opto 5344 physiology & molecular biology · igg or igm against normal or altered cell component...

OPTO 5344

Physiology & Molecular Biology

Immunopathology

Rachel Redfern, OD,PhD,FAAO

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

Hypersensitivity

IgG/M binds to normal FIXED Ag

IgG/M/binds to normal FREE

(III) Ag

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”


Sensitized!

1st

2nd


Mast Cell

1. 2. 3.

1.

2.

3.

Type I Hypersensitivity: Bee Sting

Type I Hypersensitivity: Eczema

Type I Hypersensitivity: house mite

Type I Hypersensitivity: Vernal (Seasonal)


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


Antigen: normal

cell/tissue!!!

Damage to normal tissue!!

II: IgG/M binds to normal FIXED Ag


Host cells or tissue can opsonized by antibodies or complement and then either occurs:

• Phagocytosis

• Frustrated phagocytosis



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


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


Good Pastures Syndrome: • An autoimmune disease in which

antibodies attack the collagen in the lungs and kidneys

• cause damage to kidney and lung



• Antibody Dependent Hypersensitivity







• Antibody-dependent cell-mediated cytotoxicity

• NK cells bind to Fc region of

antibody to kill cell



• Antibody-dependent cell-mediated cytotoxicity

• Autoimmune thyroiditis • Antibodies against to antigen

on thyroid cells • Thyroid cell death and

hypothyroidism



• Antibody Dependent Hypersensitivity





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



Graves disease where antibodies to

TSH receptor ↓

ACTIVATION!! ↓

OVER ACTIVITY of the thyroid gland

thyroid stimulating hormone (TSH)


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


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


Ig-Ag form in circulation ↓

activate complement in BV ↓

basophils release histamine ↓

vascular permeability!

FREE Ig-Ab III!

Normal Removal


FREE (III) Ag


neutrophils recruited and try to engulf large complex

↓ Lysosomal enzymes damage

tissue ↓

Complexes migrate to tissues


FREE (III) Ag


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


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


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


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


Ig-Ag in alveoli → inflammation/fibrosis

Local reactions • AKA: Arthus reaction

• Ig-Ag accumulate in vessels and fix complement causing local damage

INJECTION!!


FREE (III) Ag

opto 5344 physiology & molecular biology · igg or igm against normal or altered cell component...

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