Clinical Immunology When the Immune System Causes Disease or Doesn’t Work
Nov 02, 2014
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