Skip to content
GERICLINICS

GeriQBank · Paper III · Q7

Immunology and Ageing — Innate and Adaptive Immune Systems; Immunosenescence and Cancer

High YieldAsked ×215-mark essay + 7-mark note
Topic
Haematology, Oncology & Screening
Chapter
Frailty, Sarcopenia, Deconditioning & Biology of Ageing
Years asked
Not recorded in the source
Frequency
Set 2× in Paper III (2009–2025)

As set in the university paper

  • Immunology and ageing — elaborate on the innate and adaptive immune systems and the impact of ageing, with a note on immunosenescence and cancer.

    Paper III · Infections & Immunity · asked ×2 · 15-mark essay + 7-mark note · see in paper list

Answer framework

  1. General concept — remodelling rather than decline; innate and adaptive arms both less effective; healthy ageing
  2. Adaptive immunity — thymic involution; T-cell changes; IL-2 and IL-6; the signalling defect; B cells; immune risk phenotype
  3. Innate immunity — neutrophils, Langerhans cells, NK cells, skin immunity
  4. Inflammaging — a hallmark of ageing; frailty biomarkers; centenarians
  5. Immunosenescence and cancer — reduced surveillance; shared pathways; replicative senescence and telomeres; stress-induced senescence; cancer risk and undertreatment
  6. Recent updates — enhanced vaccines (influenza, zoster, RSV), CMV, refined mechanisms, rejuvenation trials, immunotherapy, dysbiosis, Indian immunisation

An exam answer plan drawn from the detailed answer below. Use it to attempt the question first.

Detailed answer

Pro · free in beta
Attempt it firstOutline your answer as a 15-mark essay + 7-mark note before revealing it — definition, causes, evaluation, management and the geriatric angle.Reveal answer

Short revision answer

  • The ageing immune system is remodelled (some functions go down, some up) rather than simply declining. Both innate and adaptive immunity become less effective, raising the risk of infection and cancer. Healthy ageing reflects low inflammation with efficient neutralisation of antigens.
  • Adaptive immunity: thymic involution after puberty and falling thymosins; fewer naive and more memory T cells; reduced proliferation; IL-2 production and receptor expression fall while IL-6 rises. The defect lies in signal transduction and is reversible in vitro.
  • B cells: fewer precursors and altered isotype switching. Function is intact but dysregulated, with more autoantibodies and monoclonal protein (hence MGUS).
  • Immune risk phenotype (Wikby, Swedish NONA study): a CD4/CD8 ratio below 1, with raised IL-6, predicting mortality.
  • Innate immunity: reduced neutrophil phagocytosis and fewer Langerhans cells in skin. NK function matters — better NK function predicts lower cancer rates ten years later. Declining skin immunity explains herpes zoster, candidiasis and delayed wound healing.
  • Inflammaging and immunosenescence are "two sides of the same coin". TNF-α, IL-6 and CRP predict mortality in frail older people, and high pre-operative IL-6 predicts delirium. Centenarians have exceptional adaptive reserve.
  • Cancer: impaired surveillance and shared molecular pathways (DNA damage, hypomethylation, chromosomal breaks) raise risk. But cancer needs limitless replication, whereas normal cells manage 60–70 doublings — telomerase is the difference. Over 70, the probability of cancer is one in three for men and one in four for women, and older people are undertreated and under-represented in trials.
  • Vaccines are the main clinical application: high-dose or adjuvanted influenza vaccine and recombinant zoster vaccine (over 90% efficacy) for those aged 65 and above; RSV vaccines from 2023 (ACIP: everyone aged 75 and above, and at-risk adults aged 50–74).
  • CMV drives the immune risk phenotype. mTOR inhibitors and senolytics are experimental. Checkpoint inhibitors work broadly in older patients — select by geriatric assessment, not age. Dysbiosis became a hallmark of ageing in 2023.
  • India: adult vaccine uptake is very low and cost is the main barrier. Correcting undernutrition and vitamin D deficiency, controlling diabetes, stopping smoking and staying active also improve immunity.

Condensed by GeriClinics from the detailed answer below, with no new facts added.

Note on sources: Pathy's 6th edition does not carry a single dedicated chapter on the ageing immune system. The textbook content below is assembled from the chapters where it is covered — Cancer and Ageing, Geriatric Dermatology, Modern Use of Biomarkers in Geriatric Medicine, Centenarians, and Kane's chapter on the clinical implications of the ageing process.

15–20 High-Yield Points (Textbook)

A. General Concept

1.

The immune system is one of the most important master regulatory systems in humans; its relationship with ageing has been re-evaluated away from a purely senescent, declining system to one that undergoes remodelling, with both up- and downregulation of immune functions.

