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CHAPTER 18 Neoplasia
321
BOX 18.2 Commonest Cancers by Sex
Male Female
Carcinoma of the
prostate
Bronchopulmonary
carcinoma
Colorectal
adenocarcinoma
Urinary tract carcinoma Uterine carcinoma
Carcinoma of the breast
Bronchopulmonary
carcinoma
Colorectal adenocarcinoma
• Familial neoplasms occur at a younger age than sporadic neoplasms.
• Individual neoplasms have their own specic age distribution, e.g. broadenoma of the breast (18–35 years),
carcinoma of the breast (more common aer the menopause), neuroblastoma (childhood).
Sex
• Carcinoma of the breast is 200 times more common in
women than in men.
• e commonest tumours in men and women dier, and
current statistics can be seen in Box 18.2.
PREMALIGNANT DISEASE
A premalignant lesion is a discrete identiable lesion associated with an increased risk of progression to a malignant
neoplasm.
Examples include:
• benign neoplasms that can become malignant, e.g.
colorectal adenoma–carcinoma sequence (Fig. 18.1)
• dysplasia/in situ malignancy
• metaplasia–dysplasia sequence (Table 18.3).
A premalignant condition is a non-neoplastic condition
which is associated with an increased risk of developing
malignant tumours. Examples of premalignant lesions and
conditions are shown in Box 18.3.
Carcinogenic Process
Multistep Theory
• Latency: the causal event is usually followed by a variable but usually lengthy delayed period. is is because:
• more than one eect is required for cancer to develop
(multistep)
• it takes time for the mutated cell to produce a clone
of a signicant number of cells to produce signs and
symptoms.
• Initiation: exposure of cell/tissue to carcinogen and
induction of lesion in cell’s genome bestowing neoplastic potential; irreversible.
• Promotion: the event stimulating clonal proliferation
of the initiated transformed cell. A promoter is a substance that will cause cancer in an initiated cell but not a
normal cell, e.g. croton oil in experimental skin cancers
initiated by methylcholanthrene.
• Persistence: initiators and promoters no longer
required. e tumour becomes autonomous with vascular ingrowth, increased growth rate, invasiveness and
metastasis.
Genetics of Cancer
An increased predisposition to development of malignant
neoplasm may be inherited as:
• part of a clinical syndrome with other diagnostic features in addition to the increased risk of malignancy,
e.g. acute leukaemia in Down’s syndrome
• an increased likelihood of neoplasia developing as the only
manifestation, e.g. familial retinoblastoma syndrome.
Inherited syndromes associated with an increased risk of
malignancy are:
• syndromes with a major chromosomal abnormality, e.g.
Down’s syndrome and acute leukaemia
• syndromes determined by single gene defects, e.g.
familial polyposis coli and colorectal cancer.
Evidence for Genetic Alterations Causing Cancer
• Translocations: part of one chromosome becomes attached
to another, e.g. Philadelphia chromosome and chronic
myeloid leukaemia (CML), Burkitt’s lymphoma.
• Extra chromosomes: usually trisomies (i.e. three copies of a chromosome rather than two), e.g. trisomy 21
(Down’s syndrome), acute leukaemia.
• Familial aggregations, e.g. retinoblastoma.
• Increased risk of malignancy associated with incapacity
to repair damaged DNA, e.g. xeroderma pigmentosum
and skin cancers.
• Association between chemical mutagens and their carcinogenic eects (see above).
• Evidence that mutation or unregulated expression of
certain genes converts normal cells to malignant cells.
Genetic Mechanisms in Carcinogenesis
Two important genetic mechanisms leading to neoplasia are:
• abnormal or excessive expression of dominant stimulatory genes – oncogenes
• loss or inactivation of recessive inhibitory genes –
tumour suppressor genes.
