Clinical Immunology When the Immune System Causes Disease
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Transcript of Clinical Immunology When the Immune System Causes Disease
Clinical Immunology
When the Immune System Causes Disease
or Doesn’t Work
Immune Deficiencies and Hypersensitivities
Allergies and Autoimmunity
• Allergies are IgE immune responses to harmless antigens
• The immune response causes the disease = hypersensitivity
• Other hypersensitivities are caused by IgG or by Th1 or Tc activities
• Autoimmune reactions occur against self antigens
Hypersensitivities
Type I Hypersensitivity: Allergy
• Immediate hypersensitivity
• Reaction in ~ 30 minutes
• Inflammation• Symptoms
depend on where allergen enters
Common Allergens
• Pollens
• Cat dander
• Dust mite feces
• Food antigens
Type I (Immediate) Hypersensitivity
Effects of Allergic Mediators
• Systemic anaphylaxis: inflammation throughout circulation death
IgE Effector Function
• Eosinophils bind an IgE-coated schistosome larva via Fc receptors
Hygiene Hypothesis
• Asthma rates are increasing in the US
• Children in day care have lower asthma rates than children kept at home
• People from areas with high helminth infections have low allergy rates
– When those people move to the US, their allergy rates increase
Strategies for Avoiding Allergic Symptoms
Allergy Shots
• Shots induce IgG formation; IgG binds all the allergen so it can’t reach IgE on mast cells
Hypersensitivities
Type II Hypersensitivity
• IgG/IgM antibodies bind RBC antigens
• Complement is activated, lyses RBC
• ADCC: macrophages or NK cells bind antibody-coated RBC, kill them
Hemolytic Disease of the Newborn
Prevention of Hemolytic Disease of the Newborn
Other Type II Hypersensitivities
• Medication allergies
• Mismatched blood (transfusion rxn)
• Rheumatic fever (Strep throat)
• Autoimmune hemolytic anemia
Hypersensitivities
Immune Complex Disease
Type III Hypersensitivities
• Serum sickness: horse anti-snake venom
• Lyme arthritis
• Systemic lupus erythematosis (SLE): autoimmune disease
Hypersensitivities
Type IV:T-Cell
Mediated
Poison Ivy
Contact Dermatitis
Type IV Hypersensitivities
• TB Skin test
• Contact dermatitis to nickel
• Chronic asthma
• Autoimmune diabetes (Type I)
• Transplant rejection
Transplant Rejection Responses
Transplant Rejection
• Organ grafts: Host T cells kill cells in graft with foreign MHC I and II
• Bone Marrow Transplant: mature T cells in graft kill cells in host with foreign MHC I and II
MHC Inheritance
Transplant Rejection
• We each have ~6 different Class I and ~6 different Class II MHC proteins; each has many alleles
• Best chance of sharing MHC alleles is between close blood relatives
• No time for tissue typing in heart transplants; just do blood typing
Anti-Rejection Drugs
• Block inflammation
– corticosteroids
• Block T cell activity
– Cyclosporine A
– monoclonal antibodies
Autoimmunity
• Often triggered by an infection
• Molecular mimicry: Immune response to a pathogen antigen generates antibodies and T cells that also bind self antigens
• Linked to certain MHC alleles
Autoimmune (Type I) Diabetes
• Virus infection (Coxsackie)
• Anti-virus T cells recognize self peptides on islets
• Islets destroyed --> insulin dependence
Role of MHC in Diabetes
©1999 by Elsevier Science Ltd/Garland Publishing From Immunobiology: The immune system in health and disease by Charles A. Janeway
Immune Deficiencies
• Inborn– usually a problem in cell
development or mutation in gene for an essential protein
• Acquired– usually due to microbe virulence
factors
Immune Deficiencies
• Also deficiencies of innate immunity
David the “Bubble Boy”
• SCID: no T or B cells
• Kept alive in sterile environment
• Died from cancer caused by EBV in bone marrow transplant from his sister
What You Should Know
• Mechanisms of hypersensitivities
• Normal function of IgE
• Role of MHC in transplant rejection and autoimmunity
• Molecular mimicry trigger for autoimmunity
• SCID