Chapter 3 “Immunopathology” in Pathology for the Health-Related Professions by Damjanov
“Immunology”5th Edition, by Riott, Brostoff, Male
Reading
Immunization
Vaccination or active immunization
Inject antigen → acquired immune response → memory cells
Antigen 1. live but attenuated organisms 2. killed organisms 3. treated toxin
Booster shots are given at various time intervals to ensure continued immunity
Immunization
Problems: 1. Attenuated organism may
convert back to original pathogenic form
2. Immunodeficient individuals may be susceptible to attenuated vaccine
3. Hypersensitivity
4. Quality control
Immunization Passive Immunization
• Inject serum with antibodies from immunized individual
• Only beneficial for lifetime of
those antibodies (days to weeks)
Uses: 1. Prophylactic: protect travelers
against hepatitis A 2. Post-exposure to a life threatening
antigen e.g. rabies, snake bites
Immunopathology
• Over activity Hypersensitivity Autoimmune diseases • Under activity Immunodeficiency diseases • Transplantation
• Tumor Immunology
Hypersensitivity
• An exaggerated/inappropriate acquired immune response
• Inflammatory reactions and tissue damage
• 1st Exposure = OK 2nd Exposure = hypersensitivity
• Four types of response: I – III: Antibody mediated IV: T cell/macrophage mediated
Type I Hypersensitivity
• AKA Immediate hypersensitivity, allergy, anaphylaxis, atopic disease
• Most common immunologic disorder (1 in 5): • Hayfever (35mill in USA), asthma (2mill in USA)
• Genetic pre-disposition
• Production of IgE
• Antigen = allergen “changed reactivity”
Type I Hypersensitivity
Some Treatments: 1. Anti-histamines
2. Block degranulation
3. Block IgE (drugXab)
4. Steroids to suppress 1. T cell activation 2. Antibody production
5. Desensitization isotype switch IgE -> IgG/M
1. Avoidance!
Anaphylactic Shock
• Life threatening systemic release of histamine & inflammatory mediators
• Allergens - bee venom, peanuts, seafood
• Very rapid onset
Anaphylactic Shock
SYMPTOMS:
• Begins with itching and redness
• Bronchioconstriction= wheezing and shortness of breath
• swelling of throat
• Vasodilation= accumulation of fluid in lungs and tissues, reduced BP and cardiac output
• Requires immediate medical attention
Anaphylactic Shock
Treatment: • Epinephrine to stimulate arterial and
heart contraction to restore blood pressure
• Bronchodilators to open airways Otherwise circulatory shock (i.e.
under perfusion of vital organs)
Type II Hypersensitivity
• AKA Cytotoxic
• Antibody Dependent Hypersensitivity (Historically)
• IgG or IgM against normal or altered cell component
• Antigen FIXED on cell surface or extracellular matrix
• Common mechanism in autoimmune diseases
• Three types of reaction : Complement mediated reactions Antibody-dependent cell-mediated cytotoxicity Antibody-mediated cellular dysfunction
IgG/M binds to normal FIXED Ag
Type II Hypersensitivity
Host cells or tissue can opsonized by antibodies or complement and then either occurs:
• Phagocytosis
• Frustrated phagocytosis
II: IgG/M binds to normal FIXED Ag
Type II Hypersensitivity
Example: • Donor is type A • Recipient is type B
• IgG to A antigen in serum • Recipient antibodies (against A
antigen) bind to donor A RBC’s causing lysis!
• Released hemoglobin causes jaundice and kidney damage which may be fatal!
