Immuno Flashcards
Describe the ways in which physical barriers prevent infection by microorganisms.
1) Skin - has tightly packed keratinised cells, low pH and low oxygen tension to reduce likelihood of colonisation
- sebaceous glans produce hydrophic oils, lysozyme and ammonia/defensins
2) Mucosa - mucous traps pathogens
- IgA prevents attachment
- lysozyme and antimicrobial peptides kill pathogens
- lactoferin starves bacteria of iron
- cilia trap pathogens and waft away mucous
How does IgA deficiency present?
1/600 Caucasians, 70% asymptomatic but may otherwise be associated with recurrent gastrointestinal and respiratory infections
Name the innate immune system defect:
A 4 year old child presents to A&E with a cough and a fever. His PMHx shows frequent infections, including impetigo, osteomyelitis and abscesses. A CXR shows multiple pulmonary nodules and a bronchoalveolar lavage culture is positive for Aspergillus spp. A nitro-blue tetrazolium test confirms the diagnosis.
a) Reticular dysgenesis
b) Kostmann syndrome
c) Cyclic neutropenia
d) Leukocyte adhesion deficiency (type 1)
e) Leukocyte adhesion deficiency (type 2)
f) Chronic granulomatous disease
g) IFN-gamma receptor deficiency
h) Natural killer cell deficiency
f) Chronic granulomatous disease
This is an inherited condition (mostly X-linked) where there is a deficiency of a component of NADPH oxidase and therefore an inability to generate oxygen radicals. This reduces IC killing of pathogens, leads to chronic inflammation and the formation of granulomas.
Symptoms are of recurrent infections, which may include regular bowel disturbances or a ‘constantly runny nose’. Signs include hepatosplenomegaly and lymphadenopathy. Infection is usually with catalase positive organisms (PLACESS): Pseudomonas, Listeria, Aspergillus, Candida, E.coli, S.aureus and Serratia. Fungal pneumonias should increase suspicion of this diagnosis.
Ix - abnormal NBT test: stays yellow after hydrogen peroxide due to inability of NADPH oxidase to produce H2O2 and oxygen radicals.
- dihydrorhodamine (DHR) flow cytometry: lack of fluorescent rhodamine seen with H2O2 oxidation
Mx - prophylactic trimethoprim, itraconazole, IFN
Name the innate immune system defect:
A 3 week old baby is brought to the GP by her mother. She says that the baby has become more irritable over the last 2 days, looks lethargic and is refusing to take feeds. The GP measures the baby’s temperature at 35.5 degrees. The baby is immediately sent to hospital and blood tests show a severe neutropenia.
a) Reticular dysgenesis
b) Kostmann syndrome
c) Cyclic neutropenia
d) Leukocyte adhesion deficiency (type 1)
e) Leukocyte adhesion deficiency (type 2)
f) Chronic granulomatous disease
g) IFN-gamma receptor deficiency
h) Natural killer cell deficiency
b) Kostmann syndrome a.k.a. severe congenital neutropenia
An autosomal recessive condition, usually caused by a mutation in HCLS-1 associated protein X-1 (HAX 1). 50% of infants with this condition present within the first month of life. It commonly presents with infections caused by Staphylococcus aureus, including abscesses, pneumonia and sepsis.
Ix will show a chronic neutropenia and arrest of neutrophil precursor maturation in the bone marrow.
Treatment is with G-CSF and prophylactic antibiotics e.g. septrin. Definitive treatment is with a bone marrow transplant.
