Immunodeficiencies Flashcards
What are primary immunodeficiencies?
→condition resulting from a genetic or developmental defect
→defect is present from birth and is mostly inherited
→May not be clinically observed until later in life
What are secondary immunodeficiencies?
→a result of malnutrition, cancer, drug treatment or infection
What are the clinical features of PIDs?
→Recurrent infections
→Severe infections,
→unusual pathogens
→unusual sites
What are defects in innate immunity caused by?
→defect in phagocytic or complement function
What are PIDs mostly caused by?
→antibody disorders
Give examples of causes of PID in haematopoiesis?
→reticular dysgenesis →congenital agranulocytosis →SCID →leucocyte-adhesion deficiency →X-linked agammaglobulinemia →Di-George →Wiskott-Aldrich →X-linked hyper-IgM syndrome
What do Tcell defects result inn?
→impair antibody production
Give examples of major B cell disorders
→X-linked agammaglobulinaemia (Bruton’s disease)
→Common variable immunodeficiency (CVID)
→Selective IgA deficiency
→ IgG2 subclass deficiency
→ Specific Ig deficiency with normal Igs
What gene defect causes XLA?
→BTK gene on X chromosome
What does BTK gene encode?
→Bruton’s tyrosine kinase
What are the results of XLA?
→Block in early B-cell development (stop at pre-B cells)
→Recurrent severe bacterial infections
→Autoimmune diseases
Why is Bruton’s tyrosine kinase important in B-cell development?
→needed for pre-B cell receptor signalling
How is XLA diagnosed?
→B cells absent / low; plasma cells absent
→All immunoglobulins absent / very low
→T cells and T cell-mediated responses normal
→using immunoelectrophoresis
How is XLA treated?
→IVIg
→subcutaneous Ig weekly
→prompt antibiotic therapy (URI /LRI)
→Do not give live-attenuated vaccines
What is selective IgA deficiency?
→Low levels serum & secretory IgA
→Sometimes: increased incidence allergic disease
Which lymphocytes does ataxia telangiectasia affect?
→T and B cells
Give examples of predominant T-cell disorders
→DiGeorge syndrome
→Wiskott-Aldrich syndrome
→Ataxia-telagiectasia
Give examples of causes of SCID
→Common cytokine receptor γ-chain defect
→RAG-1/RAG-2 defect => no T and B cells
→ADA (adenosine deaminase deficiency)
Why is gamma-chain important for cytokines?
→signal transducing component of receptors for IL-2, IL-4, IL-7, IL-9, IL-11, IL-15, IL-21
What is the function of IL-7?
→for survival T cell precursors
What are RAG proteins?
→required for T and B cell receptor rearrangement
What are the patterns of SCID?
→T cell function reduced proliferation
→reduced cytokine production
How is SCID treated?
→Isolation to prevent further infections
→Blood products from CMV-negative donors
→IV Ig replacement
→Infection prophylaxis
→Bone marrow/haematopoietic stem cell transplant
→Gene therapy (for ADA and γ-chain genes)
What are the physical symptoms of DiGeroge syndrome?
→Dysmorphic face:
→cleft palate,
→low-set ears,
→fish-shaped mouth
What are the types of DiGeorge synrome?
→Complete DiGeorge- absent thymus
→Incomplete DiGeorge - reduced thymus
What is thymic hypoplasia in DiGeroge syndrome due to?
→22q11 deletion
→Results in failure development 3+4th pharyngeal pouches
How can DiGeorge be treated?
→thymus transplantation
→thymus from donor and transplanted
What mode of inheritance is Wiskott-Aldrich syndrome?
→ X-linked
What is the cause of W-A syndrome?
→Defect in WASP
→protein involved in actin polymerization
What are the symptoms of W-A syndrome?
→Thrombocytopenia, eczema, infections
→Progressive immunodeficiency (T cell loss)
→Progressive reduction of T cells; reduction of T cell proliferation
→ Antibody production (reduced IgM, IgG; high IgE, IgA)
What type of defect is chronic granulomatous disease?
→phagocyte defect
→Defective oxidative killing of phagocytosed microbes
→mutation in phagocyte oxidase (NADPH) components
How is chronic granulomatous disease diagnosed?
→Nitro blue tetrazolium reduction test
→Dihydrorhodamine assay
How is chronic granulomatous disease diagnosed?flow cytometry
→Becomes fluorescent in presence of NADPH activity
What defct causes Chediak-Higashi syndrome?
→Defect in LYST gene (regulates lysosome traffic)
What are the effects of C-H syndrome?
→Neutrophils have defective phagocytosis
→Repetitive, severe infections
How is C-H syndrome diagnosed?
→Decreased number neutrophils
→Neutrophils have giant granules with phagosome
What is leucocyte adhesion deficiency(LAD)?
→Defect in β2-chain integrins
→Defect in sialyl-Lewis X (selectin ligand)
→Delayed umbilical cord separation => diagnosis defect in β2-chain integrins
What are the presentations of LAD?
→Skin, GIT infections and perianal ulcers
How is LAD diagnosed?
→Low Neutrophil chemotaxis
→Low Integrins expression on phagocytes (flow cytometry)
Describe PID gene editing
→Bone marrow cells removed →Separation of immune cell progenitors →Immune cell progenitors infected with virus to introduce a correct copy of mutated gene →Cells take up normal gene →Cells return to patient →Immune reconstitution
What are the treatments for HIV/AIDS?
→HAART
→PrEP
Which is more common- PID or secondary?
→secondary
