Transcript Chapter 12 - Clayton State University

Chapter 12
Disorders Associated
with the Immune System
Disorders Associated with the
Immune System
• Harmful immune responses
– Allergies
– Transplant rejection
– Autoimmunity
– Superantigens cause release of cytokines that
cause adverse host responses.
• Immunodeficiencies
Hypersensitivity Reactions
• Response to antigens (allergens) leading
to damage.
• Require sensitizing dose(s).
Type I (Anaphylactic) Reactions
• Involve IgE
antibodies.
• Localized: Hives
or asthma from
contact or
inhaled antigens.
• Systemic: Shock
from ingested or
injected
antigens.
Figure 19.1a
Type I (Anaphylactic) Reactions
• Skin testing
• Desensitization
Figure 19.3
Type II (Cytotoxic) Reactions
• Involve IgG or IgM antibodies and
complement.
• Complement activation causes cell lysis or
damage by macrophages.
ABO Blood Group System
Table 19.2
Hemolytic Disease of the
Newborn
Figure 19.4
Drug-induced Thrombocytopenic
Purpura
Figure 19.5
Type III (Immune Complex)
Reactions
• IgG antibodies and antigens form complexes that lodge
in basement membranes.
Figure 19.6
Type IV (Cell-Mediated) Reactions
• Delayed-type
hypersensitivities
due to TD cells.
• Cytokines attract
macrophages and
initiate tissue
damage.
Figure 19.8
Autoimmune Diseases
• Clonal deletion during fetal development
ensures
self-tolerance.
• Autoimmunity is loss of self-tolerance.
Autoimmune Diseases
• Type I — Due to antibodies against
pathogens.
• Type II — Antibodies react with cellsurface antigens.
• Type III (Immune Complex) — IgM, IgG,
complement immune complexes deposit in
tissues.
• Type IV — Mediated by T cells.
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
Diseases Related to Specific HLAs
Table 19.3
HLA Typing
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.
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 nonhuman tissue.
• Graft-versus-host disease can result from
transplanted bone marrow that contains
immunocompetent cells.
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.
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.
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.
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.
Acquired Immunodeficiency
Syndrome (AIDS)
• 1981: In United States, 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)
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 world-wide through modern transportation
and unsafe sexual practices.
• Norwegian sailor who died in 1976 is the first known case in
Western world.
HIV Infection
Figure 19.12b
HIV Infection
Figure 13.19
HIV Infection
Figure 19.13
HIV Infection
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, and
Kaposi's sarcoma
The Stages of HIV Infection
Figure 19.15
Some Common Diseases
Associated with AIDS
Table 19.5
Diagnostic Methods
•
•
•
•
Seroconversion takes up to three months.
HIV antibodies detected by ELISA.
HIV antigens detected by Western blotting.
Plasma viral load is determined by PCR or
nucleic acid hybridization.
HIV Transmission
• HIV survives 6 hours outside a cell
• HIV survives less than 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
Modes of HIV Transmission
Figure 19.17
AIDS Worldwide
• United States, Canada, western Europe,
Australia, northern Africa, and South America
– Injecting drug use and male-to-male sexual
contact.
• Sub-Saharan Africa
– Heterosexual contact.
• Eastern Europe, Middles East, and Asia
– Injecting drug use, heterosexual contact.
AIDS Worldwide
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, and E are in south and
southeast Asia.
• HIV-2 is seen in western Africa.
Prevention of AIDS
• Use of condoms and sterile needles.
• Health care workers use Universal
Precautions
– Wear gloves, gowns, masks, and goggles.
– Do not recap needles.
– Risk of infection from infected needlestick injury
is 0.3%.
Vaccine Difficulties
•
•
•
•
•
•
Mutations
Clades
Antibody-binding sites “hidden”
Infected cells not susceptible to CTLs
Proviruses
Latent viruses
Chemotherapy
• Nucleotide reverse transcriptase inhibitors.
• Non-nucleoside reverse transcriptase
inhibitors.
• Protease inhibitors.
• Fusion inhibitors
Highly Active Antiretroviral
Therapy (HAART)
• Combinations of nucleoside reverse
transcriptase inhibitors plus
– Non-nucleoside reverse transcriptase inhibitor
or
– Protease inhibitor
Table