Primary Immune Deficiencies Flashcards
Selective IgA Deficiency - what type of infections? epidemiology?
Most Common defiency Recurrent gastro and resp infections affects 1/600 Caucasians but 70% are asymptomatic
Complement Deficiencies - Treatment?
Vaccination, prophylactic Abx, high levels of suspicion, screen family members
Leukocyte Adhesion Deficiency- what is it? deficiency in?
Failure to express leukocyte adhesion markers. Deficiency of the beta-2 integrin subunit (CD18) of the Leukocyte adhesion molecule in LAD1 LAD2 is much rarer and has severe growth restriction and mental retardation
B cell deficiencies - Consequences
Increased susceptibility to bacterial and some viral infections and toxins (tetanus, diphtheria)
Cyclic Neutropenia - what causes it?
caused by mutations in the ELA1 gene
Kostmann Syndrome - Treatment?
Treatment includes G-CSF, prophylactic antibiotics and BMT if G-CSF is ineffective
IgM immunity?
on surface of B cells
Chronic Granulomatous Disease - associated diseases?
PLACESS Pseudomonas Listeria Aspergillus Candida E. coli Staph aureus Serratia patients can resist catalase-negative bacteria
Severe Combined Immune Deficiency (SCID) - defect in? blood results?
defect in lymphoid precursors (IL2-R), leading to low or normal B cells, reduced T cells and low antibodies
DiGeorge’s Syndrome - what is it?
Impaired development of the 3rd and 4th pharyngeal pouches (oesophagus, thymus, heart)
Hyper-IgM Syndrome - chromosome? defect in? how does it cause symptoms?
X-Linked Condition - Xq26 CD40L, CD40, AlCDA or CD154 defect Activated T cells can’t interact with B-cells to class switch therefore B cells can’t make IgA and IgG but instead IgM levels increases
T cell deficiencies - Consequences
Increased susceptibility to viral, fungal and bacterial infections and early malignancy
Common Variable Immune Deficiency - signs/symptoms/diagnosis
Frequent infections during early life, increased incidence of autoimmune or inflammatory manifestations, granulomata and increased susceptibility to cancer. Both males and females can get the deficiency, most likely to be diagnosed in 3rd/4th decade of life although 20% are found to be immunodeficient in childhood
Cyclic Neutropenia - Treatment
Treat with G-CSF
Brutons Agammaglobinemia - symptoms and age of onset?
recurrent and severe bacterial infections from 3-6 months old when maternal IgG denature. Most common infections are • Ear infections • Sinusitis • Pneumonia • Diarrhea due to a parasite called Giardia
Ig half life?
18 days
2 syndromes of T cell deficiencies?
Bare Lymphocyte Syndrome DiGeorge’s Syndrome
Common Variable Immune Deficiency - Ig levels? cause?
Low IgG, IgE and IgA many genetic causes
Complement Deficiencies - Lectin Pathway Deficiency
Very common, 10% are MBL deficient. Not so clinically important
IgG immunity?
can cross from placenta to foetus
IgA immunity?
Mucosal areas, saliva, tears, breast milk
Reticular Dysgenesis - is a form of what deficiency? causes a deficiency in what? treatment?
most severe form of SCID (Severe Combined Immune Deficiency) (AK2) Causes an absolute deficiency in Neutrophils, Lymphocytes, Monocytes/ Macrophages, Platelets Fatal in v. early life unless treated by BMT
Kostmann Syndrome - what is it? dominant or recessive? prevalence?
A severe congenital neutropenia (increased risk of infection) Mainly Autosomal Recessive (HAX-1) 1-2cases per million
Chronic Granulomatous Disease - treatment?
Treatment involves prophylactic Trimethoprim and Itraconazole and Interferon. Sometimes use stem cell transplant
DiGeorge’s Syndrome - what chromosome?
deletion of 22q11.2
Chronic Granulomatous Disease - what test is used to diagnose?
Negative Nitro-Blue Tetrazolium (NBT) test. NBT is a dye that changes colour from yellow to blue following interaction with hydrogen peroxide. Also use Dihydrorhodamine (DHR) flow cytometry test. DHR is oxidised to rhodamine, which is strongly fluorescent, following interaction with hydrogen peroxide
B cell deficiencies - Treatment
Ig replacement BMT in some situations vaccination (not effective except in IgA deficiency)
Leukocyte Adhesion Deficiency - features of disease
High neutrophil count and delayed umbilical cord separation
Which cytokines/receptors can we be deficient in? What are these molecules all involved in?
