Case 5: Itching to get better.

6th November

1.

What is an allergen?
Any substance which causes an allergic reaction. Allergens are environmental antigens which provoke a type 1
hypersensitivity reaction. Atopic individuals have a genetic predisposition to development of type 1 hypersensitivity. In
their case harmless antigens stimulate an Ig-E response inappropriately which leads to the allergic reaction.

2.

What is histamine?
Histamine (C5H9N3) is released from mast cells and basophils in an allergic reaction. It is made by removing a CO2
molecule from the amino acid histidine with the enzyme L-histidine decarboxylase. It is then inactivated by other
enzymes and stored in granules in mast and basophil cells.
Histamine binds to histamine receptors of which there are 4 types H1- H4, all of which are members of the G proteincoupled family of receptors. H1 receptors are found on most cells but predominantly on smooth muscle, the CNS and
vascular endothelial cells. Binding to H1 brings around most of the effects associated with histamine release including
contraction of intestinal and bronchial smooth muscle, increased venule permeability and increased mucus secretion. H 2
receptors are bound to adenylate cyclise via another protein and receptor activation stimulates cAMP production and
2+
increases the concentration of Ca Binding of histamine to H2 receptors increases vasopermeability and vasodilatation,
stimulates exocrine glands and increases the production of stomach acid. When histamine binds to H 2 receptors a
negative feedback loop is established and degranulation is suppressed. H3 receptors are found in the nervous system
(mainly the CNS). They act as receptors for histamine when it is functioning as a neurotransmitter for histaminergic
neurons. Activation of the receptor leads to inhibition of histamine and cAMP formation, neurotransmitter release and
induction of sleepiness. H4 receptors are highly expressed in bone marrow and white blood cells and regulates
neutrophil release from bone marrow. They are also found in the colon, liver, lung, small intestine, spleen, testes,
thymus, tonsils, and trachea. They mediate chemotaxic signaling from mast cells by decreasing cAMP levels. Inhibition of
H4 receptors can be used to treat allergies and atopic asthma as if the mast cells cant release their cytokines,
lymphocytes dont flock to the area so no inflammatory response is brought about.
Itching caused by histamine is thought to be due to H1 and H4 receptors being stimulated by histamine. H3 antagonists
have the reverse effect and relieve the itching sensation. When histamine and H1 bind, phospholipase C is activated
which increases the amount of Ca2+ in the unmyelinated sensory neurons which causes an action potential to the brain.
Activation of H4 receptors also increases Ca2+ levels in the cell. As it exists in sensory neurons an action potential is
triggered. Itch receptors are only found in the epidermis and dermis, mostly in the stratum basale.

3.

What is antihistamine?
Antihistamines are also called H1 antagonists they counteract the physiological effects of histamine. This is achieved by
competing for the receptors. They suppress the vasodilatation, itching and scratching caused by histamine release.

4.

How is histamine involved in the immune response?

Histamine release causes the inflammatory response and constriction of smooth muscle. Its release causes
vasodilatation, increased capillary permeability, increased blood flow to the area and glandular hypersecretion (more
mucus). It is involved in inhibition of lectin- or antigen-induced proliferation of T cells, release of cytokines from T cells,
the induction of cytoxic T cells, cytolysis by mature cytoxic T cells, B cell differentiation, lysozyme enzyme release in
neutrophils, IgE-mediated histamine release from basophils, and in chemotaxic effects on neutrophils and eosinophils.
These actions can be blocked by H2 antagonists. Many of these effects on leukocyte function are inhibitory and can be
seen as anti-inflammatory actions, which can limit antibody hypersensitivity. However, H1 effects of histamine on blood
vessels and skin encourage inflammation and occur during hypersensitivity reactions.
Degranulation occurs when IgE bound to Fc receptors is cross linked by an allergenic antigen. Tyrosine kinase cascade
reactions are initiated which leads to IP3 and DAG production along with Ca2+ being released from the ER. This is
needed to move the granules to the cell membrane where SNARG proteins on the granule and membrane fuse, causing
exocytosis

5.