Name the innate immune system defect:
A 9 month old is brought to the GP by her father after he noticed that her gums have looked very sore for the past month. On questioning, he reports that she had delayed separation of the umbilical cord after birth. A nitro-blue tetrazolium test returns a normal result but the GP notices a neutrophilia on the baby’s blood tests.
a) Reticular dysgenesis
b) Kostmann syndrome
c) Cyclic neutropenia
d) Leukocyte adhesion deficiency (type 1)
e) Leukocyte adhesion deficiency (type 2)
f) Chronic granulomatous disease
g) IFN-gamma receptor deficiency
h) Natural killer cell deficiency
d) Leukocyte adhesion deficiency (type 1)
This is the most common type of LAD. It causes a deficiency of the beta 2 integrin subunit, CD18. normally, CD18/11alpha allow neutrophils to bind to the ligand ICAM-1 on endothelial cells and therefore migrate out of the bloodstream. Failure to do this in LAD-1 leads to a neutrophilia and absence of pus in localised infections.
LAD-1 is associated with neonatal infection, including gingivitis, and delayed umbilical cord separation at 3/4 weeks after birth. LAD-2 is less common and presents with severe growth restriction and mental retardation.
The only definitive treatment is with a bone marrow transplant.
Name the innate immune system defect:
A 3 year old who has just started nursery is brought to the GP by her parents. She has had severe vomiting and diarrhoea for the past 2 days and her parents are worried that she might have more than a normal ‘tummy bug’. Blood tests are all normal except a raised WCC and CRP. Blood cultures come back positive for Salmonella.
a) Reticular dysgenesis
b) Kostmann syndrome
c) Cyclic neutropenia
d) Leukocyte adhesion deficiency (type 1)
e) Leukocyte adhesion deficiency (type 2)
f) Chronic granulomatous disease
g) IFN-gamma receptor deficiency
h) Natural killer cell deficiency
g) IFN-gamma receptor deficiency
Out of the options, this is the most likely disease to predispose children to Salmonella infection. Mycobacterial infections are also more common in this condition.
The loss of the action of IFN-gamma on macrophages and neutrophils (positive feedback) leads to reduced TNF release and reduced production of oxygen radicals by NADPH oxidase. Patients are unable to form granulomata.
What mutation is associated with cyclic neutropenia?
Mutation in neutrophil elastase (ELA-2); autosomal dominant condition
What mutation is associated with cyclic neutropenia?
Mutation in neutrophil elastase (ELA-2); autosomal dominant condition
What type of infections are people with natural killer cell deficiencies most susceptible to?
Viral infections e.g. herpes, VZV, EBV
This is because NK cells usually regulate infected cells by cytotoxic killing of these cells and the release of cytokines to promote dendritic cell function. Infected cells lack sufficient MHC class I as it is downregulated by the infecting virus. Inhibitory receptors on NK cells would normally bind to MHC class I, therefore preventing cytotoxic killing, but if this is not present then the binding of activating receptors will lead to destruction of the infected cells.
Describe the 3 ways in which the complement common pathway can be activated.
1) Classical - antibody-antigen binding causes formation of C1qrs complex on surface of pathogen via antibody Fc component binding to C1. This then leads to conversion of C4 to C4b and then C4b2 to C4b2a (C3 convertase)
2) Mannose binding lectin - binding to specific carbohydrates on the surface of pathogens leads to conversion of C4 to C4b and then C4b2 to C4b2a (C3 convertase)
3) Alternative - spontaneous C3 degradation to C3a and C3b. C3b joins to factor B to produce C3bBb, which is a C3 convertase, thus leading to positive feedback
What are the functions of complement?
1) Formation of membrane attack complex
2) Opsonisation of pathogens
3) Activation of phagocytes and mast cell degranulation
4) Increase vascular permeability and cell trafficking to sites of infection
How do the membrane attack complex form and lead to pore formation in the membranes of bacteria?
The C3 convertase C3bBb is formed following the classical, MBL or alternative pathways. The addition of another C3b then causes the formation of a C5 convertase, which splits C5 on the pathogen membrane into C5a and C5b. C5b acts as a foundation for C6, 7, 8 to link on to the surface of the pathogen and then finally for several molecules of C9 (10-16) to link together. C9 is added until a pore is formed, which compromises the membrane integrity of the pathogen and leads to eventual lysis.
