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Year 2 MCD 2 > Immunology > Flashcards

Immunology Flashcards

1
Q

What is the difference between allergy and atopy?

A

Atopy is having an allergic sensitisation - producing abnormally high IgE to otherwise harmless environmental substances.
Allergy is having allergic symptoms/disease because of atopy.

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2
Q

When is an immune response appropriate?

A

Appropriate immune responses take place when we mount an immune response to foreign harmful agents such as viruses, bacteria, fungi or parasites. The response is necessary to eliminate pathogens. Requires antigen recognition by the cells of the immune system and antibody production.

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3
Q

When is immune tolerance appropriate?

A

Appropriate immune tolerance takes place when tolerance occurs to self-proteins and foreign harmless particles such as pollen, foods etc. Antigens recognised in the absence of danger signals leads to tolerance, the presence of danger signals will result in a response.

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4
Q

When is an immune response inappropriate?

A

Hypersensitivity reactions occur when immune responses are mounded inappropriately, such as to:

  • Harmless foreign antigens –> allergy, contact hypersensitivity
  • Autoantigens –> autoimmune diseases
  • Alloantigens –> serum sickness, transfusion reactions and graft rejection
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5
Q

What are the four types of hypersensitivity reactions?

A

Type I: Immediate Sensitivity
Type II: Antibody-Dependent Cytotoxicity
Type III: Immune Complex Dependent
Type IV: Delated Cell Mediated

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6
Q

Describe the pathophysiology of type I hypersensitivity

A

This occurs when primary antigen exposure sensitises the body to an antigen, leading to IgE production aided by B and T cells. IgE binds to IgE receptors on mast cells and basophils. The IgE coated basophils are now sensitised.

The second exposure leads to more IgE production –> IgE receptor cross-linked on mast cells and basophils. This causes them to release more inflammatory mediators such as histamine, which leads to symptoms.

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7
Q

What diseases have type 1 hypersensitivity components?

A

The most common Type 1 hypersensitivity reactions include food allergy, anaphylaxis, asthma and allergic rhinitis (hay fever). Allergic rhinitis can either be seasonal or perennial (antigen present all year round).

NOT related to autoimmunity

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8
Q

Describe the pathophysiology of type II hypersensitivity

A

This occurs when IgG antibodies are released into the bloodstream targeting antigens on the surface of our cells or tissues. This leads to local inflammation and results in autoimmune diseases.

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9
Q

What diseases have type II hypersensitivity components?

A

autoimmune diseases such as pernicious anaemia, myasthenia gravis, haemolytic thombocytopaenia etc

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10
Q

What are the antibody targets in the pathophysiology of:

  • Myasthenia gravis
  • Glomerulonephritis
  • Pemphigus vulgaris
  • Pernicious anaemia
A
  • Myasthenia gravis (anti-AChR Ab)
  • Glomerulonephritis (anti-glomerular basement membrane Ab)
  • Pemphigus vulgaris (anti-epithelial cell cement Ab)
  • Pernicious Anaemia (intrinsic factor blocking Ab)
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11
Q

How can antibodies be detected in the aid of diagnosing autoimmune conditions?

A

Antibodies can be detected in aiding diagnosis through immunofluorescence or Enzyme-Linked Immunosorbent Assay (ELISA).

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12
Q

Describe the pathophysiology of type III hypersensitivity

A

This is when antibodies in the blood form antigen-antibody COMPLEXES in the blood. These complexes are deposited in small blood vessels in tissues leading to complement cascade activation and inflammatory cell recruitment and activation. This leads to tissue damage such as vasculitis.

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13
Q

What areas are most affected by vasculitis?

A

Areas most affected by vasculitis are the kidneys, skin, joints and lungs.

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14
Q

Describe the pathophysiology of type IV hypersensitivity

A

T-cells are the main drivers of type IV hypersensitivity:

  • Th1 produce INF-γ and IL-2 in large amounts activating macrophages, which release TNF-α.
  • Cytotoxic T-cells are activated by IL-2, and seek to destroy the cells with the antigen on its surface.
  • When the inflammation is chronic, Th1 cells can release FGF (Fibroblast Growth Factor) which activates fibroblasts angiogenesis and fibrosis.
  • Much of the tissue damage is caused by TNF-α.
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15
Q

What diseases are caused by Type IV hypersensitivity reactions?

