Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.
-
Upload
sade-pulford -
Category
Documents
-
view
222 -
download
3
Transcript of Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.
![Page 1: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/1.jpg)
Primary Immunodeficiency
Conleth FeigheryDept. of Immunology
3rd Med February 2010
![Page 2: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/2.jpg)
Primary Immunodeficiency
• Great advances in genetic identification in late 1980s, early 1990s
• Over 150 genetic disorders now recognised• Selection of disorders presented here
![Page 3: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/3.jpg)
Learning objectives
Primary immuno-deficiency – rare genetic disordersSecondary immuno-deficiency – common quantitative,
disordersHow to suspect its presence, importance of early
diagnosisTests employed in diagnosis Implications of immuno-deficiency: infection,
malignancy, auto-immunity Specific treatment of immuno-deficiency states.
![Page 4: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/4.jpg)
Secondary immunodeficiency
• Multiple factors can affect immune function• Age - reduced function in young, old• Nutrition - dietary defects eg. iron deficient• Developing world - malnutrition• Other disease - eg. cancer• Therapy - drugs, radiation• Viruses - HIV, others
![Page 5: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/5.jpg)
Primary Immunodeficiency – molecular causes
• Failure of antibody production – cause: btk defect
• Failure of T cell:APC interaction – cause: CD40 ligand defect
• Failure of T cell development – cause: IL-7 receptor gamma chain defect
• Failure of neutrophil killing – cause: NADPH oxidase defect
![Page 6: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/6.jpg)
Primary Immunodeficiency - examples
• Rare disorders c. 1: 20, 000 populationDiagnosis depends on• Clinical awareness/experience• Unusual but characteristic presentation • History of unusual infections, symptoms• Family history +
![Page 7: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/7.jpg)
Primary immuno-deficiency
Case histories
![Page 8: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/8.jpg)
Immunodeficiency - case history.
• BB - 40 year old male – unwell as child• Lobar pneumonia x 3• Family history - 2 brothers died
following recurrent lung infections• Investigations - absence of antibodies -
IgG, IgA, IgM• DIAGNOSIS - X-linked
agammaglobulinaemia
![Page 9: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/9.jpg)
BB - patient with XLA
![Page 10: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/10.jpg)
Antibody deficiency – infection sites
Pneumonia - affecting right lower lobe Otitis media
![Page 11: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/11.jpg)
CT scan of lung - bronchiectasis
![Page 12: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/12.jpg)
Essential role of BTK
![Page 13: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/13.jpg)
XLA - BTK defect
• Defect in B cell maturation
• Genetic disorder - gene on X-chromosome
• codes for Bruton’s tyrosine kinase - BTK essential for B cell development
![Page 14: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/14.jpg)
Common variable immunodeficiency – case 2
• AB - 29 year old male• Recurrent ear and sinus infections• Strep. pneumoniae lung infection • Malabsorbtion - Giardiasis lamblia
infection
• DIAGNOSIS - Common Variable Immunodeficiency - CVID
![Page 15: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/15.jpg)
Antibody deficiency 2.
• Common variable immunodeficiency - CVID• Incidence - 1:20,000• Heterogeneous - group of disorders• Males and females affected• Some genes now identified* – but account for
only 10% of patients• * ICOS, CD19, TACI, BAFF-R
![Page 16: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/16.jpg)
Antibody deficiency
• Encapsulated organisms • “Pyogenic”• Strep pneumonia, Haemophilus influenza• ENT, lungs• Immunoglobulin measurement – easy – if you
think of it• Test IgG, IgA, IgM
![Page 17: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/17.jpg)
Antibody deficiency - treatment
• Replace IgG – intravenous, sub-cutaneous• Antibiotics• Expectoration – frequent!
![Page 18: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/18.jpg)
Case history 3 .
• PO, aged 25 years• Recurrent bacterial infections,
early childhood• Tuberculosis, disseminated aged 6
years• Brother with similar history died
from brain inflammatory disorder
![Page 19: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/19.jpg)
Case history 3 - diagnosis?
• Low IgG, low IgA but IgM normal• B cells present• Tuberculosis – uncommon in pure
Ig deficiency
![Page 20: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/20.jpg)
Case history 3 - diagnosis
• Hyper-IgM syndrome• Significant T cell defect – absence
of CD40 ligand
![Page 21: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/21.jpg)
Antibody deficiency 3.
Diagnosis -• Hyper IgM syndrome• Rare – 1 in million?
