Immunology - immunodeficiency Flashcards
What are the hallmarks of immune deficiency?
Serious Infection: unresponsive to oral antibiotics
Persistent Infection
Unusual Infection
Recurrent Infection
What is secondary immunodeficiency?
- acquired
- common, subtle
- inolves more than one component of immune system
What is primary immunodeficiency?
rare
congenital
Where can secondary immunodeficiencies arise from?
Infection (HIV, measles)
Treatment interventions (cancer therapy, steroids)
Malignancy (cancer of immune system, mets)
Biochem and nutritional disease (malnutrition, diabetes)
What is reticular dysgenesis?
Failure of stem cells to differentiate along myeloid lineage
Primary
What is Kotsmann syndrome?
Failure of neutrophil maturation
Primary
What is the management of Kotsmann syndrome?
Supportive treatment inc. prophylactic antifungals & antibiotics
Mortality 70% w/out definitve treatment
(stem cell transplant or Granylocyte colony stimulating factor. GF stimulat maturation neutrophils)
What is leukocyte adhesion deficiency?
Failure to recognise selectins on endothelium surface
Problem with leukocyte integrins
No adhesion or migration
What is the clinical picture of LAD?
Marked leukocytosis (increase WBCs in plasma) Localised bacterial infections difficult to detect
TRUE/FALSE
Defect in opsonin receptors may cause significant disease
FALSE
Opsonin receptors enhance phagocytosis, defect may cause defective phagocytosis but significant redundancy of opsonin receptors means this generally does not cause significant disease
TRUE/FALSE
Any defect of complement or antibody production will also result in decreased efficiency of opsonisation
TRUE
antibodies and complement (C3B) are opsonins
What is chronic granulomatous disease?
Failure of oxidative killing mechanism.
Impaired killing of intra-cellular micro-organisms
This leads to failure to DEGRADE chemoattractants and antigens. Persistant accumularion of WBCs and lymphocytes
= THIS LEADS TO GRANULOMA FORMATION
What are some features of chronic granulomatous disease?
Recurrent bacterial and fungal infections failure to thrive lymphadenopathy (swelling lymph nodes) hepatosplenomegaly granuloma
What is the lab investigation of chronic granulomatous disease?
Nitroblue Tetrazolium test
sensitive to products of hydrogen perioxide (product of resp burst)
How does body defend against intracellular organisms?
Infected macrophages produce IL-12
IL-12 stimulates TH1,TC&NK cells to release secrete interferon gamma
interferon gamma stimulates TNF which activates NADPH oxidase and respiratory burst
What are the gene defects associated with susceptibility to intracellular bacteria? MACROPHAGE CYTOKINES
IL-12 deficit
IL-12 receptor deficit
Tests for phagocyte recruitment?
Full blood count
Presence of pus
Expression of neutrophil adhesion molecules
Test results for Congenital neutropaenia?
Neutrophil count: absent
Pus: absent
Leukocyte adhesion markers: normal
NBT: no phagocytosis
Test results for leukocyte adhesion defect?
Neutrophil count: increased during infection
Pus: no
LD markers: absent
NBT: normal
Test results for chronic granulomatous disease?
Neutrophil count: normal
Pus: yes
LD markers: normal
NBT: abnormal
What is SCID?
Severe combined immunodeficiency
Failure of differentiated stem cells to mature into lymphocytes.
Lots of pathways for this to happen.
What is the commonest cause of SCID?
X-Linked, mutation of IL 2 receptor
What does IL 2 do?
Activated T cells and B cells
Activates NK cells
What does IL 12 do?
Enhances cytotoxic activity - stimulates TH1 cells to release secrete interferon gamma
interferon gamma stimulates TNF which activates NADPH oxidase and respiratory burst
What are the clinical features of DiGeorge syndrome?
Failure development thymus (pharyngeal pouch embryo)
Hypoparathyroidism
What would laboratory investigations of Digeorge syndrome show?
- Absent or decreased no. T cells
- Normal or increased B cells
- Normal NK cell numbers
What are some disorders of T cell effector (helper and cytotoxic) functions?
- cytokine production
- cytotoxicity
- T-B cell communication
What are the gene defects associated with susceptibility to intracellular bacteria? T CELL CYTOKINES
IFNy (stimulates TNFa) receptor deficit
IFNy deficit
What is the function of the IL12/IFNy axis?
Defence against intracellular bacteria
Macrophage release IL 12
IL 12 ctivates T helper cells which enhances cytotoxic activity of CD8 and NK cells
IL 12 stimulates production of IFNy (from TH1, cytotoxic T cells and NK) IL IL 12 stimulates production of TNFa (from macrophages)
Where can phagocyte deficiencies manifest?
Stem cell prod/differentiation Neutrophil adhesion/endothelial migration Recognition pathogens Phagocytosis and killing Activation of other components
What are the first line investigations of T cell deficiencies?
- Total WBC count
- Serum immunoglobins (functional effector cells promote creation of these)
- Quantify lymphocyte populations
What does CATCH 22 represent?
Problems associated with DiGeorge syndrome Cardiac problems Abnormal face Thymic dysfunction Cleft deformities Hypocalcaemia, hypoparathyroidism 22 mutations chromosome 22
What are the SECOND line investigations of T cell deficiencies?
Test for
FUNCTION
PROLIFERATION
HIV
How do antibody deficiencies present?
Recurrent bacterial infections
with COMMON bacteria
Viral infections may occur
What is Bruton’s X-linked hypogammaglobulinaemia?
Failure B cells to mature
- NO circulating B cells or plasma cells
- NO circulating antibodies 6 months after BIRTH!
What is selective IgA deficiency?
No production IgA (breast milk, tears, mucosal sites, mucus)
1/3rd RECURRENT RESP TRACT INFECTION
2/3 ASYMPTOMATIC
What is common variable immune deficiency?
Low IgG, IgA and IgE Consider immunoglobin function IgG: agglutination, opsonisation, complement activation IgE: allergies IgA: Mucosal sites, breast milk, tears associated autoimmune disease
What are the clinical features of CVID?
Recurrent bacterial infections Often with severe end-organ damage Bronchiectasis, persistent sinusitis, recurrent gastrointestinal infection Autoimmune disease Granulomatous disease
How can B cell deficit be managed?
- Treat infection aggressively
- Immunoglobin replacement therapy
- Stem cell transplant sometimes
What are the first line investigations of B cells?
Total WBC count
Serum immunoglobins
Serum and urine protein ELECTROPHORESIS (measure of immunoglobins/ proteins)
What are the second line investigations of B cells?
Quantify no. T cells and B cells
Meausre SPECIFIC ANTIBODY FUNCTION to known pathogens
- IgG against tetanus
-Immunise with vaccine and measure antibody
failure to moutn response= defect?
