Adaptive immunity

A vaccine contains no weapon. It creates no toxin, no antimicrobial drug and no phagocyte; it presents an antigen, and everything that follows is performed by the person’s own lymphocytes. The antigen may be an inactivated pathogen, an attenuated strain that can replicate a little but not cause disease, a toxoid such as the detoxified tetanal or diphtheritic toxin, a polysaccharide coupled to a carrier protein, or a single surface protein manufactured by recombinant technology, as in the hepatitis B vaccine. Dendritic cells and macrophages at the injection site capture this antigen and carry it to the draining lymph node, where they display fragments of it to the lymphocytes that happen to fit. The selected B cells then undergo two changes that a first encounter with the living pathogen would also produce but far more dangerously: class switching, in which the antibody changes from immunoglobulin M, the first and relatively weak antibody made by a new plasma cell, to immunoglobulin G, a smaller and more versatile molecule; and affinity maturation, a process of mutation and selection among the multiplying B cells that raises the strength with which the antibody grips its antigen. Immunoglobulin M appears about five to seven days after a primary exposure, peaks early and disappears relatively quickly; immunoglobulin G appears later, rises over two to three weeks and is the antibody a laboratory measures to judge protection. What remains after the antigen is gone is the memory population, and this population is the entire purpose of vaccination. It is also the reason a booster is needed. Memory is not eternal: memory B cells slowly decline in number, and the antibody level they maintain falls over years, so a person may still respond well while carrying too little antibody for immediate neutralisation. A booster re-introduces the antigen, re-selects the surviving memory cells and expands them again, which restores the antibody level within days rather than the weeks a primary course requires. Because the response is secondary, one dose usually suffices. Boosters are therefore scheduled for two separate reasons: to raise a falling antibody titre above the protective threshold, and to broaden protection when the pathogen’s circulating antigens drift, as happens with influenza. This is why the timing on a vaccination schedule is not arbitrary. A dose given too early after a first course may be partly neutralised by the antibody still in circulation, while a dose given years later arrives when the memory has faded. What matters is that the vaccine is given early enough for the secondary response to develop. For tetanus and rabies the vaccine is in fact given after exposure, because the incubation period is long enough for that response to arrive, and passive antibody covers the dangerous interval until it does.

The adaptive system can fail in three broad ways, and each has a different clinical face. It can be absent from birth, as in severe combined immunodeficiency, where a genetic defect prevents lymphocytes from developing and the infant suffers repeated infections from the first months of life. It can be deliberately suppressed, as in a patient receiving chemotherapy or a transplant, or in the malnutrition that is common in many of the settings where this course is taught. Or it can be destroyed by an organism that has learned to attack it, and the clearest example is the human immunodeficiency virus. HIV is a retrovirus whose envelope protein binds the CD4 receptor together with a co-receptor on the surface of helper T cells, and also on macrophages and dendritic cells. After entry the virus copies its RNA genome into DNA, integrates that DNA into the host cell’s own chromosome, and can then either produce new virions that kill the cell or remain latent for years. The numerical consequence is the heart of the matter: the normal CD4 helper T cell count is roughly 500 to 1500 cells per microlitre of blood, and as the count falls the coordination that helper T cells provide is progressively lost. Below about 200 cells per microlitre the patient enters the stage of acquired immunodeficiency syndrome, and the infections that define it are characteristically those that a competent cell-mediated response would have contained: Pneumocystis jirovecii pneumonia, tuberculosis, cryptococcal meningitis, cytomegalovirus disease and several cancers, notably Kaposi sarcoma and lymphomas. The reason these ordinarily manageable infections become fatal is precisely the loss of coordination described earlier in this section. Without helper T cells, B cells cannot be efficiently selected to produce antibody, cytotoxic T cells cannot be expanded to kill infected cells, and macrophages are not activated to destroy the bacteria they have engulfed. An organism that a healthy adult clears in a week, such as Mycobacterium tuberculosis or a fungus of low virulence, is therefore able to multiply unchecked. Two nursing consequences follow directly. First, a CD4 count and a viral load are not laboratory curiosities; they measure the exact capacity the patient has left to mount an adaptive response, so a falling count predicts which infections to anticipate and explains why prophylaxis is started at defined thresholds. Second, live vaccines are dangerous in these patients, because an attenuated organism that a healthy immune system would quickly control may multiply without limit when cell-mediated immunity is destroyed. Antiretroviral therapy works by blocking the steps of the viral cycle, and its success is measured by a rising CD4 count, that is, by the reconstruction of the very coordination the virus had removed.

The distinction between active and passive immunity is made in two places a nurse works every day. In the nursery, a newborn arrives with immunoglobulin G that crossed the placenta during the third trimester, transferred actively by a receptor on the placental surface, so the baby is temporarily protected against the same antigens the mother has met. That borrowed antibody explains several practical facts: it protects the infant during the first months when its own system is still naive, it is the reason live vaccines such as measles are scheduled after the maternal antibody has decayed, usually at about nine months in high-transmission settings, and it is why a mother who is immune to rubella passes that protection on while one who is not does not. The protection fades predictably because no memory cells were transferred; the infant’s own memory must be built by infection or vaccination later. Breast milk adds a second, different gift: secretory immunoglobulin A, which coats the infant’s gut and respiratory mucosa and interferes with attachment by pathogens there. This mucosal antibody is not absorbed into the blood and works only while breastfeeding continues. In the emergency room the same principle appears in reverse. A patient with a deep, dirty wound, or a midwife with a needle-stick injury from a patient carrying hepatitis B, may be given ready-made antibodies — tetanus immunoglobulin, hepatitis B immunoglobulin, rabies immunoglobulin, or a specific antitoxin — because the exposure has already happened and there is no time to wait for a primary response. Passive antibody acts within hours, which is exactly what the emergency requires, but it is eliminated over weeks and it can blunt a simultaneously given vaccine by neutralising the antigen before the lymphocytes see it, which is why the vaccine is injected at a different site and the schedule is adjusted. Some preparations are deliberately mixed for this reason: the tetanus regimen after a dirty wound combines toxoid, to start active memory, with immunoglobulin, to cover the dangerous interval. A third pattern is the monoclonal antibody, a single antibody produced industrially against one chosen target and used as passive therapy for example against respiratory syncytial virus in high-risk infants. In every case the rule for the nurse is the same: passive immunity is fast, temporary and borrowed; active immunity is slow, durable and the patient’s own. That single sentence decides whether a patient needs an injection now, a vaccine course later, or both at once.