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BoD > Autoimmunity and Hypersensitivity > Flashcards

Autoimmunity and Hypersensitivity Flashcards

1
Q

How common are autoimmune reactions

A

Mostly short-lived, self-resolving sequelae of infection. However in some 2-3%
of individuals the reaction is chronic, debilitating and even life-threatening.

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2
Q

What is autoimmunity considered to be generally

A

a failure of self tolerance

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3
Q

Describe the different types of molecule involved in an autoimmune reaction

A

Antibodies (autoantibodies) or T cells (autoimmune T cells) are
directed to antigens on target tissues, known as autoantige

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4
Q

What is an explanation for the increase in autoimmune conditions in developed countries

A

hygiene hypothesis:

immune system is no longer conditioned by early exposure to infection

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5
Q

What has decreased while autoimmunity has increased?

A

infections

such as measles, mumps and TB

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6
Q

What may cause autoimmunity

A

some autoimmune
conditions are caused by infectious organisms that have not been identified: the Cryptic Infection
hypothesis.

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7
Q

Name an autoimmune disease that is highly tissue specific

Name one that is systemic

A

Graves’ disease

SLE (lupus)

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8
Q

Name 2 autoimmune diseases that attack the thyroid

A

Graves’ disease

Hashimoto’s thyroiditis

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9
Q

What is pernicious anaemia

A

Lack of intrinsic factor due to autoimmune attack on parietal cells and a resulting lack of B12

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10
Q

Which autoimmune disease can target the following:
skin
kidney
joints

How can these diseases be considered

A

skin (scleroderma),
kidney (SLE)
joints (RA)

non-organ specific autoimmune diseases

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11
Q

How do the 3 general autoimmune mechanisms parallel hypersensitivity?

A

parallels Hypersensitivity types II, III and IV

no autoimmune diseases are IgE mediated like type 1 hypersensitivity

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12
Q

What is the autoantibody mediating Graves’ disease

A

anti-TSH receptor antibody

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13
Q

How does the antibody against the TSH receptor differ from TSH itself

A

antibody is not subject to the negative feedback on TSH, results in hyperthyroidism

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14
Q

why is Graves’ disease considered a Th2 type response

A

there is little inflammation or lymphocyte infiltration

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15
Q

What type of autoimmune response is Hashimoto’s thyroiditis

A

Th1 - lymphocytes invade the organ

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16
Q

How does Hashimoto’s thyroiditis affect the thyroid

A

lymphocytes infiltrate the
organ. Nevertheless, antibodies are generated
which block hormone production, causing
hypothyroidism

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17
Q

Which of the following result in a goiter
Graves’ disease
Hashimoto’s Thyroiditis

A

both

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18
Q

What happens in myasthenia gravis

A 
autoantibodies to the
AChR diminish
neuromuscular transmission from
cholinergic neurons by blocking
the binding of ACh and by
causing downregulation
(degradation) of its receptor
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19
Q

Name an autoimmune disease caused by direct tissue pathology following antibody binding

A

rheumatic fever

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20
Q

How can immune complexes be cleared

A

complement binding on the complex to the complement receptor on RBCs

RBCs carry bound complex to liver and spleen where they are phagocytosed

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21
Q

Name 2 diseases that are caused by autoantibody-antigen complexes

A

SLE

Vasculitis

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22
Q

Which organ is particularly sensitive to immune complex deposition

A

kidney

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23
Q

What happens in SLE

A

systemic lupus erythematosus

patients have a wide variety of anti-cytoplasmic and anti-nuclear
auto-antibodies

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24
Q

Visible sign of SLE

A

butterfly/ wolf rash on face

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25
Q

Who is SLE more common in

A

African and Asian women

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26
Q

What is a predisposing factor for LSE

A

, complement deficiencies that impair immune
clearance, such as C1, C2, C4

there is often a complement depletion in SLE patients

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27
Q

What is the autoimmune mechanism behind T1D and MS

A

T cell mediated

T cell mediated damage leads to tissue destruction without requiring the production of
autoantibody

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28
Q

What are the different mechanisms of T cell mediated autoimmunity

A

cytotoxicity by CD8 T cells;

direct destruction by TNF;

recruitment of
macrophages and subsequent bystander killing;

induction of apoptosis by Fas Ligand.

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29
Q

What % of the population suffer RA

How is this changing

A

3%

decreasing as more people give up smoking

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30
Q

What is EAE

A

a model of MS

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31
Q

How can we show that MS can be transferred with T cells using EAE

A

The rat is immunised with myelin basic protein (MBP) in complete Freund’s adjuvant.