What is Ig-E?
An antibody produced in the lungs, skin and mucosa. Normally makes up 0.05% of serum antibody levels but it is still
capable of providing a very strong response. IgE binds very tightly to Fc receptors on basophils, mast cells and
neutrophils before interacting with antigen. As a result of its binding to basophils and mast cells, IgE is involved in
allergic reactions. Binding of the allergen to the IgE on the cells results in the release of histamine and heparin granules.
IgE levels also rise in parasitic diseases, measuring IgE levels is helpful in diagnosing parasitic infections. Eosinophils have
Fc receptors for IgE and binding of eosinophils to IgE-coated helminths results in killing of the parasite.
Atopic individuals have up to 10x more IgE in their blood which leads to more degranulation of histamine, even when
there is only a small amount of antigen present. Mast cells are primed for histamine release from their long term IgE Fc
interaction.
Somatic rearrangement of antibodies (V (D) J rearrangement) involves the rearrangement of DNA in somatic cells so the
recombined genes are not passes between generations. Therefore each individual has their own unique Ig repertoire.
The process is regulated by enzymes. Exons are rearranged by cleaving the DNA before transcription which leads to a
variety of light and heavy chains being formed.
-3
Somatic hypermutations occur commonly (1x10 mutations per base pair per generation). Individual nucleotides are
substituted altering the specificity of the antibody. It is more common in IgG and IgA than in IgM antibodies and affects
the heavy chain more than the light chain.

Type

Description

IgA

Found in mucosal areas, such as the gut, respiratory tract and urogenital tract, and prevents
colonization by pathogens. Also found in saliva, tears, and breast milk.

IgD

Functions mainly as an antigen receptor on B cells that have not been exposed to antigens. It has
been shown to activate basophils and mast cells to produce antimicrobial factors.

IgE

Binds to allergens and triggers histamine release from mast cells and basophils, and is involved in
allergy. Also protects against parasitic worms.

IgG

In its four forms, provides the majority of antibody-based immunity against invading pathogens. The
only antibody capable of crossing the placenta to give passive immunity to fetus.

IgM

Expressed on the surface of B cells and in a secreted form with very high avidity. Eliminates
pathogens in the early stages of B cell mediated (humoral) immunity before there is sufficient IgG.

6.

Structure and function of the skin? (Integumentary system)

The epidermis is the most superficial layer, made of stratified
squamous epithelium. It doesnt have any blood supply so relies on
diffusion of nutrients. The total thickness of the epidermis is
usually about 0.5 - 1 mm. It has 4 different layers in thin skin and 5
in thicker skin (palms and soles of feet). It is made of three types of
cells: keratinocytes, melanocytes and Langerhans cells.
Keratinocytes are the most common cell type in the epidermis.
They are found at the lowermost layer of epidermis, the basal
lamina. As they mature, keratinocytes lose water, flatten out and
move upward. Eventually, at the end of their life cycle, they reach
the stratum corneum. Stratum corneum consists mainly of dead
keratinocytes, hardened proteins (keratins) and lipids, forming a
protective crust. Dead cells from the stratum corneum
continuously rub off and are replaced by new ones coming from
below. The skin completely renews itself every 3 - 5 weeks.
Melanocytes are responsible for producing melanin, the pigment
responsible for skin tone and colour. Finally, Langerhans cells
(specialised dendritic cells) are the main part of the immune
system in the epidermis, found in the stratum spinosum. They
recognise unwanted foreign substances which have penetrated the
skin, take up the foreign antigens and turn into antigen presenting cells (APCs). The APCs then migrate to lymph nodes
where they activate T helper cells which secrete cytokines which activate and assist the immune response.
The dermis is located between the epidermis and subcutaneous tissue. It is the thickest layer of skin and comprises a
tight mesh of collagen and elastin fibres. Collagen is responsible for structural support of the skin and elastin for the
resilience of the skin. The key cell type is fibroblasts, which synthesize collagen, elastin and other structural molecules.
The dermis also contains capillaries for oxygenating and nourishing the skin and lymph nodes for protection from
invading microorganisms. The dermis also contains sebaceous glands, sweat glands, hair follicles as well as a relatively
small number of nerve and muscle cells. Sebaceous glands, located around hair follicles, are of particular importance for
skin health as they produce sebum, which lubricates and waterproofs the skin and hair.
The hypodermis is the innermost layer of the skin located under the dermis and consisting mainly of adipose tissue.
Subcutaneous fat acts as a shock absorber and heat insulator, protecting underlying tissues from cold and mechanical
trauma. Sweat glands and arrector pili muscles originate in subcutaneous tissue.
Function: protects underlying tissues from impact, abrasion, dehydration, chemical exposure
Produces melanin to protect from UV radiation
Excretion if salts, water and waste
Produces keratin to repel water
Detect temperature
Detect pain
Production of vitamin D
Thermoregulation
Storage of lipids
Detect pressure

