Hypersensitivity and the lung Flashcards
What is innate immunity?
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
What is innate immunity?
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
What is adaptive immunity?
E.g. Pus, swelling, granuloma
- Often the second line
- Delayed response time, often > 4 days
- B and T -lymphocytes
What are the cellular components of the immune system?
- Phagocytes e.g. monocytes and neutrophils
- Lymphocytes: make and release antibodies and kill diseased cells
What are the humoral components of the immune system?
- Immunoglobulins
- Complement (form membrane attack complex)
- Cytokines (allow communication between WBC and tissue cells)
What are antibodies produced by?
B-lymphocytes (plasma cells)
What do antibodies do?
- Neutralise or eliminate pathogens
- Can also cause disease
What are the 5 classifications of antibodies?
IgM, IgG, IgE, IgA, IgD
What are IgM antibodies?
they are circulating tetramers (a molecule (as an enzyme or a polymer) that consists of four structural subunits) made at the beginning of infection
What are IgG antibodies?
Monomer highly specific antibodies targeting single epitopes (pathogenic site)
What are IgE antibodies?
Likely to have developed in response to parasitic threats. Implicated in allergy, particularly alongside eosinophils
What are IgA antibodies?
Expressed in mucosal tissue. Forms dimers (a pair or them stuck together). Protects the neonatal gut
What are IgD antibodies?
Monomers, induction of antibodies in B cells, activates basophils and mast cells
What is Type I hypersensitivity?
- Mediated by IgE antibodies (+ eosinophils)
- Immediate (within an hour)
E.g. anaphylaxis and hay fever
What is Type II hypersensitivity?
- 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
What is Type III hypersensitivity?
- Mediated by deposition of immune complexes
- Comes on typically 7-21 days
E.g. Hypersensitivity pneumonitis; post streptococcal glomerulonephritis
What is Type IV hypersensitivity?
- Mediated by T-Cells (lymphocytes)
- Takes days to weeks or months to come on
E.g. Tuberculosis; Stevens-Johnson syndrome
How does Type I hypersensitivity cause a reaction?
- Antigen interacts with IgE bound to mast cells or basophils
- Degranulation of mediators lead to local effects
- Histamine is the predominant mediator
What is anaphylaxis?
- 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)
How to manage anaphlyaxis?
- Adrenaline 0.5mg or auto injector
- Steroids
- Antihistamines
- Second peak may occur after 12 hours
- Measure tryptase
How does Type II hypersensitivity cause a reaction?
- 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
What is Anti-Glomerular Basement Membrane Disease
- 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
How do we treat AGBMD?
- With plasmapheresis (remove plasma to extract offending Abs)
- Immune suppression (Steroids)
- Supportive lung treatment (ventilation) and kidneys (filtration)
What is Mycoplasma Pneumonia?
- Type II HS
- Antibodies also attack red blood cells causing agglutination and haemolysis (rupture and destruction of RBC)
How does Type III hypersensitivity cause a reaction?
- Antigen-immunoglobulin complexes formed on exposure of allergen
- Then deposited in tissues
- Causes local activation of complement and neutrophil attraction (inflammation)
What is Hypersensitivity pneumonitis
-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
How does Type IV hypersensitivity cause a reaction?
- 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
How can we check for type IV HS?
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
What is Sarcoidosis?
- Possibly reaction to mycobacteria
- Multisystem disease causing granuloma
Eyes, skin, lungs, heart, nervous system… - 80% regress spontaneously
- Some require systemic treatment – steroids, methotrexate, others
What are some common drugs that are implicated in lung disease?
- Amiodarone
- ACE-inhibitors
- Bleomycin
- Methotrexate
- Nitrofurantoin
- Checkpoint inhibitors
How do checkpoint inhibitors work?
- 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
What are three consequences of T-cell hypersensitivity?
- Diabetes
- Thyroid disease
- Hepatitis
Any –itis! - Pneumonitis (life-threatening)
What may those with eosinophilic asthma have?
- Atopic or non-atopic
Each different type can be treated based on the phenotype. Target the specific type of hypersensitivity causing the problem.
