IMMUNO; Lecture 1, 2, 3, 4 and 5 - Hypersensitivity, Transplantation, Tolerance and Autoimmunity, Tumour immunology and immunotherapy of cancer, Inflammatory dermatoses Flashcards

Question 1

Q

Immuno

When do appropriate immune reactions occur and what do they involve?

Answer

A

To foreign harmful agents = viruses, bacteria, fungi and parasites -> concomitant tissue damage as side effect, but as long as pathogen removed quickly, then minimal and easily repaired. Involve antigen recognition by cells of immune system and Ab production

Question 2

Q

Immuno

What is appropriate immune tolerance and what does it involve?

Answer

A

Occurs to self and other harmless proteins (food, pollens, plant proteins, animal proteins). Involves Ag recognition and generation of Treg and regulatory Ab production (IgG4) -> sense of ‘danger’ cna lead to tolerance (if none) and reactivity (if present)

Question 3

Q

Immuno

When do hypersensitivity reactions occur?

Answer

A

When IR are mounted against -> foreign Ag (allergy, contact hypersensitivity), autoAg (AI disease), alloantigens (serum sickness, transfusion reactions, graft rejections)

Question 4

Q

Immuno

What are the classifications of hypersensitivity reactions?

Answer

A

I = immediate hypersensitivity; II = Ab-dependent cytotoxicity; III = immune complex mediated; IV = delayed cell mediated -> I-III depend on interaction of Ag with Ab; IV involves T cell recognition and because of longer time scale = delayed type hypersensitivity

Question 5

Q

Immuno

Which diseases have Type I immediate hypersensitivity?

Answer

A

Anaphylaxis, asthma, rhinitis (seasonal and perennial), food allergy

Question 6

Q

Immuno

What is the mechanism of action of type I immediate hypersensitivity?

Answer

A

1ry Ag exposure -> IgE production, sensitisation not tolerance, IgE binds to mast cells and basophils; 2ry Ag exposure -> more IgE is produced, Ag cross-links with basophils/mast cells and degranulation occurs

Question 7

Q

Immuno

What is the clinical presentation of Type II Ab-dependent hypersensitivity?

Answer

A

Depends on target tissue -> organ specific AI disease [myasthenia gravis (anti-ACh R Ab), glomerulonephritis (anti-glomerular basement membrane Ab), pemphigus vulgaris (anti-epithelial cell cement protein Ab), pernicious anaemia (IF blocking Ab)] and AI cytopenias (thrombocytopenia, haemolytic anaemia and neutropenia - Ab mediated blood cell destruction)

Question 8

Q

Immuno

How do you test for Type II sensitivity?

Answer

A

Test for specific autoAb, immunofluourescence, ELISA (anti-CCP for Rheumatoid arthritis)

Question 9

Q

Immuno

What is the mechanism of Type III Immune complex mediated hypersensitivity?

Answer

A

Formation of Ag-Ab complexes in blood, deposition of the complexes in tissue, complement and cell recruitment/activation, activation of other cascades and clotting leading to tissue damage (vasculitis - commonly in renal, skin, joints and lung) = e.g. SLE, Vasculitides (polyarteritis nodosum)

Question 10

Q

Immuno

Which diseases have Type IV delayed hypersensitivity response?

Answer

A

Chronic graft rejection, graft vs host disease, coeliac, contact hypersensitivity, asthma, rhinitis, eczema

Question 11

Q

Immuno

What is the mechanism of Type IV hypersensitivity?

Answer

A

Th1 = gamma interferon and is important in most hypersensitivity reactions; Th2 releases IL-4,5 and 13, mediating allergic inflammation (asthma, rhinitis and eczema)

Question 12

Q

Immuno

How can you distinguish between hypersensitivity types 1-3?

Answer

A

All mediated by Ab and distinguished by type of Ag that they recognise. Type 2 recognises cell surface/matrix bound antigens; type 3 soluble Ag

Question 13

Q

Immuno

Summarise the 4 types of hypersensitivities?