The skin protects from

infection by acting as a
physical barrier. It is part
of the innate immune system
st
so is part of the 1 defence
and is non-specific. The epidermis
is continually shedding itself which
removes pathogens which may be
living upon it.

7.

What accessory structures are found within the skin?

Skin produces associated structures of the integumentary system such as sudoriferous (sweat) and sebaceous
(oil) glands, fingernails, hair, and sensory receptors that enable
humans to feel pressure, temperature, and pain.
Sudoriferous glands (sweat glands) are in most of the body and
there are 2 types: eccrine glands are coiled ducts deep in the skin
that connect to the surface, apocrine glands are in armpits,
areolae of nipples, and the genital region. Eccrine glands secrete
sweat, a mixture of 99 percent water and 1 percent salts and fats.
In warm conditions with low humidity, perspiration (secretion of
sweat) and evaporation cool the body. Apocrine glands, which
become active at puberty, are larger, deeper, and produce thicker
secretions than eccrine glands. The apocrine glands secretions
contain pheromones, substances that enable olfactory (sense of
smell) communication with other members of the species which
provokes certain behavioural responses. Unlike eccrine glands
that respond to heat, apocrine glands respond to stress and
sexual activity by secreting sweat with a characteristic odour. This
odour differs from body odour that results from bacteria decomposing skin secretions on the skin. Types of
modified apocrine glands: Ceruminous glands are in the external ear canal lining and secrete cerumen
(earwax) which is thought to repel foreign material. Mammary glands in female breasts are adapted to secrete
milk instead of sweat.
Sebaceous glands (oil glands) are all over the body except on
the palms of hands and soles of feet. The glands empty via
ducts into the bases of hair follicles and secrete sebum (a
mixture of fats, waxes, and hydrocarbons). Sebum keeps hair
moist and prevents skin from drying. Sebaceous glands are
numerous on the face and scalp. During puberty, increased sex
hormone levels in the blood may produce excessive sebum.
This over secretion plugs the hair and gland follicle and results
in acne.

8.

