Immunodeficiencies Flashcards
Prevalence
What is immunodefiency and what can it lead to?
- Defects in one or more components of the immune system
- Serious + fatal syndromes/diseases
- Data difficult to estimate
- No current screening programme at birth
Describe the classification of immunodefiencies?
- Primary (congenital) immunodeficiency -> genetic or developmental defect -> Present from birth + mostly inherited -> not clinically observed until later in life
- Secondary immunodeficiency -> Originates via malnutrition, cancer, drug treatment OR infection -> most common is AIDS
Describe clinical features of immunodefiency?
- Recurrent infections, severe infections, unusual pathogens + unusual sites
- Unusual as in they wouldn’t normally cause symptoms within them
Describe the cause of primary immuno-deficency?
- Affects Innate or Adaptive Immune system
- Defects in Innate
- Caused via defect in phagocytic or complement function
- Lymphoid cell disorders affect TOR B cells or both combined ID)
State what components of the immune system targeted lead to PID and what else can it lead to?
- AB
- Cell-mediated immunity
- Complement + phagocytosis
- Can lead to Immunodeficiency + autoimmune disease
Describe how defects during haematopoiesis will affect the consequences?
- Haematopoiesis = formation of blood cellular components via differentiation of stem cells
- Defect -> Depends upon number + type of immune system component involved -> defect in earlier SC - affects entire IS + defect in later SC -> Increase restricted pathology
State what cellular component will be affected via defect causing ID from the colours in this diagram VD
Red= phagocytic
Green= B cell and antibody
Purple= thymic epithelial cell mediated
Blue = combined T and B cell
Primary immunodefiency - Adaptive
Describe the components affected in adaptive immunity in PID?
- B, T cells, both
- T cell defect -> causes AB production impaired -> defect in lymphocyte development or activation (mutation)
What is X-linked agammaglobulinaemia, how does it occur + state clinical symptoms?
- Also Bruton’s disease (X-linked disease)
- Defect in Bruton’s Tyrosine Kinase gene (X chromosome) -> defect in Btk protein -> required for pre-B Cell Receptor signalling -> blocks B-cell development at pre-B stage
- Clinical symptoms: Recurrent severe bacterial infections, 2nd half of first yr (lung, ears, GI) + autoimmune disease (35% of patients)
Describe the diagnosis of X-linked agammaglobulinaemia?
- B cells absent/decrease plasma cells A, all Igs A/V, T-cells + response = normal
- Vla flow cytometry (B + T) + immunoelectorphoresis (Ig)
Describe the treatment for X-linked agammaglobulinaemia?
- URI = upper respiratory infection, LRI = Lower respiratory infection
- IVof Ig: 200-600mg/kg/month at 2-3 wk intervals
- Or subcutaneous Ig weekly
- Prompt antibiotic therapy (URI /LRI)
- Do not give live-attenuated vaccines -> ID -> unable to clear A pathogen
Describe the signs of selective IgA deficiency?
- Asymptomatic cases (sometimes infect resp, uro or GI)
- Increased serum + secretory IgA
- Sometimes increase incidence allergic disease
Describe the causes of severe combined Immunodeficiencies?
- Cytokine receptor v-chain defect (signal transducing component of receptors for many ILs) -> Affects IL-7 - survival T cell precursors -> defective T cell development + concomitant lack in B cell help (low AB)
- RAG-1/RAG-2 defect => noT + B cells
- Adenosine deaminase deficiency -> accumulation of deovadenosine & deoxy-ATP - toxic for thymocytes + die
Describe the characteristics of Severe combined immunodeficiency
- Decrease total lymphocyte count (T,B + NK) = SCID -> Pattern: V/A T; normal/absent B, possible absent NK (v-chain defect affecting IL- 15 receptor),
- Decreased Igs -> Decreased T cell function, proliferation + cytokine
Describe the technique used for diagnosis of SCID?
- Flow cytometry -> B + T cell plots VD