![Page 22: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/22.jpg)
CD40 ligand
T h B
Cytokines - IL-4, 5, 6
CD40 ligand
Essential for “class switching – to IgA, IgG synthesis
![Page 23: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/23.jpg)
CD40 ligand
T hMacroph
Cytokine – IFN-gamma
CD40 ligand
APC
Essential for killing of intra-cellular infections
![Page 24: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/24.jpg)
Hyper-IgM - HIGM
• Patients may have elevated IgM levels• Low levels of IgG, IgA• Cause - CD40 ligand deficiency• Incidence < 1: million
![Page 25: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/25.jpg)
HIGM - infections
Major cause of morbidity and mortalitySusceptible to -• Pyogenic bacteriaAlso - “Opportunistic” infections - • Pneumocystis carinii• Cryptosporidium parvum - in drinking water• Toxoplasma gondii
![Page 26: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/26.jpg)
HIGM - treatment
• IgG replacement• Prophylaxis – co-trimoxazole• Boiled, filtred drinking water• Bone marrow transplant
![Page 27: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/27.jpg)
Case history 4
• 1 year old boy• Recurrent chest infections - viral, fungal,
bacterial• Constantly in hospital• Severe “failure to thrive”• Blood tests - low lymphocyte count
![Page 28: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/28.jpg)
Case history 4
• Diagnosis ?
![Page 29: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/29.jpg)
Case history 4
• Diagnosis ?• Low IgG, IgA and IgM• T cells low
![Page 30: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/30.jpg)
David, the ‘boy in the bubble’
![Page 31: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/31.jpg)
David, the ‘boy in the bubble’
• Severe combined immunodeficiency = SCID• Rare – 1 in 100 000• Treatment – urgent bone marrow transplant• IgG replacement• Negative pressure isolation
![Page 32: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/32.jpg)
SCID - treatment
• Make the diagnosis - rapidly fatal• Negative pressure isolation• Urgent bone marrow transplant• IgG replacement
![Page 33: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/33.jpg)
Early diagnosis important
SYMPTOMS -• Present early - by 3 months• Oral candidiasis• Lung inflammation “pneumonitis”• Diarrhoea• Failure to thrive !!!
![Page 34: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/34.jpg)
SCID
• Various molecular causes• X-linked form - absence of gamma chain in
cytokine receptor - commonest form• Defect in IL-7 function
![Page 35: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/35.jpg)
X-linked SCID
chain gene - forcytokine receptors
![Page 36: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/36.jpg)
Case history 5.
• Cells may be present – but not functioning
• Neutrophil disorder
![Page 37: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/37.jpg)
Case history 5.
• Neutrophils present• Able to migrate to target organisms• Able to phagocytose• Unable to kill certain organisms
![Page 38: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/38.jpg)
Case history 5.
• 30 year old male• History of skin abscesses - Staph aureus• Lung and liver abscesses• Lung abscess, extending to spinal cord -
Aspergillus
![Page 39: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/39.jpg)
Case history 5.
• Neutrophils – key role in protection against fungal infection
• Killing involves “respiratory burst” – increased oxygen utilisation
• NADPH oxidase defect
![Page 40: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/40.jpg)
Chronic Granulomatous Disease
![Page 41: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/41.jpg)
Chronic Granulomatous Disease
• Staph aureus• Burkholderia cepacia• Serratia marcescens• Nocardia• Aspergillus
![Page 42: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/42.jpg)
Chronic Granulomatous Disease
• Treatment• Bone marrow transplant• Prophylaxis – co-trimoxazole, itraconazole
![Page 43: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/43.jpg)
Immunodeficiency – defects in ….
T cell
B cell
lymphocytes
neutrophilAPCs
Complement proteins
![Page 44: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/44.jpg)
Immunodeficiency - diagnosis
• Delay in diagnosis – significant issue• Consider if …• Chronic infection• Atypical infection• Atypical response to infection
![Page 45: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/45.jpg)
Immunodeficiency - tests
• Many are simple, readily available• Tests and interpretation often requires
specialist input• Some disorders are complex to investigate –
become essentially research projects
![Page 46: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/46.jpg)
Immunodeficiency - tests
• White cell count and differential• IgG, IgA, IgM levels• Complement function (2 pathways)• Lymphocyte subsets
• If the above are normal, unless strong clinical suspicion, unlikely to be a significant defect
![Page 47: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/47.jpg)
Immunodeficiency tests
• “Routine” tests initially performed• Complex tests - dependent on the likely defect• Guided by infectious agents, clinical scenario
![Page 48: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/48.jpg)
Take home messages
• Well described human immune deficiency disorders
• Diagnosis important - treatment, prognosis• Help in understanding the molecular basis of
immune system
![Page 49: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/49.jpg)
Immunodeficiency slides
• Some additional slides• Other examples of immunodeficiency• Background literature• Some repetition!