CD4+ T cells specific to MBP are isolated and can subsequently cause disease if injected into another animal.

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32
Q

What are most autoimmune diseases associated with genetically

A

one or more HLA allotype

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33
Q

Are the HLA allotypes associated with autoimmune diseases ‘mutant alleles’

A

no they are polymorphic variants in the normal populations

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34
Q

Give a good way to express the way allotypes influence disease

A

Relative Risk

in comparison with HLADQ6-ve people, HLA-DQ6+ves are 12 times more likely to develop multiple sclerosis. But HLA-DQ6 is
common in normal healthy individuals. Conversely, not all patients who develop the disease have this
allotype and only a fraction of DQ6+ves will succumb

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35
Q

What is a common haplotype in caucasian populations that is associated with T1D, SLE, Graves’ disease and myasthenia gravis

A

A1-B8-DR3-

DQ2.

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36
Q

What position on the MHC molecule plays a major role in T1D

A

position 57 in the HLA-DQβ

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37
Q

What does the different HLA types being associated with different autoimmune diseases reflect

A

binding of different peptides to the grooves of HLA

For example, a residue at position 57 of the beta chain of HLA-DQ is protective if charged
(aspartate) but not if hydrophobic, reflecting binding of different diabetogenic peptides

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38
Q

True or false:
T1D only involves 1 genetic locus

What is this referred to

What other disease can be placed in this categry

A

false
multiple loci are involved

multigenic disorders

rheumatoid arthritis

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39
Q

How does incidence of autoimmunity differ between sexes? Give specific examples (4)

A

e Grave’s
and Hashimoto’s are 4-5 times, and SLE 10 times, more common in females.

Ankylosing Spondylitis is 3-4
more frequent in males.

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40
Q

What is the twin concordance rate for common autoimmune diseases eg T1D and RA

A

20-40%

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41
Q

Give examples of autoimmune diseases being directly caused by infection

A

rheumatic fever can follow Streptococcal
infection;

reactive arthritis after Yersinia, Shigella or
Chlamydia.

Non-specific infection is known to cause a flare-up of MS

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42
Q

How much are environmental factors thought to contribute to T1D

Break this down

A

50%

The MHC contributes about 25% and the other
25% comprises a variety of other genes.

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43
Q

Describe how release of a sequestered antigen can result in autoimmunity, using an example to demonstrate

A

In the case of autoimmune sympathetic ophthalmia, damage to one eye leads to subsequent
autoimmune attack of the contralateral eye.

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44
Q

How can T cell tolerance be bypassed

A

modification - generation of neoantigens recognized by T cells

this results in breaking of tolerance to a self antigen

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45
Q

Give an example of modification allowing bypassing of T cell tolerance

A

e.g. by modification of proteins, such as

citrullination, by environmental factors, such as smoking

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46
Q

Why is coeliac not strictly an autoimmune disease

A

it is dependent on eating gluten

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47
Q

What does coeliac disease involve presentation of

A

deamidated gliadin peptides by specific HLA-DQ molecules

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48
Q

True or false

Rheumatoid arthritis may involve protein modification

A

true
protein citrullination by peptidylarginine deiminase.

Initially, occurs in the lung (there is a strong link between RA and smoking). Antibodies to the modified proteins: ACPA (anti-citrullinated protein antibodies) are present in most patients with RA.

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49
Q

How can gum infection lead to autoimmunity

A

periodontitis

Infection of teeth and gums with P. gingivalis can result in citrullination of epitopes which again result in ACPA

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50
Q

What do both periodontitis and RA have in common

A

both involve bone erosion

both have risk factors involving smoking and ageing

periodontitis often precedes RA

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51
Q

What are the 2 distinct types of animal models

A

spontaneous

induced

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52
Q

Describe spontaneous autoimmune disease models

A

They exist as a result of deliberate inbreeding of strains of animals
for particular characteristics including the incidence of autoimmune disease.

Such inbred strains are therefore
genetically susceptible and spontaneously develop disease

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53
Q

Give an example of spontaneous autoimmune disease models

A

the non-obese diabetic

(NOD) mouse

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54
Q

Describe induced autoimmune disease models

A

require some treatment of the animal to trigger the disease. They also generally require the presence of some genetic susceptibility factors

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55
Q

How can you induce MS in mice

A

inject mouse with spinal chord extract and powerful adjuvants will trigger an autoimmune encephalomyelitis (EAE) but only
in a few inbred strains. This disease resembles multiple sclerosis, as introduced above in the T cell transfer
experiment in rats.

