Primary Immunodeficiency Diseases Flashcards
When to suspect immunodeficiency
Severe infection (e.g. complicated pneumonia, sepsis, OM)
Unusual infection (e.g. VZV, HZV, HPV)
Persistent infection (e.g. chronic diarrhoea, oral candidiasis)
Recurrent infection (e.g. chest/sinus/otitis media)
Malignancy
Autoimmune deficiency
Not gaining weight (failure to thrive)
Other:
Immune dysregulation:
Family history
Classification of PID
- Combined Immunodeficiency
- Well defined syndromes with immunodeficiency
- Antibody defects
- Defect of immune dysregulation
- Phagocytic defect
- Defect of innate immunity
- Autoinflammatory disorder
- Complement deficiency
- Bone marrow failure
- Phenocopies of PID
What is the most common type of PID?
Antibody disorder and T+B cell deficiency
Chronic granulomatous Disease
impaired phagocytic killing by neutrophils and macrophage
Clinical features of Chronic Granulomatous disease
- bacterial/fungal abscesses in LN, lungs, liver, bone.
- recurrent skin infection (folliculitis)
- recurrent unusual bacterial infection (serratia, pneumocystis, klebsiella, E. Coli, Salmonella).
- recurrent fungal infection (candida, aspergillus, nocardia)
- sterile granulomata causing obstruction (bladder) and colitis.
Treatment of Chronic Granulomatous disease
Cotrimoxazole and itraconazole prophylaxis. IFN gamma IL1 inhibitor (anakinra) HSCT Gene therapy
Leucocyte adhesion deficiency
autosomal recessive
deficiency of adhesive glycoproteins on the surfaces of white blood cells (WBCs);
Deficiencies impair the ability of granulocytes (and lymphocytes) to migrate out of the intravascular compartment, to engage in cytotoxic reactions, and to phagocytose bacteria.
What happens when you have deficiency in the classical pathway?
Remember: classical pathway is antigen/antibody complex
So deficiencies in this causes recurrent infections.
What happens when you have deficiency in the alternative pathway?
Remember: alternative pathway is activated by tumour cells and microbes.
Low C3: recurrent/severe infection
Low factor B, propederin and factor D: more neisserial and bacterial infection
What happens if you have deficiency in lytic phase? (C5, 6, 7, 8, 9)
Increased systemic infection to neisseria = because can’t lyse thick cell wall of this kind of bacteria.
What investigations must you do to test for complement deficiency?
Classical and alternative complement (C3/C4)
Measure of regulation protein (Factor I, H, C1 inhibitor).
ELISA assay:
CH50: (volume dilution of serum that lyses 50% of erythrocyte in reaction)
AH50: similar test but alternative pathway
How do you treat complement deficiencies?
Prophylactic penicillin
Vaccine for meningococcul, haemophillus and pneumococcus.
TLR3 deficiency
TLR 3, 7, 8, 9 = recognise RNA/DNA. So deficiency in this predisposes to HSE (Herpes Simplex Encephalitis)
GATA2 deficiency
aka. monocytopenia with nontuberculous mycobacteria
Deficiency in monocytopenia, dendritic and lymphoid (B+NK) cell deficiency.
Causes lymphodema, myelodysplasia, AML and increased infection.
Features of B-cell immunodeficiency
B-cell makes AB.
- No ABs lead to increased pyogenic bacterial infection.
- resp: recurrent sinus and chest infection = bronchiectasis, cor pulmonale, death.
