection
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Figure 19.14
The Stages of HIV Infection
• Category A
Asymptomatic or persistent
lymphadenopathy
• Category B
Persistent Candida albicans infections
• Category C
Clinical AIDS. CMV, TB,
Pneumocystis, toxoplasmosis,
Kaposi's sarcoma
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The Stages of HIV Infection
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Figure 19.15
Some Common Diseases Associated with AIDS
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Table 19.5
Diagnostic Methods
• Seroconversion takes up to 3 months
• HIV antibodies detected by ELISA
• HIV antigens detected by Western blotting
• Plasma viral load is determined by PCR or nucleic acid
hybridization
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HIV Transmission
• HIV survives 6 hours outside a cell
• HIV survives >1.5 days inside a cell
• Infected body fluids transmit HIV via:
• Sexual contact
• Breast milk
• Transplacental infection of fetus
• Blood-contaminated needles
• Organ transplants
• Artificial insemination
• Blood transfusion
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Modes of HIV Transmission
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Figure 19.17
AIDS Worldwide
• U.S., Canada, western Europe, Australia, northern
Africa, South America
• Injecting drug use, male-to-male sexual contact
• Sub-Saharan Africa
• Heterosexual contact
• Eastern Europe, Middles East, Asia
• Injecting drug use, heterosexual contact
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AIDS Worldwide
2008
Figure 19.16
Clades
• HIV-1 is the most common. It has 11 clades:
• 90% of U.S. infections caused by clade B
• Clade C predominates in sub-Saharan African
• Clades B, C, & E are in south and southeast Asia
• HIV-2 is seen in western Africa
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Prevention of AIDS
• Use of condoms and sterile needles
• Health-case workers use universal precautions
• Wear gloves, gowns, masks, goggles
• Do not recap needles
• Risk of infection from infected needlestick injury is
0.3%
2008
Vaccines in Clinical
• Whole-cell Salmonella with gp120 gene
• Subunit vaccine using gp120 expressed in
Saccharomyces
• Canarypox virus with HIV capsid protein genes
• Naked DNA consisting of tat (transcription factor) or
gag (capsid protein) genes
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Chemotherapy
• Nucleotide Reverse Transcriptase Inhibitors
• Non- Nucleoside Reverse Transcriptase Inhibitors
• Protease Inhibitors
• Virus decoys
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Highly Active Antiretroviral Therapy (HAART):
• Combinations of nucleoside reverse transcriptase
inhibitors +
• Non-nucleoside reverse transcriptase inhibitor or
• Protease inhibitor
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