What is eczema?
A form of dermatitis/ inflammation of the epidermis. Symptoms include dry, itchy, red sin which is often
thickened in affected areas from scarring - a protective response caused by continual scratching. Lumps and
blisters may be present form separation of dermis and epidermis. Infections often occur as bacteria enter
through weakened epithelium (stratum corneum often completely removed by scratching -> reduced physical
barrier to external environment). There are several types of eczema; atopic (allergic), irritant, contact, discoid
(random regions on otherwise normal skin) and seborrhoeic (nappy areas, scalp, folds of nose and mouth often caused by yeast). Crusty skin is caused by oozing of tissue fluid containing proteins. When the liquid
evaporates the proteins remain, usually occurs in conjunction with an infection (Staph. aureus -> yellow crust).
th
Prevalence of eczema has rapidly increased in the 20 century. 75% of children get eczema at some point,
10% still have it at adulthood.
Atopic, or endogenous, eczema has a genetic influence. Skin reacts abnormally
easily to allergens which causes a flaky, red appearance. Flexures are commonly
affected skin hardens on flexures making the joint harder to move which can cause
deep cracks and fissures. Sufferers are usually diagnosed before the age of 1 (50%)
and usually have serum IgE levels up to 10 times higher than normal -> easy to
trigger major immune response.
Treatments: avoid the irritant (to avoid an inflammatory response hard to implement), moisturisers (frequent
application even when not flared up), steroids (reduce inflammation), antibiotics (treat any secondary
st
infections), 1 generation antihistamines (sedative effect to help sleep and reduce the itch).

9.

What are corticosteroids?

Steroids produced in the adrenal cortex from cholesterol to regulate inflammation, carbohydrate
metabolism and blood electrolyte levels. Glucocorticoids control glucose metabolism and
mineralocorticoids influence toe mineral/ H2O balance. They can be
administered as tablets, topically as a cream, by inhalation of a powder or
injected intravenously.
Mechanism: they diffuse through plasma membrane to intracellular receptors
where a hormone-receptor complex is formed, this then enters
the
nucleus and interacts with glucocorticoid response elements (with
transcription
factors transcription rate is raised or lowered which
changes the metabolic rate. This process takes around an hour from the time of administration. In the
inflammatory response, the glucocorticoid response element causes the production of the enzyme
phospholipase A2 which makes arachidonic acid. This is essential for formation of inflammatory mediators such
as histamine.

10. What are emollients?

Substances to soften and soothe the skin. They are often found as ingredients in moisturisers. They relieve
dryness and itching of the skin. Emollients should be applied several times a day during a flare or daily when
not flared up. Apply after any topical steroids as if the other way around the steroid wont be absorbed.
Mechanisms: Occlusion total air and water barrier. Oil layer on surface of skin reduces water loss which
increases the water content in the stratum corneum. Humectants attract water molecules from the
surroundings by containing hydrophilic groups. Needs to soak into dermis in order to work. Lubricants reduce
friction between the skin and clothing so less epithelium is lost.
11. What is Staphylococcus aureus?
A gram positive, catalase positive (converts H2O2 to H2O and O2 distinguishes
staph aureus from enterococci and streptococci), spherical bacteria which is
commonly found on the skin and inside the nose.
If Staph is resistant to methicillin, MRSA is the result. It is resistant as it
produces lactamase which leaves the lactam ring found in all penicillins.
Therefore MRSA must be treated with antibiotics which do not contain the
lactam ring, such as vancomycin (a glycopeptides antibiotic). However
vancomycin use is limited to prevent widespread resistance developing. VRSA is
a strain of Staph aureus already resistant to vancomycin.
12. What is a secondary infection of the skin?
One which sets in during/ immediately after treatment for another infection/
disease. E.g. if taking antibiotics the immune system is suppressed so its
easier for other bacteria to take hold.
In atopic dermatitis patients are more susceptible to secondary staph
infections. Staph is usually resistant to penicillins so oxacillin or flucoxacillin
can be used to treat the infection. In secondary Staphylococcal infections,
the bacteria enters the epidermis through a wound boils and scalded skin
syndrome appear. In severe infections staphylococcal endocarditis
(infection of heart valves) and pneumonia may occur.
13. What is interferon?
A glycoprotein secreted into interstitial fluid by lymphocytes in the presence of cells infected with a virus. This
allows 2 enzymes to be produced, 1 which reduces mRNA translation, the other degrades both host and viral
mRNA. It is part of the innate immune system.