322
Small adenoma
K-ras mutation
DCC = deleted in colon cancer gene (Chromosomal location 18q 21.3)
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SECTION III Pathology
Normal epithelium
5q deletion
APC mutation
MCC mutation
c-myc activation
bcl-2 mutation
Large adenoma
Invasive adenocarcinoma
APC = adenomatous polyposis coli gene (Chromosomal location 5q 21)
MCC = mutated in colon cancer gene (Chromosomal location 5q 21)
18q deletion
DCC mutation
17p deletion
p53 mutation
Fig. 18.1 Molecular genetics of the adenoma–carcinoma sequence.
TABLE 18.3 Examples of Metaplasia–Dysplasia Sequence
Organ Metaplasia Undergoing Dysplasia Resulting Malignancy
Oesophagus Barrett’s oesophagus (intestinal metaplasia) Oesophageal adenocarcinoma
Stomach Intestinal metaplasia (associated with
Gastric adenocarcinoma
achlorhydria)
Bronchus Squamous metaplasia (smokers) Bronchogenic squamous cell carcinoma
Cervix Squamous metaplasia Squamous cell carcinoma
Kidney (renal pelvis) Squamous metaplasia (stone or chronic infection) Squamous cell carcinoma of renal pelvis
Abnormal expression of oncogenes drives normal cells
towards a neoplastic state. Loss of tumour suppressor gene
function allows neoplastic transformation as a result of
Oncogenes
• Genes whose presence in certain forms and/or activity
can stimulate the development of cancer.
oncogene expression.
CHAPTER 18 Neoplasia
323
• Oncogenes contribute to the development of cancer by
instructing cells to make proteins that stimulate excessive growth and cell division.
• Oncogenes are related to normal genes called protooncogenes.
• Proto-oncogenes are a family of normal genes that code
for proteins involved in the normal growth-control
pathway of a cell.
• Growth factors, receptors, signalling enzymes and transcription factors are encoded by proto-oncogenes.
• Oncogenes arise from mutations of proto-oncogenes.
• Oncogenes code for altered versions or excessive quantities of growth-controlled proteins that disrupt the
growth-signalling pathway of the cell.
• e growth-signalling pathway becomes hyperactive
and cells grow and divide more rapidly.
BOX 18.3 Examples of Premalignant
Conditions
Premalignant Lesion/
Condition Cancer Risk
Colorectal adenomatous
polyp
Epithelial hyperplasia of the
breast
Cervical epithelial dysplasia Carcinoma of the cervix
Ulcerative colitis Colorectal
Xeroderma pigmentosum Skin cancer
Cirrhosis of the liver Hepatocellular carcinoma
Paget’s disease of bone Osteogenic sarcoma
Colorectal
adenocarcinoma
Carcinoma of the breast
adenocarcinoma
Bile duct carcinoma
• A cancer cell may contain one or more oncogenes, such
that one or more components of the pathway may be
abnormal.
Examples of oncogenes and their products are shown
in Table 18.4.
Tumour Suppressor Genes
• Normal genes whose absence can lead to the development of cancer.
• Tumour suppressor genes are categorized according to
their mechanism of action (Table 18.5):
• caretaker genes maintain the integrity of the genome
by repairing DNA damage
• gatekeeper genes inhibit proliferation, or promote
the death of cells with damaged DNA.
• If a pair of tumour suppressor genes are lost from a cell,
or inactivated by mutation, cancer can result.
• Individuals who inherit an increased risk of developing cancer are oen born with a defective copy on one
tumour suppressor gene.
• Because genes come in pairs, an inherited defect in one
copy will not cause cancer if the other normal copy is
functional.
• If the second copy undergoes mutation, then cancer
may occur because there is no longer a functional copy
of the gene.
Examples of Tumour Suppressor Genes
Rb gene and retinoblastoma
• Individuals with an inherited predisposition to develop
retinoblastoma are born with absence of one of normally paired Rb1 suppressor genes. Only one further
mutational loss of the remaining Rb1 gene is required
for retinoblastoma to develop. High risk of bilateral
familial retinoblastoma.