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56
Q

Describe the non obese diabetic mouse

A

a spontaneous T1D model,

The islets of these mice are infiltrated
with T cells and macrophages, with associated cytokine release and production of autoantibodies that could kill cells by ADCC

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57
Q

What do the immune mechanisms in NOD mice lead to

A

abnormalities in glucose metabolism and

ketoacidosis, a breakdown product of fat

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58
Q

What happens if you switch bone marrow cells between NOD and normal mice

A

induces T1D in normal mouse

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59
Q

How were Tregs implicated in protection against T1D

A

n using the NOD model as it was
demonstrated, using GFP-tagged FoxP3, that this transcription factor was key in
controlling the development of regulatory T cells and thus the disease.

60
Q

Can the immune system return to a tolerised state

A

yes a number of induced autoimmune diseases resolve themselves

61
Q

Treatment against autoimmune conditions is usually ineffective except in which case?

A

organ specific cases s where specific

agents can be used to exert metabolic control, such as thyroxine for hypothyroidism

62
Q

What is the blunt tool to use to treat autoimmunity

A

immunosuppressive drugs

63
Q

Describe a promising new treatment for RA

A

Blocking reagents such as anti-TNF antibodies or soluble receptor

64
Q

Why is the Th1/Th2 paradigm useful for thinking about autoimmunity?

A

in some cases a predominantly cytotoxic response

is required and in others emphasis is more on antibody production.

65
Q

Other than Th1/2 what other Th is involved in autoimmunity

A

Th17

66
Q

What is a useful method to identify different subsets of T cells

A

staining for the associated transcription factors

67
Q

What does Th2 make

Whhat does this drive

A

IL-4

M2 macrophages production

68
Q

When do Th17 cells function primarily

What do they do

A

used in anti microbial immunity at epithelial barriers

promote recruitment of neutrophils to sites of bacterial and fungal infection

69
Q

What do Tfh cells do

A

localise in
B cell follicles and activate B cells.

responsible for Ab development, isotype switching and affinity maturation

70
Q

What is the issue with immunosuppressants?

Name some immunosuppressive agents

A

long term use has unwanted side effects

cyclosporin and rapamycin

71
Q

What are cyclosporin and rapamycin

A

potent inhibitors of T cell activation

72
Q

Why is blocking TNF alpha considered anti-inflammatory

A

TNFα is generally produced by innate

immune cells

73
Q

What is CTLA4-Ig?

What does it do?

What is it approved for treatment for?

A

a fusion protein which binds CD80 and CD86 with high affinity,

prevents co-stimulation of
T cells via CD28

RA

74
Q

What is hypersensitivity

A

to immune responses that are damaging rather than helpful to the host. In
other words, these are over-reactions of the immune system.

75
Q

How many types of hypersensitivity are there

A

4:
3 Ab mediated
1 T cell mediated

76
Q

Which hypersensitivity uderlie rapid allergic reactions

A

type 1

77
Q

Name 3 kinds of type 1 hypersensitivity

A

hayfever
eczema
asthma

78
Q

what is allergic rhinitis

A

hay fever - a type 1 hypersensitive reaction to pollen

79
Q

What is the cause of a type 1 hypersensitive reaction

A

contact with antigen to which the host has pre-existing IgE and a Th2 type response is elicited

80
Q

What happens after an allergen is detected in type 1 sensitivity
Give 3 stages

A

mast cells are activated by cross linking of FcεRI via antigen binding to the bound IgE molecule

mast cells release serotonin and histamine

six hours later, secondary inflammatory mediators are released in the later response

81
Q

What are the different categories of allergens in involved in Type 1 hypersensitivity

Give examples of each

A

Pollens: birch tree/ragweed/oil seed rape
Foods: nuts/eggs/seafood
Drugs: penicillin/aspirin
Insect products: bee venom/house dust mite
Animal hair: cat hair and dander.

82
Q

What distinguishes allergens which stimulate strong IgE responses from other antigens? (4)

A

no single common factor
often proteases
low MW
highly soluble (so diffuse readily into mucus)
generally stable and can survive as a desiccated particle

83
Q

Can allergens which stimulate a type 1 hypersensitive response activate T cells

A

yes - they contain peptides that bind MHC Class II to prime t cells
the low dose encountered favours IL-4 producing, Th2 response

BUT REMEBER TPE 1 IS IgE MEDIATED (NOT T CELL MEDIATED)

84
Q

How can you diagnose a type 1 hypersensitivity to an allergen

A

wheal and flare test

prick patient’s skin with the allergen and wait for a reaction

85
Q

Describe the wheal and flare test

A

prick patient’s skin with suspected allergen
if they’re allergic, ‘wheal and flare’ reaction appears at the site of infection within a few minutes.

wheal= swelling (edema)

subsequent redness (flare or erythema) = from increased blood flow.