14. What is innate immunity?

The innate immune system is non-specific and responds immediately to pathogenic invasion.
It includes phagocytosis, natural killer cells, stomach acid, the cough reflex, digestive enzymes, skin, mucosa and
lysozyme. It usually works in pattern recognition it recognises non self proteins on cell membranes. If the same antigen
enters the body a second time the response will be exactly the same the innate system has no antigenic memory.
Natural Killer Cells (NKCs) are large granular leukocytes which induce apoptosis in APCs. The granules in the cytoplasm
contain special proteins such as perforin and proteases known as granzymes. Upon release in close proximity to a cell
slated for killing, perforin forms pores in the cell membrane of the target cell through which the granzymes and
associated molecules can enter, inducing apoptosis. The NKC is unaffected by this process.
Lysozyme is an enzyme responsible for breaking down the polysaccharide walls of gram positive bacteria. Children fed
infant formula lacking lysozyme in their diet have three times the rate of diarrheal disease. Since lysozyme is a natural
form of protection from pathogens like Salmonella, E. coli, and Pseudomonas, a deficiency due to infant formula feeding
can lead to increased incidence of disease. Whereas the skin is a protective barrier due to its dryness and acidity, the
conjunctiva (membrane covering the eye) is, instead, protected by secreted enzymes, mainly lysozyme and defensin.
However, when these protective barriers fail, conjunctivitis results.
Phagocytosis is a form of endocytosis in which a pathogen is ingested by a leukocyte. The plasma membrane expands
around the particulate material to form large vesicles called phagosomes (10-20times larger than endosome). Only
specialized cells are capable of phagocytosis, whereas endocytosis is carried out by virtually all cells. Once particulate
matter is ingested into phagosomes, the phagosomes fuse with lysosomes and the ingested material is then digested by
a process similar to that seen in endocytosis. The so-called "professional phagocytes" include: monocytes &
macrophages, neutrophils, and dendritic cells. There are a few other cells which can be induced to become phagocytic
under certain circumstances (i.e. during intense inflammation); both fibroblasts and epithelial cells are known as "nonprofessional" phagocytes.

15. What is the adaptive immune system?

It recognises and eliminates specific antigens and members of the same species will have different responses depending
on their personal antibody profile. Immunological memory leads to a heightened response if a second infection occurs,
lifelong immunity can be gained after the first exposure to an antigen. Non-self cells are recognised. Immunity must be
acquired as there isnt physically enough room to have lymphocytes able to make the millions of different types of
antibody that we may, but most likely wont, need during our lifetime.
Humoral response occurs in the blood (B cells), the cell mediated response occurs around infected tissues (T cells).
Antibodies evolved to be able to activate the compliment system (see above), activate phagocytes and to be able to bind
to specific antigens.
Activation of lymphocytes:
The B or T cell encounters their antigen and their behaviour changes form non-dividing to proliferative. This means they
can produce large amounts of antibody or cytokine to help repel the pathogen.
T cells need to see their antigen on the class I MHC molecule.
Lymphocytes: B lymphocytes mature in the bone marrow. They each have a unique antigen receptor on their surface.
When a naive b call encounters its antigen for the first time it rapidly divides to form plasma and memory B cells.
T lymphocytes mature in the thymus gland. During the maturation process they have a T cell receptor appear on their
membranes. T helper cells have the CD4 glycoprotein receptor whilst cytoxic T cells have the CD8 receptor. T cells
recognise antigens when theyre bound to MHC proteins. When they recognise their specific antigen on the MHC
molecule they proliferate rapidly and differentiate into memory and effector cells.
Some C3b coated pathogens may bind to macrophages but not be phagocytised. However in the presence of antigens
the pathogen will be taken in and digested as antibody receptors will cross link on the phagocyte. Antibodies are made
by B cells which have differentiated into plasma cells their sole job is to produce large amounts of a specific antibody
to treat the current infection.
Primary infections: when a lymphocyte binds to a
complimentary antigen for the first time, clonal
proliferation occurs. B cells differentiate into plasma cells
and memory cells the plasma cells produce the antibody
to the specific antigen encountered whilst the memory cells
go into storage. They are able to stimulate production of
the antibody much faster should a second infection by the
same organism occur. It may take several days for
significant levels of the antibody to appear in the blood on
the first infection but only a matter of hours in subsequent
infections. The secondary response is of much greater
magnitude as well as being much faster.
Cell mediated immunity: T cells recognise antigens on the
surface of a body cell when bound to the MHC class II
receptors. They then produce cytokines which attract
macrophages, B lymphocytes and dendrites to the antigen
presenting cell. They contain enzymes which digest the APC. Some fragments combine with human leukocyte antigen
and are presented on the surface of cell making it recognisable as infected to cytoxic T cells. The T C then attaches to the
class I MHC complex and releases interferon which induces apoptosis.