TABLE 18.4 Examples of Oncogenes
Oncogene Protein Produced Abbreviated From
Growth factors and their receptors
sis Platelet-derived growth factor Simian sarcoma virus
erb-B Epidermal growth factor receptor Erythroblastosis virus
fms Macrophage colony-stimulating factor receptor Feline McDonagh Sarcoma virus
Signal transduction molecules
ras G-protein Rat Sarcoma virus
abl Tyrosine kinase Abelson murine leukaemia virus
Transcription factors
myc DNA binding proteins Myelocytomatosis virus
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SECTION III Pathology
TABLE 18.5 Tumour Suppressor Genes and Associated Tumours
Category Gene Tumour Susceptibility if Mutation Other Associations
Gatekeepers p53 Li–Fraumeni syndrome (predisposed to wide
range of tumours, e.g. breast, ovary, sarcoma)
Rb1 Familial retinoblastoma
APC Familial adenomatous polyposis Often mutated in sporadic
Caretakers BRCA1 Familial breast and ovarian cancer Rarely mutated in sporadic
BRCA2 Familial breast cancer
Mutated in 50% of human
epithelial cancers
colorectal cancers
breast cancers
• Individuals with paired Rb1 genes have a low incidence
of retinoblastoma because two mutational losses in the
same cell or daughter cells would be required; hence,
sporadic retinoblastoma is very rare. Risk of unilateral
retinoblastoma.
p53 tumour suppressor gene
• Situated on short arm of chromosome 17.
• Most frequently mutated of the class of genes.
• Normal functions are:
• repair of damaged DNA before S phase of cycle by
arresting cell cycle in G phase until damage is repaired
• apoptotic cell death if DNA damage is extensive.
• Inherited germ line mutations of p53 occur in the rare
Li–Fraumeni syndrome, giving an inherited predisposition to a wide range of tumours.
BEHAVIOUR OF TUMOURS
Invasion
Invasion is the sole most important criterion for malignancy. Metastases are a consequence of invasion. Invasion
demands that tumours should be removed in continuity
with a wide margin of apparently normal tissue.
Factors inuencing tumour invasion include:
• Abnormal or increased motility:
• malignant cells are more mobile than their normal
counterparts.
• Secretion of proteolytic enzymes:
• matrix metalloproteinases are secreted by malignant
cells
• they digest surrounding connective tissue, e.g. intersti-
tial collagenases degrade collagens Type I, II and III.
• Decreased cellular adhesion:
• loss of surface adhesion molecules, e.g. cadherins
enable migration of individual cells.
Clinical Consequences of Local Invasion
Clinical consequences of local invasion depend upon the
site of the tumour. Box 18.4 indicates some of the clinical
consequences of local invasion of bronchial carcinoma.
BOX 18.4 Clinical Consequences of Local
Invasion of Bronchial Carcinoma
Structure Invaded Consequence
Oesophagus Dysphagia
Thoracic major vessels Massive haemoptysis
Superior vena cava Facial oedema/cyanosis
Recurrent laryngeal nerve Hoarseness
Sympathetic chain Horner’s syndrome
Brachial plexus Pancoast syndrome
(also Horner's
syndrome and
unilateral recurrent
laryngeal nerve palsy)
Phrenic nerve Paralysis of
hemidiaphragm
Pericardium Pericardial effusion
Metastasis
Metastasis is the process whereby malignant tumours
spread from their site of origin (primary) to form other
tumours (secondary) at distant sites. Metastasis is tumour
spread in discontinuity as distinct from invasion, which is
spread in continuity.
Steps in the Metastatic Cascade
• Detachment of tumour cells.
• Invasion of surrounding tissues to reach vessels.
• Intravasation into lumen of vessels (blood and
lymphatics).
• Evasion of host defence mechanisms.
• Adherence to endothelium at remote location.
• Extravasation from vessel lumen into surrounding
tissue.
• Survival and growth within the tissue.
• Establishment of own blood supply.
CHAPTER 18 Neoplasia
325
Routes of Metastasis
• Lymphatic: regional lymph nodes.
• Haematogenous: via the bloodstream.
• Transcoelomic: across peritoneal, pleural and pericardial cavities.
• Seeding or implantation during surgery.
Lymphatic
• Most carcinomas spread via lymphatics.
