Immunology 2 - Hypersensitivity & Autoimmune Diseases

Question 1

Type 1 Hypersensitivity:

1. characteristics? [3]
2. what is it responsible for? [1]

Answer 1

1. Specific characteristics:
   
   • response to challenge occurs immediately
   • tends to increase in severity with repeated challenge
   • predominantly mediated by lgE bound to mast cells
2. Responsible for most “allergies”
   
   • asthma
   • eczema
   • hayfever

Question 2

Describe the pathophysiology of a type 1 hypersensitivity reaction [6]

Answer 2

1. sensitisation
2. mast cells primed with lgE
3. re-exposure to antigen
4. antigen binds to lgE associated with mast cells
5. mast cells degranulate releasing:
   
   • toxins (i.e. histamine)
   • tryptase
   • pro-inflammatory cytokines
   • chemokines
   • prostaglandins
   • leukotrienes
6. pro-imflammatory process stimulates and amplifies future responses

Question 3

Describe tissue effects during the different phases of an allergic reaction:

1. the early phase? [4]
2. the late phase? [4]

Answer 3

1. Early Phase:
   
   • occurs within minutes of exposure to antigen
   • occurs largely as a result of histamine and prostaglandins which results in:
     
     • smooth muscle contraction
     • increased vascular permeability
2. Late Phase
   
   • occurs over hours to days after exposure to antigen
   • principally mediated through recruitment of T-cells and other immune cells to site
   • results in:
     
     • sustained smooth muscle contraction/hypertrophy
     • tissue remodelling

Question 4

What is anaphylaxis and describe its pathogenesis [6]

Answer 4

• severe, systemic type I hypersensitivity
  
  • widespread mast cell degranulation caused by systemic exposure to antigen (i.e. penicillin)
  • vascular permeability is principle immediate danger:
    
    • soft tissue swelling threatening airway
    • loss of circulatory volume causing shock
  • can be rapidly fatal

Question 5

Type 2 Hypersensitivity

1. causes of type 2 hypersensitivity? [2]
2. what is it responsible for? [1]
3. pathophysiology of type 2 hypersensitivity reaction? [4]

Answer 5

1. caused by binding of antibodies directed against human cells
2. lgG is the usual cause (sometimes IgM, IgA)
3. common cause of autoimmune disease and an uncommon cause of allergy (drug associated haemolysis)
4. pathophysiology:
   
   • sensitisation
   • opsonisation of cells
   • cytotoxicity
     
     • complement activation
     • inflammation
     • tissue destruction

Question 6

Type 3 Hypersensitivity

1. cause of type 3 hypersensitivity (what is it mediated by?) [1]
2. what conditions does it cause? [2]
3. complications of type 3 hypersensitivity? [4]

Answer 6

1. mediated by immune complexes bound to soluble antigen
2. cause of autoimmune disease and drug allergy
3. complications:
   
   • aggregate in small blood vessels resulting in
     
     • direct occlusion
     • complement activation
     • perivascular inflammation

Question 7

Type 4 Hypersensitivity

1. what is type 4 hypersensitivity mediated by? [1]
2. when does it present? [1]

Answer 7

1. mediated by the action of lymphocytes infiltrating area
2. presents several days after exposure

Question 8

Define the term autoimmune disease [1]

Answer 8

harmful inflammatory response directed against ‘self’ tissue by the adaptive immune response that can be either organ specific or systemic

Question 9

Type 1 Diabetes

1. definition? [1]
2. what types of hypersensitivity are involved? [2]
3. complications? [2]

Answer 9

1. selective, autoimmune destruction of the pancreatic ß-cells
2. often mix of Type Il & Type IV
3. causes profound insulin deficiency and death if not treated with insulin replacement

Question 10

Myasthenia Gravis

1. Definition? [1]
2. Cause? [2]

Answer 10

1. syndrome of fatigable muscle weakness affecting limbs, respiratory system & head and neck
2. caused by lgG antibody acting against acetylcholine receptor preventing signal transduction

Question 11

Give 5 examples of systemic autoimmune diseases [5]

Answer 11

1. Rheumatoid arthritis
2. Systemic lupus erythematosus
3. Inflammatory bowel disease
4. Connective tissue disease
5. Systemic vasculitis

Question 12

Rheumatoid Arthritis

1. signs & symptoms? [7]
2. pathophysiology? [8]

Answer 12

1. signs & symptoms:
   
   • pulmonary nodules and fibrosis
   • pericarditis & valvular inflammation
   • small vessel vasculitis
   • soft tissue nodules
   • skin inflammation
   • weight loss
   • anaemia
2. Pathophysiology
   
   • Rheumatoid Factor is lgM and lgA directed against lgG Fc region which forms large immune complexes within synovial fluid
   • Inflammation leads to release of PAD from inflammatory cells
   • Alters variety of proteins by converting alanine to citrulline
     
     • in RA, anti-citrullinated protein/peptide antibodies are common
   • Amplification of inflammatory cascade
   • Further chemoatraction of inflammatory cells into synovium:
     
     • macrophages
     • neutrophils
     • lymphocytes
   • Osteoclast activation and joint destruction
   • Fibroblast activation and synovial hyperplasia
   • Systemic inflammation

Question 13

Treatment of Autoimmune Conditions: State the type of agent each of these drugs are and what they target:

1. infliximab? [2]
2. etanercept? [2]
3. rituximab? [2]

Answer 13

1. Infliximab
   
   • monoclonal antibody
   • targets soluble cytokines
2. Etanercept
   
   • soluble receptor
   • targets soluble cytokines
3. Rituximab
   
   • monoclonal antibody
   • targets surface markers