Revision session Flashcards
Type I allergy mechanism
mast cells and IgE
Test for type I allergy
skin prick
Examples of type I allergy
Anaphylaxis
Rhinitis
Asthma
Mechanism of type II allergy
antibody and antigen
Mechanism of tpye III allergy
immune complex
Mechanism of type IV allergy
delayed hypersensitivity
CD4+ Th1 cells
Examples of type IV
allergic contact dermatitis
Hashimoto’s thyroiditis
IDDM
Myasthenia gravis
Test for type IV allergy
Patch
Large vessel vasculitises
Giant cell
Takayasu
Medium vessel vasculitis
Polyarteriitis nodosa
Kawasaki
ANCA positive small vessels
Wegener’s (cANCA)
MPA, Churg Strauss (pANCA)
Features of SLE
ANA, dsDNA
type 3 hypersensitivity
cANCA binds to
cytoplasmic proteins
PR3
pANCA binds to
perinuclear proteins
MPO
B cell functions
- Differentiates into plasma cells producing antibodies
- Opsonization
- Complement activation
- Toxin neutralization
T cell functions
Helper T cells provide B cells with signals necessary for antibody production
Cytotoxic T cells destroy virally infected cells and tumour cells
T regulatory cells suppress auto-reacitve T cells
Phagocyte functions
Engulf and destroys microbes
Antigen presentation
Complement functions
Opsonization (C3b)
Terminal components create the membrane attack complex
NK cell functions
Destroys virally infected cells and tumour cells
- recurrent bacterial sinopulmonary (nasal sinuses and lungs) infections (encapsulated organisms)
- chronic or recurrent gastroenteritis (enterovirus, giardia)
- chronic enteroviral meningoencephalitis
- septic arthritis (mycoplasma, ureasplasma)
- bronchiectasia
B cell deficiency
- fungal infections
- severe or unusual viral infections
- failure to thrive
- chronic diarrhoea
- pneumocystis jiroveci pneumonia
- GVHD (rash, abnormal LFTs)
- autoimmune disease
T cell deficiency
- skin abcesses or lymphadenitis
- bacterial pneumonia
- poor wound healing
- delayed separation of the umbilical cord
- chronic gingivitis, periodontal disease, mucosal ulcerations
- disseminated mycobacterial infection
Phagocyte deficiency
- Recurrent Neisserial infections
- Pyogenic bacterial infections
- Autoimmune disease
- Angioedema of face, hands, feet, GI tract
Complement deficiency
- Severe or recurrent Herpes virus infections
- Hemophagocytic lymphohistiocytosis
NK cell deficiency
Investigations for B cell problems
Quantitative
- FBC plus Igs
- B cell no. by flowcytometery
Qualitative
- Look at vaccine responses to tetanus, diptheria and pneumococcal serotypes 4-6 weeks after
Investigations for T cell problems
Quantitative
- FBC with lymphocyte populations
Qualitative
- T cell proliferation
Investigations for phagocyte problems
Quantitative
- FBC with absolute neutrophil and or monocyte count
Qualitative
- neutrophil oxidative burst assay (dihydrorhodamine assay or NBT test)
Investigations for complement problems
Quantitative
- individual complement components
Qualitative
- Haemolytic activity (CH50, AP50)
Investigations for NK cell problems
Quantitative
- NK cell numbers by flow cytometery
Qualitative
- NK cell function tests
Examples of B cell deficiencies
- Selective IgA deficiency
- Common variable immunodeficiency disorders
- X-linked agammaglobulinemia
Examples of T cell deficiencies
- Wiskott-Aldrich syndrome
- Digeorge syndrome
Examples of B and T cell deficiencies
Severe combined immunodeficiency
Hyper IgM syndrome
Examples of phagocyte deficiencies
- Chronic granulomatous disease
- cyclic neutropenia
- leukocyte adhesion deficiency
Examples of complement deficiency
hereditary angioedema
Examples of NK cell deficiency
X-linked lymphoproliferative syndrome
primary HLH
What causes a puffy face in hereditary angioedema?
Bradykinin
C1 inhibitor deficiency
meningococcus/gonococcus
Terminal complement C5-9
CVID criteria for diagnosis
Male/female patients with ALL of:
- aged >4 years
- serum IgG and IgA +/- IgM less than lower limit of normal for age
- poor IgG response to vaccines
- Normal or low B cell numbers
- secondary antibody deficiency excluded (e.g drugs)
- history of recurrent upper and lower respiratory tract infections due to encapsulated bacteria such as H. influenza and Strep. pneumo.
