Immunodeficiency and transplantation
Introduced| English | Meaning |
|---|---|
| chronic granulomatous disease | chronic granulomatous disease |
| severe combined immunodeficiency | severe combined immunodeficiency |
| rejection | rejection |
The germ tells you what is broken
- A child with repeated pneumonia, an adult with meningitis from the same bacterium three times, a baby with thrush that will not clear: each points to a different broken part of the immune system.
- At the other edge, a working immune system attacks a transplanted organ. Both are read from the same cell map.
Phagocytes and complement
- Neutrophil defects let bacteria and fungi cause deep abscesses. In chronic granulomatous disease 慢性肉芽肿病 neutrophils cannot make oxygen radicals, so catalase-positive organisms such as Staphylococcus aureus and Aspergillus survive.
- Missing terminal complement (C5–C9) cannot punch holes in Neisseria, so the same meningitis returns.
A young adult has had meningococcal meningitis three times. Which defect is most likely?
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Neisseria are cleared mainly by the membrane attack complex.
T-cell defects
- Without T cells, opportunists flourish: Pneumocystis, Candida, viruses and mycobacteria. Severe combined immunodeficiency 重症联合免疫缺陷 (SCID) presents in the first months with thrush, diarrhoea and poor growth.
- HIV is an acquired T-cell defect and the commonest cause of opportunistic infection worldwide. Live vaccines are not given in severe T-cell defects.
Live vaccines are safe for a baby with severe combined immunodeficiency.
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Without T cells, the weakened vaccine microbe can cause serious disease.
B-cell defects
- In X-linked agammaglobulinaemia there are almost no B cells, so no antibody. Infections with encapsulated bacteria (pneumonia, ear infections) start after about 6 months.
- The delay is the mother's IgG, which crossed the placenta and protects the baby until it decays.
Match each defect to the infections it lets through.
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Each arm clears its own kind of organism, so the organism names the failed arm.
The age clock
- T-cell defects show in the first months, neutrophil defects can show in the first weeks, and antibody defects after about 6 months.
- The age at the first serious infection is the first clue to which arm failed.
Transplant rejection
- Rejection 排斥反应 has three clocks. Hyperacute: antibody already present against the donor's blood group or HLA, within minutes to hours. Acute: T cells, over days to weeks. Chronic: antibody and scarring, over months to years.
- Matching ABO blood group and as many HLA types as possible lowers the risk.
Put the kinds of rejection in order of when they appear after transplant.
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Pre-formed antibody acts at once; T cells need days; scarring builds over years.
Drugs that turn signals down
- Tacrolimus blocks calcineurin, on the pathway from the T-cell receptor (signal 1), so IL-2 is not made. Belatacept blocks B7–CD28 (signal 2).
- Sirolimus blocks mTOR, downstream of the IL-2 receptor, and mycophenolate starves dividing lymphocytes of purines. Every drug turns down a step from 7.3.
Match each drug to the step it blocks.
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Each immunosuppressant turns down one named step of T-cell activation.
Worked example: the 6-month-old boy
- (Fictional) A boy is well until 6 months, then has pneumonia twice and repeated ear infections. His immunoglobulins are very low and he has almost no B cells; his tonsils are tiny.
- Healthy until maternal IgG ran out, then encapsulated bacteria: X-linked agammaglobulinaemia. Regular immunoglobulin replacement replaces what he cannot make.
A boy is well until 6 months, then has repeated pneumonia; he has almost no B cells. What is the diagnosis?
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Protection from maternal IgG lasts about 6 months; then the missing antibody shows.
Worked example: how fast maternal IgG fades
- (Fictional figures) A newborn's IgG is 10 g/L, all from the mother, and its half-life is about 3 weeks.
- After 12 weeks, 4 half-lives: $10 \times (1/2)^4 = 0.625$ g/L. A baby who cannot make IgG is unprotected by about 4–6 months.
A newborn's maternal IgG is 10 g/L with a half-life of 3 weeks. What is it after 12 weeks, in g/L?
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12 weeks is 4 half-lives, so 10 × (1/2)⁴ = 0.625 g/L.
Three common slips
- Forgetting HIV. It is the commonest T-cell defect, and it is acquired.
- Mixing up the rejection clocks. Hyperacute is antibody (minutes), acute is T cells (days to weeks), chronic is scarring (months to years).
- Giving live vaccines in severe combined immunodeficiency. The vaccine strain can cause disease.
Recap
- Neutrophils → catalase-positive bacteria and fungi; terminal complement → Neisseria; T cells → opportunists; B cells → encapsulated bacteria after 6 months.
- Rejection: hyperacute (antibody), acute (T cells), chronic (scarring).
- Immunosuppressants turn down signal 1 (tacrolimus), signal 2 (belatacept), IL-2 signalling (sirolimus) and lymphocyte division (mycophenolate).