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Immunity — definition

Immunity is the resistance of the host to an infectious agent or its toxic products, and it is the sum of the barriers, cells and molecules that keep one person well after an exposure that would infect another. It matters clinically because every ward decision about isolation, vaccination, immunoglobulin and prophylaxis rests on an estimate of how good, how specific and how durable a particular patient's immunity is.

Innate or non-specific immunity is present from birth, acts within minutes to hours, behaves identically on every exposure and leaves no memory; it comprises the skin and mucous membranes, cilia and the cough reflex, gastric acid, lysozyme in tears, the normal flora, phagocytes, natural killer cells, complement and the acute-phase response.
Adaptive or acquired immunity develops after exposure, takes days to weeks on the first encounter, is precisely specific to the antigen and leaves memory, so a second encounter provokes a faster, larger and higher-affinity response; its humoral arm of B cells and antibody deals with extracellular organisms and toxins, while its cell-mediated arm of T cells deals with intracellular organisms, fungi, tumour cells and grafts.
Acquired immunity is classified twice over: active, in which the person's own immune system makes the response, is slow to start and long-lasting, and passive, in which ready-made antibody is given and protection is immediate but short-lived; each of these is further natural, from infection or from the mother, or artificial, from a vaccine or an immunoglobulin preparation.
Herd immunity is the immunity of a population rather than a person, the level of protection in a community at which transmission cannot be sustained, so that the unimmunised members are protected indirectly.
Local immunity at the mucosal surface is mediated by secretory IgA and is best provoked by giving a live vaccine by the natural route of infection, which is why oral polio and rotavirus vaccines are swallowed rather than injected.
Immunity is not all-or-none: it can be partial, it wanes with time so that boosters are needed, it can be overwhelmed by a large infecting dose, and it is degraded by malnutrition, measles, HIV, diabetes, corticosteroids, cytotoxic chemotherapy, splenectomy and the extremes of age, which is the group the ward calls immunocompromised.
Species, racial and individual differences in resistance, along with age, nutrition and hormonal state, are the classical determinants of innate immunity and explain why the same exposure produces disease in one person and nothing in another.

Active immunity

Active immunity is the protection a person manufactures for himself: an antigen, whether a live or killed organism, a toxoid or a purified component, is presented to the immune system, which answers with antibody, effector T cells and, most importantly, memory cells. It is slow to appear, taking days to weeks and often needing more than one dose, but it lasts for years or for life and can be recalled by a booster, which is why every immunisation programme is built on it.

Natural active immunity follows clinical or subclinical infection, as after measles, chickenpox or hepatitis A, while artificial active immunity follows vaccination; the mechanism is identical and only the route by which the antigen arrived differs.
The primary response has a latent period of about a week, is predominantly IgM, reaches a low titre and fades; the secondary or anamnestic response on re-exposure has a latent period of only 2 to 3 days, is predominantly IgG, reaches a much higher titre and persists, and it is this response that a booster dose recalls.
Live attenuated vaccines, including BCG, oral polio, measles-rubella, rotavirus, varicella and live Japanese encephalitis vaccine, multiply in the host and give strong lasting immunity, often after a single dose; they are contraindicated in pregnancy and in severe immunodeficiency, and two live parenteral vaccines are given either on the same day or at least 4 weeks apart.
Inactivated vaccines and toxoids, including injectable polio, rabies, hepatitis A, whole-cell pertussis and the tetanus and diphtheria toxoids, cannot replicate and are safe in immunosuppression, but they need a course of doses, usually an adjuvant, and boosters to maintain protection.
Under India's Universal Immunization Programme the birth doses are BCG, the zero dose of oral polio vaccine and hepatitis B; pentavalent, oral polio and rotavirus vaccines are given at 6, 10 and 14 weeks with fractional injectable polio vaccine at 6 and 14 weeks and pneumococcal conjugate vaccine at 6 and 14 weeks; the first measles-rubella dose with a pneumococcal booster and vitamin A is given at 9 to 12 months; the second measles-rubella dose with the DPT and OPV boosters is given at 16 to 24 months; a DPT booster follows at 5 to 6 years and Td at 10 and 16 years and in pregnancy.
The cold chain protects the antigen: vaccines are held at plus 2 to plus 8 degrees Celsius in the ice-lined refrigerator at the health centre, oral polio and measles-rubella are the most heat-sensitive and sit in the coldest part, while hepatitis B, pentavalent, Td and injectable polio are freeze-sensitive and are never placed against the freezer plate or on unconditioned ice packs; the vaccine vial monitor shows heat damage and the shake test shows freezing damage.
Practical rules that recur in the exam: the interval between doses may be lengthened without restarting the course but never shortened, an interrupted schedule is resumed rather than begun again, mild illness or low-grade fever is not a contraindication, and anaphylaxis to a previous dose is the one absolute contraindication.
Every session keeps an anaphylaxis kit with adrenaline, observes each recipient for 20 to 30 minutes, records the dose in the immunisation and mother-and-child protection cards, and reports any serious adverse event following immunisation through the AEFI surveillance system.