Question 14

Q

Immuno

What is inflammation?

Answer

A

Body’s response to tissue injury, rapid attempt to bring body’s defences to the site of injury and once immune cells reach the site of damage then release cytokines that lead to features of inflammation

Question 15

Q

Immuno

What are the features of inflammation?

Answer

A

Vasodilation, increased blood flow, increased vascular permeability (C3a, C5a, histamine and leukotrienes), inflammatory mediators and cytokines, inflammatory cells and tissue damage -> with redness, heat, pain and swelling

Question 16

Q

Immuno

Which cell mediators are used in inflammation?

Answer

A

C3a, C5a, histamine and leukotrienes cause increased vascular perm; cytokines = IL-1,6,2, TNF, IFN-gamma; chemokines = IL-8/CXCL8, IP-10/CXCL10

Question 17

Q

Immuno

Which inflammatory cells infiltrate and take part in inflammation?

Answer

A

Cell trafficking by chemotaxis; neutrophils, macrophages, lymphocytes, mast cells -> cell activation is caused

Question 18

Q

Immuno

What is atopy?

Answer

A

Form of allergy where there is a hereditary or constitutional tendency to develop hypersensitivity reactions in response to allergens -> very common, in 50% of YA in UK -> risk factors = genetic and environmental

Question 19

Q

Immuno

How does severity of atopy vary?

Answer

A

Mild, occasional symptoms, severe chronic asthma, life threatening anaphylaxis

Question 20

Q

Immuno

What are the genetic risk factors for atopy?

Question 21

Q

Immuno

What are the environmental risk factors for atopy?

Question 22

Q

Immuno

What are the types of inflammation in allergy and which type of hypersensitivity caused it?

Question 23

Q

Immuno

What is needed to express a disease?

Answer

A

Development of sensitisation to allergens instead of developing tolerance; exposure to produce disease (memory response)

Question 24

Q

Immuno

How does sensitisation in atopic airway disease occur?

Answer

A

Naive T cells haven’t seen the Ag; when CD4+ Tcells are activated by APC hey become specific to Ag and become -> Th1 (IFN-g), Th2 (activate B cells) and i Ag is harmless then become Treg

Question 25

Q

Immuno

How does subsequent exposure after sensitisation affect inflammation?

Answer

A

Allergens presented by APC to Th2, which release IL-5 causing degranulation of eosinophils;

also release IL-4 and 13 which stimulate IgE production by plasma cells. IgE then mobilised onto mast cell surface ->

Ag cross-link wiith IgE onto surface of mast cells and causes degranulation ->

massive release of inflammatory mediators, giving rise to effects seen in allergic reaction

Question 26

Q

Immuno

What are eosinophils?

Answer

A

2-5% of blood leukocytes, present in blood but more reside in tissues; recruited during allergic inflammation; generated from bone marrow; polymorphous nucleus (2 lobes); contains large granules full of toxic proteins; leads to tissue damage

Question 27

Q

Immuno

What are mast cells?

Answer

A

Tissue resident cells which have IgE receptors on surface, crosslinking of IgE leads to mediator release -> pre-formed: histamine, cytokines and toxic proteins; newly synthesised: leukotrienes, prostaglandins -> all leading to acute inflammation

Question 28

Q

Immuno

What are neutrophils?

Answer

A

Important in virus induced asthma, severe asthma and atopic eczema; 55-60% of blood leukocytes, multilobed nucelus, granules contain digestive enzymes and neutrophils can also synthesise: oxidant radical, cytokines and leukotrienes

Question 29

Q

Immuno

What is the acute asthma immunopathogenesis?

Answer

A

Mixture of type I and IV

Question 30

Q

Immuno

What are the 3 processes leading to airway narrowing in acute asthma?

Answer

A

Vascular leakage leading to airway wall oedema, mucus secretion filling up the lumen and smooth muscle contraction around the bronchi

Question 31

Q

Immuno

What is the chronic asthma immunopathogenesis?