Name the complement deficiency described below:
Found in 6-10% of individuals and increases their susceptibility to infection and other forms of immune impairment.
a) Classical pathway
b) Lectin pathway
c) Alternative pathway
d) C3 deficiency (common pathway)
e) C9 deficiency (common pathway)
b) Lectin pathway - no MBL in 6-10% of individuals
Name the complement deficiency described below:
Failure to generate and stabilise the C3 convertase, C3bBb leads to poor complement response to encapsulated bacteria.
a) Classical pathway
b) Lectin pathway
c) Alternative pathway
d) C3 deficiency (common pathway)
e) C9 deficiency (common pathway)
c) Alternative pathway
Factor B binds to C3b to form C3bB and then factor D cleaves the product to form C3bBb. Factor P (properdin) is involved in stabilising the C3 convertase complex on the bacterial cell wall surface. A deficiency in any of these factors leads to an ineffective alternative pathway.
Patients with these deficiencies have recurrent infections with encapsulated bacteria. Mnemonic: Some Nasty Killers Have Some Capsule Protection
- Streptococcus pneumoniae
- Neisseria meningitidis
- Klebsiella pneumonia
- Haemophilus influenzae
- Salmonella typhi
- Cryptococcus neoformans
- Pseudomonas aeruginosa
Name the complement deficiency described below:
There is a failure to form the membrane attack complex. Patients with have low levels of CH50 and AP50. This deficiency is also sometimes secondary to increased immune complex deposition and complement consumption in SLE.
a) Classical pathway
b) Lectin pathway
c) Alternative pathway
d) C3 deficiency (common pathway)
e) C9 deficiency (common pathway)
e) C9 deficiency (common pathway)
Failure to lyse encapsulated bacteria leads to high incidence of meningitis and pneumonia. It is also associated with membranoproliferative glomerulonephritis as nephritic factors stabilise C3 convertase.
Name the complement deficiency described below:
Decreased clearance of immune complexes by erythrocytes leads to the deposition of immune complexes and local inflammation. There is an increase in self antigens and susceptibility to autoimmunity.
a) Classical pathway
b) Lectin pathway
c) Alternative pathway
d) C3 deficiency (common pathway)
e) C9 deficiency (common pathway)
a) Classical pathway
Associated with the development of SLE, skin diseases and increased rates of infection. C2 deficiency is the most common. C1q deficiency has been associated with mesangial proliferative glomerulonephritis. Investigations will show reduced CH50.
Outline the process of immunoglobulin isotype switching.
Early response to antigen by B cells is the production of IgM.
Presentation of the antigen by dendritic cells to CD4+ cells in the lymph nodes leads to activated T cells. These cells can then bind to undifferentiated B cells via CD40L:CD40 binding, stimulating proliferation of B cells with somatic hypermutation and increased isotype switching. IgG, A and E are produced.
A 3 month old baby is brought to A&E by his parents. Over the past 2 weeks, the baby has become increasingly unwell with a cough and now has a fever and is refusing to feed. The red book shows that he has also been failing to put on weight.
They report that they live in a household with many relatives and the baby’s uncle visited from India 1 month ago. The mother’s sister had a baby who died at 4 months old from an infection.
A WCC with differentials shows a low lymphocyte count. What is the likely diagnosis and the underlying cause?
This baby is likely to have TB, caught by exposure to someone with active TB infection. The underlying cause here is Severe Combined Immune Deficiency (SCID). Thsi causes a mixed B and T cell deficiency. 45% of cases of SCID are X-linked genetic causes e.g. Xq13.1 which causes a defect in the IL-2 R.
Defects in lymphoid precursors lead to a predisposition to early infection with CMV/TB and early malignancy. Most are unwell by 3 months old and have recurrent infections with failure to thrive. They may have persistent diarrhoea or present with GVHD, due to bone marrow colonisation by maternal lymphocytes. There may be a family history of early infant death.