Passive immunity

Passive immunity is protection borrowed rather than earned: ready-made antibody is transferred to the host, so protection begins within hours but ends as that antibody is catabolised, in a few weeks to a few months. There is no antigen, no memory cell and no booster response, so passive immunity is used to cover the dangerous gap while active immunity is being built, or to protect a patient who cannot mount a response at all.

Natural passive immunity is maternal IgG crossing the placenta, mostly in the third trimester after about 28 weeks, which protects the infant for roughly the first 6 months and leaves a preterm baby with less; secretory IgA in colostrum and breast milk protects the infant's gut mucosa but is not absorbed into the bloodstream.
Artificial passive immunity comes from human normal immunoglobulin, hyperimmune human immunoglobulins against hepatitis B, tetanus, rabies and varicella-zoster, anti-D immunoglobulin, equine antisera such as anti-tetanus serum, anti-diphtheritic serum and anti-snake venom, monoclonal antibodies and convalescent plasma.
Onset is immediate because no immune response has to be generated, and duration is short, about 2 to 3 weeks for an injected immunoglobulin and up to about 6 months for transplacental maternal IgG.
The doses and windows that recur in examinations are hepatitis B immunoglobulin 0.5 mL to the newborn of an HBsAg-positive mother within 12 hours of birth at a site different from the birth dose of vaccine; human rabies immunoglobulin 20 IU/kg or equine rabies immunoglobulin 40 IU/kg infiltrated into and around the wound in a category III exposure; anti-D immunoglobulin to an Rh-negative mother within 72 hours of delivery or of a sensitising event; and human tetanus immunoglobulin for a tetanus-prone wound in an unimmunised person, given with but never in the same syringe or site as the tetanus toxoid.
Equine antisera carry a real risk of anaphylaxis within minutes and of serum sickness about 7 to 10 days later, so a test dose is given, adrenaline is kept drawn up and the patient is observed; human immunoglobulins are far safer and are used wherever they are available.
Passive antibody blunts a live vaccine, so a live parenteral vaccine such as measles-rubella is given at least 2 weeks before an immunoglobulin or deferred for about 3 months after it; the deliberate exception is rabies, in which the immunoglobulin and the vaccine are given on the same day at different sites with different syringes.
Maternal antibody is also the reason the schedule is built as it is: it protects the infant but neutralises vaccine virus, which is why the first measles-rubella dose waits until 9 months of age.
Combined passive and active immunisation gives cover today and protection for the future, and is standard for a category III rabies exposure, a tetanus-prone wound in an unimmunised person and the newborn of a hepatitis B carrier mother.

Herd immunity

Herd immunity is the resistance of a whole community to the spread of an infection, which appears when so large a proportion of the population is immune that the chain of transmission cannot be sustained and the remaining susceptibles are protected indirectly. It matters because it is the only protection available to the people who cannot be vaccinated, the young infant, the pregnant woman, the patient on chemotherapy and the child with immunodeficiency, and because it collapses quickly once coverage falls.