Maturation of specialised cells in the immune system

16. What are hypersensitivity reactions?

Type 1 (IgE mediated hypersensitivity): The response is induced by allergens and causes a humoral antibody response.
Plasma cells secrete IgE which binds to Fc receptors on mast/ basophil cells. If there is a second exposure to the antigen,
cross links form between cell bound IgE which causes degranulation of the mast cells and basophils. Histamine, heparin,
prostaglandins and various leukotrines are released. Can be systemic (-> anaphylaxis) or localised (acute inflammation).
Inflammation occurs at a late phase after eosinophils, neutrophils and T H2 build up. Eosinophils bind to the antibody
coated antigen which causes them to release inflammatory mediators.
Type 2 (antibody mediated cytoxic hypersensitivity): antibodies bound to surface antigens activate the complement
system which causes pores to form in the pathogenic cell membrane. The antibodies produced by the immune response
bind to antigens on the patient's own cell surfaces. The antigens recognized in this way may either be intrinsic ("self"
antigen, innately part of the patient's cells) or extrinsic (absorbed onto the cells during exposure to some foreign
antigen, possibly as part of infection with a pathogen). These cells are recognized by macrophages and dendritic cells
which act as APCs, which causes a B cell to differentiate into a plasma cell which produces antibodies against the foreign
antigen. IgG and IgM antibodies bind to these foreign antigens to form complexes which activate the complement
system which kills cells presenting foreign antigens. Mediators of acute inflammation are generated at the site and MAC
cause cell lysis and death. The reaction takes hours to a day.
Another form of type II hypersensitivity is antibody-dependent cell-mediated cytotoxicity (ADCC). Here, cells exhibiting
the foreign antigen are tagged with IgG or IgM antibodies. These tagged cells are then recognised by natural killer (NK)
cells and macrophages (recognized by the IgG which is bound via the Fc receptors to the effector cell surface receptor)
which in turn kill these tagged cells.
Type 3 (immune-complex mediated hypersensitivity): high IgG and IgM antigen levels lead to cross links forming
antibody complexes forming. Tissue damage occurs as cytoxic cells produce lytic enzymes. Soluble antigens which arent
bound to a cell surface bind to antibodies forming free complexes in the blood. Macrophages are very effective at
phagocytising larger complexes but smaller complexes often evade the system. They insert themselves into to cell walls
of blood vessels and joints, inducing an inflammatory response. The complement system is activated which attracts
neutrophils to the area. Lytic enzymes are released with the purpose of digesting the immune complexes however some
tissue damage is inevitable. The process can take hours, days or weeks to develop.
Type 4 (delayed T cell mediated hypersensitivity): CD8 and CD4 cells recognize antigen in a complex with either type 1 or
2 MHC. The APCs in this case are macrophages which secrete Interleukin-12, which stimulates the proliferation of
further CD4 T cells. CD4 T cells secrete Interleukin-2 and interferon gamma, which induces the release of other
cytokines, regulating the immune response. Activated CD8 cells destroy APCs on contact, whilst macrophages produce
hydrolytic enzymes and, on presentation with certain intracellular pathogens, transform into multinucleated giant cells.
It usually occurs 24-72 hours after exposure to the antigen.
17. How does breast milk aid development of the immune system?
Contains IgA and other molecules to prevent infection. Provides the infant with a form of passive immunity and is
essential in maintaining infant health. Macrophages and neutrophils are secreted for bacterial defence and E coli
antibodies are passes to the infant to prevent fatal diarrhoea. Milk also contains lysozyme to kill bacteria. If a formula
supplement is used instead of breast milk the infant will have a weakened immune system and will be more likely to
develop allergies and infections. Breast milk is essential whilst the infant builds up their own immune system and B cell
collection. Memory and plasma B cells require an initial antigen exposure before they form so it takes time for the infant
to build up immunity to common environmental antigens.