- 20% of patients develop complications with autoimmune manifestations, non-caseating granulomas in lung, lymph nodes, skin and liver, and GI and lymphoid malignancy
Common variable immunodeficiency disorders
What is Dermatitis herpetiformis and where is the rash usually seen?
gluten sensitivity usually affects the forehead and other areas
d acute wheeze, breathlessness, dizziness, felt faint and had a sensation of “impending doom” a few minutes after being stung by a bee
Anaphylaxis. IM adrenaline
ACE inhibitors and anaphylaxis
ACE inhibitor treatment will increase the severity (increased oedema, hypotension) of any future reaction (to stings or immunotherapy), through increased bradykinin levels.
When would you expect symptoms if you were allergic to house dust mites?
All year round, worse during winter
Hayfever worse…
From May, in evenings
Which auto antibodies can cross the placnta?
TSH receptor (Graves) Acetylcholine R (Myasthenia gravis) Desmoglein 3 (phemphigus)
Granuloma forming vasculitises
Giant cell arteritis
Takayasu
GPA
Churg-Strauss syndrome
large/medium arteries of head and neck, HLA DR4, intimal thickening and oedema, ‘skip’ lesions, women >55 years, sudden onset blindness, polymyalgia rheumatica
Giant cell
Granulomatous, aortic arch and origins of great arteries, young to middle aged women, Asian, ischaemia in arms
Takayasu
Uncommon in young children, inflammation of media of arteries supplying viscera (e.g kidney, heart, liver, mesentery), aneurysm formation, thrombosis, ischaemia
Polyarteritis Nodosa
HepB assoicated
PAN
Mucocutaneous lymph node syndrome
Kawasaki’s disease
infants and children, fever, lymphadenopathy, skin rash, oral/conjuctival erythema, coronary areritis, MI, possibly viral cause, self limiting
Kawasaki
Systemic features of small vessel vasculitis
Malaise
Fever
Arthralgia
Weightloss
Arthralgia
Joint pain
Sites affected by GPA
Upper airways
Lower respiratory tract
Kidneys
Granulomatous infalmmation
Sites affected by microscopic polyangiitis
Kindey
Lungs
Sites affected by Chrug-Strauss syndrome
Lower airways, asthma
Eosinophilia
Eosinophilic inflammaiton
Investigations of small vessel vasculitis
CRP
FBC
kidney and liver function tests
ANCA
mainly affects the skin (purpura), gut, kidneys, joints, IgA complexes
Henoch Schonlein Prupura
Decreases of C1Q or C4 put you at risk of….
developing auto immunity
HLA A1 B8 CR3
Sjogren’s syndrome
dry eyes, dry mouth, arthritis
Sjogren’s syndrome
Investigations for Sjogren’s
Schirmer’s test for tear production
ANA, Ro, La
Biopsy minor salivary gland (inflammation with CD4 T-cell infiltration
ANA, Anti Scl70 (topoisomerase)
Systemic scleroderma
ANA, anti centromere
Limited scleroderma
Fatiguable weakness
MG
What’s overlap syndrome?
Symptoms of myositis and lupus
Function of Th1 cells
CD4+ promote inflammation (delayed hypersensitivity)
Function of Th2 cells
CD4+ anti parasite immunity
Function fo Th17 cells
mucosal immunity
combined T and B cell (antibody) deficiency, X linked, recurrent bacterial infection plus infection with cryptosporidium, pneumocystis etc
Hyper IgM syndrome
defects on chromosome 22q11, 3rd and 4th pharyngeal pouch abnormalities, cleft palate, abnormal face, lack or parathyroid glands (hypocalcaemia and neonatal tetany), congenital heart disease, thymic aplasia (so impaired T cell development), normal B cells,
Di George syndrome
low C4, normal C3, angioedema
C1 inhibitor deficiency
C1 inhibitor levels might be normal but non functional
An 8-month-old boy was born at full-term by normal vaginal delivery. When he was 5 weeks old he developed a large abscess of the chest wall. This required incision and drainage of the pus and 4 weeks of antibiotics. At 5 months of age he developed a large abscess in his axilla and at 7 months he was admitted to hospital with a spreading infection around his nose. He was the second child born to unrelated parents. Their first son, died at 18 months of age after repeated infections.
Swab from the infection around his nose: Heavy growth of Staphylococcus aureus
C-reactive protein 186 mg/L (<8)
Haemoglobin 98g/L
White cell count 23.5x109
/L, 80% neutrophils
Glucose 4.3mmol/L (3.0-5.5)
IgG 7.1 g/L (6-13) IgA 0.9 g/L (0.7-3.0) IgM 0.5 g/L (0.4-2.5)
Complement C3 and C4 were normal
Nitroblue tetrazolium (NBT) and di-hydro-rhodamine reduction (DHR) tests were negative (normal control positive) consistent with defective neutrophil ‘respiratory burst’.
Chronic Granulomatous disease