The basic reproduction number R0 is the average number of secondary cases that one case produces in a wholly susceptible population, and the herd immunity threshold is 1 minus 1 divided by R0, so the more infectious the organism the higher the coverage that is needed.
Measles is the extreme case, with an R0 of roughly 12 to 18 and a threshold of about 92 to 95 percent, which is why measles is always the first disease to return when coverage slips; diphtheria and rubella need in the region of 85 percent and polio in the region of 80 to 86 percent.
Herd immunity works only for infections transmitted from person to person; it does not exist for tetanus, which is acquired from spores in soil, so every individual must be immunised in his own right whatever the community coverage is.
Herd immunity is built by vaccination or by past infection and is eroded by the birth of new susceptibles, waning immunity, migration, refusal and above all by clustering, since a district average of 90 percent can conceal a slum or a hamlet at 40 percent, and that is where the outbreak begins.
Some vaccines contribute more than others: oral polio and rotavirus vaccines produce gut immunity and reduce shedding, so they interrupt transmission, whereas a vaccine that prevents disease but not carriage protects the recipient without protecting the neighbour.
In India the measles-rubella vaccine is given at 9 to 12 months and again at 16 to 24 months, and the elimination strategy depends on both doses reaching more than 95 percent of children in every block, supported by campaigns and catch-up rounds.
The practical work that maintains herd immunity is tracking left-outs and drop-outs from the due list, holding sessions in underserved pockets, keeping the cold chain intact and responding to any outbreak with catch-up immunisation of the surrounding area.
Herd immunity is a population statistic and never a bedside guarantee, so the immunocompromised child on a ward that holds a measles case must still be physically separated from that case.

Innate immunity

Innate or non-specific immunity is the defence a person is born with, made up of barriers, secretions, resident flora, phagocytes, natural killer cells and the complement and acute-phase systems, and it acts within minutes of any breach and behaves exactly the same on the hundredth exposure as on the first. It matters at the bedside because most of what nursing care does to prevent infection is the protection of these barriers: intact skin, early removal of devices, mouth care, chest physiotherapy and hand hygiene.

The first line is mechanical: intact skin with its keratin layer and constant desquamation, mucous membranes and the mucus blanket, the ciliary escalator of the respiratory tract, the cough and sneeze reflexes, the flushing action of tears, saliva and urine, and the normal flora that occupy the ground and compete with pathogens.
The chemical barriers are gastric acid at a pH of 1 to 2, lysozyme in tears and saliva, the lactic acid and fatty acids of sebum, the acid vaginal pH maintained by lactobacilli, and antimicrobial peptides such as defensins and lactoferrin.
The cellular defences are neutrophils and macrophages, which recognise conserved microbial patterns through receptors such as the Toll-like receptors and then phagocytose and kill by the oxidative burst and lysosomal enzymes, natural killer cells, which destroy virus-infected and tumour cells that have lost their MHC class I molecules, and dendritic cells, which carry antigen to the lymph node and form the bridge to adaptive immunity.
The humoral defences are the complement system, activated without antibody by the alternative and lectin pathways to opsonise, attract neutrophils and lyse organisms, the interferons alpha and beta, which make neighbouring cells resistant to a virus, and the acute-phase proteins such as C-reactive protein and mannose-binding lectin.
Inflammation and fever are innate responses: vasodilatation, increased vascular permeability and neutrophil migration produce the redness, heat, swelling, pain and loss of function, while interleukin-1, interleukin-6 and tumour necrosis factor acting on the hypothalamus produce the fever.
Innate immunity has no antigen specificity and no memory, so it neither improves with repetition nor can be boosted by a vaccine; its value is its speed, and it holds the infection while the adaptive response is being built.
It is weakened by exactly the things a ward controls or watches: broken skin and indwelling devices, malnutrition, the extremes of age, neutropenia, diabetes, corticosteroids, acid-suppressing drugs that lower the gastric barrier to enteric pathogens, and broad-spectrum antibiotics that destroy the protective normal flora and let Clostridioides difficile and Candida take over.

Artificial immunity

Artificial immunity is immunity produced deliberately by a medical intervention rather than by nature, and it has two halves: artificial active immunity from a vaccine or toxoid, and artificial passive immunity from an injection of ready-made antibody. The two are frequently used together, the immunoglobulin covering the patient today while the vaccine builds the protection that will still be there next month, and post-exposure prophylaxis for rabies, tetanus, hepatitis B and HIV is the everyday example on which nurses are examined.