18. What is allergy testing?

Process: A microscopic amount of an allergen is introduced to a patient's skin by various means. If an immune-response
is seen in the form of a rash, Urticaria, or in extreme cases anaphylaxis, it can be concluded that the patient has a
hypersensitivity (or allergy) to that allergen. Further testing can be done to identify the particular allergen. As a control,
known antigens such as histamine are injected. You expect to find a wheal here; if not all negative results are
interpreted as falsely negative.
Scratch test - very commonly used as an allergen test. A similar test involving injecting the allergen is also used, but is
not quite as common due to increased likelihood of infection and general ineffectiveness by comparison. There are
other methods available to test for allergy. Some allergies are identified in a few minutes but others may take several
days depending on the hypersensitivity reaction occurring. In all cases a positive results will show by the skin becoming
raised, red and feeling itchy. A negative test does not mean that the subject is not allergic; simply that either the right
concentration was not used or the body failed to elicit a response.
Prick test - a few drops of the purified allergen are gently pricked on to the skin surface, usually the forearm. This test is
usually done in order to identify allergies to pet dander, dust, pollen, foods or dust mites. Intradermal injections are
done by injecting a small amount of allergen just beneath the skin surface. The test is done to assess allergies to drugs
like penicillin or bee venom.
Patch test - a large patch which has different allergens on it is applied onto the skin, usually on the back. The allergens
on the patch include latex, medications, preservatives, hair dyes, fragrances, resins and various metals. When a patch is
applied the subject should avoid bathing or exercise for at least 48 hours.
Skin end point titration (SET) uses an intradermal injection of allergens of increasing concentrations to measure allergic
response. To prevent a severe allergic reaction, the test is started with a very dilute solution. After 10 minutes, the
injection site is measured to look for growth of wheal, a small swelling of the skin. Two millimeters of growth in 10
minutes is considered positive. If 2 mm of growth is noted, then a second injection at a higher concentration is given to
confirm the response. The end point is the concentration of antigen that causes an increase in the size of the wheal
followed by confirmatory whealing. If the wheal grows larger than 13 mm, then no further injection are given since this
is considered a major reaction.
19. What is Urticaria?
A rash with pale red, itchy bumps usually caused by allergens/ Causes wheals (raised skin with red base). Trigger is
usually allergic with high levels of inflammatory mediators (histamine) which causes the leakage of interstitial fluid from
capillaries. Treated with histamine antagonists.
20. What is angiodema?
Swelling of the dermis, subcutaneous tissue, mucosa and submucosal tissue. Can he allergic, hereditary (autosomal dominant) or
a side effect of medication (ACE inhibitors for high BP). Tue skin swells and it itchy and painful. Urticaria often occurs simultaneously,
except in hereditary angiodema. Treat with antihistamines and avoiding the allergen.

21. What is ichthyosis vulgaris?

An autosomal dominant skin disorder resulting in dry scaly skin. Affects 1/250. Usually develops between 3 months and 5 years.
Symptoms usually fade by puberty but become more severe in old age.