A

Examples of diseases caused by Type IV hypersensitivity include chronic graft rejection, coeliac disease, contact hypersensitivity and many others. Type I hypersensitivity reactions can occur upon the background of Type IV, such diseases include asthma, rhinitis and eczema.

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16
Q

What diseases have a mixture of Type I and Type IV hypersensitivity components?

A
  • Asthma
  • Rhinitis
  • Eczema
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17
Q

What are the four signs of inflammation?

A
  • redness
  • temperatures
  • pain
  • swelling
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18
Q

What are the features of inflammation that lead to the signs of inflammation?

A
  • Vasodilation with increased blood flow
  • Increased vascular permeability with increased leakage of serum into tissue, causing swelling
  • Release of inflammatory mediators
  • Recruitment and activation of inflammatory cells and tissue damage
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19
Q

What are the pro-inflammatory cytokines?

A
  • IL-1
  • IL-2
  • IL-6
  • TNF-a
  • INF-y
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20
Q

What percentage of topics have a family history?

A

80%

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21
Q

What genes are related to atopy?

A
  • genes of the IL-4 gene cluster linked to atopy, asthma and raised IgE
  • genes related to IgE receptor (that make it more likely to bind to mast cells) also linked to atopy and asthma
  • genes linked to structural cells linked to asthma
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22
Q

What are the environmental risk factors for allergy?

A
  • Age: atopy increases from infancy, peaks at teen years and reduces in adulthood
  • Gender: asthma is more common in males in childhood, but females in adulthood
  • Family size: more common in smaller families, and in firstborns
  • Infections: exposure to infections in early life is protective in the development of atopy
  • Animals: exposure to animals is also protective
  • Diet: anti-oxidants, breast feeding and fatty acids are protective
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23
Q

Describe the immunopathogeneis of an allergic reaction

A

Inhaled protein allergen (e.g dust mite) is picked up by dendritic cells (APC) which digests the peptide and presents it to naïve CD4+ T-cells. The T-cell differentiates into a Th2 cell.

Th2 cells produce IL-4, IL-5 and IL-13. IL-4 and IL-13 signal to B cells to switch from IgM and IgG to IgE antibody production against the allergen, also stimulating the plasma cells.
Specific IgE binds to Fc receptors on mast cells and basophils, which are now sensitised – ‘loaded’ and ready to ‘fire’.

On subsequent exposure, Th2 memory cells and the mast cells and basophils are ready to mount an immune response. When the antigen is presented to the Th2 memory cell again, it produces IL-5 again which activates eosinophils, causing them to release inflammatory mediators. More plasma cells produce more IgE, which cross-links the Fc receptors on the mast cells and basophils, allowing them to degranulate, releasing histamine and other inflammatory mediators.

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24
Q

What cytokines do Th1 and Th2 produce and what does this cause?

A

Th1 produce:

  • TNF-a (causing systemic inflammation)
  • INF-y (activates macrophages and induces MHC-Class 2)
  • IL-2 (promotes differentiation to cytotoxic and memory T-cells)

Th2 produce:

  • IL-4 (promotion of Th2 and Ab class switch to IgE)
  • IL-5 (activates eosinophils)
  • IL-13 (Ab class switch to IgE)
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25
Q

What are the clinical features of allergic rhinitis?

A

Allergic rhinitis is often associated with sinusitis, otitis media, allergic conjunctivitis, and asthma.

Symptoms include sneezing, rhinorrhoea (runny nose), itchy nose and eyes, nasal blockage, sinusitis, and a loss of taste and smell.

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26
Q

What are the two types of allergic rhinitis?

A

Seasonal and perennial

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27
Q

What are the symptoms and clinical features associated with asthma?

A
  • Reversible generalised airway obstruction
  • Bronchial hyper-responsiveness and irritability
  • Airway inflammation
  • Cough
  • Mucus production
  • Breathlessness
  • Chest tightness
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28
Q

What are the mechanisms behind away narrowing in asthma?

A

a) mucosal oedema
b) increased mucus secretion
c) smooth muscle contraction

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29
Q

What are the chronic features of asthma?

A
  • smooth muscle hypertrophy
  • mucus plugging
  • epithelial shedding
  • sub endothelial fibrosis
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30
Q

What are the features of allergic eczema?

A

Allergic eczema is characterised by a chronic itchy skin rash, flexures of arms and legs, house dust mite sensitisation, and dry cracked skin.

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31
Q

What are the common food allergies in kids, and the common allergies in adults?