Artificial active immunity comes from live attenuated, killed, toxoid, subunit, conjugate and mRNA vaccines; it takes days to weeks to appear, usually needs a course with boosters, and leaves lasting memory.
Artificial passive immunity comes from hyperimmune human immunoglobulin, equine antiserum or a monoclonal antibody; it protects within hours, lasts only a few weeks and leaves no memory at all.
Rabies post-exposure prophylaxis begins with washing the wound with soap and running water for about 15 minutes and applying a virucidal agent such as povidone iodine, and the wound is left unsutured wherever that is possible; category II exposure (nibbled uncovered skin or minor scratches without bleeding) needs vaccine alone, while category III exposure (transdermal bites, bleeding scratches, licks on broken skin or mucosa and any bat contact) needs vaccine plus rabies immunoglobulin infiltrated into and around the wound.
Rabies vaccine may be given by the intramuscular Essen schedule of one dose on days 0, 3, 7, 14 and 28, or by the intradermal route as 0.1 mL at two sites per visit on the schedule laid down by the national programme in use; a person already fully immunised needs only two booster doses and no immunoglobulin.
For a tetanus-prone wound the surgical toilet matters as much as the drugs: a person with three or more documented doses needs a tetanus toxoid booster, given in India as Td, if the last dose was more than 5 years ago (more than 10 years for a clean minor wound), while an unimmunised person or one whose history is unknown needs the full course plus human tetanus immunoglobulin, given at a different site with a different syringe.
After a needle-stick with hepatitis B risk, check the source's HBsAg and the exposed worker's vaccination and anti-HBs status: a vaccinated responder needs nothing, while an unvaccinated worker or a known non-responder needs hepatitis B immunoglobulin as early as possible, ideally within 24 hours, together with the vaccine course.
After a needle-stick with HIV risk, wash the site with soap and running water without squeezing, scrubbing or applying bleach or spirit, report it immediately to the designated officer, test the source with consent, and start post-exposure prophylaxis as early as possible, preferably within 2 hours and never after 72 hours, continuing the prescribed regimen for 28 days with the follow-up testing that NACO specifies.
Live parenteral vaccines and immunoglobulins are kept apart in time, the vaccine given at least 2 weeks before or about 3 months after the immunoglobulin, with the deliberate exception of rabies, where both are given on day 0 at different sites.

Hypersensitivity reactions (I-IV)

Hypersensitivity is an immune response that is exaggerated or misdirected so that it damages the host's own tissues instead of protecting them, and the Gell and Coombs classification separates it into four types by mechanism and by timing. The distinction is practical rather than academic: types I, II and III are antibody-mediated and begin within minutes to hours, while type IV is cell-mediated and takes one to three days, which is exactly why a Mantoux is read at 48 to 72 hours and an anaphylaxis is treated in the first minute.

