Lyrics · 完整歌詞
Although primary immunodeficiencies are diverse,
the pattern
and timing of infection can help identify the affected component of immune defence.
The pattern of infection is the fingerprint of the missing arm.
Two clues, the pathogen and the age of onset, solve most cases.
Antibody deficiency presents after six months, once maternal IgG has waned,
with encapsulated bacteria such as pneumococcus and Haemophilus, enteroviruses and Giardia.
T-cell deficiency presents early and severely with viruses, Candida,
Pneumocystis and intracellular organisms, and live vaccines may be lethal.
Phagocyte defects produce abscesses and granulomas from catalase-positive organisms,
because the pathogen destroys the hydrogen peroxide the cell fails to make.
Deficiency of complement components C5 to C9 leaves Neisseria unkilled,
causing recurrent meningococcal disease.
Severe combined immunodeficiency is the emergency of this field.
The commonest form is X-linked,
caused by mutation of the common gamma chain shared by the receptors for interleukins
2,
4, 7, 9, 15 and 21.
Loss of IL-7 signalling abolishes T cells
and loss of IL-15 signalling abolishes NK cells,
so the phenotype is T-negative, B-positive, NK-negative.
Adenosine deaminase deficiency instead accumulates toxic deoxyadenosine triphosphate and destroys T,
B and NK cells alike.
In either form a total lymphocyte count below 2.5 × 10⁹/L in
an infant is a red flag.
Live vaccines, including rotavirus and BCG, are absolutely contraindicated,
and haematopoietic stem cell transplantation before infection sets in offers the best survival.
Newborn screening for T-cell receptor excision circles now detects most cases before the first
pneumonia.
Although primary immunodeficiencies are diverse,
the pattern
and timing of infection can help identify the affected component of immune defence.
Gene-to-syndrome pairs recur.
X-linked agammaglobulinaemia is a BTK defect arresting B cells at the pre-B stage.
Hyper-IgM syndrome is a defect of CD40 ligand, CD40 or AID,
preventing class switching.
Wiskott–Aldrich syndrome is a WASp cytoskeletal defect, not an NF-κB defect,
producing eczema, small platelets and infection.
DiGeorge syndrome is a 22q11.2 deletion with thymic and parathyroid hypoplasia.
Chronic granulomatous disease is NADPH oxidase deficiency,
confirmed by an abnormal dihydrorhodamine test.
Vaccination is the same logic reversed:
a safe antigen trains a chosen arm.
Live attenuated vaccines replicate, inducing strong, durable cellular and humoral immunity,
but they are forbidden in pregnancy and significant immunodeficiency.
Inactivated, toxoid and subunit vaccines cannot replicate and are safe,
but they stimulate mainly antibody and need adjuvants and boosters.
Route matters as well.
Oral vaccines generate secretory IgA at the mucosa,
whereas injected vaccines generate systemic IgG.
The conjugate vaccine is the most examinable idea.
Plain capsular polysaccharide is a T-independent antigen,
so infants below two years make no memory
and no booster response to it.
Coupling the polysaccharide to a protein carrier converts it into a T-dependent antigen.
B cells present carrier peptides to follicular helper T cells,
receive CD40–CD40L help, and switch to high-affinity IgG with memory.
The T cell recognises the carrier, not the sugar,
yet the protective antibody targets the sugar.
This is why conjugate pneumococcal, Hib and meningococcal vaccines protect infants,
while the plain polysaccharide vaccine waits until age two.
Although primary immunodeficiencies are diverse,
the pattern
and timing of infection can help identify the affected component of immune defence.