A

Infants-3yr olds: common allergies are to eggs and cow milk.

In adults: commonly to to peanuts, shell fish, nuts, soya, cereals and fruits.

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32
Q

What are the symptoms caused by food allergies?

A

They can cause mild symptoms such as itchy lips and mouth, angioedema, and urticaria. However, food allergies can also lead to more severe symptoms such as nausea, abdominal pain, diarrhoea and even anaphylaxis.

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33
Q

What is the pathophysiology of anaphylaxis?

A

It is caused by the generalised degranulation of mast cells.

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34
Q

What are the consequences of anaphylaxis?

A

Cardiovascular: vasodilation, cardiovascular collapse (anaphylactic shock)
Respiratory: bronchospasm and laryngeal oedema
Skin: vasodilatation, erythema, urticaria and angioedema
GI: vomiting and diarrhoea

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35
Q

What are the symptoms of anaphylaxis?

A
  • Itchiness around mouth, pharynx and lips
  • Swelling of the lips, throat and other parts of the body
  • Wheeze, chest tightness and dyspnoea
  • Faintness and collapse
  • Diarrhoea and vomiting
  • Death if severe and untreated.
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36
Q

What tools can we use in diagnosing allergy?

A
  • A careful history
  • Skin prick tests can show immediate hypersensitivity (type I hypersensitivity). An allergen is pricked into the skin before the skin is observed for any redness.
  • A RAST test can sample the blood for a specific IgE antibody
  • Total IgE can also be measured
  • Lung function tests can be useful in diagnosing asthma.
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37
Q

How is anaphylaxis treated?

A

Anaphylaxis is a medical emergency. Treatment is by immediate injection of adrenaline followed by an anaphylaxis kit (which contains antihistamines, steroids and adrenaline). Prevention is the best strategy against anaphylaxis. Avoid the known allergen and always carry an anaphylaxis kit and EpiPen as well as informing family and friends of the allergy.

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38
Q

How is allergic rhinitis treated?

A

Allergic rhinitis is treated using anti-histamines which are effective at relieving sneezing, itching of eyes and nose, and rhinorrhea. A nasal steroid spray can help alleviate nasal blockage symptoms and cromoglycate can also be given as eye drops to alleviate eye symptoms.

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39
Q

How can eczema be treated?

A

Eczema is treated with emollients and topical steroid cream. Severe allergies can be treated with anti IL-5, IL-4 or IL-13 antibodies.

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40
Q

What are the different ‘steps’ in treating asthma?

A
  1. Mild forms of asthma treated with short acting β2 agonist such as salbutamol.
  2. More severe asthma may also require an inhaled steroid (low-moderate dose). This is often beclomethasone or fluticasone.
  3. If this is not sufficient, further therapy is added. This can be a long-acting β2 agonist with a leukotriene antagonist. A greater dose of steroid is also prescribed.
  4. If the asthma is very severe, a course of oral steroids such as prednisolone is prescribed. An anti-IgE antibody treatment can also be recommended.
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41
Q

How can immunotherapy be used to treat single-antigen allergies?

A

The antigen is purified and administered in increasing doses subcutaneously or sublingually.

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42
Q

Define autoimmunity

A

Autoimmunity is an adaptive immune response with specificity to self antigens

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43
Q

What hypersensitivity types are involved in allergy?

A

Type I and IV

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44
Q

What percentage of the population suffers from autoimmune disorders?

A

5%

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45
Q

What percentage of autoimmune patients are female?

A

75%

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46
Q

Why is the incidence of autoimmunity and hypersensitivity diseases increasing?

A

The hygiene hypothesis

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47
Q

What are the major autoimmune diseases?

A
  • Rheumatoid Arthritis
  • Type I Diabetes
  • Multiple Sclerosis
  • Systemic Lupus Erythematosus
  • Autoimmune thyroid disease
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48
Q

Describe the pathophysiology of Goodpasture’s Syndrome and Grave’s disease

A
  • Goodpasture’s Syndrome where antibodies are developed against type IV collagen in the basement membrane. Because this particularly affects the kidney, it causes glomerulonephritis. The antibodies in the basement membrane cause inflammation, neutrophil infiltration, and complement activation, causing damage to the nephron.
  • In Grave’s disease, anti-TSH receptor antibody binds to the TSH receptor, causing levels of T3 and T4 to rise in circulation. As the antibody can cause this effect irrespective to the pituitary, there is no negative feedback mechanism dampening this response.
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49
Q

Describe the major autoimmune disorder that causes disease through type III hypersensitivity

A

An example of type III reaction lead damage is in the case of Systemic Lupus Erythematosus (although may also contain elements of a type II reaction). Here autoantibodies are produced against DNA, histones, ribosomes, snRNP and scRNP. The antibodies bind to these components and deposit in various places depending on their size –> vasculitis, glomerulonephritis and arthritis.