After 6 hours there may be a late-phase reaction where the swelling spreads to involve the surrounding tissue.

86
Q

How common is type 1 hypersensitivity

A

30% of some populations

87
Q

is there a genetic component to type 1 hypersensitivity

A

Having two susceptible

parents doubles the risk of an affected child, indicating a genetic component

88
Q

How can you recognise a child who atopic to type 1 hypersensitivity

A

have serum IgE raised 10-100 times the usual level

89
Q

Is there a selective advantage to having type 1 hypersensitivity

A

increased protection against parasites (common in tropical countries)

90
Q

When can extreme type 1 hypersensitive reactions occur

What can result

A

if the antigen is directly injected into the blood
stream.

In systemic anaphylaxis the increased permeability of blood vessels results in extreme drop in blood
pressure and anaphylactic shock, which can be fatal

91
Q

What is the difference between systemic anaphylaxis and anaphylactic shock

A

In systemic anaphylaxis the increased permeability of blood vessels results in extreme drop in blood
pressure and anaphylactic shock, which can be fatal

92
Q

How can you treat type 1 hypersensitivity

A

identification and avoidance of the
antigen;

antihistamine and corticosteroids, which suppress leukocyte function.

In some cases,
desensitisation may be achieved by gradual exposure to increased dose of antigen, to convert Th2 to Th1
and/or iTreg responses.

93
Q

Which immune cells are involved in asthma (5)

A

increased TH2

lymphocytes, eosinophils, neutrophils and basophils, which amplify inflammation and airway remodeling.

94
Q

Name some genetic susceptibility loci implicated in asthma (5)

A

HLA class II,

TCR

genes which affect the TH1/TH2 balance

genes which affect IgE receptor and cytokines eg IL-4

effects of non-immune genes such as those influencing smooth muscle cell behavior, bronchial
physiology and tissue repair

95
Q

How can you induce asthma in mice genetically

A

. Mice lacking the T-Bet transcription factor, which drives T cells to differentiate into TH1 cells, and suppresses the TH2 pathway, have increased levels of IL-4, IL-5 and IL-13 cytokines and have a disease similar to human asthma

96
Q

True or false
the skin prick test cannot be used to test if an asthmatic person is allergic to a certain allergen because asthma is not a type 1 hypersensitivity

A

false

asthma IS type 1 hypersensitivity

skin prick test is unsuitable so a breathing exhalation rate is tested after exposure to inhaled antigen

97
Q

Describe the reaction an asthmatic person would have after inhaling an allergen

A

acute constriction of bronchial smooth muscle in an attempt to expel the antigen (lasts an hour)

late response after 6 hours - more damaging and if the antigen persists, asthma becomes chronic and re-exposure to antigen can trigger further attacks

98
Q

Describe the cell mediators underlying each stage of the asthmatic reaction following inhalation of the allergen

A 
a) immediate bronchial constriction:
due to
degranulation of mast cells in the
respiratory tract, armed with allergen-specific IgE. 
Ends after an hour

b) late response follows after
about 6 hours, due to leukotrienes and
other inflammatory mediators. This phase is most damaging and leads to recruitment of eosinophils and TH2
lymphocytes.
If the antigen persists the condition may become chronic, whereby allergen-specific TH2 cells
promote further IgE production and recruitment of eosinophils and neutrophils.
The condition may deteriorate and the airways become occluded by mucus plugs. Re-exposure to antigen can trigger further attacks

99
Q

How can asthma be exacerbated

A

by bacterial and viral infections, dominated by TH2 cells and a type IV
hypersensitivity response

100
Q

What is type 2 hypersensitivity

A

IgM / IgG mediated
tends to lead to destruction of RBCs (hemolytic anemia) or platelets
(thrombocytopenia)

101
Q

Give an example of type 2 hypersensitivity

A

uncommon side effect of penicillin

drug binds to self cell surface and is a target for Igs
cell-bound antibody triggers clearance of the cell by tissue macrophages in the spleen, which
bear Fcγ receptors, or by complement lysis.