Depending on the cause, investigations will show either a decrease or absence of B cells with low T cell numbers or absent T cells with a normal or increase in B cells, associated with poor thymus development (X-linked is the latter). There will be a lack of circulating antibodies. The only treatment is a bone marrow transplant.
A 1 week old neonate is seen by a health visitor. The parents are worried because the baby has ‘a weird mouth’ and doesn’t seem to be able to latch on to breastfeed. She notices that the baby has abnormal looking facies, with a high forehead and low set folded ears. She recommends that they bring the baby into hospital and doctors note a low calcium, normal number of B cells and lack of mature T cells on blood tests. They send the baby for an echo. What causes this condition?
Di George syndrome - 22q11.2 deletion (75% sporadic) leads to a developmental defect of the 3rd and 4th pharyngeal pouches, which is involved in the development of the oesophagus, thymus and heart.
Mnemonic = CATCH 22 Cardiac abnormalities Abnormal facies - including high forehead, low set folded ears, small mouth and jaw Thymic absence Cleft palate Hypocalcaemia (secondary to low PTH)
Ix show a depletion of mature T cells due to the thymic absence. B cells and IgM may be normal or reduced and IgG is reduced. This improves with age. Definitive treatment is with a thymic transplant.
A 2 month old neonate who has had recurrent infections since birth and failure to thrive. She has now been admitted to the paediatric ward with 3 days of severe diarrhoea. The paediatricians suspect a defect in HLA expression is the underlying cause. What is this condition caused and how is it diagnosed?
Bare lymphocyte syndrome - defect of regulatory factor X or class II transactivator leads to absent HLA expression and failure of lymphocytes to develop. There are 2 types: type 1 has absent MHC class I which leads to reduced CD8+ cells and type 2 has absent MHC class II and reduced CD4+ cells. Type 2 is more common.
There are also reduced levels of IgA and IgG due to a lack of class switching. Investigations include WCC, lymphocyte subsets, serum Ig/protein electrophoresis and functional tests.
Mx - infection prophylaxis, Ig replacement and aggressive management of infections
Name the condition outlined below:
A defect in tyrosine kinase leads to failure to develop mature B cells and a failure to produce antibodies.
Bruton’s X-linked Hypergammaglobulinaemia
Tyrosine kinase defect leads to recurrent bacterial infections. Usually presents between 3 and 6 months.
A 14 month old presents with a cough. A CXR shows widespread pulmonary infiltrates and her PO2 is 8kPa. Blood tests show normal numbers of B+T cells and serum electrophoresis show increased serum IgM with no other immunoglobulins. The diagnosis is confirmed and her parents are advised that she is at a higher risk of autoimmunity and malignancy. What condition does she have and what is the underlying problem?
Hyper IgM syndrome - X-linked condition
Defects in CD40L:CD40, AICDA and CD154 leads to a failure of activated T cells to bind to B cells and stimulate proliferation and class switching. There is no production of IgA/G/E.
Patients present in the first few years with recurrent bacterial infections e.g. pneumocystis carinii pneumonia, which causes failure to thrive. The increased risk of autoimmunity and malignancy is due to defective regulation and apoptosis. There is also reduced germinal centre development (lymph nodes and spleen).
What B cell deficiency most frequently presents with failure to thrive, autoimmune conditions and gastrointestinal disease, associated with reduced B cell differentials?
Common variable immune deficiency - caused by a number of different genetic causes leading to decreased B cell differentiation (but normal numbers of B cells) and reduced production of IgG, E and A.
There is no response to vaccines.
Summarise the main clinical features of B cell deficiencies.
1) Recurrent bacterial infections - may lead to severe end organ damage
2) Pulmonary disease - obstructive, interstitial and granulomatous interstitial disease
3) GI disease e.g. ‘IBD-like’ or ‘sprue like’
4) Autoimmune e.g. AIHA, AITP, RA, pernicious anaemia, thyroiditis
5) Malignancy - non-Hodgkin lymphoma
How can type 1 hypersensitivity reactions be investigated?