Type I, immediate or anaphylactic: an allergen cross-links IgE bound to mast cells and basophils, releasing preformed histamine within minutes and then leukotrienes and prostaglandins; it produces anaphylaxis, urticaria and angio-oedema, allergic rhinitis, atopic asthma and food, drug and latex protein allergy, is investigated by skin prick testing and allergen-specific IgE, and is treated with adrenaline. A late-phase reaction may return 4 to 12 hours later and a biphasic anaphylaxis several hours after apparent recovery, so the patient is kept under observation.
Type II, antibody-mediated cytotoxic: IgG or IgM binds an antigen on the surface of the patient's own cell and destroys it through complement, phagocytosis or antibody-dependent cell-mediated cytotoxicity; examples are the ABO-incompatible transfusion reaction, haemolytic disease of the newborn from Rh incompatibility, autoimmune haemolytic anaemia, immune thrombocytopenia, Goodpasture syndrome, myasthenia gravis and Graves disease, and the diagnostic test is the direct and indirect Coombs antiglobulin test.
Type III, immune complex mediated: soluble antigen-antibody complexes that are not cleared deposit in vessel walls, glomeruli, joints and skin, fix complement and draw in neutrophils; examples are serum sickness about 7 to 10 days after a foreign antiserum, the local Arthus reaction at 4 to 10 hours, systemic lupus erythematosus and post-streptococcal glomerulonephritis 1 to 3 weeks after a throat or skin infection, with a falling C3 and granular lumpy-bumpy deposits on immunofluorescence.
Type IV, delayed cell-mediated: sensitised CD4 T cells release cytokines that recruit and activate macrophages, with no antibody involved, and the reaction peaks at 48 to 72 hours; examples are the tuberculin and lepromin tests, contact dermatitis to nickel, chromates and rubber accelerators, granuloma formation in tuberculosis and leprosy, graft rejection and many drug eruptions. It is transferable by cells and not by serum, which is the classical distinction from the antibody-mediated types.
Mantoux technique and reading: 5 tuberculin units in 0.1 mL are injected intradermally on the flexor forearm to raise a wheal, and the transverse diameter of induration, never the redness, is measured at 48 to 72 hours; 10 mm or more is generally taken as positive, and 5 mm or more in HIV infection, in severe malnutrition and in close contacts of infectious tuberculosis. A positive test means infection or past BCG and never active disease by itself.
Latex shows both faces of hypersensitivity: an IgE-mediated type I reaction to the natural rubber protein that can be anaphylactic, and a type IV contact dermatitis to the manufacturing chemicals that appears a day later, so a patient with documented type I latex allergy needs a latex-free trolley and a first-on-the-list theatre slot.
Anaphylaxis management: stop the drug or infusion, call for help, give 0.5 mg of adrenaline as 0.5 mL of the 1 in 1000 solution intramuscularly into the anterolateral thigh of an adult and repeat every 5 minutes as needed; lay the patient flat with the legs raised, or in the left lateral position in pregnancy, give high-flow oxygen and rapid intravenous crystalloid, and use antihistamine and hydrocortisone only as second-line drugs, never before adrenaline.
The order of the four types is remembered as ACID: Anaphylactic, Cytotoxic, Immune complex and Delayed.

Immunoglobulin classes (IgA-IgM)

Immunoglobulins are the antigen-binding glycoproteins secreted by plasma cells, built on a four-chain unit of two identical heavy and two identical light chains in which the variable regions form the antigen-binding site and the constant region of the heavy chain decides the class and everything the antibody can do besides bind. The five classes, IgG, IgM, IgA, IgE and IgD, are separated by their heavy chains gamma, mu, alpha, epsilon and delta, and the class explains where the antibody is found and what it accomplishes, which is why the papers ask which class crosses the placenta and which one is in breast milk.

Structure: two heavy and two light chains linked by disulphide bonds with a hinge region, two Fab fragments that bind antigen and one Fc fragment that fixes complement and binds cell receptors; papain digestion yields two Fab fragments and one Fc, while pepsin yields a single F(ab')2 fragment and degraded Fc.
IgG is the most abundant class at about 75 to 80 percent of serum immunoglobulin, a monomer with the longest half-life of roughly 3 weeks, the antibody of the secondary response, the only class that crosses the placenta, an efficient opsonin and complement fixer, and the main constituent of therapeutic immunoglobulin preparations.
IgM is a pentamer held by a J chain, the largest immunoglobulin and so called the millionaire molecule, confined largely to the bloodstream; it is the first antibody produced in a primary response and the first the fetus can make, it is the most efficient activator of complement, and the natural anti-A and anti-B isohaemagglutinins are IgM, which is why ABO incompatibility does not cause haemolytic disease of the newborn while Rh IgG antibodies do. IgM in cord blood or in a neonate indicates intrauterine infection, since maternal IgM cannot cross the placenta.
IgA is the second most abundant class in serum as a monomer and the dominant antibody of secretions as a dimer carrying a J chain and a secretory component that protects it from digestive enzymes; it is found in colostrum and breast milk, saliva, tears, and nasal, bronchial and intestinal secretions, and it works chiefly by neutralisation and by preventing adherence rather than by fixing complement. Selective IgA deficiency is the commonest primary immunodeficiency and can cause reactions to blood products that contain IgA.
IgE is present in the lowest serum concentration and has the shortest half-life; it binds through its Fc region to mast cells and basophils and mediates type I hypersensitivity and the defence against helminths, and it is raised in atopy, in worm infestation and markedly in allergic bronchopulmonary aspergillosis.
IgD is present in trace amounts in serum and sits with IgM on the surface of the mature naive B cell as its antigen receptor; its serum function remains unsettled.
The two responses in time: the primary response takes about a week, is mainly IgM and fades, while the secondary response takes 2 to 3 days, is mainly IgG, reaches a far higher titre and lasts, the difference being class switching and memory. A raised specific IgM therefore means recent or current infection and a raised IgG alone means past infection or immunisation, which is the rule behind hepatitis, dengue, rubella and toxoplasma serology reports.
Clinical uses that follow from the classes: anti-HBs measured after hepatitis B vaccination shows whether the person responded, a fourfold rise in paired sera confirms recent infection, and pooled human IgG given intravenously is used in Kawasaki disease, immune thrombocytopenia, Guillain-Barre syndrome and primary antibody deficiency.