• May remain discrete in lymph nodes or invade outside
nodes, involving adjacent nodes and connective tissue
when they become matted together.
• Melanomas may permeate lymphatics and appear as
black streaks in subcutaneous tissue.
• Lymphatic blockage causes lymphoedema of tissues; in
the breast it is associated with peau d’orange.
Haematogenous
• Bone is a favoured site for haematogenous spread from
ve carcinomas: lung, breast, thyroid, kidney and prostate.
• Other favoured sites are lung, liver and brain.
• Sarcomas spread by the bloodstream and NOT lymphatics.
Transcoelomic
• Spread of carcinoma of stomach to ovaries (Krukenberg
tumours).
• Spread of ovarian cancer to omentum and peritoneum
(ascites).
• Spread of bronchial carcinoma to pleura (pleural eusion).
Seeding or Implantation at Surgery
• Tumour grows in sites of surgical incision or investigation, e.g. FNA.
CLINICAL EFFECTS OF TUMOURS
ese may be:
• local
• systemic
• paraneoplastic
• metabolic
• others.
Local
• Mass.
• Bleeding due to ulceration: haematemesis, haematuria.
• Pain.
• Obstruction: hollow tube, e.g. large bowel obstruction
with carcinoma.
• Irritation at tissue of origin, e.g. cough due to bronchial
tumour.
• Pressure on adjacent structures, e.g. nerves, blood vessels, bile ducts (cancer of head of pancreas and obstructive jaundice).
Systemic
Effects of Metastases
• Enlarged lymph nodes: may be discrete or hard, irregular and matted.
• Hepatomegaly: primary tumour in stomach, colon,
bronchus or breast.
• Jaundice: nodes in porta hepatis with primary tumour
in stomach, pancreas or colon.
• Ascites: ovarian or any gastrointestinal (GI) malignancy.
• Abdominal mass due to omental secondaries oen in
association with ascites.
• Pathological fractures due to bony metastases: breast,
bronchus, thyroid, prostate or kidney.
• Pleural eusion: bronchial carcinoma and breast cancer.
• Fits, confusion, personality change from cerebral metastases, e.g. breast, bronchus or malignant melanoma.
• Anaemia – pancytopenia: bone marrow deposits.
Paraneoplastic Effects
ese are eects that occur in the presence of a neoplasm
which are not directly caused by the tumour itself or metastases. ey can be divided as follows:
• humoral (mediated by a tumour-secreted product)
• immunological (usually autoimmune).
Humoral
• Bronchial carcinoma and Cushing's syndrome due to
inappropriate secretion of adrenocorticotrophic hormone (ACTH).
• Bronchial carcinoma and inappropriate secretion of
antidiuretic hormone (ADH, vasopressin).
• Hypercalcaemia of malignancy caused by secretion of
parathyroid hormone-related peptide.
• Carcinoid syndrome with liver metastases from a carcinoid tumour due to 5-hydroxytryptamine (5HT,
serotonin).
Immunological
• Autoimmune disease may be triggered by malignancy.
• Dermatomyositis developing in later life may be due to
an underlying malignancy.
• Membranous glomerulonephritis can be initiated by an
underlying malignancy.
Metabolic Effects
ese are usually hormonal and reect appropriate secretion of hormones:
• thyrotoxicosis from thyroid adenoma
• Cushing's syndrome from adrenal cortical adenoma
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SECTION III Pathology
• hyperparathyroidism from parathyroid adenoma
• insulin from an insulinoma.
Others
• Cachexia: all tumours; probably multifactorial.
• Pyrexia of unknown origin (PUO): lymphoma,
hypernephroma.
• Hypertrophic pulmonary osteoarthropathy associated
with bronchial carcinoma.
• rombophlebitis migrans associated with visceral cancer, usually carcinoma of the head of the pancreas.
• Acanthosis nigricans associated with carcinoma of the
pancreas.
Tumour Markers
Neoplastic cells oen have quantitative and qualitative
abnormalities of protein synthesis. ey may either overproduce a normal product or they may produce a substance which is abnormal for their tissue of origin. Protein
production by some tumours has been utilized clinically as
tumour markers. Examples of tumour markers are shown
in Box 18.5.