Acute - serum mast cell tryptase; peaks at 1-2h and returns to baseline by 6-12h after event
Elective
- skin prick: allergen extract vs. dilutent as -ve control and histamine as +ve control (+ve is wheal more than 2mm bigger than negative control)
- specific IgE test (RAST): specific IgE binds to allergen in serum and is tagged with anti-IgE Ab fluorescent markers
- challenge test (gold standard for food allergies): titrated increase in ingestion of substance involved
- component resolved diagnostics: to specify allergen protein
What is the definition of anaphylaxis?
A severe systemic allergic reaction with a sudden onset and rapid progression of life-threatening airway and circulatory symptoms with skin or mucosal damage.
Give the drugs (including doses) used in the management of anaphylaxis.
1) 100% oxygen
2) IM adrenaline 500 micrograms (0.5ml of 1:1000)
3) Hydrocortisone 100mg IV
4) Inhaled bronchodilators
5) Chlorphenamine 10mg IV (antihistamine)
N.B. adult epipen contains 300 micrograms of adrenaline; child’s contains 150 micrograms
Name the type 1 hypersensitivity reaction described below:
Crossreactivity between allergens leads to symptoms which are limited to the mouth. 2% present with anaphylaxis.
a) Food allergy
b) Oral allergy syndrome
c) Allergic rhinitis
d) Atopic dermatitis
e) Latex food syndrome
f) Acute urticaria
b) Oral allergy syndrome
Examples of allergens causing crossreactivity include birch pollen with rosacea fruit and ragweed with melons. Exposure to the allergen will lead to food allergy due to the homologous nature of the proteins involved.
Mx - food avoidance, anti-histamine mouth wash
Name the type 1 hypersensitivity reaction described below:
50% of cases are idiopathic and 50% are secondary to food, drugs, latex and viral illness. The process is Ig-E mediated and leads to wheals which resolves within 6 weeks.
a) Food allergy
b) Oral allergy syndrome
c) Allergic rhinitis
d) Atopic dermatitis
e) Latex food syndrome
f) Acute urticaria
f) Acute urticaria
Ix - clinical with or without skin prick
Mx - allergen avoidance and anti-histamines
Name the type 1 hypersensitivity reaction described below:
May be an association between kiwi and latex, for example. It is diagnosed with a skin prick test.
a) Food allergy
b) Oral allergy syndrome
c) Allergic rhinitis
d) Atopic dermatitis
e) Latex food syndrome
f) Acute urticaria
e) Latex food syndrome
Latex allergy associated with chestnuts, avocado, banana, potato, tomato and kiwi.
Name the type 1 hypersensitivity reaction described below:
Associated with a defect in beta-defensin and the presence of staphylococcus aureus. 80% of cases present within the first year of life.
a) Food allergy
b) Oral allergy syndrome
c) Allergic rhinitis
d) Atopic dermatitis
e) Latex food syndrome
f) Acute urticaria
d) Atopic dermatitis
Diagnosis is clinical. Management is with emollients, skin oil, topical steroids and PUVA.
What are the findings on examination in patients with allergic rhinitis?
Symptoms - nasal itch and congestion, runny nose, loss of smell, itchy eyes
Examination - pale bluish swollen nasal mucosa
Treatment is with oral antihistamines and steroid nasal spray.
What is the mechanism of type 2 hypersensitivity reactions?
Antibody driven - IgG/M reacts with cell or matrix associated self antigen leads to tissue damage and receptor blockade
Name the type 2 hypersensitivity reaction outlined in the case below:
The 36 year old owner of a drycleaners presents to A&E with rapidly progressive shortness of breath and a bad cough. He complains of feeling achy and lethargic for the last 24 hours and within the past few hours he has noticed some blood when he has been coughing. The FY2 in A&E notes that he has swollen legs. A urine dipstick reveals haematuria.