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50
Q

Describe the notable autoimmune conditions that cause disease through type IV hypersensitivity

A

Notable autoimmune conditions characterised by type IV reactions include:

  • Type I Diabetes Mellitus where the autoantigen is on the pancreatic β-cells, causing β-cell destruction and insulin deficiency.
  • Rheumatoid arthritis where the autoantigen is an unknown synovial joint agent(s), leading to joint inflammation and destruction
  • Multiple Sclerosis where the autoantigen is myelin basic protein and proteolipid protein leading to demyelination, brain degeneration and eventually paralysis.
51
Q

What genes are the strongest genetic factor affecting susceptibility to autoimmune diseases?

A

HLA genes

52
Q

Define tolerance

A

Tolerance is the acquired inability to react to an antigen.

53
Q

What are the two major mechanisms used to achieve tolerance?

A
  • Central tolerance is the removal of problematic lymphocytes during development
  • Peripheral tolerance is the controlling of problematic cells that escaped the destruction during maturation.
54
Q

What are the ways in which peripheral tolerance takes place?

A
  • Anergy
  • Immune privilege
  • Active regulation
55
Q

Where does B-cell central tolerance take place?

A

Bone marrow

56
Q

Describe the process of B-cell central tolerance

A

Developing B-cell expresses IgM on surface:

  • If binds to self-antigen that cross-links the IgM receptors, it signals the cell to undergo apoptosis or to rearrange the receptor.
  • If binds to a small soluble self molecule it will become anergic, where it cannot react to antigen in the periphery and has a relatively short life.
  • If the B-cell binds in a low-affinity and non-cross-linking way to a self-molecule, it migrates to the periphery and becomes a clonally ignorant mature B-cell. These types of B-cells have the potential be auto-reactive if the antigen is in high concentration and under inflammatory conditions.
57
Q

Where does T-cell central tolerance take place?

A

Thymus

58
Q

What cells present self-peptides by MHC to the T-cells during T-cell maturation?

A
  • Thymic epithelial cells

- Dendritic cells

59
Q

Describe the process of T-cell central tolerance

A
  • Immature T-cells with TCRs (T-cell receptors) that cannot recognise the MHC peptide with antigen at all will die by apoptosis as it is useless if it cannot do so.
  • Immature T-cells that bind to the MHC peptide with antigen weakly will receive signal to survive (positive selection).
  • Immature T-cells that bind to the MHC peptide with antigen strongly will receive the signal to diet by apoptosis (negative selection).
60
Q

What percentages of thymocytes survive maturation?

A

5%

61
Q

What causes APECED?

A

APECED (Autoimmune PolyEndocrinopathy Candidiasis-Ectodermal Dystrophy) is a rare autoimmune disease which affects the endocrine glands. It occurs due to mutations in the AIRE (autoimmune regulatory gene) which is important in allowing the thymus to express genes from around the body. Therefore there is a failure in central immunity multiple autoimmune problems.

62
Q

What gene allows the thymic endothelial cells to produce peptides from all over the body?

A

AIRE

63
Q

When do T-cells become anergic?

A

Anergy is the refractory state resulting from antigenic stimulation under unusual conditions (absence of co-stimulation). Naïve T-cells require co-stimulation as well as antigen presentation before they become fully activated. The co-stimulatory molecules found in APCs are not present in most cells of the body. This leads to anergy instead of proliferation.

64
Q

Give an example of a condition of when immunological ignorance fails

A

sympathetic opthalmia where trauma in one eye releases antigens not previously seen. APCs take the antigens to the lymph node where it activates T-cells before they travel to the eyes and cause damage.

65
Q

What are the two types of T-regulatory cells?

A
  • Natural T-reg cells produced and developed as such in the thymus
  • Induced T-reg cells which are produced as part of the normal immune response against foreign antigen to dampen down response.
66
Q

What surface proteins do T-reg cells express?

A

CD4, CD25, CTLA-4 and FOXP3

67
Q

What disorder arrises from a mutation in the FOXP3 gene?

