Immuno: Primary Immune Deficiencies Pt.1 Flashcards
In which physiological states might you expect a relative degree of immunodeficiency?
- Neonates
- Elderly
- Pregnancy
List some examples of secondary immunodeficiency.
- Infection - HIV, measles
- Biochemical disorders - malnutrition, zinc/iron deficiency, renal impairment
- Malignancy - myeloma, leukaemia, lymphoma
- Drugs - corticosteroids, cytotoxic
What are some major clinical features of immunodeficiency?
- 2 major OR 1 major + recurrent minor infections in one year
- Unusual organisms
- Unusual sites
- Unresponsive to treatment
- Chronic infections
- Early structural damage
List some features that may suggest primary immunodeficiency.
- Family history
- Young age at presentation
- Failure to thrive
Broadly speaking, what are the four mechanisms of phagocyte deficiency?
- Failure to produce neutrophils
- Defect of phagocyte migration
- Failure of oxidative killing
- Cytokine deficiency
Give three examples of failure of neutrophil production and outline their mechanism.
Reticular dysgenesis
- Autosomal recessive severe SCID with no production of lymphoid or myeloid cells
- Caused by failure of stem cells to differentiate along lymphoid or myeloid lineage
Kostmann syndrome
- Autosomal recessive congenital neutropenia
Cyclic neutropaenia
- Autosomal dominant episodic neutropaenia
- Occurs every 21 days
Name a phagocyte deficiency caused by failure of phagocyte migration.
Leukocyte adhesion deficiency
Describe the pathophysiology of leucocyte adhesion deficiency.
- Caused by deficiency of CD18 (β2 integrin)
- CD18 normally combined with CD11a to produce LFA-1 (lymphocyte function associated antigen 1)
- LFA-1 normally binds to ICAM-1 (intercellular adhesion molecule 1) on endothelial cells to mediate neutrophil adhesions and transmigration
- A lack of CD18 means a lack of LFA-1, so neutrophils cannot enter tissues
- During an infection, neutrophils will be mobilised from the bone marrow (HIGH neutrophils in the blood) but they will not be able to cross into the site of infection (NO pus formation)
Name a phagocyte deficiency caused by failure of oxidative killing mechanisms.
Chronic granulomatous disease
Outline the pathophysiology of chronic granulomatous disease + clinical features
- Absent respiratory burst (deficiency of components of NADPH oxidase leads to inability to generate oxygen free radicals)
- Excessive inflammation (persistent neutrophils and macrophage accumulation with failure to degrade antigens)
- Granuloma formation
- Lymphadenopathy and hepatosplenomegaly
Which bacteria are more likey to infect someone with Chronic Granulomatous Disease
PLACESS
Catalase positive bacteria
- E coli
- Staphylococcus Aureus
- Listeria spp
- Klebsiella spp
- Serratia marcescens
- Candida spp
Describe the cytokine cycle between macrophages and T cells.
- Macrophages produce IL12 which stimulates T cells, which then produce IFN-gamma
- IFN-gamma acts back on the macrophages and stimulates the production of TNF-alpha and free radicals
- Deficiencies in IL12, IL12R, IFN-gamma or IFN-gamma receptor can cause immunodeficiency
What type of infection do patients with IL12/IL12R or IFN-gamma/IFN-gamma receptor deficiencies tend to present with?
Organisms that infect macrophage (usually atypical mycobacteria)
Name and decribe the colour changes of two tests used to investigate chronic granulomatous disease.
- Nitroblue Tetrazolium (NBT) - yellow to blue
- Dihydrorhodamine (DHR) - fluorescent (main test)
NOTE: both of these tests are looking at the ability of neutrophils to produce hydrogen peroxide and oxidative stress
Which types of infection tend to occur in patients with phagocyte deficiency?
- Recurrent skin and mouth infections
- Bacteria - Staphylococcus aureus, enteric bacteria
- Fungi - Candida albicans, Aspergillus fumigatus
- Mycobacterial infections (particularly with IL12 deficiency)
- TB, atypical mycobacteria
What are the two different types of NK cell deficiency?
- Classical NK deficiency - absence of NK cells in the peripheral blood
- Functional NK deficiency - NK cells are present but function is abnormal