Deficiencies in IFN-gamma, IFN-gamma receptor, IL-12 and IL_12 receptor. all involved in signalling between T-cells and macrophages to stimulate TNF and activate NADPH oxidase
4 Phagocyte deficiencies?
Kostmann Syndrome Leukocyte Adhesion Deficiency Chronic Granulomatous Disease Cyclic Neutropenia
Kostmann Syndrome - when? diagnosis?
infections start shortly after birth Diagnosis based on chronically low neutrophil count and bone marrow test showing an arrest of neutrophil precursor maturation
Bare Lymphocyte Syndrome (BLS) is a defect in what?
Regulatory Factor X or Class 2 transactivator
Hyper-IgM Syndrome - presentation
Boys present first years of life with recurrent bacterial infections especially Pneumocystis carinii and failure to thrive. Increased risk of autoimmunity and malignancy
Complement Deficiencies - Classical Pathway Deficiency. Associated with? What test is abnormal?
Involves lack of C1q/r/s, C2 is the commonest and C4 Associated with SLE as classical pathway involved in removing immune complexes CH50 test is abnormal
Phagocyte deficiencies - Consequences?
Increased susceptibility to bacterial and fungal infections, often with deep abscesses
Severe Combined Immune Deficiency (SCID) - symptoms?
recurrent infections - Failure to thrive and persistent diarrhoea and early infant death
Complement Deficiencies - Consequences?
Increased susceptibility to encapsulated bacterial infections
Cytokine Deficiencies - associated infections..
predisposed to infections caused by Salmonella, atypical Mycobacteria, TB and BCG. Patients are unable to form granulomata
Cyclic Neutropenia - what is it?
Episodic neutropenia occurring every 3 weeks and lasting several days
IgE immunity?
Allergy - Histamine released from Mast cells
What disease is BLS associated with?
Sclerosing Cholangitis (uncommon chronic liver disease in which the bile ducts inside and outside the liver progressively decrease in size due to inflammation and scarring (fibrosis)
Bare Lymphocyte Syndrome (BLS) 7 main symptoms and age of onset?
Persistent diarrhea Malabsorption Mucocutaneous candidiasis Upper respiratory tract bacterial infection Lower respiratory tract bacterial infection Failure to thrive Fatigue unwell by 3months of age
Leukocyte Adhesion Deficiency - Treatment
BMT is treatment of choice
Mixed B and T cell deficiency?
SCID
DiGeorge’s Syndrome - physical features, blood test results
Low set ears, cleft lip and palate Low Calcium, Low number of mature T cells Sesceptible to viral infections
Severe Combined Immune Deficiency (SCID) - X linked?
45% are X-linked
Bare Lymphocyte Syndrome (BLS) is the absent expression of…?
HLA molecules within the thymus causing lymphocytes to fail to develop
T cell deficiencies - Treatment
Infection prophylaxis Ig replacement if necessary specific other treatments
Complement Deficiencies - Common and Terminal Pathway Deficiency Associated with? whats abnormal?
Involves lack of C3, 5-9 Susceptibility to bacterial infections (Meningitis/Pneumoniae) May be associated with membranoproligerative glomerulonephritis. Cannot form MAC to kill bacteria, Both CH50 and AP50 abnormal
What are the different types of Bare Lymphocyte Syndrome? Which cells are depleted in each type?
Type 1 - MHC I absent - decreased CD8 cells Type 2 - MHC II absent - decreased CD4 cells (more common) B-cell class switch needs CD4 therefore less IgA and IgG made
Chronic Granulomatous Disease - what is it? defect in?
Failure of oxidative killing - defect of NADPH oxidase leading to reduced reactive oxygen species Due to many mutations, mostly X-linked
Severe Combined Immune Deficiency (SCID) - treatment
BTM only established treatment
DiGeorge’s Syndrome - Treatment?
Thymus Transplant
Bruton’s Agammaglobinemia - defect and mutation in? leading to a failure to produce..?
X- linked Tyrosine Kinase Defect Mutation in BTK gene Fail to produce mature B-cells and no antibodies
Complement Deficiencies - Alternative Pathway Deficiency what infections do they get? what test is abnormal?
Involves Factors B/I/P infections with Encapsulated bacteria such as -Streptococcus pneumoniae (Pneumococcus) -Group B streptococcus Haemophilus influenza -Neisseria meningitides (Meningococcus) alternative pathway only involved in killing bacteria AP50 test is abnormal