A

IPEX (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked inheritance syndrome) is a fatal recessive disorder due to the mutation of the FOXP3 gene leading to the accumulation of auto-reactive T-cells. Symptoms include early onset of diabetes, severe enteropathy, eczema, variable autoimmune phenomena, and severe infections.

68
Q

What infections have been associated with development of Lupus?

A

EBV and Measles

69
Q

What are the 6 ways in which infections can break peripheral tolerance and trigger autoimmune diseases

A
  • Molecular mimicry of self-molecules - if pathogen expresses a molecule that is similar in structure to self-molecule, then the immune response against the pathogen molecule can also react to self.
  • Infections can induce changes in the expression and recognition of self-proteins.
  • A pro-inflammatory environment provides the co-stimulation for lymphocyte activation, and up-regulate MHC Class II molecules on non-antigen-presenting cells.
  • Infection of Treg cells
  • Immune deviation: type of immune response can bias the immune response against self-antigens (shift in the immune response from Th1 to Th2).
  • Infections in immunologically privileged sites.
70
Q

When is the immune system’s role in tumour surveillance clinically relevant?

A

Paraneoplastic syndrome can be caused by cytokines released due to an immune response against the tumour.

71
Q

Why can breast cancer often lead to paraneoplastic cerebellar degradation?

A

The CDR2 proteins are normally expressed on Purkinje cells in the cerebellum. In some breast cancer patients, CDR2 antigen is ectopically presented on the breast tumour cells. This instigates a spontaneous humoral response against the tumour-expressed antigen, leading to an autoimmune neurological disease.

72
Q

What evidence do we have that tumour immunosurvailance can keep cancer down?

A
  1. Autopsies of accident victims shows that many adults have microcolonies of cancer cells, with no symptoms of the disease.
  2. Patients treated for melanoma, and after many years free of disease can be used for organ transplants. Transplant recipients have developed tumours.
73
Q

How would the immune system battle cancer?

A

Tumours express tumour-associated antigens.

  1. Cancer cell death causes release of cancer cell antigens
  2. Dendritic cells that are monitoring the tissues, engulf them and present the antigens on MHC class II molecules.
  3. They migrate to the lymph nodes, in search for a naïve T-cell.
  4. Activated effector T-cells migrate to the tumour site, where they infiltrate into the tumour
  5. They recognise and attempt to eliminate the cancer cells. This leads to cancer cell death and more release of antigens.
74
Q

Why is tumour development allowed by the immune system?

A

This is because the gradual accumulation of genetic mutations produces no inflammation and so is ignored by the immune system. Eventually, mutations occur which give the cell a growth advantage resulting in tumour growth. Eventually, after the tumour has reached a certain size, it induces inflammatory signals which attracts an immune response. However, at this stage the tumour is already established

75
Q

What are the requirements for an adaptive immune response to a tumour?

A

1) local inflammation in and surrounding tumour

2) Expression of tumour-associated antigens

76
Q

What are the problems preventing the immune system battling cancer?

A

1) takes a while for the tumour to cause inflammation. By the time it does, it is big and strong
2) Antigenic differences between normal and tumour cells can be very subtle.

77
Q

Give examples of tumour-specific antigens

A

Viral proteins:
- EBV proteins in transformed B-cells (causing lymphoma)
- HPV
Mutated Cellular proteins:
- TGF-beta is a receptor often mutated in colon cancer
- Bcr-Abl fusion protein in leukaemia

78
Q

What viruses cause cancer in immunosuppressed people?

A
  • Epstein-Barr causes B-cell lymphoma

- HHV8 causes Kaposi’s sarcoma

79
Q

What viruses cause cancer in immunocompetent people?

A
  • HTLV1 associated leukaemia/lymphoma
  • HepB and HepC virus in hepatocellular carcinoma
  • HPV positive genital tumours
80
Q

Why is the immune system’s response to viral-induced tumours is more effective than tumours which do not involve a virus?

A

they cause inflammation through by PAMPs

81
Q

How does HPV cause cervical cancer?

A

Cervical cancer is induced and maintained by E6 and E7 oncoproteins of the HPV virus, which do not have a role in its cell cycle. They affect cellular pathways involved in progression through the cell cycle and apoptosis.

82
Q

How does the HPV vaccine work?

A

It targets late-genes expressed by the HPV virus that are responsible for the viral particle. Therefore, the virus is unable to infect. This is used prophylactically.