universal recipient
universal donor
universal recipient
universal donor
II: IgG/M binds to normal FIXED Ag
Type II Hypersensitivity:Erythroblastosis Fetalis
This can be prevented by injection of blocking antibodies (RhoGam, anti-Rh factor) to bind up fetal Rh antigens
Rh Factor (D antigen)
Presentation: 1. Rash 2. Anemia 3. Impaired liver function and build up of
hemoglobin breakdown products 4. Heart failure 5. Generalized edema 6. Brain damage
Type II Hypersensitivity:Erythroblastosis Fetalis
Type II Hypersensitivity
Good Pastures Syndrome: • An autoimmune disease in which
antibodies attack the collagen in the lungs and kidneys
• cause damage to kidney and lung
II: IgG/M binds to normal FIXED Ag
Type II Hypersensitivity
• Antibody Dependent Hypersensitivity
• IgG or IgM against normal or altered cell component
• Antigen FIXED on cell surface or extracellular matrix
• Common mechanism in autoimmune diseases
• Three types of reaction : Complement mediated reactions Antibody-dependent cell-mediated cytotoxicity Antibody-mediated cellular dysfunction
II: IgG/M binds to normal FIXED Ag
Type II Hypersensitivity
• Antibody-dependent cell-mediated cytotoxicity
• NK cells bind to Fc region of
antibody to kill cell
II: IgG/M binds to normal FIXED Ag
Type II Hypersensitivity
• Antibody-dependent cell-mediated cytotoxicity
• Autoimmune thyroiditis • Antibodies against to antigen
on thyroid cells • Thyroid cell death and
hypothyroidism
II: IgG/M binds to normal FIXED Ag
Type II Hypersensitivity
• Antibody Dependent Hypersensitivity
• IgG or IgM against normal or altered cell component
• Antigen FIXED on cell surface or extracellular matrix
• Common mechanism in autoimmune diseases
• Three types of reaction : Complement mediated reactions Antibody-dependent cell-mediated cytotoxicity Antibody-mediated cellular dysfunction
Type II Hypersensitivity • Antibodies to cell-surface antigen
• On binding to antigen the antibodies alter
function rather than causing direct injury
Myasthenia gravis Self-antibodies to AChR on striated muscle
↓ block receptor activation Normal Ach production
↓ muscle weakness, atrophy and paralysis
striated muscle
II: IgG/M binds to normal FIXED Ag
Type II Hypersensitivity
Graves disease where antibodies to
TSH receptor ↓
ACTIVATION!! ↓
OVER ACTIVITY of the thyroid gland
thyroid stimulating hormone (TSH)
II: IgG/M binds to normal FIXED Ag
NAUGHTY B Cell!
Hypersensitivity
1. Immediate Hypersensitivity Allergy
2. Anaphylaxis 3. Atopic disease
1. Complemented mediated • Blood Transfusions • Rhesus incompatibility • Goodpasture’s syndrome (type IV collagen)
2. Ab-Depend. Cell mediated cytotoxicity!
• Autoimmune thyroiditis
3. Antibody mediated-cellular dysfunction • Myasthenia gravis (Ach R) →BLOCK • Graves disease (TSH R) →ACTIVATION
IgG/M binds to normal FIXED Ag
Type III Hypersensitivity
• IMMUNE COMPLEX Mediated Hypersensitivity
• Antibodies and “FREE” antigen form immune complexes (Ig-Ag)
• Immune complexes normally rapidly removed
• Complexes not removed are deposited in tissues/organs
• Antiserum used to protect individual who has been exposed pathogen/toxin
• Common mechanism in autoimmune diseases!!
IgG/M binds to normal
FREE (III) Ag
Type III Hypersensitivity
Ig-Ag form in circulation ↓
activate complement in BV ↓
basophils release histamine ↓
vascular permeability!
FREE Ig-Ab III!
Normal Removal
IgG/M binds to normal
FREE (III) Ag
Type III Hypersensitivity
neutrophils recruited and try to engulf large complex
↓ Lysosomal enzymes damage
tissue ↓
Complexes migrate to tissues
IgG/M binds to normal
FREE (III) Ag
Type III Hypersensitivity
Examples of Systemic: Complexes form in circulation 1. Serum sickness: Example is passive immunization
(rabies tx) Reaction against protein in donor serum/plasma
2. SLE 3. RA 4. Polyarteritis nodosa= complication of Hep B infection
• Complex of virus Ag-Ig in artery
IgG/M binds to normal
FREE (III) Ag
Systemic Lupus Erythematosus (SLE)
• Immune complex deposition • Arthritis (95%) • Joint pain (95%) • Skin lesion (75%) • Renal dysfunction (50%) → renal
transplant • Occlusive vasculitis in NFL causes CWS
(20%)
•Treatment is immunosuppressive therapy
•75% survival after 10yrs
UV → DNA Damage → DNA-Ab → Rash
IgG/M binds to normal
FREE (III) Ag
Rheumatoid Arthritis
Pathogenesis: • Autoimmune reaction against
antigen in synovium leads to pannus formation
• Lab tests: 1. Antinuclear antibodies 2. Rheumatoid Factor:
Antibody against IgG 3. X-rays
IgG/M binds to normal
FREE (III) Ag
• Examples: 1. Farmer’s lung - antigen (fungal in origin) is inhaled 2. Pigeon fanciers lung - antigen (fungal in origin) is inhaled 3. Occurs at sites of repeated vaccinations
Type III Hypersensitivity
Ig-Ag in alveoli → inflammation/fibrosis
Local reactions • AKA: Arthus reaction
• Ig-Ag accumulate in vessels and fix complement causing local damage
INJECTION!!
IgG/M binds to normal
FREE (III) Ag