Answer

A

Chronic inflammation of the airways, with the lumen being very narrow and airway wall grossly thickened; cellular infiltration of Th2 and eosinophils; smooth muscle hypertrophy, mucus plugging, epithelial shedding and sub-epithelial fibrosis

Question 32

Q

Immuno

What are the important clinical features of asthma and what’s a typical day like?

Question 33

Q

Immuno

What is allergic rhinitis and what are the symptoms?

Answer

A

Seasonal = hay fever (grass, tree pollens), perennial (house dust mite, animal) -> sneezing, rhinorrhoea, itchy nose and eyes, nasal blockage, sinusitis, loss of smell/taste

Question 34

Q

Immuno

What is allergic eczema?

Answer

A

Chronic itchy skin rash, most commonly found in flexures of arms and legs; lead to house dust mite sensitisation -> complicated by bacterial and viral (rare) infections -> 50% cleared by 7y, 90% by adulthood

Question 35

Q

Immuno

What are food allergies?

Answer

A

Type 1 -> IgE mediated; common foods change with age -> infancy-3y = egg, cows milk; children/adults = peanuts, shellfish, nuts, fruits, cereals, soya

Question 36

Q

Immuno

What are the mild and severe reactions to food allergies?

Answer

A

Mild: itchy lips and mouth, angioedema, urticaria; severe: nausea, abdo pain, diarrhoea, anaphylaxis

Question 37

Q

Immuno

What is anaphylaxis?

Answer

A

Severe generalised allergic reaction -> uncommon and potentially fatal = generalised degranulation of IgE sensitised mast cells

Question 38

Q

Immuno

What are the symptoms and systems involved in anaphylaxis?

Question 39

Q

Immuno

What investigations can you carry out to diagnose allergies/hypersensitivity?

Answer

A

Careful history = essential -> skin prick test, RAST (tests for amount of specific IgE in blood), IgE total measure, lung function in asthma

Question 40

Q

Immuno

How do you treat anaphylaxis?

Answer

A

EMERGENCY = epipen and anaphylaxis kit; if mild = antihistamine (backed with steroid injection), if severe = adrenaline injection. PREVENTION= avoidance of known allergen, always carry anaphylaxis kit and epipen, inform immediate family and caregivers, wear medicalert bracelet

Question 41

Q

Immuno

How do you treat rhinitis and eczema?

Answer

A

Allergic rhinitis: anti-histamines (help sneezing, itching and rhinorrhoea) nasal steroid therapy (nasal decongestant) and cromoglycate (in children, eyes). Eczema: emolients (maintain moisture to reinforce barrier function) and topic steroid cream. SEVERE: anti IgE mAb, anti IL4/13 mAb, anti-IL5 mAb

Question 42

Q

Immuno

How do you treat asthma?

Question 43

Q

Immuno

What is immunotherapy?

Answer

A

Effective for single Ag hypersensitivities = venom allergy (bee/wasp stings), pollens, HDM; Ag used is purified. Subcut (SCIT) = 3 y needed with weekly/monthly 2 hr clinic visits; sublingual (SLIT) = 2-3y enough and can be taken at home

Question 44

Q

Immuno

What are the 2 reasons for transplantation?

Answer

A

Life saving (other life-supportive methods aren’t fully developed (heart and liver)) or life enhancing (other life supportive methods are less good (kidneys with dialysis, pancreas where in some cases it can be better than insulin injections)

Question 45

Q

Immuno

Why do organs (cornea, skin, bone marrow, kidney, liver, heart) fail?

Question 46

Q

Immuno

What are the different types of transplantation?

Answer

A

Xenografts -> heart valves from pigs/cows, skin;

allografts -> solid organs (kidney, liver, heart, lung, pancreas), small bowel, free cells, temporary (blood, skin), cornea, framework (bone, cartilage, tendon, nerve), composite (hands, face, larynx)

Question 47

Q

Immuno

What are the kinds of donors of allografts?

Answer

A

Deceased donor, living donor (bone marrow, kidney, liver; geneticall related/unrelated)

Question 48

Q

Immuno

What are the 2 types of deceased donors?