a) Haemolytic disease of the newborn
b) Autoimmune haemolytic anaemia
c) Autoimmune thrombocytopaenia
d) Goodpasture’s
e) Pemphigus vulgaris
f) Graves disease
g) Myasthenia gravis
h) Acute rheumatic fever
i) Pernicious anaemia
j) Churg-Strauss
k) Wegener’s granulomatosis
l) Microscopic polyangitis
m) Chronic urticaria
d) Goodpasture’s syndrome
Patients present with glomerulonephritis and pulmonary symptoms due to the production of antibodies to type IV collagen. The progression of symptoms is often very rapid, with pulmonary symptoms, such as shortness of breath and haemoptysis secondary to pulmonary haemorrhage, and renal symptoms, including nephrotic syndrome and haematuria, usually presenting at the same time.
The cause is unknown but it has been associated with smoking and exposure to certain dyes, organic solvents and metallic dust.
Ix - anti-GBM antibodies
- linear smooth immunoflourescent staining of the basement membrane IgG deposits on biopsy
Mx - corticosteroids and immunosuppression
Name the type 2 hypersensitivity reaction outlined in the case below:
An 8 year old girl presents to A&E with bruising and discoloured non-blanching purple spots on her skin. Her parents say that she had a cold last week. Her platelet count is 15 x 10^9/L but her Hb and WCC are normal.
a) Haemolytic disease of the newborn
b) Autoimmune haemolytic anaemia
c) Autoimmune thrombocytopaenic purpura
d) Goodpasture’s
e) Pemphigus vulgaris
f) Graves disease
g) Myasthenia gravis
h) Acute rheumatic fever
i) Pernicious anaemia
j) Churg-Strauss
k) Wegener’s granulomatosis
l) Microscopic polyangitis
m) Chronic urticaria
c) Autoimmune thrombocytopaenic purpura
Acute cases are usually triggered by a virus, found in children and associated with a platelet count of <20 x 10^9/L. Chronic cases are found in adults.
Antibodies against glycoprotein IIb/IIIa coat the platelets and allow opsonisation and phagocytosis by spleen macrophages. Antibodies may also damage megakaryocytes and prevent replacement platelets being produced.
Mx - steroids, IVIG, anti-D antibodies, splenectomy
Name the type 2 hypersensitivity reaction outlined in the case below:
A neonate presents with severe jaundice 6 hours after birth. On investigations, there is a reticulocytosis, anaemia and a positive direct Coomb’s test.
a) Haemolytic disease of the newborn
b) Autoimmune haemolytic anaemia
c) Autoimmune thrombocytopaenia
d) Goodpasture’s
e) Pemphigus vulgaris
f) Graves disease
g) Myasthenia gravis
h) Acute rheumatic fever
i) Pernicious anaemia
j) Churg-Strauss
k) Wegener’s granulomatosis
l) Microscopic polyangitis
m) Chronic urticaria
a) Haemolytic disease of the newborn
Maternal IgG against neonatal erythrocyte antigens leads to widespread destruction of red blood cells and a haemolytic anaemia.
Mx - exchange transfusion
Name the type 2 hypersensitivity reaction outlined in the case below:
A 40 year old woman returns to her GP for a prescription of pyridostigmine.
a) Haemolytic disease of the newborn
b) Autoimmune haemolytic anaemia
c) Autoimmune thrombocytopaenia
d) Goodpasture’s
e) Pemphigus vulgaris
f) Graves disease
g) Myasthenia gravis
h) Acute rheumatic fever
i) Pernicious anaemia
j) Churg-Strauss
k) Wegener’s granulomatosis
l) Microscopic polyangitis
m) Chronic urticaria
g) Myasthenia gravis
Antibodies against the acetylcholine receptor leads to progressive muscle weakness, particularly in the facial muscles. It may present with drooping eyelids, double vision and difficulty talking or chewing. The weakness comes and goes and may have noticeable triggers, such as fatigue or stress.
