Clinical immunology Flashcards
Why are antibodies important?
Bacteria = opsonisation of non-encapsulated and encapsulated bacteria
Viruses = neutralisation (intracellular killing of non-enveloped viruses) and NK ADCC killing of enveloped viruses
underpin vaccination strategies
bacterial exotoxins - high affinity germinal centre dependent
What issues arise when there are defects in B cell function?
Recurrent pyogenic infections
Upper and Lower RTI (pneumonia, sinusitis)
Diarrhoea - campylobacter jejuni, giariasis
Organisms - encapsulated and non-encapsulated bacteria
Viruses - rare except for enteroviruses, avoid live polio in past
fungal infections uncommon
infections with intracellular organisms are not usually a problem although there is some evidence
What is the aetiology of B cell defects?
Genetics: X linked so males affected and females carriers, presents when maternal antibodies wane
In pts >50 B cell malignancy
What are examples of acquired forms of antibody deficiency ?
HIV
common variable antibody deficiency (cause mainly unknown)
What comes under secondary B cell depletion?
secondary to immunosuppresion- B cell depletion in autoimmune disease - RA, vasculitis, SLE
How are defects in B cell function diagnosed?
serum Igs and electrophoresis - total Ig levels, paraprotein (multiple myeloma)
functional antibodies - tetanus and diptheria toxins, pneumococcal and H influenzae polysaccharides
Test immunization - prevenar 13, menitorix
What is the treatment for B cell defects?
replacement treatment with IgG
antibiotics if there is established lung disease or GI symptoms
Case 1:
2 year old - septic arthritis in R knee, Haemophilus influenzae b isolated, had recurrent chest infections and otitis media
normal Hb, normal total lymphocyte, normal neutrophils
CRP >40
What investigations do you arrange and how do you treat?
serological = immunoglobin GAM, electrophoresis
Functional serological tests = functional ab, test immunisation, menitorix and prevenar 13 (conjugate vaccinations)
cell tests = surface markers for B and T cells
treatment: IV or SC immunoglobulin replacement
Case 2:
54 year old man, 2 day hx cough with purulent sputum and fever with chills
R sided pleuritic pain
WBC = 50x10^9/L
Physical exam:
- consolidation, abnormal breath sounds (?pneumonia)
- lymphadenopathy, splenomegaly, anaemia, bruising
- Hb 10, Neutrophil 15x10^9, lymphocyte 35x10^9, normal platelets
blood and sputum culture - s. pneumoniae
What tests would you perform and what treatments?
lymphocyte surface markers
serum immunoglobulins and electrophoresis
chemotherapy
antibiotics
treat underlying condition
With innate immunodeficiency what factors will have problems?
neutrophils / macrophages complement toll receptors, cytokines NK cells splenectomy
With adaptive defectives in immunodeficiency what factors will have problems?
antibody deficiency
T cell disorders
What arises with a C3 deficiency?
defective opsonin
pyogenic infections
What arises with a C1qrsC4C2 deficiency?
- defective clearance of apoptotic cells
- immunogenic
- SLE (ANA, DNA)
- immune complex disease
What arises with a C5-9 deficiency?
neiserria infections
Case 3: 3 year old, photophobia, fever, drowsiness of 6h, fine day before ? bacterial meningitis Clinical signs: - neck stiffness - Rash What do you need to ask in PMH?
if this has happened before:
- 2 previous episodes and 1 episode of pneumonococcal septicaemia
Case 3:
3 year old, photophobia, fever, drowsiness of 6h, fine day before
? bacterial meningitis
Clinical signs:
- neck stiffness
- Rash
What specific immunological tests would you order?
serum Igs
functional Abs
functional tests of complement
spleen
What can cause neutrophil defects?
drugs and leukaemia
How are neutrophil defects treated?
G-CSF
antifungals and abx
What happens in neutrophil defects?
neutrophil migration and adhesion
neutrophil killing- respiratory burst = acidification inside the phagosome, allows the activation of neutrophil enzymes
What is absent in adhesion LFA-1 deficiency?
infection without pus
What are the features of chronic granulomatous disease?
defective neutrophil killing
- fungal and staphylococcal infections
- no respiratory burst
- X linked
Why are splenectomy’s important to consider in patients?
2nd major phagocytic organ that filters blood
increased risk of septicaemia - pneumoococci, meningocooci, malaria
critical contribution of IgM in early infection - IgM opsonizes encapsulated bacteria that are phagocytosed in kuppfer macrophages in the liver
splenic vein joins mesenteric veins to form portal vein
How do you treat people with splenectomy?
immunize with menitorix and prevenar
prophylactic abx
What can viruses do? e.g. herpes virus zoster, CMV
downregulate expression of HLA class 1