Answer

A

Donor after brain death (RTA, massive cerebral haemorrhage, confirm brain death; harvest organs and cool to minimise ischaemic damage), donor after cardiac death (heart stopped before organ harvest, longer period of warm ischaemia time and suitable for kidneys)

Question 49

Q

Immuno

How do you confirm brain death?

Question 50

Q

Immuno

What needs to be done for all donors before transplantation?

Question 51

Q

Immuno

What are the steps that recipients take part in when receiving transplants?

Answer

A

Transplant selection (access to waiting list) and transplant allocation (access to organ)

Question 52

Q

Immuno

How is transplant selection carried out?

Question 53

Q

Immuno

How is transplant allocation carried out?

Question 54

Q

Immuno

What are the steps to allocate a kidney to a patient?

Question 55

Q

Immuno

How can you decide whether they should allocate the organ locally or nationally?

Answer

A

Heart needs very little cold ischaemic time and lungs need to be a size match

Question 56

Q

Immuno

What strategies can increase transplantation activity?

Answer

A

Donor transplant coordinators (registered trained nurses in critical care); increase donations (marginal donors = DCD, elderly patients, sick), living donation (transplant across tissue compatibility barriers and exchange programmes), xenotransplantation? stem cell research?

Question 57

Q

Immuno

What are the most important and variable protein variations in clinical transplantation?

Answer

A

ABO blood groups; HLA coded on chromosome 6 by MHC

Question 58

Q

Immuno

What is the difference between each ABO blood group?

Question 59

Q

Immuno

How does Ab-mediated rejection occur?

Answer

A

Circulating, pre-formed, recipient anti-B antibody binds to B blood group antigens on donor endothelium.

Abs Recruit complement and macrophage activation which then fix onto endothelium; complement makes holes in endothelium, thrombus.

Question 60

Q

Immuno

How do we do ABO-incompatible transplantation?

Answer

A

Remove the antibodies in the recipient (plasma exchange) Good outcomes (even if the antibody comes back) Kidney, heart, liver

Question 61

Q

Immuno

What is HLA?

Answer

A

Cell surface proteins Highly variable portion Variability of HLA molecules important in defense against infections and neoplasia Foreign proteins are presented to immune cells in the context of HLA molecules recognised by the immune cells as “self”

Question 62

Q

Immuno

What is rejection?

Answer

A

Most common cause of graft failure

Diagnosis = histological examination of a graft biopsy

Treatment = immunosuppressive drugs

Question 63

Q

Immuno

How does T-cell mediated rejection occur?

Answer

A

Interstitial infiltrate ; CD4+ T cells recruit CD8+ cells and macrophages

Question 64

Q

Immuno

Which cells are involved in t-cell mediated rejeciton?

Answer 50

A

Ab against graft HLA and AB Ag, with Ab arising pre (Sensitised) and post-transplant (de novo)

Answer 51

A

Maximise HLA compatibility, life-long immunosuppressants

Answer 52

A

Target T cell activation and proliferation; target B cell activation and proliferation and Ab production

Answer 53

A

Increased risk for conventional infections Bacterial, viral, fungal Opportunistic infections – normally relatively harmless infectious agents give severe infections because of immune compromise Cytomegalovirus (owl eye appearance) BK virus Pneumocytis carinii

Answer 54

A

Skin cancer Post transplant lymphoproliferative disorder – Epstein Barr virus driven Others

Answer 55

A

See peptides exhibited on a definite framework

Answer 56

A

Presenting HLA on HLA molecule, causing a delayed hypersensitivity response

Answer 57

A

Class I (ABC) - on all cells; class II (DR DQ DP) - on all APC but can be upregulated on other cells -> all are highly polymorphic with lots of alleles for each locus, with each individual often having 2 types for each HLA molecule.

