What immunologic phenomenon leads to toxic shock syndrome?
binding of bacterial superantigens, outside the MHC grove leading to massive activation of T-cells, cytokine release
What infections does a lack of neutrophils/monocytes cause?
High grade bacterial infections - Staph aureus, gram negative bacteria (E.coli, proteus, serratia, pseudomonas)
Invasive fungal infections (aspergillus, candida)
What infections does lack of T-cells result in?
Fungi (typically mucosal candida) Mycobacteria Viruses (CMV, VZV, HSV, Protozoa) Protozoa (pneumocystits) Listeria
What infections does lack of antibody response result in?
Recurrent sinopulmonary and gut infections
Infections by
- polysaccharide encaspulated organisims (Strep pneumoniae, H.influenzae, Strep pyogenes, Branhamella)
- staph aureus
- Giardia
- campylobacter
What does a lack of early complement components (C1, C2, C3) lead to?
Autoimmune disease, such as SLE, vasculitis, GN
What does a lack of later complement products lead to?
Infection with Neisseria - often disseminated
Why is nephrotic syndrome an immunosuppressed state?
Loss of IgG with loss of albumin
What is the most common cause of a low CH50 (total haemolytic complement)?
Delay in specimen transport to lab
What are the lab findings in CVID (common variable immunodeficiency)?
Low IgG (and one or both of low IgA and IgM)
B cell count normal in most
Electrophoresis - hypogamma
Impaired vaccination response as no memory B cells
What is the treatment for CVID?
IV immunoglobulin - every month due to the half life of IgG
Antibiotics for infections
Avoid live vaccines
What are some clinical manifestations of CVID?
Recurrent sinopulmonary infections
Gastrointestinal infections
Skin infections
Autoimmunity (immune cytopenias, thyroid, pernicious anaemia, polyarthropathy, polymyositis, vitiligo)
Increased risk of cancer - lymphoma, gastric cancer
Allergic disease, chronic infections, amyloid
What is Brutons syndrome?
X-linked agammaglobulinemia with no B-cells and no immunoglobulin production
Absence of Brutons tyrosine kinase which is a signalling molecule that matures B-cells
What are some conditions associated with IgA deficiency?
Atopic disease Cows milk allergy Coeliac disease Inflammatory bowel disase RA, SLE, dermatomyositis, sjogrens ITP, Pernicious anaemia, thyroiditis, addisons Anaphylaxis to blood transfusion
Treatment for IgA deficiency?
No role for IvIg
Prompt antibiotics
Transfusions from IgA deficient donors or washed
What is Hyper IgM syndrome?
X-linked CD40 ligand deficiency = absence of T and B-cell communication = failure of B-cell isotype switching and memory B cell generation
Features similar but more severe then CVID and addition of T-cell related infections ie. PCP
Lab findings in Hyper IgM syndrome?
Low IgA, IgG, IgE but normal or increased IgM (as not able to class switch) Normal circulating B cells (but only express IgM and IgD = naive B cell markers) Flow cytometry positive for CD40L
What is chronic granulomatous disease?
Deficiency in the NADPH oxidase leading to inability to create oxidative burst inside the neutrophil and kill the organism - therefore neutrophils engulf pathogens but are unable to kill them (granuloma formation)
Clinical features of chronic granulomatous disease?
Recurrent infections of skin/lungs with coagulase negative bacteria/fungi Staph infections of skin Purulent dermatitis Broncopneumonia Chrons like syndrome
Test for chronic granulomatous disease?
Ability of granuloctyes to generate an oxidative burst
= NBT test (nitroblue tetrazolium test) induces oxidative response in normal neutrophils
What is a type 1 hypersensitivity reaction?
Immediate
IgE mediated
Urticaria, angioedema, anaphylaxis, asthma, rhinitis, conjunctivitis
What is a type 2 hypersensitivity reaction and examples?
Cytotoxic
Antibody directed against antigen on cells or cell membrane and result in activation of complement via the classic pathway
Examples: Transfusion reactions, autoimmune haemolytic anaemia, good pastures syndrome
What is a type 3 hypersensitivity reaction and examples?
Immune complex mediated
Antibody-antigen complexes are circulating and become trapped in a cell component and activate complement via the alternate pathway
Examples: Glomerulonephritis, serum sickness, vasculitits
What is a type 4 hypersensitivity reaction and examples?
Delayed hypersensitivity
T-cell mediated
Takes 2-3 days to develop
Inappropriate or excessive immune response by CD4 subsets (TH1 and TH17)
Examples: contact dermatitis, SJS, TEN, DRESS, delayed urticaria
Investigations in allergic rhinitis?
Skin prick testing Specific IgE (RAST test) - less favoured, radioimmunoassay that detects specific IgE to known allergens
Management of allergic rhinitis?
Avoid allergen Intra-nasal corticosteroids Anti-histamines Decongestants Can do desensitisation in severe disease
What are some contrindications to skin prick testing?
Antihistamines (false negatives) TCAs Topical steroids Severe eczema Dermatographism
What is the cellular change behind desensitisation/immunotherapy?
Down regulation of the TH2 response and up-regulation of the TH1 response
What are the common foods causing allergies?
Cows milk Egg Wheat Soy Seafood Nuts
What food allergies are you less likely to grow out of?
Seafood
Nuts (peanut)
Investigation of food allergy?
Skin prick testing
Specific IgE (RAST)
Oral food challenge (gold standard but only used if above is abnormal)
Management of food allergy?
High risk allergen - e.g. peanut and asthma = give epipen
Avoid certain foods
Watch for cross-reactivity e.g latex and avocado/kiwfruit
Immunotherapy under trial
What is the peak time for tryptase?
peaks in 60-90 minutes, last 5 hours
What is hereditary angioedema?
Mutation in SERPING1 gene which codes for C1 inhibitor protein
- leads to deficiency or loss of function of C1 inhibitor with increased production of bradykinnin down kallkrenin pathway
What are the 3 types of HAE?
Type 1 - low levels of C1INH
Type 2 - dysfunctional C1INH but normal levels
Type 3 - mutation in gene encoding factor XII which has a role in bradykinin synthesis
Tests in Type 1 HAE
low C4
low C1-INH both level and function
*must be less than 50% on 2 occasions
normal C1q (determines it from aquired AE)
Tests in Type 2 HAE
low C4
normal or high C1-INH levels but low function, less than 50% on 2 occasions
normal C1q
Inheritance of HAE?
Autosomal dominant
Age of onset of HAE?
Less than 40 years
- typically less than 20 years of age
Presentation of HAE?
Angiodema without urticaria or puritis
Triggers - physical/emotional stress, drugs, oestrogen
gradual onset of either
- gut odema = abdo pain, vomitting, diarrhoea
- skin = face, lips, limb swelling
- upper airways = larnyneal odema
Treatment of HAE?
Doesn’t respond to steroids, anti histamines, adrenaline
Treatment
- C1 INH plasma concentrate from pooled plasma
- Bradykinin-2-receptor antagonist e.g Icadibant
- Ecallantide (only available in USA, kalikrenin inhibitor)
- if above unavailable can give FFP
What is acquired angiodema?
similar to HAE but not hereditary, develops in older people, over the age of 40
due to lymphoproliferative disorders or autoimmune disease
Tests in AAE?
low C4 low C1q (different from HAE) low or normal C1 inhibitor level with low C1 inhibitor function