2.

Both the innate and the adaptive immune systems become less effective with age, leading to increased risk of infection and of malignancy.

3.

Healthy ageing is believed to result from low pro-inflammatory activity combined with an efficient network capable of neutralising antigenic insults — that is, from successful immune remodelling rather than preserved youthful immunity.

B. Changes in the Adaptive Immune System

4.

Thymic involution occurs after puberty; the bone marrow diminishes in mass, and levels of thymic hormones (thymosins) fall.

5.

T cells: reduced proliferation, an increased proportion of memory cells and a decrease in naive T cells; T cells are also less able to differentiate into specific subtypes.

6.

Lymphocytes from older adults show a diminished proliferative response to mitogens, due both to reduced lymphokine production and to reduced response to extracellular signals.

7.

Interleukin-2: basal and stimulated production and responsiveness both fall, at least partly because of decreased IL-2 receptor expression. Conversely, IL-6 levels rise.

8.

The T-cell defect appears to lie in the transduction of extracellular signals to intracellular function: the proliferative defect can be reversed in vitro by calcium ionophores and activators of protein kinase C, and some functions are restored by adding thymic hormones in vitro or administering them to aged animals.

9.

B cells: production of B-cell precursors diminishes, and the ability to isotype-switch is altered, reducing the variety of antibodies and the diversity of functional B cells. B-cell function is intact but dysregulated, with increased autoantibody formation and increased monoclonal protein production (the basis of the high prevalence of MGUS in old age).

10.

The immune risk phenotype (IRP), defined in the Swedish NONA longitudinal study by Wikby, is a CD4/CD8 ratio of less than 1; it is associated with raised IL-6 in the terminal decline stage and predicts mortality. The CD4/CD8 ratio is listed among the candidate immune biomarkers of frailty.

C. Changes in the Innate Immune System

11.

Neutrophils show decreased phagocytic ability.

12.

Antigen-presenting cells: there is a reduction in Langerhans cells in ageing skin, impairing cutaneous immune surveillance.

13.

Natural killer cells: NK function is a clinically relevant variable — a prospective cohort study showed that individuals with better NK cell function had lower rates of cancer ten years later.

14.

Impaired innate, humoral and cell-mediated immunity within the skin explains the increased risk of herpes zoster and cutaneous candidiasis in older people, and the delayed wound healing that follows reduced growth factor sensitivity of aged fibroblasts.

D. Inflammaging

15.

Chronic low-grade inflammation ("inflammaging") is one of the major hallmarks of individual ageing. Immunosenescence and inflammaging are described as two sides of the same coin.

16.

The three inflammatory markers most cited as biomarkers of frailty are TNF-α (and its receptor TNFR2), IL-6 and CRP; all three predict increased mortality among frail older people, and pre-operative high IL-6 is a risk factor for post-operative delirium.

17.

Franceschi's network/remodelling theory and the hormesis concept explain why some centenarians tolerate a high inflammatory load: they possess extraordinary adaptive capacity and functional reserve. Centenarians are classified as "survivors", "delayers" and "escapers".

E. Immunosenescence and Cancer

18.

Immune dysregulation associated with ageing may contribute to the increased incidence of cancer with age — reduced T-cell proliferation, fewer naive T cells, altered B-cell regulation, falling IL-2 and rising IL-6, and reduced NK function all impair immune surveillance.

19.

Ageing and carcinogenesis share molecular pathways: DNA damage from random events or free radicals causes either cellular dysfunction and death (ageing) or mutations in proto-oncogenes and tumour suppressors (carcinogenesis). DNA adduct formation, DNA hypomethylation, and chromosomal breakage and translocation all increase with age and raise susceptibility to late-stage carcinogens.

20.

Yet ageing and cancer are also at odds: cancer requires limitless replicative potential, whereas finite replicative potential (replicative senescence) is a hallmark of ageing. Normal cells manage 60–70 doublings and lose telomeres; malignant cells maintain telomeres through telomerase and replicate indefinitely.

21.

Stress-induced premature senescence — triggered by oncogene mutation or by double-stranded DNA breaks from chemotherapy — drives clonal cells into permanent growth arrest and may be as effective as apoptosis as an anticancer mechanism.

22.

Clinically, the probability of developing cancer over the age of 70 is one in three in men and one in four in women; cancer-specific death rates have fallen in the young while rising in older individuals, partly because of delayed diagnosis, incomplete evaluation, undertreatment and under-representation of older people in clinical trials.