Cell-mediated immunity

Cell-mediated immunity is the arm of the adaptive response carried by T lymphocytes rather than by antibody; it is transferable by cells and not by serum, and it deals with organisms that hide inside host cells where antibody cannot reach them. It is the immunity that controls tuberculosis, leprosy, fungi, viruses, tumour cells and grafts, which is why the patients who lose it, those with advanced HIV, transplant recipients and people on corticosteroids or chemotherapy, present with exactly those infections.

T cells mature and are selected in the thymus; CD4 helper cells recognise antigen presented on MHC class II by macrophages, dendritic cells and B cells, while CD8 cytotoxic cells recognise antigen on MHC class I, which every nucleated cell carries, and the rule of eight is the memory aid, since CD4 times class II and CD8 times class I both make eight.
The CD4 subsets divide the work: Th1 cells secrete interferon gamma and interleukin-2 and activate macrophages against intracellular organisms and drive delayed hypersensitivity, Th2 cells secrete interleukins 4, 5 and 13 and drive antibody, eosinophils and the response to helminths, Th17 cells recruit neutrophils to mucosal surfaces, and regulatory T cells restrain the response and prevent autoimmunity.
CD8 cytotoxic T cells kill virus-infected and tumour cells by perforin and granzymes and through the Fas pathway; natural killer cells do a comparable job without prior sensitisation but belong to innate immunity.
Cell-mediated immunity is what the tuberculin (Mantoux) test and the interferon-gamma release assays measure, what builds the granuloma in tuberculosis, leprosy and sarcoidosis, and what rejects a graft; in leprosy it is intact in the tuberculoid form and absent in the lepromatous form, which is why the bacillary load and the lepromin reaction run in opposite directions.
Failure of cell-mediated immunity announces itself as tuberculosis and its reactivation, disseminated fungal infection, Pneumocystis jirovecii pneumonia, cryptococcal meningitis, cytomegalovirus retinitis, herpes zoster and disseminated Mycobacterium avium complex; the normal CD4 count is roughly 500 to 1500 cells per microlitre, and in HIV the risk rises steeply as it falls, with Pneumocystis appearing below about 200 and cytomegalovirus and disseminated Mycobacterium avium complex below about 50.
Management follows the national programmes: antiretroviral therapy is offered to every person diagnosed with HIV whatever the CD4 count under NACO's test-and-treat policy, co-trimoxazole preventive therapy and tuberculosis preventive treatment are given on the criteria set out in the national guidelines and only after active tuberculosis has been excluded, live vaccines are avoided in severe immunosuppression, and a rising CD4 count with an undetectable viral load marks a response.
Immune reconstitution inflammatory syndrome can make a hidden infection flare in the first weeks after antiretroviral therapy is started, so new or worsening fever, lymphadenopathy or breathlessness in that window is reported rather than assumed to be treatment failure.
Nursing implications: the usual signs of inflammation are blunted in these patients, so any fever is investigated promptly, the four-symptom tuberculosis screen of current cough, fever, weight loss and night sweats is applied at every visit in HIV care, and airborne precautions are started for anyone with a suspicious cough before the diagnosis is confirmed.

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