A tumour marker:
• May be a substance which is secreted into the blood
or other body uid or expressed on the cell surface
of malignant cells in larger quantities than in normal
counterparts.
• Detection is by measuring the concentration of the
marker in the body uids, usually by immunoassay.
• Some markers may be detected in histological sections
using immunohistochemistry.
• Tumour markers are rarely suciently specic to be of
absolute diagnostic value.
BOX 18.5 Examples of Tumour Markers
Tumour Marker
Prostatic
adenocarcinoma
Hepatocellular
carcinoma
Testicular cancer
Choriocarcinoma
Ovarian carcinoma CA 125
Colorectal cancer Carcinoembryonic antigen (CEA)
Prostate-specific antigen (PSA)
α-fetoprotein
β-Human Chorionic Gonadotropin
(HCG), α-fetoprotein, placental
alkaline phosphatase
β-HCG
• e main value of tumour markers is in following
the course of a malignant disease and monitoring the
response to treatment and hence prognosis.
• Tumour markers can also be used for tumour localization and antibody-directed therapy.
TUMOUR DEPENDENCY
Although the growth of tumours is autonomous, some
retain a requirement for growth factors/endocrine support.
Good examples of those requiring endocrine support are
carcinomas of the breast, prostate and thyroid.
Breast
• A large proportion of breast carcinomas express oestrogen receptors.
• e degree of oestrogen-receptor expression correlates well with the response of the tumour to oestrogen
blockade, e.g. with the selective oestrogen receptormodulating drug tamoxifen.
• Oestrogen-receptor-positive tumours tend to be of a
lower grade and have a better prognosis than oestrogenreceptor-negative tumours.
Prostate
• Prostatic epithelium is dependent on androgenic
stimulation.
• Castration results in apoptosis of prostate epithelial cells
and partial involution of the gland.
• Many prostatic carcinomas retain the above characteristics, allowing their growth to be inhibited by androgen
blockade.
• Androgen blockade can be achieved by:
• orchidectomy
• oestrogens (side eects unacceptable)
• luteinizing hormone (LH) released from pituitary
stimulates androgen production by Leydig cells. LH
production can be inhibited by luteinizing hormone
releasing hormone (LHRH), which, aer transient
stimulation, causes long-term depression of LH release.
• Aer a period of time, androgen sensitivity is lost and
therefore the above treatments are not curative.
Thyroid
• Papillary and follicular carcinoma respond in the same
way as normal thyroid epithelium to thyroid-stimulating hormone (TSH).
• TSH suppression with thyroxine, in conjunction with
surgery and radioiodine therapy, is used to treat these
neoplasms.
CHAPTER 18 Neoplasia
327
PROGNOSIS OF TUMOURS
is depends on:
• type of tumour
• stage (extent of spread)
• grade (degree of dierentiation)
• surface receptors, e.g. oestrogen receptors in breast
cancer
• gene expression
• sensitivity to treatment modalities
• age
• nutritional status
• immune status and human leucocyte antigen (HLA) type.
Tumour Staging
is represents the extent of spread. Staging can be assessed
as follows:
• clinical assessment
• imaging techniques
• histopathological examination of resected specimen.
Some types of staging rely on one of the above alone
(e.g. Dukes’ classication) and some rely on a combination
(TNM). Staging is designed to dene prognosis.
Dukes’ Classification
A pathological classication drawn up by Cuthbert Dukes
(pathologist) originally to stage rectal cancer but now
extrapolated to colorectal cancer.
• Dukes A: invasion into, but not through, the bowel wall.
• Dukes B: invasion through the bowel wall.
• Dukes C: involvement of regional lymph nodes.
• Dukes D was not in the original classication but was
added later: indicates distant metastases.
TNM Classification
• T: primary tumour. Number sux indicates tumour
extent or size.
• N: lymph nodes. Number sux indicates number of
lymph nodes or groups of lymph nodes involved.
• M: metastases. Number sux indicates presence or
absence.