Most important for transplants are A, B and DR as they are the most likely to produce an immune response (most polymorphic)

Answer 58

A

Should only be from 0 to 6 mismatches

Answer 59

A

Mother and father you will share 3 loci; siblings have high chance of having up to 6 in common

Answer 60

A

An adaptive immune response with specificity for self antigens -> always involved lymphocytes (receptors formed by random recombination of gene segments, so possibility of self receptors to form), and we all have normal autoimmunity (lymphocytes capable of recognising self Ag)

Answer 61

A

Genetic suscepitibility, infections, environmental factors -> leading to breakdown of self-tolerance and progression to AI disease

Answer 62

A

More common in females, but some like T1DM is more common in men -> oestrogen is a hypothesis for high incidence in females

Answer 63

A

Organs affected, involvement of specific autoantigens and types of immune responses

Answer 64

A

AutoAb against RBC were responsible -> bind to RBC and activate complement, resulting in clearance and complement-mediated lysis of autologous erythrocytes

Answer 65

A

Antibody response to cellular or extracellular matrix antigen (Type II) Immune complex formed by antibody against soluble antigen (Type III) T-cell mediated disease (Delayed type hypersensitivity reaction, Type IV)

Answer 66

A

IgG Ab against Type IV collagen found on basement membrane, with deposition of autoAb in renal corpuscle, mainly affecting kidneys -> once Ab deposited in renal corpuscle, it activates complement, attracting inflammatory cells, which can cause damage

Answer 67

A

AutoAb that can bind to TSH receptor and mimic action of TSH, stimulating T3/4 production; autoAb isn’t under -ve feedback, so constant stimulation of thyroid hormone production leading to hyperthyroidism

Answer 68

A

SLE -> immune complex deposition in glomerulus; Ab binding to soluble Ag and forming immune complexes which can circulate to different places in body and deposit in tissues, which in kidneys can cause problems. Also affects joints, causing joint pain

Answer 69

A

Difference in type II and III is that Ag is insoluble in type II and soluble in type III;
both types can recruit inflammatory cells which bind via Fc receptors to Fc portion of Ab.
Type II: causes more localised tissue injury;
Type III: immune complexes can deposit in various sites, effector mechanisms are same as type II

Answer 70

A

Normal response of T-cell to antigens: Ag presented to T cells by MHC expressed on surface of APC, with CD4=MHCII and CD8=MHCI, and costimulation from APC is needed for activation and proliferation

Answer 71

A

MHC are the strongest genetic link to AI disease, with mostly class II genes and good evidence that T cells are involved in AI disease

Answer 72

A

Acquired inability to respond to antigenic stimulus -> Acquired (involves cells of acquired immune system and is learned), Ag specific and Active process in neonates, with effects maintained through life

Answer 73

A

Central tolerance (during lymphocyte development) and peripheral tolerance (generated by 3 mechanisms once mature lymphocyte formed -> anergy, immune privilege/ignorance of Ag, regulation (active suppression). Failure of these mechanisms of tolerance may result in AI

Answer 74

A

Mechanism of deletion of autoreactive T and B cells in primary lymphoid organs.

All lymphocytes come from stem cells in the bone marrow, with precursors of T cells then migrating to thymus where they develop into mature T cells, undergoing rigorous selection process in thymus (B cells occur in bone marrow)

Answer 75

A

Involves extent of binding of TCR to the MHC molecules, with 2 cell popn (CD4+ and CD8+) depending on which MHC molecule they bind to best; with 3 possible outcomes that can occur; only 5% of thymocytes survive selection

Answer 76

A

Selection takes place in bone marrow; NOT MHC restricted, selected based on interaction between the B cell receptor and the Ag present in bone marrow;
no self reaction and B cells go on to become mature B cells which express IgD and IgM -> if they do recognise self Ag they will usually die by apoptosis;
Receptor editing (second chance for B cells to amend themselves) occurs;
if they recognise soluble autoAg, they will migrate to the periphery but don’t express normal levels of IgM and they are anergic.
If they have a weak interaction with soluble Ag the B cells will develop fine and there will be normal levels of cell surface receptors;
cells that recognise self weakly have the potential to cause AI disease

