Immuno Flashcards
Reticular dysgenesis
Cause
Mutation
FBC findings
Failure of HSC differentiation
autosomal recessive adenylate kinase mutation
Everything is low except rbc
Kostmann syndrome
Severe congenital neutropenia
Failure of neutrophil precursors to differentiate
Autosomal recessive HAX mutation
Recurrent bacterial infections
Cyclic neutropenia
Failure of neutrophil differentiation
5 day period every three weeks where immunity fails and bacterial and fungal infections but good health in the interim
Autosomal dominant
ELA1 GENE
Leukocyte adhesion deficiency
CD18 deficiency ( beta 2 integrity) Granulocytes can’t extravate into infected tissues
Investigations for innate immune system
FBC- NEUTROPHIL COUNT
Leukocyte adhesion marker assay
dihydrorhodamine flow cytometry- fluorescence means oxidative killing
NBT- nitroblue tetrazolium test- if it turns blue oxidative killing
Encapsulated bacteria you are susceptible to in complement deficiency
Strep pneumoniae Haemophilus influenzae Klebsiella pneumoniae Neisseria meningitidus Salmonella typhi Cryptococcus neoformams Pseudomonas aerugosa
Common and terminal pathway deficiency
Cannot form MAC so susceptible to bacterial infections
CH50 and AP50 are abnormal
C3,5,6,7,8,9 are low
Classical pathway deficiency
C2 deficiency is common but C1q/r/s is also seen as is C4 deficiency
CH50 is abnormal
Associated with SLE because of CH50 abnormality
Alternative pathway deficiency
AP50 test is abnormal
Deficiency of factor P/I/B
Risk of infection with encapsulated bacteria
Lectin deficiency
MBL deficiency in 10%
Very common
SCID
X linked
Adenosine delaminates deficiency
Adaptive immunity disorder
Disorder in LYMPHOCYTE proliferation linked to IL2
Adaptive immune disorder
Di George syndrome
Cardiac dysfunction(ToF) Abnormal fancies Thymic aplastic Cleft palate and oesophageal atresia Hypocalcaemia due to low PTH
22Q11 DELETIONS
Adaptive immune disorder
Bare lymphocyte syndrome
Type 1 (rare) MHC I deficiency Type 2 MHC II deficiency In type 2 there are reduced CD4 cells and therefore reduced IgA and IgG as CD4 mediated class switching can’t occur Recurrent viral infections
Type 1 hypersensitivity reaction
IgE mediated
Anaphylaxis, eczema
Type 2 hypersensitivity
Antibody against a cellular antigen
Churg -Strauss,goodpastures, graves
Do a Coombes test
Type 3 hypersensitivity
Antibody against immune complex
SLE, RA, polyarteritis nodosa
Type 4 hypersensitivity
T cell mediated
Delayed onset
Contact dermatitis, Graft rejection, T1DM
Foreign antigen rejection order
HLA DR >B>A
Acute graft rejection
Donor APC presents donor MHC/ antigen to host T cell
Chronic graft rejection
Host APC present donor MHC/ antigens to host T cell
Bare lymphocyte syndrome
Defect in regulatory factor x or class 2 transactivator
Type 1 bare lymphocyte syndrome
No CD8+ T cells
What condition is bare lymphocyte syndrome associated with and when does it present?
Associated with primary sclerosis cholangitis
Presents at 3 months of age
Why do lymphocytes fail to develop in BLS?
There is no HLA expression in the thymus so lymphocytes can’t develop
Why are there low mature T cells in di George syndrome?
The thymus is absent so can’t mature lymphocytes
What are the T cell mediated immune deficiencies
Di George syndrome
Bare lymphocyte syndrome
How to treat T cell mediated immune deficiencies
Thymus transplant in Di George syndrome
Infection prophylaxis
Complement replacement
Which CD factors to T cells require for activation?
