- Compare innate and adaptive immunity by their cells, speed and specificity
- Explain antigen presentation, activation of B and T cells and the functions of antibodies
- Describe primary and secondary responses and vaccine types, and calculate the herd-immunity threshold
For centuries smallpox killed millions of people. In 1796 the English doctor Edward Jenner protected a boy from smallpox by inoculating him with material from cowpox — and vaccination began. In 1980 the World Health Organization declared smallpox eradicated: the first human disease ever wiped out. Behind this success lies the key feature of the immune system — memory.
Two lines of defence
| Feature | Innate immunity | Adaptive immunity |
|---|---|---|
| Speed | Minutes to hours | Days the first time |
| What it recognises | Patterns shared by many microbes (e.g. bacterial wall components) | A specific part of a specific antigen — the epitope |
| Receptors | Encoded ready-made in the genome (e.g. Toll-like receptors) | Made anew in each lymphocyte by rearranging gene segments |
| Memory | None in the classic sense | Yes — memory cells |
| Players | Skin and mucous membranes, neutrophils, macrophages, dendritic cells, NK cells, mast cells, complement | B lymphocytes and antibodies, T lymphocytes |
The first barriers are the skin, mucus, the enzyme lysozyme in tears and saliva, and the acid of the stomach. When a microbe gets in, macrophages recognise it with their receptors and engulf it (phagocytosis), and mast cells release histamine: blood vessels widen and become leaky, producing the classic signs of inflammation — redness, heat, swelling and pain. Complement proteins in the plasma tag microbes and punch holes in their membranes. Virus-infected cells release interferons to warn their neighbours, and NK cells kill cells that show too few MHC I molecules. Dendritic cells carry pieces of the microbe to the lymph nodes and switch on adaptive immunity.
Adaptive immunity: B and T cells
All lymphocytes are made in the bone marrow; B cells mature there and T cells mature in the thymus. Each lymphocyte carries only one kind of receptor and recognises only one epitope. Lymphocytes that react against the body's own tissues are eliminated as they mature — this is immune tolerance. When an antigen finds “its” lymphocyte, that cell multiplies (clonal selection, F. M. Burnet) and gives rise to two kinds of offspring: working effector cells and long-lived memory cells.
T cells do not recognise free antigen but peptides “displayed” on the cell surface by MHC molecules. MHC I is on all nucleated cells and shows fragments of proteins made inside the cell (for example viral proteins) to cytotoxic CD8⁺ T cells, which kill the infected cell with perforin and granzymes. MHC II is found only on antigen-presenting cells (dendritic cells, macrophages, B cells) and shows fragments of engulfed microbes to CD4⁺ helper T cells. Helper T cells release cytokines (such as interleukin-2) that activate B cells and cytotoxic T cells. Activated B cells become antibody-secreting plasma cells.
Antibodies
An antibody (immunoglobulin) is a Y-shaped protein: two heavy and two light chains joined by disulfide bridges. The variable regions at the tips of the “arms” form two identical antigen-binding sites, while the “stem”, the constant region (Fc), sets the antibody's class and function. Antibodies neutralise microbes (stopping toxins and viruses from binding to cells), opsonise them (tag them for phagocytes), agglutinate them (clump them together) and activate complement.
| Class | Form | Key feature |
|---|---|---|
| IgG | Monomer | Most abundant in blood; crosses the placenta; main antibody of the secondary response |
| IgM | Pentamer | Made first in the primary response; strong activator of complement |
| IgA | Dimer (in secretions) | In saliva, tears, mucus and breast milk; guards mucous membranes |
| IgE | Monomer | Binds mast cells; allergy and defence against parasites |
| IgD | Monomer | Mainly on the surface of mature, not yet activated B cells |
How do millions of different antibodies arise from only a few hundred gene segments? S. Tonegawa (Nobel Prize, 1987) showed that in each B cell the V, D and J segments of the heavy chain and the V and J segments of the light chain are picked at random and joined (V(D)J recombination). Imprecise joining and later somatic hypermutation increase the diversity even further.
- VH, DH, JHnumbers of functional heavy-chain V, D and J segments
- VL, JLnumbers of light-chain V and J segments (κ and λ are counted separately and added)
Combinatorial diversity only; junctional diversity and hypermutation multiply this number many times over.
Approximate textbook numbers for humans: heavy chain — 40 V, 23 D, 6 J; κ light chain — 40 V, 5 J; λ light chain — 30 V, 4 J. Calculate the combinatorial diversity.
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Light chain: κ 40 · 5 = 200, λ 30 · 4 = 120; total 320.
Pairs: 5520 · 320 = 1,766,400 ≈ 1.8 · 10⁶.
About two million combinations from only ~250 gene segments — and junctional diversity and hypermutation come on top. Note: the number of functional segments varies somewhat between people and sources.
Memory, vaccines and herd immunity
At the first encounter (primary response) antibodies take about a week or more to appear, and at first they are mainly IgM. At a second encounter with the same antigen (secondary response) memory cells make the response start within a few days; it is much stronger and longer-lasting, mainly IgG, and the antibodies bind the antigen more tightly (affinity maturation). A vaccine creates this memory without the disease.
| Natural | Artificial | |
|---|---|---|
| Active (own antibodies, memory) | After having the infection | After vaccination |
| Passive (ready-made antibodies, no memory) | IgG across the placenta, IgA in breast milk | Antivenom, monoclonal antibodies |
- R₀basic reproduction number: the average number of people one case infects in a fully susceptible population
- Hherd-immunity threshold — the share that must be immune
- Vc, Erequired vaccine coverage and vaccine effectiveness (0–1)
- R, seffective reproduction number and the susceptible fraction; the epidemic dies out when R < 1
H comes from the condition R = R₀ · (1 − H) = 1.
a) For measles R₀ ≈ 12–18. Find the herd-immunity threshold. b) With R₀ = 15 and a two-dose effectiveness of 97%, what vaccine coverage is needed? c) For an infection with R₀ = 3, 60% of the population is immune. Will an epidemic grow?
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b) Vc = (1 − 1/15) ÷ 0.97 = 0.933 ÷ 0.97 ≈ 96%. That is why measles needs very high coverage, and even small gaps can let outbreaks start.
c) R = 3 · 0.4 = 1.2 > 1 — an epidemic can still grow; the threshold is 1 − 1/3 ≈ 67%.
When the immune system makes mistakes, disease follows. In allergy, IgE is made against a harmless antigen (pollen, food) and mast cells release histamine; the severe reaction, anaphylaxis, is treated with adrenaline. In autoimmune diseases (type 1 diabetes, multiple sclerosis, rheumatoid arthritis) tolerance breaks down. HIV infects CD4⁺ helper T cells; AIDS is diagnosed when their count falls below 200 per microlitre. In transplantation, matching the HLA (human MHC) molecules of donor and recipient is important.
Key points
- Innate immunity is fast and non-specific; adaptive immunity is specific and has memory.
- CD8⁺ killers recognise peptides on MHC I and CD4⁺ helpers on MHC II (the rule of 8).
- IgM comes first in the primary response; IgG dominates the secondary response and crosses the placenta; IgA is in secretions; IgE drives allergy.
- V(D)J recombination creates millions of antibodies from a few hundred segments.
- Herd-immunity threshold H = 1 − 1/R₀; required coverage (1 − 1/R₀)/E.
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