Hypersensitivity and the lung

Question 1

What is innate immunity?

Answer 1

E.g. sputum and cilia in lungs
- It is the first line in defence and has an immediate response.
- It is composed of phagocytes, mast cells

Question 1

What is innate immunity?

Answer 1

E.g. sputum and cilia in lungs
- It is the first line in defence and has an immediate response.
- It is composed of phagocytes, mast cells

Question 2

What is adaptive immunity?

Answer 2

E.g. Pus, swelling, granuloma
- Often the second line
- Delayed response time, often > 4 days
- B and T -lymphocytes

Question 3

What are the cellular components of the immune system?

Answer 3

• Phagocytes e.g. monocytes and neutrophils
• Lymphocytes: make and release antibodies and kill diseased cells

Question 4

What are the humoral components of the immune system?

Answer 4

• Immunoglobulins
• Complement (form membrane attack complex)
• Cytokines (allow communication between WBC and tissue cells)

Question 5

What are antibodies produced by?

Answer 5

B-lymphocytes (plasma cells)

Question 6

What do antibodies do?

Answer 6

• Neutralise or eliminate pathogens
• Can also cause disease

Question 7

What are the 5 classifications of antibodies?

Answer 7

IgM, IgG, IgE, IgA, IgD

Question 8

What are IgM antibodies?

Answer 8

they are circulating tetramers (a molecule (as an enzyme or a polymer) that consists of four structural subunits) made at the beginning of infection

Question 9

What are IgG antibodies?

Answer 9

Monomer highly specific antibodies targeting single epitopes (pathogenic site)

Question 10

What are IgE antibodies?

Answer 10

Likely to have developed in response to parasitic threats. Implicated in allergy, particularly alongside eosinophils

Question 11

What are IgA antibodies?

Answer 11

Expressed in mucosal tissue. Forms dimers (a pair or them stuck together). Protects the neonatal gut

Question 12

What are IgD antibodies?

Answer 12

Monomers, induction of antibodies in B cells, activates basophils and mast cells

Question 13

What is Type I hypersensitivity?

Answer 13

• Mediated by IgE antibodies (+ eosinophils)
• Immediate (within an hour)
  E.g. anaphylaxis and hay fever

Question 14

What is Type II hypersensitivity?

Answer 14

• Mediated by cytotoxic antibodies bind to the cell antigen
• Comes on in hours to days
  E.g. Transfusion reactions and Goodpastures (Anti GBM disease) - antibodies attack the basement membrane in lungs and kidneys

Question 15

What is Type III hypersensitivity?

Answer 15

• Mediated by deposition of immune complexes
• Comes on typically 7-21 days
  E.g. Hypersensitivity pneumonitis; post streptococcal glomerulonephritis

Question 16

What is Type IV hypersensitivity?

Answer 16

• Mediated by T-Cells (lymphocytes)
• Takes days to weeks or months to come on
  E.g. Tuberculosis; Stevens-Johnson syndrome

Question 17

How does Type I hypersensitivity cause a reaction?

Answer 17

• Antigen interacts with IgE bound to mast cells or basophils
• Degranulation of mediators lead to local effects
• Histamine is the predominant mediator

Question 18

What is anaphylaxis?

Answer 18

• Sudden onset
• Systemic degranulation of mast cells and histamine release
• Skin, eyes, lips swelling, hypotension
• Bronchospasm can result in airway occlusion and death if not managed
  (Type I Hypersensitivity)

Question 19

How to manage anaphlyaxis?

Answer 19

• Adrenaline 0.5mg or auto injector
• Steroids
• Antihistamines
• Second peak may occur after 12 hours
• Measure tryptase

Question 20

How does Type II hypersensitivity cause a reaction?

Answer 20

• Antibodies reacting with antigenic determinants on the host cell membrane
• Usually IgG or IgM
• Outcome depends on whether complement is activated and if metabolism of cell is affected

Question 21

What is Anti-Glomerular Basement Membrane Disease

Answer 21

• Rare but deadly Type II HS disease
• Alveolar involvement
• GBM made of type IV collagen present in alveoli
• The Alpha 3 subunit of this collagen becomes antigenic
  Very rare

Question 22

How do we treat AGBMD?

Answer 22

• With plasmapheresis (remove plasma to extract offending Abs)
• Immune suppression (Steroids)
• Supportive lung treatment (ventilation) and kidneys (filtration)

Question 23

What is Mycoplasma Pneumonia?

Answer 23

• Type II HS
• Antibodies also attack red blood cells causing agglutination and haemolysis (rupture and destruction of RBC)

Question 24

How does Type III hypersensitivity cause a reaction?

Answer 24

- Antigen-immunoglobulin complexes formed on exposure of allergen - Then deposited in tissues - Causes local activation of complement and neutrophil attraction (inflammation)

Question 25

What is Hypersensitivity pneumonitis

Answer 25

-Formerly “extrinsic allergic alveolitis” (EAA) - Immune complexes formed with a range of different antigens - Deposited in the acinar airways leading to inflammation acutely and scarring chronically - Treatment by removal of antigen +/- immunosuppression

Question 26

How does Type IV hypersensitivity cause a reaction?

Answer 26

- T-cell mediated, releasing IL2, IFᵧ and other cytokines - Requires primary sensitisation (doesn't happen first time you are exposed) - Secondary reaction takes 2-3 days to develop - May result from normal immune reaction – if macrophages cannot destroy pathogen, they become giant cells and form granuloma

Question 27

How can we check for type IV HS?

Answer 27

Patch testing: - Control test - Other test - Positive test Or tuberculin skin test (only positive if been exposed before or had the vaccine) - Takes several days for it to come up

Question 28

What is Sarcoidosis?

Answer 28

- Possibly reaction to mycobacteria - Multisystem disease causing granuloma Eyes, skin, lungs, heart, nervous system… - 80% regress spontaneously - Some require systemic treatment – steroids, methotrexate, others

Question 29

What are some common drugs that are implicated in lung disease?

Answer 29

- Amiodarone - ACE-inhibitors - Bleomycin - Methotrexate - Nitrofurantoin - Checkpoint inhibitors

Question 30

How do checkpoint inhibitors work?

Answer 30

- Cancer cell presents PD-L1 allowing it to disguise as not foreign - Checkpoint inhibitors block the PD-L1 and PD-1 system - Allows T-Cell to recognise cancer as foreign so can be destroyed normally

Question 31

What are three consequences of T-cell hypersensitivity?

Answer 31

- Diabetes - Thyroid disease - Hepatitis Any –itis! - Pneumonitis (life-threatening)

Question 32

What may those with eosinophilic asthma have?

Answer 32

- Atopic or non-atopic Each different type can be treated based on the phenotype. Target the specific type of hypersensitivity causing the problem.