Answer 77

A

Auto-immune Polyendocrinopathy-candidiasis-Ectodermal Dystrophy (AI polyglandular disease), which affects the endocrine glands: Thyroid Kidneys Chronic mucocutaneous candidiasis Gonadal failure Diabetes mellitus Pernicious anaemia

Answer 78

A

Failure to delete T cells in thymus, due to mutations in the AIRE gene (important for expression of tissue specific genes in the thymus, involved in negative selection of self reactive T cells in thymus)

Answer 79

A

Genes can affect multiple biologicl pathways and may lead to failure of immune tolerance -> main processes affected are induction of tolerance, apoptosis and clearance of antigen

Answer 80

A

Some Ag might not be present in the thymus/bone marrow and may be expressed when immune system has matured -> mechanisms to prevent auto-reactivity of mature lymphocytes = anergy, suppression by Treg and ignorance of Ag

Answer 81

A

Subsequent stimulation even in the presence of costimulation leads to anergy

Answer 82

A

Sympathetic ophthlmia as an example

Answer 83

A

Treg are specialised cells that regulate activity of other T cells, expressing CD4, CD25 (IL-2 receptor), CTLA-4 and FOXP3 (transcription factor used as marker for Treg

Answer 84

A

ACCUMULATION OF AUTOREACTIVE T CELLS

Answer 85

A

Natural = generated in thymus; inducible = produced as part of normal T cell response as a mechanism for dampening down an immune response after it happened

Answer 86

A

APCs present self peptides always, which T cells are tolerant to;

APCs when activated by pathogens, present pathogen AND self peptide at the same time, and upregulation of costimulatory molecules occurs, which could trigger T cell activation for self protein, leading to AI

Answer 87

A

Immune response against tumour (breast for e.g.) which resulted in degeneration of cerebellum leading to dizziness, vertigo, untintelligible speech truncal and appendicular ataxia;

cerebellum degeneration-related Ag 2 detected in serum.

Spontaneous immune response was acting somewhere else in body with self tissue, in this case led to elimination of Purkinje cells in brain.

Certain tumours can express antigens which are absent from corresponding normal tissues, immune system can detect such abnormally expressed Ag and launch an attack against tumour, which may result in AI destruction of normal somatic tissues

Answer 88

A

Accident victim autopsies reveal that many adults have microscopic colonies of cancer cells with no symptoms of disease; patients treated for melanoma and after many years are apparently free of disease have been used as donors of organs for transplantation, with recipients developing tumours as they didn’t develop ‘immunity’ to melanoma; deiberate immunosuppression increases risk of malignancy and men have 2x chance of dying from malignant cancer than women (stronger immune responses) -> maybe immunosurveillance exists with malignant cells generally controlled by action of immune system

Answer 89

A

Release of Ag from cancer cells, which are captured by professions APCs which then migrate to local draining lymph nodes;
if enough costimulation then you will get activation of T cell response, which brings an Ab response;
T cell responses are particularly important against tumours because the Ag are intracellular and once T cells activated, they return to tumour (tumour infiltrating T cells), with processed tumour Ag recognised by T cells which can kill cancer cells ->
immune selection pressure on tumour cells, cause a form of antibiotic resistance, which makes them able to evade killing by Tcells.
After being exposed to same Ag several times T cell expresses PD-1 receptor;
tumour cells upregulate expression of ligand PDL-1 which can bind to PD-1 and downregulate T cell response ->
blocking of PD1-PDL1 interaction could help stimulate T cell response

Answer 90

A

Results from multiple sporadic events over time: irradiation, chemical mutagens, spontaneous errors during DNA replication, tumour virus induced changes (inflammation amount varies) in genome which induces mutations in cellular DNA.
Viral = lots of pattern recognition receptors, lots of cytokines and lots of inflammation;
tumour = NOT very inflammatory, so can be missed by the immune system, but once sufficient inflammation then innate immune cells recruited (dendritic, macrophages and NK cells) DC capture Ag from tumour cells and go to lymph nodes, present to circulating T cells, followed by recruitment of adaptive, Ag-specific immunity

