Innate immunity
Introduzido| English | Significado |
|---|---|
| complement/ˈkɒmplɪmənt/ | complement |
| neutrophils | neutrophils |
| macrophages | macrophages |
| natural killer cells | natural killer cells |
| pattern recognition receptors | pattern recognition receptors |
| dendritic cells | dendritic cells |
Red, hot and swollen by lunchtime
- A splinter goes in at 9 a.m. By lunchtime the finger is red, warm and swollen, and white cells are already fighting, days before any antibody exists.
- That first defence is innate immunity: you are born with it, it acts in minutes to hours, and it never learns.
Barriers and complement
- Skin, stomach acid and mucus stop most microbes. Behind them is complement 补体, a set of blood proteins that coat microbes so phagocytes eat them, and punch holes in some membranes.
- Complement can start without any antibody (the alternative and lectin pathways) or be triggered by antibody (the classical pathway).
How can complement be activated before any antibody has been made?
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Only the classical pathway is triggered by antibody; the other two start on microbial surfaces.
Neutrophils: first and short-lived
- Neutrophils 中性粒细胞 are 50–70% of white blood cells (normal count about 2–7 × 10⁹/L). They squeeze out of the blood within the first hour, dominate the first 6–24 hours, and die in the pus.
- They eat bacteria and fungi and kill them with enzymes and oxygen radicals.
Macrophages and NK cells
- Monocytes leave the blood and become macrophages 巨噬细胞, which take over at 24–48 hours, clear debris and show antigen to T cells.
- Natural killer cells NK细胞 are innate lymphocytes. They kill virus-infected and stressed cells, especially cells that have lost their MHC class I, without needing antibody.
Put the response to a cut in the skin in order of time.
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Innate cells hold the line for days while the adaptive response is built.
NK cells need antibody before they can kill a virus-infected cell.
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NK cells kill stressed cells and cells that have lost MHC class I directly; antibody can help but is not required.
Fixed receptors for common patterns
- Innate cells use pattern recognition receptors 模式识别受体: receptors coded directly in the genome that bind patterns shared by many microbes, such as bacterial lipopolysaccharide binding TLR4.
- No genes are rearranged, so the response is fast and the same every time; there is no memory.
Why do innate responses have no memory?
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Memory comes from expanding clones with rearranged receptors; innate receptors are the same every time.
Dendritic cells carry the news
- Dendritic cells 树突状细胞 sample antigen in the tissues, travel to a lymph node and show it to T cells, together with the second signal that switches T cells on.
- So innate immunity cannot learn, but it decides whether the adaptive response starts at all.
Match each innate component to its job.
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Each cell has its own timing and job.
Worked example: the marrow's output
- The marrow makes about 10¹¹ neutrophils a day in health. A day has 1440 minutes, so that is $10^{11} \div 1440 \approx 7 \times 10^{7}$, about 70 million a minute.
- In severe infection the marrow raises that several-fold, which is why a high neutrophil count is a sign of bacterial infection.
The marrow makes 10¹¹ neutrophils a day. How many million is that per minute?
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10¹¹ ÷ 1440 ≈ 6.94 × 10⁷, about 69 million a minute.
Worked example: fever without neutrophils
- (Fictional) A patient on chemotherapy has a fever and a neutrophil count of 0.3 × 10⁹/L, about a seventh of the lower limit of 2.
- The first responders are gone and the adaptive response is days too slow, so sepsis can develop within hours. Febrile neutropenia is treated as an emergency.
A neutrophil count of 0.3 × 10⁹/L is what percentage of the lower normal limit of 2 × 10⁹/L?
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0.3 ÷ 2 = 0.15 = 15%, severe neutropenia.
Three common slips
- "NK cells are adaptive." They are innate lymphocytes with no rearranged receptor.
- "Complement needs antibody." The alternative and lectin pathways start without it.
- "Innate immunity just waits for the real response." Its dendritic cells decide whether that response happens.
Recap
- Barriers, then complement, then neutrophils (first 6–24 hours), then macrophages (24–48 hours).
- NK cells kill infected cells without antibody; pattern recognition receptors are fixed, with no memory.
- Dendritic cells carry antigen and the "go" signal to T cells.