22. Duties of a doctor as a teacher and a learner?

GMC guidelines: Keep professional knowledge and skills up to date.
Drs should be actively involved in teaching, training, appraising and assessing other Drs and students
When involved in teaching Drs should have the correct skills attitudes and practices
Should have knowledge of new laws, codes of practice, treatment guidelines and developments in particular speciality
23. Protocol for involving students in consultations?
Student must be supervised at all times when with patient
Confidentiality most patients realise medical training requires access to patients so will give consent. If trainees are
part of the team treating the patient they are allowed access to records and personal info. If they are not treating the
patient, anonymised data should be supplied or patients consent should be gained before showing the student.
Students shouldnt discuss anything they see or hear with anyone other than their clinical tutor.
Consent ask permission for the student to observe the consultation and respect the patients decision. Dont assume
the patient will be comfortable talking openly in front of the student may not divulge full information.

Lecture notes case 5

Autoimmune disease incidence has gone up (MS, type 1 diabetes, rheumatoid arthritis, atherosclerosis,
alzeimhers, Parkinsons disease, certain cancers)

Infection
1.
2.
3.
4.

Entry to body skin, mucosa, mucus secretions, gut bacteria, stomach acid normal barriers
Replication and spreading of bacteria within body
Disease symptoms
Exit from the body and infection of other individuals

Innate
Viral infections within cells lead to interferon production acts on cells for protection and antiviral response
Natural killer cells recognise injected cells and kill them without being damaged in the process. Stops viral replication

Specific
Lymphocytes migrate to lymph nodes
Spleen removes old red blood cells
Antigens are usually proteins but can also be carbohydrates, lipids or DNA
Antibodies recognise part of the antigen
CD8 T cells kill virally infected cells
MHC is a protein complex on the surface of cells which binds to antigen fragments. Reacts with CD8 cells
Memory B cells provide a bigger, faster response to secondary infections

Biological barriers
Skin functions:

protection (keratin, innate immune system, physical barrier)

Thermoregulation (capillaries, sweat glands, erector pili muscles for hairs)
Immunological (inflammation, infection control)

Skin epidermis is acidic and dry inhospitable to bacteria. Resident flora includes Staphylococcus (epidermidis and aureus) and
streptococci.
Skin dermis contains fibroblasts, lymphocytes, adipocytes, mast cells, macrophages, nerves, lymphatics, connective tissue,
Pacinian corpuscles, Merkel cells, Meisseners corpuscles, deep and superficial vascular plexuses.

Defence against infection

0-4 hours after infection: immediate response, preformed immunological mediators
4-96 hours after infection: innate cells recruited
>96 hours after infection: adaptive acquired immune response
The pathogen enters the blood/fluid and encounters a naive B cell (with a very small cytoplasm) with a specific antibody. The B
cell is then activated in the lymph nodes where it differentiates into memory and plasma cells. Plasma cells have a much larger
cytoplasm with lots of endoplasmic reticulum for synthesising the specific antibody required.
Antibodies and immunoglobulin are the same thing. They have 3 heavy and 2 light chains with a variable region for antigens to
attach to. Neutrophils recognise the Fc region at the base of the heavy chains and engulf the pathogen.
In DiGeorge syndrome yo9u have normal IgM and love IgG levels. T cells dont mature as the thymus is absent -> no IgG
produced. IgM production in the B cells is unaffected.
CD8 kills virally infected cells
CD4, TH1 activate macrophages
CD4, TH2 activates B cells -> IgM produced.
Dendritic cells take pathogens to lymph nodes where they present antigens on their surface. Digested pathogen fragments
attach to the MHC class II protein which is then recognised by TH2 cells in order to activate B cells.
Opsonition is essential for neutrophil phagocytosis
CD8 recognises MHC class I.
CD8 cells are activated by MHC I on dendritic cells. They kill by apoptosis. They recognise the pathogen, puncture a hole in its
membrane and release granules into the affected cell. The infected cell dies whilst the CD8 is unaffected.
Normally lysosomes digest phagosomes. TH activated by interferon causes macrophages to digest the pathogen in the
phagosomes.