Answer 91

A

Local inflammation in the tumour 2. Expression and recognition of tumour antigens NB: inflammation necessary for stimulation of expression of costimulatory molecules

Answer 92

A

Antigenic differences between normal and tumour cells can be very subtle and it takes the tumour a while to cause local inflammation

Answer 93

A

Patients with cancer haven’t formed a good immune response, or the cancer hasn’t produced enough inflammation or expression of Ag to trigger response, so immunotherapy conditions the patient’s immune system so that it is better able to stimulate an effective immune response against the tumour

Answer 94

A

MCH I presents endogenous peptides on cell surface for T cell regulation, and should normally be self-peptides being shown; in tumours then tumour specific Ag can be presented by MHC molecules -> sometimes mutated cellular proteins are presented or chromosomal translocations might generate new combinations of protein sequences that are presented by MHC molecules

Answer 95

A

Tumour cells in cervical cancer express viral proteins, so there are tumour specific viral Ag and the immune system can detect these tumour cells and can kill them, with most people generating this immune system quite well

Answer 96

A

Induced and maintained by the E6 and E7 oncoproteins of HPV, which are intracellular Ag; peptides usually presented by MHC on cell surface. Gardasil (HPV vaccine) doesn’t use E6 and E7 oncoproteins = uses structural proteins to generate virus like particles

Answer 97

A

Most people generate a good immune response against HPV and have no problems and no tumours, but for a small minority, they don’t and could go on to have immune failure and develop neoplasia

Answer 98

A

2 times: preventative vaccination or therapeutic vaccination (try to control disease once it has occurred)

Answer 99

A

Generally derived from normal cellular proteins which are aberrantly expressed (timing, location or quantity), and immune system isn’t tolerant and they become immunogenic when expressed by tumour -> abnormal expression of normal cellular protein -> examples =

Answer 100

A

If immune response is generated against TAA then it could cause AI type problems as the TAAs are normal proteins that are expressed elsewhere in the body;

IR may be good at dealing with the cancer, but could cause AI;

e.g. in melanoma patients taking a cancer ‘vaccination’, this frequently causes AI depigmentation in melanoma patients

Answer 101

A

AI responses against normal tissues; immunological tolerance = normal tolerance to auto-antigens and tumour induced tolerance

Answer 102

A

Antibody-based therapy Therapeutic vaccination (stimulate natural anti-tumour responses) Immune checkpoint blockade Adoptive transfer of immune cells Combinations of 1) to 4) above

Answer 103

A

Basal Cell -> Prickle Cell -> Granular Cell (at Granulosum) -> Keratin

Answer 104

A

Developed keratinocytes and lipids -> defects in barrier function causing eczema

Answer 105

A

Atopy = tendency to develop hypersensitivty; diseases inc. atopic eczema (relapsing and remitting), asthma and hayfever -> atopic march is shows tendency for each atopy to progress with age to different diseases

Answer 106

A

Common itchy skin condition, onset around 6m, with many children growing out of it

Answer 107

A

Defective barrier function of the skin, leading to dry skin.
Filagrin gene mutations in 10% of cases.
Filagrin is an epidermal protein important in maintaining barrier function of the skin.
Filagrin mutation is denoted by palmar hyperlinearity.
Causes Intrinsically dry and flakey skin.
Defective barrier function allows penetration of irritants, allergens (eg house dust mite particles) and pathogens eg staph aureus.
S. Aureus infection exacerbates eczema.
Inflammation of the skin then occurs as APCs take up allergens and present them to T cells (sensitisation). ->
HSV can also attach to eczematous skin forming widespread lesions, small punched out ulcers which are 3-4 mm

Answer 108

A

3m old at presentation in places the baby can scratch affected the most; erythmatous at acute stage; weepy, eroded skin with poorly defined margins -> adult eczema presents at skin folds, hands and face, with lichenification (thickening of skin at chronic stages) occurring in both types

Answer 109

A

A very common type of eczema affecting babies and adults. Often not itchy. There is overgrowth of malassezia species of yeast on the skin with associated skin inflammation. The rash has a distinctive distribution including nasolabial folds, eyebrows, scalp, central chest and sometimes axillae and groins.