CD80
CD86
What are the B cell mediated immune deficiencies
Selective IgA deficiency
Bruton’s agammaglobulinaemia
Combined variable immune deficiency
Hyper IgM syndrome
Brutons agammaglobulinaemia
B cell mediated disorder
Inheritance
Mutation
Presentation
No antibodies
BTK gene
X linked tyrosine kinase mutation
FAILURE TO PRODUCE MATURE B CELLS, SYMPTOMS AT 3-6 MONTHS
Common variable immune deficiency
B cell mediated
IgA,IgE, IgG are low ( think AGE)
B cells do not differentiate
Many causes
Presents as failure to thrive, granulomatous disease and autoimmunity
Elective IgA deficiency
1/600 Caucasians
Recurrent respiratory and gastro infections
Vaccination is helpful
70% asymptomatic
Ig pattern in hyper IgM syndrome
IgM is high
Low IgA and IgG
Because B cells not present to make the ig
Mutation and inheritance in hyper IgM syndrome
X linked
Xq26 mutation
CD154, CD40, CD40L AND AICDA defect
Mechanism of disease in hyper IgM syndrome
Activated T cells cannot activate B cells to class switch therefore IgA and IgG aren’t formed but IgM is.
Less lymphoid tissue as no germinal centre
What conditions are you susceptible to in B cell deficiencies
Tetanus
Diphtheria
Some viral and bacterial infections
Treatment of B cell deficiencies
BMT transplant
Ig prophylaxis
If IgA deficiency then vaccination
WBC in SCID
Low B cell
Low T cell
Low antibodies
No B cell can be normal
How do you diagnose kostmannsyndrome
1) chronically low neutrophil count
2) bone marrow scan showing arrest of neutrophil precursor maturation
Treatment of kostmann syndrome
G-CSF
BMT
prophylactic abx
Chronic granulotomous disease
Reduced oxidative killing because NADPH is defective
Chronic granulotomous disease test and treatment
NBT test
DHR test
Infections you are susceptible to if chronic granulotomous disease
Catalase positive organisms Pseudomonas Listeria Aspergillus Candida E.coli Staph aureus Serattia
Treatment of chronic granulotomous disease
Prophylactic trimethoprim, itraconazole and interferon
Inflammatory cytokines
Il1
IL6
IL12
TNF
Anti inflammatory cytokines
TGF beta
IL10
What conditions are you predisposed to in cytokines deficiencies?
Salmonella
BCG
atypical mycobacterium
TB
What do cytokines do
They signal between T cells and macrophages
Stimulate NAPDH oxidative killing
Activate TNF
Treatment of anaphylaxis
Elevate legs 100%O2 IV was 100mcg hydrocortisone Salbutamol IM adrenaline 500mcg IV chlorphenamine 10mcg IV fluids Seek help
Investigations in allergy
Ski. Prick test( positive test is wheal greater than 2mm than negative control- dilutant)
RAST ( check IgE response)
Component resolved diagnostics- tests specific IgE response to a specific allergen protein
Challenge test
What do you measure in an acute allergy reaction?
Mast cell tryptase (peaks 1-2 hours and baseline at 6 hours)
Limited cutaneous scleroderma
AKA CREST SYNDROME
Calcinosis Raynauds Esophageal dysmotility Sclerodactily Telangectasia
+ primary pulmonary hypertension
Antibody in crest syndrome
Anticentromere ab
Diffuse scleroderma
Crest+ pulmonary six+ GIT sx+ renal sx
Topoisomerase ab
Scl70 ab
RNA polymerase I, II, III ab
Fibrillarin ab
Sjorens syndrome ab
Anti ro and anti la
Sjorens syndrome symptoms
Dry mouth, dry eyes, PNS and pancreatic dysfunction
Keratoconjunctivitis sicca and xerostomia
IPEX syndrome
What does IPEX stand for
Immune dysregulation, polyendocrinopathy, enteropathy, X linked inheritance and autoimmune diseases
How is IPEX inherited
X linked recessive
Typical conditions in IPEX sufferers
Alopecia univeralis
Bulbous pemphagoid
Eczematous dermatitis
Nail dystrophy
Coeliac disease antibodies
What type of ab are they?
