Flashcards in Respiratory - Immune Deficiencies 1 - Week 4 Deck (40):
Which acronym is used to prompt consideration of immune deficiencies?
What does SPUR stand for?
Serious infections, Persistent infections, Unusual infections, Recurrent infections
What is meant by a 'serious' infection?
Not responsive to antibiotics
What is meant by a persistent infection?
Early structural damage or chronic infections
How is 'recurrent infection' classified?
2 major or one major and many minor infections in one year
How do chronic infections develop?
Degranulation of neutrophils releases destructive enzymes which create the niche for chronic infection to develop
What is the single greatest indicator of immune deficiency?
Family history of immune deficiency - they're usually genetically encoded
Give 3 symptoms (outwith SPUR) that may suggest immunodeficiency.
Failure to thrive, chronic diarrhoea, weight loss
What is meant by secondary immunodeficiency?
Another condition/factor causes the immunodeficiency rather than the body itself
Give 5 examples of conditions which may cause secondary immunodeficiency?
Extremes of age, infection (such as HIV), treatments (eg. immunosuppressants), malignancy, nutritional disorders
What is the role of TNF-alpha in the innate immune response?
Triggers vasodilation & production of heat.
Which of the leukocytes are phagocytes?
Macrophage & Neutrophil
What are the typical clinical features of phagocyte deficiency?
Infection at unusual sites, common & unusual bacteria, typical & atypical mycobacterium, fungal infections
State 2 reasons which can cause Neutrophils to not be produced or not be produced properly.
Failure to differentiate along the myeloid lineage or failure of naive neutrophils to mature
Give a primary defect which would cause failure of a cell to differentiate along the myeloid lineage.
What is reticular dysgenesis?
Most severe form of Inborn Severe Combined Immunodeficiency (SCID) - no neutrophils & few lymphocytes --> Fatal septicaemia within days of birth
Give a secondary defect which would cause failure of a cell to differentiate along the myeloid lineage.
After stem cell transplant
Give 2 examples of conditions caused by failure of neutrophils to be able to mature.
Kostmann Syndrome, Cyclic neutropaenia
What is the mechanism of reticular dysgenesis?
Stem cell cannot differentiate into common myeloid progenitor or common lymphoid progenitor
What is the mechanism of Kostmann Syndrome?
Granulocyte-Monocyte progenitor cannot differentiate into a neutrophil as there is a defect in G-CSF cytokine or receptor
State 4 clinical presentations of Kostmann Syndrome.
Severe chronic neutropenia, recurrent bacterial infections usually 2 weeks after birth, fever, irritability, failure to thrive
State 2 supportive treatments of Kostmann Syndrome.
Prophylactic antibiotics & prophylactic anti-fungals
State 2 definitive treatments of Kostmann Syndrome.
Stem cell transplantation (if problem in Neutrophil pre-cursor), G-CSF (if defect in cytokine)
If a patient's phagocytes were unable to bind to adhesion molecules, what clinical signs would be seen?
High neutrophil numbers in blood, no pus formation in tissue infections, recurrent bacterial & fungal infections
Failure to recognise activation markers expressed on endothelial cells is called...
Leukocyte Adhesion Deficiency
Leukocyte adhesion deficiency is caused by...
A defect in the CD-18 leukocyte integrin
What kind of receptors do phagocytes express?
What is the role of Fc receptors in phagocytes?
Allows any antibody-antigen complex to attach
Which receptor on phagocytes binds to complement fragments bound to an antigen?
Complement receptor 1 (CRI)
State 2 potential reasons behind defective phagocytosis.
Defect in opsonin receptors (Fc or CRI) or defect in complement or antibody production
Failure of oxidative killing mechanisms is called...
Chronic Granulomatous Disease
Chronic Granulomatous Disease results in...
inability of phagocytes to kill by oxidative killing as they cannot produce free radicals
State 5 clinical features of Chronic Granulomatous Disease.
Recurrent deep bacterial infections, recurrent fungal infection, failure to thrive, Lymphadenopathy and hepatosplenomegaly (enlarged spleen & liver), granuloma formation
Which test is used to test for Chronic Granulomatous Disease?
What does the NBT test test for?
Whether neutrophils can kill via production of oxidative free radicals
Give 2 examples of supportive treatments for Chronic Granulomatous Disease.
Prophylactic antibiotics & anti-fungals
Give 2 examples of definitive treatments for Chronic Granulomatous Disease.
Stem cell transplantation or Gene therapy
Explain the immunological pathway involved in TB.
Infected macrophage produces IL-12 which stimulates Th1 cells to produce interferon gamma which acts on neutrophils & macrophages to produce TNF-alpha. This triggers oxidative killing mechanisms.
IFNg receptor deficiency, IL-12 deficiency and
IL-12 receptor deficiency can all cause...
Increased susceptibility to mycobacterial infections