Immunopathology I & II – the 4 types of hypersensitivity reactions and rejection

Question 1

List five stimulations that can lead to mast cell degranulation.

Answer 1

1. IgE mediated cross-linking (most common)
2. Anaphylatotins (C3a and C5a)
3. Interleukins: IL-1, IL-3, IL-8 and GM-CSF
4. Amines: Morphine, codeine
5. Physical stimuli: Vibration, heat & cold
6. Neuropeptides
7. Ionophores
8. Histamine-releasing activities

Question 2

Explain how IgE leads to mast cell activation.

Answer 2

• IgE binds to Fc receptors
• Cross links receptors
• Degranulation or preformed substances

Question 3

Name the preformed and synthesized mediators produced by an activated mast cell.

Answer 3

• Histamine
• Proteases – Vasculature leaky
• Acid hydrolysases
• Oxidatie enzymes
• Chemoattractants
- Eosiniphilic chemosttractant factor (ECF-A)
- Neutrophil Chemosttractant (NCA)

Question 4

Give three examples of localized and two of systemic type I hypersensitivity reactions.

Answer 4

•	Localized Hypersensitivity Type I
       -	Urticaria (hot and cold triggers mast cell degranulation)
       -	Atopic kkaratoconjunctivitis
       -	Asmtha
•	Systemic Type I Hypersensitivity
       -	Bee stings
       -	Drug reactions

Question 5

Explain the basic mechanism active in type II hypersensitivity reactions.

Answer 5

• Abs bind to auto-antigens
• Fix complement
• Severe disease & tissue injury

Question 6

Explain the difference between acute and delayed transfusion reactions.

Answer 6

• Acute Transfusion Hemolysis
- Pre-existing antibodies bind to RBC
- Phagocytosis in spleen and hemolysis through complement (MAC complex)
- INTRAVASCULAR HEMOLYSIS
• Delayed Transfusion Meholysis
- 1-2 weeks for Ab production
- Slow EXTRAVASCULAR HEMOLYSIS

Question 7

Explain the etiology and pathogenic mechanism of erythroblastosis fetalis.

Answer 7

• Hemolytic diseases of the new born
• Mother Rh – and has Rh + child
• First child OK
• Second child: mother will have Abs
• Liver filled erythroblast precursors in the sinusoids

Question 8

Explain the mechanism and distinctions between thyrotoxicosis (Grave’s disease) and myasthenia gravis.

Answer 8

Grave’s Disease
- Ab binds to TSH receptor so ↑ thyroid hormone

Myasthenia gravis
- Ab binds to Ach receptor so blocks natural neural signaling

Question 9

Name the Streptococcal antigens that cross react with human tissues in producing the phenomena of rheumatic fever.

Answer 9

Group A Beta hemolytic streptococcal
       -	Vegetations
       -	Thickening, shortening & fusion of chordae tendineae
       -	Fish mouth deformity of aortic valve
       -	Localized inflammation
           o	Ascoff body
           o	Aschoff Giant Cell
           o	Antischkow monocyte

Question 10

Describe the immunological phenomena causing type III hypersensitivity reactions.

Answer 10

Deposition of Ab-Antigen complexes

1. Sensitization and Ab production
2. Continuous and repeated antigen exposure
3. Ag-Ab complexes deposited
4. Complex cascade
5. Neutrophil & macrophage activation
6. Focal acute inflammation
7. Tissue degradation

Question 11

List four diseases that are type III hypersensitivity diseases.

Answer 11

• Systemic
o Serum Sickness
- Ag levels drop as they become bound to Ab
- Free Ab levels rise and then drop as they become bound to Ag
- Ag-Ab levels rise
o Drug reactions
o SLE
• Localized
o Post-streptococcal glomerulonephritis
- Neutrophil invasion
- Lumpy-bumpy basement membrane
- IgG-antigen complexes
o Vasculitis
- Ag-Ab depositions
- Inflammatory phase followed by necrotic phase
- Small vessel vasculatis: drug reactions
o Arthritis
o Pneumonitis
o Arthus Reaction

Question 12

Discuss the role of complement in hypersensitivity diseases.

Answer 12

• Complement

* MAC complex leads to tissue damage & necrosis

Question 13

Explain the basic mechanism underlying type IV hypersensitivity.

Answer 13

• Delayed Type Hypersensitivity Reactions

- T cells & macrophages respond to self-antigens causing cell & tissue damage

Question 14

Give three examples of type IV hypersensitivity disorders.

Answer 14

o	Deleted Type Hypersensitivity (DTH)
       -	CD4+ & macrophages
       -	Tuberculin reaction
       -	Granulomatous reaction
                •	Granulomas in lymph nodes
                •	Miliary TB
o	T-cell Mediated Cytotoxicity
       -	CD8+ 
       -	Response to tumors viruses & allogeneic cells
o	Rejection of a Transplanted Organ
       -	CD4+ and CD8+
       -	B-cells and antibodies

Question 15

Explain the underlying mechanisms of hyperacute, acute and chronic allograft rejection.

Answer 15

•	Hyperacute Reaction
      o	Instant – 48 hours
      o	Preformed Abs
      o	Ag-Ab reactions against endothelium
      o	Rapid thrombosis

•	Acute Rejection
      o	Weeks – months
      o	Acute Cellular
           -	Sensitized CD4 & CD8 cells
           -	Lymphocytes & macrophage infiltrates
      o	Acute Humoral
           -	Anti-graft antibodies
           -	Vasculitis, thrombosis & endothelial proliferation

•	Chronic Reaction
      o	Months – years
      o	Chronic vasculitis
      o	Intimal fibrosis
      o	Obliteration of the lumen
      o	Organ ischemia
      o	Interstitial mononuclear cell infiltrates
      o	Organ atrophy

Question 16

Describe the cause of graft versus host disease.

Answer 16

• Post bone marrow transplantation