83
Q

What are tumour associated antigens? And how are they different from tumour specific antigens?

A

Tumour-associated antigens are antigens from NORMAL CELLULAR PROTEINS to which the immune system isn not tolerant to.
Tumour-specific antigens can be viral antigens, or fusion/abberant gene products.

84
Q

Give examples of tumour associated antigens

A
  • Cancer-testes antigens are silent in normal adult tissues except in male germ cells (in an immune privileged site) and in the placenta. They are often expressed in tumours.
  • MAGE are melanoma-associated antigens, frequently expressed in melanomas and other tumours.
85
Q

Would p53 be a tumour specific or tumour associated antigen?

A

p53 is often mutated and overexpressed in many human cancer cells. p53 can be thought of as a tumour-associated antigen as it is over-expressed in tumours, as well as a tumour-specific antigen as in its mutated form it is specific to tumours.

86
Q

What are the major obstacles for T-cell mediated immunotherapy for cancer?

A
  1. Auto-immune responses against normal tissues. For example, many of the tumour-associated genes targeted in melanoma are also present on normal skin melanocytes. Induction of auto-immune CTLs for therapy of melanoma, also causes autoimmune destruction of melanocytes (vitiligo).
  2. Immunological tolerance such as normal tolerance to auto-antigens and tumour-induced tolerance. Central tolerance is the reason why our immune response to tumour-specific antigens are weak. As T-cells that would have bound strongly to those antigens, would have been removed.
87
Q

When is a transplant life-saving and when is it life-changing?

A

transplant is life-saving when it is vital for survival as there is no long-term replacement therapy (e.g lung, kidney, liver). While a transplant is life-changing when the organ is not vital, but improves the patient’s quality of life.

88
Q

What are the different types of transplantation?

A
  • Autografts are within the same individual (e.g heart bypass and reconstructive surgery)
  • Isografts are between genetically identical members of the same species
  • Allografts are between different individuals of the same species
  • Xenografts are between members of different species (e.g heart valves from pigs/cows)
  • Prosthetic grafts involve using plastic or metal etc.
89
Q

What type of tissue can allografts be?

A
  • Solid organs such as kidneys, liver, heart, lung, pancreas
  • Small bowel
  • Free cells such as bone marrow or pancreatic islet
  • Temporary cells such as blood, or skin cells
  • Privileged sites such as the cornea
  • Framework tissue such as bones, cartilage, tendons, nerves
  • Composite (several tissues present) such as hand transplants, face and larynx transplants.
90
Q

What are the types of donors for allografts?

A
  • Living

- Dead: DBD (Donor after Brain Death) or DCD (Donor after Cardiac Death)

91
Q

Describe the differences between DBD and DCD donations

A
  • DBD (Donor after Brain Death) is when their hearts are still beating, however have been confirmed brain dead. Organs can be harvested and cooled immediately to minimise ischaemic damage to the tissues. An advantage of DBD tissue is that it is perfused up until the point of harvesting.
  • DCD (Donor after Cardiac Death) – organs are not as high quality and this leads to delayed graft function after transplantation related to ischaemic acute tubular injury. However, it is still suitable for kidney transplants.
92
Q

What are the criteria for DBD donation

A

Understandably, there are stringent criteria for DBD harvesting. The brain damage must be of known cause. An apnoeic coma must not be due to depressant drugs, metabolic or endocrine disorders, hypothermia nor neuromuscular blockers. Furthermore, the physician must demonstrate a lack of brainstem function.

93
Q

What are the basic criteria for all donor tissue

A

donors must not have any viral infections, malignancy, drug abuse (overdose
or poison) or disease of the transplanted organ so the recipient is not at risk. The removed organs must be rapidly cooled and perfused.

94
Q

What is the maximum cold ischaemia time for kidney?

A

60 hours

95
Q

How long can the cornea be preserved for?

A

96h with cryopreservation

96
Q

What tissue can living donors donate?

A

Bone marrow, kidney and part of the liver.

97
Q

What is the average half-life of a donated kidney?

A

10 years (greater if from living donor)

98
Q

What is the difference between transplant selection and transplant allocation?

A

Transplant selection is access to the waiting list. Transplant allocation is access to the organ once it becomes available.

99
Q

What is the purpose of national guidelines in transplant allocation?

A

The national guidelines have been developed to ensure equity (fair distribution – taking into account imminent death, time on waiting list etc.) and efficacy (what is best use for the organ in terms of patient survival and graft survival).

