Immunodeficiency Flashcards
What are the 2 types of immunodeficiency?
primary/congenital
secondary/acquired
What causes primary immunodeficiency?
genetic or developmental defect
What causes secondary immunodeficiency?
result of disease or therapy
What immune system components can be targeted in primary immunodeficiency?
B-cell defects (most common)
T-cell defects
B + T cell defects
phagocytic deficiencies
complement deficiencies
What type of vaccinations cannot be administered to primary immunodeficiency patients?
live vaccines
List 3 congenital/central immunodeficiencies
Bruton’s agammaglobulinaemia
DiGeorge syndrome
Severe Combined Immunodeficiency (SCID)
What mnemonic gives the presentation of DiGeorge syndrome?
CATCH-22
Cardiac malformations
Abnormal face
Thymic hypoplasia
Cleft palate
Hypocalcaemia
22q sporadic gene microdeletion
What are the midline defects seen in DiGeorge syndrome?
hypertelorism (large distance between eyes)
down-slanted eyes
cleft palate
Inheritance of ataxia-telangiectasia
autosomal recessive
chromosome 11
How does ataxia-telangiectasia present?
2nd year of life as lack of balance and slurred speech
ataxia
severe eczema
ocular telangiectasia
What is the inheritance pattern of Wiscott-Aldrich disease?
X-linked recessive
WASP gene on Xp11 chromosome (defective cytoskeleton of T cells and platelets)
Wiscott-Aldrich disease clinical presentation
thrombocytopenia
eczema
recurrent sino-pulmonary infections
HSV/CMV/PCP
small platelets
reduced T cells
increased B cells
increased IgA + E
reduced specific antibodies
Pathophysiology of Bruton’s X-linked agammaglobulinaemia
absence or deficiency of a Bruton’s tyrosine kinase
maturation arrest of pre-B cells
levels of all Ig <10% normal
small tonsils
What is CVID and how does it present?
Common variable immune deficiency
onset after 2-10y
recurrent sinopulmonary infections (H.influenzae, S.pneumoniae, S.aureus)
lymphadenopathy
splenomegaly
no specific antibody production –> no response to vaccines
anti-B cell autoantibodies
associated with other autoimmune manifestations
How does selective IgA deficiency present?
no obvious susceptibility
majority of patients clinically normal
IgA<5 = recurrent/chronic sinopulmonary + GI infections
allergy, coeliac disease, ulcerative colitis, JRA, SLE
no specific treatment, treat associated problems
Chediak-Higashi syndrome inheritance
autosomal recessive
long arm of chromosome 1 (LYST)
Pathophysiology Chediak-Higashi syndrome
lysosomes fail to fuse with the phagosome
neutropenia
diminished chemotaxis
giant lysosomes
Chediak-Higashi syndrome presentation
easy bruising (abnormal platelets)
pyogenic infections
oculocutaneous albinism
photophobia
enterocolitis
peripheral neuropathy
What infections are seen in patients with leukocyte adhesion deficiency?
widespread pyogenic bacterial infections
What infections are seen in patients with chronic granulomatous disease?
intracellular and extracellular infection
granulomas
What infections are seen in patients with G6PD deficiency?
defective respiratory burst
chronic infection
What infections are seen in patients with myeloperoxidase deficiency?
defective intracellular killing
chronic infection
What infections are seen in patients with Chediak-Higashi syndrome?
intracellular and extracellular infection
granulomas
What can be deficient in the classical complement pathway and what does this lead to?
C1, C2, C4
deficiency leads to immune-complex disease
What can be deficient in the Mannose-binding lectin complement pathway and what does this lead to?
MBL
MASP1
MASP2
C2
C4
deficiency of MBL leads to bacterial infections, mainly in childhood
What can be deficient in the alternative complement pathway and what does this lead to?
Factor D
Factor P
deficiency leads to infection with pyogenic bacteria and Neisseria spp. but no immune-complex disease
C3 deficiency effects
infection with pyogenic bacteria and Neisseria spp.
sometimes immune-complex disease
What can be deficient in the membrane attack complex and what does this lead to?
C5
C6
C7
C8
C9
infection with neisseria spp. only
Warning signs of primary immunodeficiency in a medical history
> 8 ear infections/year
2 serious sinusitis/year
2 pneumonias/year
deep-seated infections or infections in unusual areas/year
recurrent deep skin/organ abscesses
need for IV Abx to clear infection
infections with unusual/opportunistic organisms
family history of PID
Warning signs of primary immunodeficiency - physical signs
poor growth (failure to thrive)
absent lymph nodes/tonsils
skin lesions (telangiectasia, petechiae, lupus-like rash)
ataxia, ocular lesions
oral thrush after 1 year of age
oral ulcers
Cellular immunity tests
ANC (absolute neutrophil count)
ALC (absolute lymphocyte count)
Candida skin test
Humoral immunity tests
Serum IgG, A, M, E
Phagocyte function tests
CBC (complete blood count)
NBT test (Nitroblue tetrazolium test )
Complement function tests
total haemolytic complement assay:
- classical = CH50
- alternative = AH50
Which immunodeficiency syndromes can a bone marrow transplant be used in treatment?
Hyper-IgE syndrome
SCID
Wiscott-Aldrich
Chediak-Higashi
Kostmann disease
Bone marrow transplants from which donors produce the best outcomes?
HLA-identical siblings
How can primary immunodeficiencies be grouped?
by what part of the immune system is affected:
- antibody deficiencies (eg. CVID)
- combined immune deficiencies (eg. SCID)
- complement deficiencies (eg. C2 Deficiency and HAE)
- phagocytic cell deficiencies (eg. CGD)
List some immunosuppressive agents
environmental stress
infectious diseases (eg. HIV)
malnutrition
genetic and metabolic diseases
immunosuppressive drugs
surgery and trauma splenectomy
age extremes: prematurity + old age
List some causes of acquired iatrogenic immunodeficiency
caused by therapeutic intervention:
- cytotoxic drugs
- ionising radiation
- ALG (anti-lymphocyte globulin)
- cyclosporin