Latest Updates (2023–Present)

Vaccination has become the main clinical application of immunosenescence. Because standard vaccines respond poorly in older adults, enhanced formulations are now preferentially recommended for people aged 65 and above: high-dose or adjuvanted (MF59) influenza vaccine, and the recombinant adjuvanted zoster vaccine (RZV, Shingrix), which retains over 90% efficacy in the very old, unlike the older live zoster vaccine. RSV vaccines for older adults (Arexvy, Abrysvo and the mRNA vaccine mResvia) were licensed from 2023; US ACIP guidance now recommends a single dose for all adults aged 75 and above and for adults 50–74 with risk factors such as COPD, heart failure, diabetes, chronic kidney disease and immunocompromise. Cytomegalovirus is now recognised as a major driver of immunosenescence: chronic antigenic stimulation causes massive expansion of CMV-specific CD8 T cells with high PD-1 and TIGIT expression and reduced cytotoxicity, contributing to the immune risk phenotype and to poorer vaccine antibody responses in CMV-seropositive elders. The mechanistic picture has been refined to include reduced dendritic cell phagocytosis, impaired T-cell receptor signalling, accumulation of terminally differentiated CD28-negative T cells, and accumulation of myeloid-derived suppressor cells, forming a self-reinforcing immunosenescence–inflammaging loop. Interventions being tested to rejuvenate immunity: mTOR inhibitors (Mannick's trials showed improved influenza vaccine responses in older adults), senolytics (dasatinib plus quercetin, fisetin, senolytic CAR-T cells), SGLT2 inhibitors such as canagliflozin, and anti-PD-1 antibodies that clear PD-L1-positive senescent cells. Cancer immunotherapy in older adults: overall efficacy of immune checkpoint inhibitors appears broadly preserved in older patients in pooled analyses, but immunosenescence, inflammaging and cancer cachexia modify response, and older patients remain under-represented in trials. Geriatric assessment (SIOG/ASCO) before immunotherapy is recommended rather than age-based exclusion.

Dysbiosis was added as a formal hallmark of ageing in 2023, linking the gut microbiome to inflammaging and to vaccine responsiveness — a plausible future intervention target.

Indian context: adult immunisation uptake in older Indians remains very low. Association of Physicians of India and Geriatric Society of India recommendations cover annual influenza, pneumococcal (PCV followed by PPSV23), recombinant zoster, Tdap, and COVID-19 boosters for those aged 60 and above; cost is the principal barrier (RZV and RSV vaccines are largely self-financed and not covered by the national immunisation programme). Practical alternatives with proven benefit remain correction of undernutrition and vitamin D deficiency, control of diabetes, smoking cessation and physical activity, all of which improve immune competence.

Current Practice Update

Issue Textbook (Pathy 6e / Kane) Current Evidence (2023–present)

Core concept Age-related decline in immune function, with a Immune remodelling is the accepted model — note that remodelling is a better description simultaneous loss of adaptive competence and gain of inflammatory tone Driver of T-cell change Thymic involution and reduced IL-2 signalling Thymic involution plus chronic CMV-driven antigenic stimulation and accumulation of CD28-negative, PD-1/TIGIT-high exhausted T cells Vaccination Not addressed in detail Enhanced vaccines mandatory in the old:

high-dose/adjuvanted influenza, recombinant zoster, and new RSV vaccines for 75+ and at-risk 50–74 Inflammaging Described within network/remodelling theory A formal hallmark of ageing (2023), alongside dysbiosis Cancer immunity Reduced surveillance; NK function predicts cancer Same principles, plus recognition that risk immunosenescence modifies checkpoint inhibitor response; geriatric assessment rather than age-based exclusion Reversibility Some functions restorable with thymic hormones mTOR inhibitors and senolytics show partial in vitro immune rejuvenation in early human trials Exam One-Liners Adaptive changes: ↓ naive T cells, ↑ memory T cells, ↓ proliferation, ↓ IL-2, ↓ isotype switching, ↑ autoantibodies, ↑ monoclonal proteins.

Innate changes: ↓ neutrophil phagocytosis, ↓ Langerhans cells, altered NK function, ↑ IL-6. Immune risk phenotype = CD4/CD8 ratio <1 (Wikby, NONA study) — predicts mortality. Immunosenescence and inflammaging = "two sides of the same coin".

Better NK cell function predicts lower cancer incidence ten years later.

Cancer needs limitless replication; ageing shows finite replication — telomerase is the difference. Clinical translation = high-dose/adjuvanted influenza, recombinant zoster and RSV vaccines in the old.

How was your recall?

Rating marks the question complete. “Need another pass” also adds it to your bookmarks.

References

Spotted an error or something out of date?Report a problem with this page