EMA
TGT
BOTH OF THESE ARE IgA
Antigliadin (IgG)
What condition is coeliac disease associated with (3)
Down’s syndrome
Dermatitis herpetiformis
T cell lymphoma
What HLA molecules are associated with with 95% of coeliac disease
DQ8
DQ2
What is the pathology in atopic dermatitis (infantile eczema)
Beta defensin defect which predisposes to staph aureus superinfection
Treatment for infantile eczema (atopic dermatitis)
PUVA phototherapy
Emollient cream
Steroid
Topical antibiotics
How to diagnose food allergy
Food diary
RAST
skin prick test
Food challenge
What is latex food syndrome
Foods such as avacado and chestnut have latex like properties so latex allergy sufferers get IgE mediated symptoms when they eat them
Signs of allergic rhinitis
Anosmia Sneezing Blueish nasal mucosa Rhinitis Nasal obstruction
Causes of acute urticaria
50% idiopathic
Viral illness
Febrile illness
Allergen
Pathology of acute urticaria
Resolves in 6 weeks
IgE mediated
Wheals
Component resolved diagnostics for peanut allergy
Ara h8 allergic to peanut and stone fruit but reaction is only oral
Ara h2- v allergic to peanuts
Pathology and diagnosis of haemolytic disease of the newborn
Path: maternal IgG mediated reticulocytosis and anaemia
Positive Coombs test
What is the antigen for HDN
Antigens on foetal rbc
Treatment of HDN
Maternal plasma exchange
Exchange transfusion
Evans syndrome
Autoimmune haemolytic anemia plus ITP
What is the pathology in AIHA
Complement mediated destruction of rbc
Also by Fcr, phagocytes and autoantibody
Anaemia
Diagnosis and treatment of AIHA
Positive Coombes test
Anti rbc autoantibody
Treat with steroids
Autoimmune thrombocytopenic purpura antigen (2) and antibody
Antigen glpIIb
Antigen: glp IIIa
Anti platelet antibody
Treatment of autoimmune thrombocytopenic purpura
IVIG
steroids
Splenectomy
Anti D antibody
Antigen for goodpastures syndrome
Non collagenous domain of basement membrane collagen type 4
Pathology of goodpastures syndrome
Pulmonary haemmorage and glomerulonephritis
Which immunoglobulin mediated goodpastures syndrome
IgG
Diagnosis of goodpastures syndrome (2)
Anti GBM antibody
Linear smooth IF Staining of IgG deposits on basement membrane
Antigen for pemphigus vulgaris
Epidermal cadherin
Which ig antibody mediates pemphigus vulgaris
IgG
Symptoms of pemphigus vulgaris
Non tense blistering of skin and Bullae
How do you diagnose pemphigus vulgaris
Immunoflourescance showing IgG deposition
Treatment of pemphigus vulgaris
Steroids
Immunosuppression
Graves’ disease
Anti TSH-R ab
Causes hyperthyroidismism
Treat with carbimazole and propylthiouricil
Myasthenia gravis antigen
Ach-R
Symptoms of myasthenia gravis
Muscle fatigue
Double vision
Diagnosis of myasthenia gravis
Tensilon test
EMG
anti ach-r antibodies
Treatment of myasthenia gravis
Neostigmine
Pyridostigmine
If severe IVIG and plasmapheresis
Antigen for acute rheumatic fever
M protein on group a strep
Symptoms, diagnosis and treatment of rheumatic fever
Myocarditis, Sydenham’s chorea and arthritis
Jones criteria to diagnose
Aspirin, penicillin and steroids
Antigen for pernicious anaemia
IF or gastric parietal cells
Symptoms and Diagnosis of pernicious anaemia
Low B12 and anaemia
Schilling test
Anti IF AB
Anti gastric parietal cell ab
Diagnosis of churg Strauss syndrome eGPA
P-ANCA against myeloperoxidase
Also see granulomas and eosinophilia granulocytes
Wegeners granulomatosis [GPA]
C-ANCA against proteinase 3
Granulomas
Symptoms of wegeners granulomatosis
Small vessel vasculitis
Cresenteric glomerulonephritis
Lung cavitations and pulmonary haemmorage
Sinus problems
Churg Strauss syndrome symptoms
Type 2 hypersensitivity
Triad of asthma, eosinophilia and vasculitis
Diagnosis of micropolyangiitis
P-ANCA against myeloperoxidase
Treatment of micropolyangiitis
Steroids
Cyclophosphamide
Azothioprine
Plasmapheresis