• Example: TNM classication for carcinoma of the
breast:
• Tis: carcinoma in situ
• T0: no primary located
• T1: tumour <2 cm
• T2: tumour 2–5 cm
• T3: tumour >5 cm
• T4: extension to chest wall ± skin
• N0: no nodal involvement
• N1: mobile ipsilateral axillary nodes
• N2: xed ipsilateral axillary nodes
• N3: ipsilateral supraclavicular nodes
• M0: no metastases
• M1: distant metastases
• MX: metastases suspected but not conrmed.
Other Staging
• Malignant melanoma:
• Breslow’s classication (the distance between the
stratum granulosum and the deepest part of the melanoma). Directly related to survival:
• <0.76 mm: very good prognosis
• >4.0 mm: very poor prognosis and high risk of
metastases
• Clark’s classication (dened according to anatomical boundaries) relates to anatomical area of penetration, e.g. level 1: conned to epidermis, to level 5:
tumour cells present in the subcutaneous tissue.
Breslow’s classication is more widely used, and has an
inuence on the surgical margins taken. ese margins are
a source of controversy and vary between countries, but
current UK guidance states that if a lesion is less than or
equal to 1 mm thick, then a 1 cm margin is taken; 1.01–
4.0 mm, then a 2 cm margin is taken; and >4 mm, then a
3 cm margin is taken.
SCREENING
Population screening programmes are aimed at reducing
morbidity and mortality from a particular disease within
an entire population. Screening should be directed at an
asymptomatic population at risk. e principles underlying screening depend on the following:
• for screening to be cost-eective, the cancer must con-
stitute a major health risk, i.e. high incidence and high
mortality rate
• it must be a relatively common disease, e.g. breast can-
cer in the UK; gastric cancer in Japan
• there must be an established and eective treatment for
the disease
• it must be demonstrated that early diagnosis and treat-
ment do increase the cure rate
• there must be a diagnostic test available that can be
applied to a large number of people
• the test must have a high level of sensitivity and
specicity
• the test should not cause harm to the individual being
tested
• the cost of screening large populations must be justied
by the yields.
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SECTION III Pathology
Screening Programmes
Breast
• Mammographic screening.
• Women aged 50–70 years old (currently being extended
to women aged 47–73 years old in some areas of the UK
as a trial extension of the programme).
• Repeated 3-yearly.
OSCE SCENARIOS
OSCE Scenario 18.1
A 32-year-old female attends your clinic aer triple assessment has shown her breast lump to be a benign cyst. She
remains very anxious. Although she has no family history of
breast cancer, her sister-in-law has just been diagnosed with
ductal carcinoma in situ (DCIS) and is due to have a mastectomy. She wishes to know about the screening programme
for breast cancer and to discuss any risk factors she has.
1. Answer this patient’s questions about cancer and carci-
noma in situ.
2. Answer her questions about risk factors for cancer, in
particular breast cancer.
3. Explain the breast screening programme to her.
OSCE Scenario 18.2
A 58-year-old female with known breast cancer is admitted
with pain in the back and ribs which has been present for
several weeks but has suddenly become much worse. She is
in obvious pain but has no neurological symptoms. A bone
scan had been carried out 1 week previously (Fig. 18.2Q).
1. What is your suspected diagnosis? What does the bone
scan show?
e patient is admitted for pain relief and a CT scan shows
liver and bone metastases. She has completed her surgery
and chemotherapy and understands that her disease has
spread. She wishes to go home as soon as possible as her
eldest daughter is getting married in 3 weeks.
2. Aer ruling out any fractures, what multidisciplinary
treatment plan may be appropriate for her now? What
specic treatment may help her back pain?
3. How does therapeutic radiotherapy work? On which
tissues does it work best?
4. What side eects can radiotherapy have in the short and
long term?
OSCE Scenario 18.3
A 22-year-old male attends your clinic aer referral by his
GP for testicular discomfort. He describes a vague history
of trauma during football several weeks ago. Examination
Cervix
• Exfoliative cytology.
• Identication of cervical intraepithelial neoplasia
(CIN).
• Co-ordinated national screening programme in the UK.