Ix - antibodies to ACH-R, abnormal EMG, tensilon test
Mx - neostigmine, pyridostigmine, IVIG
Name the type 2 hypersensitivity reaction outlined in the case below:
A 25 year old athlete presents to her GP after becoming frustrated by an itchy rash on her skin. She says that it has been there for 2 months and gets worse when she exercises. Sometimes her hands and feet swell up at the same time.
a) Haemolytic disease of the newborn
b) Autoimmune haemolytic anaemia
c) Autoimmune thrombocytopaenia
d) Goodpasture’s
e) Pemphigus vulgaris
f) Graves disease
g) Myasthenia gravis
h) Acute rheumatic fever
i) Pernicious anaemia
j) Churg-Strauss
k) Wegener’s granulomatosis
l) Microscopic polyangitis
m) Chronic urticaria
m) Chronic urticaria
Classified as itchy wheals present for more than 6 weeks which may be associated with NSAIDs, cold, food, pressure, sun exposure, exercise, bites or have no obvious course. 50% also get angioedema.
IgG is produced against FceR1 or IgE which leads to an urticarial rash. Diagnosis is by exclusion of vasculitis, allergies and thyroid disease.
Mx - 1% menthol in aqueous cream to soothe itching, antihistamines, IM adrenaline
Name the type 2 hypersensitivity reaction outlined in the case below:
A 21 year old male with a history of allergic rhinitis and asthma, developed when he was 17, presents to A&E with fatigue, fever and myalgia. Over the past day he has noticed being more short of breath and having some central chest pain which is not relieved by his inhalers. A WCC with differentials shows an eosinophilia.
a) Haemolytic disease of the newborn
b) Autoimmune haemolytic anaemia
c) Autoimmune thrombocytopaenia
d) Goodpasture’s
e) Pemphigus vulgaris
f) Graves disease
g) Myasthenia gravis
h) Acute rheumatic fever
i) Pernicious anaemia
j) Churg-Strauss
k) Wegener’s granulomatosis
l) Microscopic polyangitis
m) Chronic urticaria
j) Churg Strauss a.k.a. eosinophilic granulomatosis with polyangitis
This is a medium to small vessel vasculitis which is associated with the development of asthma and allergies in the teenage years-early 20s. It occurs in three clinical stages:
1) Allergic stage - this is a prodromal stage characterised in almost all patients by asthma +/- allergic rhinitis. The asthma usually develops 3 to 9 years before the onset of other symptoms.
2) Eosinophilic stage - abnormally high levels of eosinophils which may lead to weight loss, night sweats, a cough, abdominal pain and gastrointestinal bleeding.
3) Vasculitic stage - may occur simultaneously with the eosinophilic stage or present months to years after. Patients have systemic symptoms due to vasculitis, which may cause complications such as thrombosis (particularly in the abdomen) and myocarditis. Granulomas may form.
pANCA, an antibody against myeloperoxidase, is found in most patients. Treatment is with prednisolone, azathioprine and cyclophosphamide.
What are the antibodies present in pemphigus vulgaris?
Antibodies against epidermal cadherin. Direct immunofluorescence of bullae will show IgG deposition.
Compare the presentations of Wegener’s granulomatosis and microscopic polyangitis.
Wegener’s - medium and small vessel vasculitis which leads to sinus problems, haemorrhagic lung cavitations and crescentic glomerulonephritis. cANCA (against proteinase 3) is found on investigation. Treatment is with corticosteroids, cyclophosphamide and co-trimoxazole.
Microscopic polyangitis - pauci-immune necrotizing small vessel vasculitis which leads to purpura, livedo and affects multiple organs. Most patients have kidney involvement, leading to haematuria and proteinuria. pANCA +ve. Treatment is with prednisolone, cyclophosphamide, azathioprine and plasmapharesis.
Outline the pathogenesis of type 3 hypersensitivity reactions.
IgG/M immune complexes of antibody and soluble antigen are deposited in blood vessels. These complexes can also activate complement and lead to infiltration of macrophages and neutrophils which produce cytokines/chemokines that increase vascular permeability and cause localised inflammation.
