Primary immunodeficiency Flashcards
What are the hallmarks of recurrent infections encountered in immune deficient patients (SPUR)?
Serious infection
Persistent
Unususual
Recurrent
What are the stages of phagocyte production, mobilisation and recruitment that can be affected by immune deficiencies?
- mobilisation of phagocytes from bone marrow
- upregulation of ednothelial adhesion molecules. Neutrophils adhere and migrate into tissues.
- Recognition of the pathogen
- Phagocytosis of the pathogen.
- Activation of other immune system components.
Failure to produce neutrophils?
- Recticular dysgenesis (primary, severy inborn SCID)
- Following cell transplantation (secondary defect)
- Kostmann sydndrome
- Cyclic neutropaenia
When does Kostmann sydnrome present?
2 weeks after birth, with recurrent bacterial infections.
Treat with:
- stem cell transplantation
- stimulate neutrophil maturation with growth factors
What are the clinical features of leukocyte adhesion deficiencies?
- recurrent infections of deep tissues
- very high blood neutrophil counts
What receptors can be faulty in defects of phagocyte’s direct recognition of pathogens?
Toll-like receptors
Scavenger receptors
Lectin receptors
-They recognise bacterial wall structures.
Fc and complement (CRI) receptors:
-bind antigen-bound opsonins
Failure to phagocytose and kill pathogens?
-Chronic granulomatous disease (failure of oxidative killing mechanisms)
What are the features of Chronic granulomatous disease?
- recurrent Staph, Aspergillus and pseudomonas infections
- atypical mucobacteria
- fungal infections
- failure to thrive
- hepatosplenomegaly
- failure to thrive
- granulomas
Lab diagnostic test for chronic granulomatous disease?
NBT (nitroblue tetrazolium) test - can neutrophils kill pathogens by producing ROS?
What is the IL-12 : IFN-gamma network?
Defence against intracellular pathogens:
- Infected macrophages produce IL-12
- IL-12 induces Th1 cells to secrete INF-gamma
- INF-gamma loops back to stimulate oxidative killing pathways by macrophages
Where do T cells undergo maturation and proliferation?
the Thymus
How are T cells formed?
- arise form haematopoietic cells in the bone marrow
- maturation and selection in the thymus
- entry into circulation and lymph nodes
Functions of T cells?
- defend against intracellular pathogens (bacteria, viruses)
- immunoregulation (helper T cells)
Functions of CD4+ T (helper) cells?
Immunoregulation:
- activate CD8+ (cytotoxic) T cells and naive B cells
- secrete cytikines
What antigenic peptides do CD4+ / T helper cells recognise?
Those bound to MHC class II
CD8+ (cytotoxic) T cells recognise antigenic peptides…
…presented bound to MHC class II
How do cytotoxic T cells kill cells?
- produce pores using perforin
- induce apoptosis of target cells
- secrete INF-gamma
Cytotoxic T cells are important in defence against…
…viral infections and tumours.
In recticular dysgenesis there is a failure to produce…
…neutrophils, B cells, T cells, Macrophages and platelets.
Death occurs without bone marrow transplantation.
In SCID (severe combined immunodeficiency) there is a failure to produce…
… lymphocytes (B cells and T cells)
What is X-linked SCID?
- mutation in the IL-2 receptors
- T calls, NK cells and B cells cannot respond to cytokines
SCID is treated with…
…stem cell transplantation
Gene therapy may work.
The clinical features of DiGeorge syndrome are?
- failed thymus development (no mature T cells)
- congenital heart defects
- cleft palate
- hypoparathyroidism
- schizophrenia, OCD
CPx of DiGeorge syndrome?
Recurrent viral, bacterial and fungal infections
Di George Syndrome - lab results?
- no T cells
- low B cells (or normal)
- low IgG, IgA and IgE
How do antibody deficiencies present?
- recurrent bacterial infections (resp, GI)
- Ig-mediated autoimmune disease
What is Bruton’s X-linked hypohammaglobulinaemia?
- a B cell maturation defect
- there are no circulating B cells or plasma cells
- no circulating antibodies
What Ig’s are low in Common variable immune deficiency?
IgG
IgA
IgE
Autoimmune and granulomatous disease are common.
Characteristics of B cell deficiencies?
-recurrent bacterial infections by common / opportunistic bacteria