• Women aged 25–49 years old, screened every 3 years;
women aged 50–64 years old, screened every 5 years.
Fig. 18.2Q The patient’s bone scan.
reveals a rm, painless mass near the superior pole of the
testis but no other clinical abnormalities.
1. What is your dierential diagnosis?
2. What other clinical features would you look for on
examination?
3. Explain to the examiners some known risk factors for tes-
ticular cancer and the most common pathological types.
4. How should this man be investigated? How are these
tumours staged?
OSCE Scenario 18.4
A 70-year-old smoker has had a cough for the last six
months and has been losing weight due to a poor appetite. e GP does some baseline blood tests and sends the
patient for a chest X-ray. e blood tests come back before
the chest X-ray and show a sodium of 120 mmol/L.
1. What are you concerned about?
2. What further tests would you need to do to secure the
diagnosis?
CHAPTER 18 Neoplasia
329
3. What type of lung condition is it most oen associated
with?
4. What is this type of condition called and can you name
any others?
1. What is the diagnosis?
2. What gene is abnormal and what group of genes is it
part of? Describe how these genes cause cancer when
they are abnormal.
3. Can you name another group of genes involved with
OSCE Scenario 18.5
A 30-year-old male is seen in the general surgery clinic
cancer and describe how abnormalities in these genes
can give rise to cancers? Give some examples.
with a history of rectal bleeding and abdominal pain. In the
process of your history-taking you discover his father died
Answers in Appendix pages 473–476
from bowel cancer at a young age. At colonoscopy you nd
hundreds of colorectal polyps.
Please check your eBook at https://studentconsult.inkling.com/ for more self-assessment questions. See inside cover for
registration details.
19
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Immunology
IMMUNITY
Immunity is a body defence mechanism characterized by
specicity and memory.
Defence against infection is accomplished by two systems:
• innate (non-specic/natural) immunity
• adaptive (specic/acquired) immunity.
Innate Immunity
• Physical barriers:
• skin
• mucous membranes.
• Mechanical factors:
• coughing
• ciliary action in respiratory tract.
• Humoral factors:
• secretions with antibacterial activity, e.g. lysozyme
in tears
• complement and interferons.
• Cellular factors:
• phagocytic cells, e.g. polymorphs, macrophages,
mast cells and basophils: produce soluble mediators
in inammatory response
• natural killer (NK) cells: kill infected tissue cells in
non-specic manner (non-MHC–restricted killing).
Adaptive Immunity
Adaptive immune responses are more eective than innate
ones. ey are mediated by lymphocytes and antibodies,
which amplify and focus responses and provide additional
eector functions.
Essential Features of the Immune System
• Specicity.
• Diversity.
• Memory.
• Recruitment of other defence systems.
Specificity
• Immune responses in mammals have specicity for one
particular antigen.
• No cross-over reaction with closely related antigens.
• Many infection antigens are similar and specicity of
response is essential.
Diversity
• Immune system encounters many dierent antigens in a
lifetime.
• Likely to encounter antigens for which it has no
programme.
• Immune system must therefore have diversity to
respond to a great range of antigens that are new to it.
Memory
• e rst time an antigen is encountered the response
may be slow and relatively non-specic as the antigen
reacts with a clone of immunologically competent cells.
• During the process memory cells are produced so that
the second and subsequent times the antigen is presented, the immune response is rapid and specic.
• is forms the basis of active immunization procedures.
Recruitment of Other Defence Mechanisms
• e immune system on its own cannot destroy and
remove all foreign material.
• Chemical messengers are therefore recruited, e.g. polymorphs, macrophages, mast cells, kinins, complement,
lytic enzyme.
Antigen
An antigen is any substance capable of producing an
immune response. More precisely, it is a substance binding
specically to an antibody or T-cell antigen receptor.
e immune system can respond to an antigen in two
ways:
• cell-mediated immunity (CMI)
• humoral immunity.
Both are dependent upon specically responsive lym-
phocytes, which recognize and react to the presented
antigen:
• CMI is attributable to T-lymphocytes
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