![Page 50: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/50.jpg)
Case 6 – 17 year old male
History• Normal health until 1 month ago• Acute episode of headache, neck stiffness• Hospital admission – meningococcal
meningitis • Treated with antibiotics – full recovery
![Page 51: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/51.jpg)
Case 4 – 17 year old male
History - continued • 3 weeks later, second episode of headache,
diminished consciousness• Hospital admission, CSF sample,
meningococcus identified• Failed to respond to treatment, died
![Page 52: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/52.jpg)
Fatal C7 deficiency
C1 C4, C2 C3 C5 C6 C7 C8,9
LYSIS
17 year old boy with 2nd episode of Meningococcal meningitis
![Page 53: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/53.jpg)
Immunodeficiency - when to suspect?
Infections• Recurrent – sinus, lungs
– abscesses; brain
• Atypical– Atypical mycobacterium e.g. M. avium– Opportunistic organisms eg. Pneumocystis carinii
– in T cell defects
![Page 54: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/54.jpg)
Immunodeficiency - when to suspect?
Syndrome features -• diGeorge – cardiac, facial, metabolic (calcium)• Wiskott-Aldrich – eczema, bleeding (low
platelets, X-linked• Ataxia-telangiectasia
![Page 55: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/55.jpg)
Classification of Immunodeficiency states
• Primary - intrinsic defect in immune system - many genes now identified.
• Secondary - known causative agent eg. HIV virus, drug
![Page 56: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/56.jpg)
Type of infection helps predict the type of immunodeficency
• B lymphocyte - pyogenic bacteria - lungs
• T lymphocyte - viruses, fungi, mycobacteria
• Complement - meningococcus - CNS
• Phagocyte - staphylococcus - skin
![Page 57: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/57.jpg)
Immunodeficiency investigations
Lymphocyte subsets -• B cell count• T cell count• Helper T cell count - low in HIV disease• Cytotoxic T cell count• Natural killer cell count
Flow cytometer - laser analysisof cell types
![Page 58: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/58.jpg)
Immunodeficiency
Treatment options
![Page 59: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/59.jpg)
Treatment
• Replacement - e.g. antibody infusions• Bone marrow transplantation - stem cell
infusions, HLA matched family member • Gene therapy• Antibiotic, anti-fungal, anti-viral drugs
![Page 60: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/60.jpg)
Immunodeficiency - other causes
• Leucocyte adhesion deficiency – LAD• White cells not able to ‘stick’ to endothelium• CD18 – the beta chain of an integrin –
required for ‘sticking’ • Gene defect – chromosome 21
![Page 61: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/61.jpg)
Leucocyte adhesion deficiency
A. Normal aggregation to stimulus
B. Failure of aggregation
C. Periodontitis
![Page 62: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/62.jpg)
Leucocyte adhesion deficiency
![Page 63: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/63.jpg)
Leucocyte adhesion deficiency
![Page 64: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/64.jpg)
Immunodeficiency - other causes
• Cytokine defects – e.g. interferon gamma – tuberculosis risk
• Cell signalling defects e.g. STAT 3 – 2007 – severe boils, lung abscesses
• Toll like receptor (TLR) 3 – herpes simplex encephalitis risk
![Page 65: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/65.jpg)
Primary Immunodeficiency
• Rosen et al. N Engl J Med 333, 431, 1995. Excellent general review.
• N Engl J Med. Last few years, series on Immunology including immunodeficiency - see Buckley RH. Nov 2000, lymphocyte defects
• Fischer, A. Lancet, 357, 1863, 2001. Lists the many types of now identified immunodeficiency states
![Page 66: Primary Immunodeficiency Conleth Feighery Dept. of Immunology 3 rd Med February 2010.](https://reader036.fdocuments.net/reader036/viewer/2022062421/56649c945503460f949507be/html5/thumbnails/66.jpg)
Primary Immunodeficiency
• Assari, TL. Review of CGD. Medical Immunology, 2006. Vol 5
• Cunningham-Rundles, C. and Ponda, PP. Molecular defects in T- and B-cell primary immunodeficiency disorders. Nature Reviews Immunology, 2005: 5, 883.