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