Answer 110

A

Delayed Type Hypersensitity reaction (IV). A pronounced eczematous skin reaction due to contact with allergen e.g Nickel.

Answer 111

A

Eczema presenting in small disc patches. Dry skin that is often due overwashing and dry climate. Typically has poorly defined margins (as opposed to psoriasis).

Answer 112

A

Starts in teens or 40/50s characterised by salmon pink patchy lesions, scale like texture and well-defined margins. 4 types: chronic plaque, guttate, palmoplantar pustulosis and generalised pustular psoriasis; psoriatic arthritis affect ~30% of patients with cutaneous disease. Commonly affects the face, knees, axillae, posterior lumbar region, umbilicus, genitals and buttocks.

Answer 113

A

Genetic susceptibility and environmental triggers are the underlying cause.

Many genes are implicated including PSOR1.

Immune process occurs where T lymphocytes move out of blood vessels into the dermis and initiate the release of cytokines, eg TNF Alpha.

The Epidermis becomes thickened and produces more keratinocytes than normal, neutrophils infiltrate the epidermis and lymphocytes infiltrate the dermis.

Triggers include infections, drugs and stress.

Hyperkeratosis = thickening of stratum corneum with keratinocytes; parakeratosis = failure to denucleate keratinocytes before reaching stratum corneum; acanthosis = generalised increased thickening of epidermis, esp at S. basale and spinosum

Answer 114

A

Can on present on soles of feet with tick yellowish scales, with symmetry; can also affect the nails causing subungual hyperkeratosis, dystrophic nail (external - oncholysis), loss of cuticle

Answer 115

A

A very common condition which mainly affects teenagers and young adults.

Commonly occurs on the face, chest and back.

Disease of the pilosebaceous unit of the skin.

Dead cells accumulate and trap bacteria within the unit.

Bacteria then accumulate protruding as a pimple (whitehead).

Upon bursting inflammation is triggered by exposed bacterial antigens (blackhead). Pathogenesis is multifactorial:

Hyperkeratinisation of the epidermis in the infundibulum of the hair follicles
Accumulation of dead keratinocytes in the lumen of the hair follicle
Increase sebum production stimulated by androgens
Proliferation of propioni bacterium acnes within the pilosebaceous unit
Rupture of the inflamed pilosebaceous unit, with further inflammation of the surrounding skin

Answer 116

A

Whiteheads (closed comedone)
Blackheads (open comedone)
Papules (lesions)
Pustules (pus filled papules)
Nodules (large papules)

Answer 117

A

An autoimmune bullous inflammatory condition most common in the elderly. Clinical features consist of intense pruritus followed by the development of tense blisters on an erythematous background of skin or mucous membranes

Answer 118

A

IgG autoantibodies to basement membrane antigens BP180 (type XVII collagen) or BP230 result in cleavage of the skin at the dermo epidermal junction leading to sub epidermal blisters.
Basement membrane zone is integral to holding the ectoderm (epidermis) and mesoderm (dermis) together.
Treatment is via PO and Topical steroids.
Note: epidermolysis bullosa – conditions characterised by any genetic defect of a BMZ protein. Skin is easily eroded and heals with scarring.

Answer 119

A

An uncommon autoimmune bullous inflammatory disease, which usually affects middle aged individuals (Asians most at risk). Clinical features include flaccid blisters which easily break leaving erosions and crusted lesions. If untreated fatal as disease spreads across body. Treatment involves immunosuppressants alongside topical and PO steroids.

Answer 120

A

IgG autoantibodies to epidermal cell surface proteins desmogleins 1 and 3 lead to loss of cell-cell adhesion (acantholysis) within the epidermis causing flaccid blisters in the skin or mucous membranes.

These proteins help join keratinocytes together in the deeper stratum.