100
Q

What authority regulates transplant allocation?

A

The NHS Blood and Transplant (NHSBT) body

101
Q

What factors are taken into account in deciding who should get a allograft from a DBD patient?

A
  • Distance between retrieval center and transplantation center.
  • Age matching of donor and recipient
  • Size matching between donor and recipient.
  • Sex matching between donor and recipient.
  • Tissue matching between donor and recipient (histocompatibility).
102
Q

What is the most important factor in allocating a:

  • kidney
  • heart
  • lung

to a patient?

A

Histocompatabililty is the most important for kidney

Size between donor and recipient is the most important in lung transplants

Distance between retrieval centre and transplantation is most important for heart transplants as cold ischaemia time is much lower.

103
Q

What organs are allocated using regional systems rather than national systems?

A 
DCD kidneys and livers.
DBD heart (unless kidney)
104
Q

What percentage of DCD donors go on to donate organs?

A

50%

105
Q

What is the main reason for why DCD donors do not go on to donate?

A

Family declining consent.

106
Q

What strategies can be employed to increase transplantation activity?

A
  • Using ‘marginal donors’ such as organs from elderly patients
  • Using more living donors, incorporating exchange programmes
  • Researching in xenotransplantation and stem cells.
107
Q

What are the two most relevant proteins in clinical transplantations?

A

ABO blood groups

HLA proteins

108
Q

Where are A and B glycoproteins found?

A
  • Blood cells

- Endothelial lining

109
Q

What happens if circulating antibodies bind to A or B glycoproteins?

A

Hyperacute rejection

  1. Complement activation will lead to complement mediated cell lysis and increased permeability
  2. This will allow rapid recruitment of other cells such as phagocytes
  3. Endothelial disruption will lead to platelet activation, inflammation and thrombosis organ becomes ischaemic and stops functioning.
110
Q

Where are HLA genes found?

A

Chromosome 6

111
Q

What are the most polymorphic MHC Class 1 isotopes?

A

HLA-A
HLA-B
HLA-C

112
Q

What are the most polymorphic MHC Class 2 isotopes?

A

HLA-DR

113
Q

What is the nature of HLA expression?

A

We have two alleles, they are expressed co-dominantly

114
Q

What are the 6 clinically relevant MHC molecules we worry about in histocompatability?

A

two allies of HLA-A, HLA-B, HLA-DR

115
Q

What is the best predictor of transplant outcome?

A

Number of mismatches in the HLAs between donor and patients

116
Q

Why are siblings a better choice than parents for organ donations

A

In finding organ donors, parents are not usually a good choice as only half of their alleles with match, and so will make a case of 3 mismatches. However, there is a 25% chance that a sibling has a 0 mismatch as well as a 25% the sibling will be a 6 mismatch (and 50% chance they will have 3 mismatches).

117
Q

What is graft rejection?

A

The immune reaction can cause graft damage and failure; the process is called rejection.

118
Q

What is the most common type of graft failure?

A

Rejection

119
Q

How is graft rejection diagnosed?

A

Graft biopsy

120
Q

What are the different rates of onset for graft rejection?

A

Hyperacute (for HBO), acute or chronic rejection.

121
Q

What are the clinical characteristics of rejection?

A
  • Deteriorating graft function – different markers and signs for different organs.
  • Pain and tenderness over the graft
  • Fever
  • Subclinical (no proper signs) and so biopsies must be performed to test for rejection.
122
Q

How can rejection be prevented?

A

We aim to prevent rejection by maximising HLA compatibility and administering life-long immunosuppressive drugs.

123
Q

Describe a standard immunosuppressive regime

A
  • Induction agent (T-cell depletion or cytokine blockade) given before transplantation to deplete immune cells.
  • Base-line immunosuppression: life-long combination of drugs (combat T cell activation in a number of ways is most effective at stopping the immune reaction)
  • Treatment of episodes of acute rejection:
124
Q

What are the risks associated with transplant immunosuppression?

A

patients are susceptible post-transplant infections:
• Increased risk for conventional infections
• Opportunistic infections which only affect immunosuppressed patients. These include CMV, BK Virus, and Pneumocytis carinii.

Patients are also more susceptible to post-transplant malignancies such as:
• Skin cancer
• Lymphoproliferative cancers (EPV driven)
• Others

Year 2 MCD 2 (5 decks)

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