102
Q

What hypersensitivity is blood grouping related to

A

type 2

103
Q

Why is the ABO blood group special

A 
it is the only histocompatibility alloantigen for which pre-existing antibody is present in naïve,
previously untransplanted (untransfused) recipients.
104
Q

Explain the ABO blood grouping

A 
RBC surface molecules consist of a core H antigen
The O (null) allele is unmodified H antigen

Sugars may be attached to this core:

The A allele adds a terminal N-acetylgalactosamine

The B allele adds a terminal galactose

AB indicates both modifications

105
Q

What are the ABO phenotype frequencies in European Caucasoid populations

A

O - 45%
A - 40 %
B - 11 %
AB - 4 %

106
Q

What kind of hypersensitivity is Rhesus reaction

A

type 2

107
Q

What is hemolytic disease of the newborn

A

Rhesus reaction

108
Q

How does the hemolytic disease of the newborn come about

A

If the mother is Rhesus negative and the child
is Rhesus positive the mother can produce antibodies to the Rhesus antigen. This happens because some Rh+ cells leak into the maternal circulation at birth. The IgG can cross the placenta and compromise the
subsequent Rh+ baby.

109
Q

How can the rhesus reaction be circumvented

A

by giving anti-Rh antibody (RhoGam) to the mother before she reacts to her child’s red blood cells. The antibody crosslinking to FcgRIIB receptor prevents activation of naïve B cells

110
Q

What is type III hypersensitivity

A

inability to clear immune complexes

IgG mediated

111
Q

What differentiates a hypersensitive response from IgE to IgG mediated

A

IgG hypersensitivity reactions occur when the antigen is soluble and in high quantities

low levels
tend to produce IgE responses

112
Q

Describe the process involved in type 3 hypersensitivity

A

individual exposed to soluble allergen in high quantity

IgG produced

Immune complexes formed and deposited in tissue

mast cells triggered via FcgRIII receptor

activation of complement and polymorphs -> local tissue damage and inflammation

113
Q

What are common examples of type III hypersensitivity reactions

A

post-infection complications such as arthritis and glomerulonephritis

114
Q

What is the Arthus reaction

A

a local type III
hypersensitivity reaction. This can be triggered in the skin of sensitized individuals who have IgG against the sensitising antigen

115
Q

Name 2 examples of type III hypersensitivity reaction where the allergen is inhaled

A

pigeon fancier’s lung or farmer’s lung

116
Q

What is serum sickness

A

a transient immune complex mediated syndrome caused by injecting horse serum (passive immunisation)

117
Q

Why could serum sickness result after being treated for pneumonia

A

horse serum which was immune to pneumonia is injected to treat the patient’s pneumonia

this leads to type III hypersensitivity

118
Q

What is delayed type hypersensitivity

A

type IV sensitivity
t cell mediated

memory t cells release cytokines that recruit and activate macrophages

119
Q

When is the maximal type IV hypersensitivity reaction

A

48-72 hours after exposure

120
Q

How much antigen is required for t celll mediated hypersensitivity compared to the other types

A

Requires MUCH more antigen (10-100x) than for Ab mediated hypersensitivity

121
Q

What kind of reaction is poison ivy implicated in

A

hapten=Urushiol – passes through endothelial layers ad taken up by a dendritic cell which uses MHCII to expose the antigen to a naïve T cell

Naïve T cell’s CD28 binds to the dendritic B7, promoting IL-12 release which makes T cell mature. Mature T cell produces. Mature T cells encourage a pro-inflammatory response, leading to dermatitis

122
Q

What is a hapten

A

a small molecule which, when combined with a larger carrier such as a protein, can elicit the production of antibodies which bind specifically to it (in the free or combined state).

123
Q

Which Th cells are involved in type IV hypersensitivity

A

Often TH1 – IV orchestrated by cytokines from TH1 CD4 cells (including TNFα IFNγ and IL-3) the recruited macrophages present antigen to T cells to amplify response

124
Q

What are contact sensitivities

Give examples

A

Cutaneous responses to haptens, which form stable complexes with host proteins.

type IV hypersensitvity

For example, poison ivy, metal salts and small reactive chemicals.

125
Q

What is Abacavir sensitivity syndrome

A 
a T cell mediated drug hypersensitivity that occurs in
individuals possessing the HLA class I allele HLA-B*57
126
Q

In humans, the situations when allogeneic cells come into contact are either:

A

Iatrogenic (effects of medical treatment), such as blood transfusion, or
Natural, such as pregnancy in placental mammals

127
Q

What is the main problem with transplantation

A

most cells express polymorphic surface

antigens encoded by the MHC.

128
Q

What are the 4 possible relationships between transplanted donor material and the recipient

A

autologous
syngeneic
allogenic
xenogenic

129
Q

What is the most common type of transplant

What does it display

A

allogenic

immunological memory

130
Q

How is the immune system primed in transplantation

A

by the allograft upon first encounter with the antigen

131
Q

What happens if a recipient that has previously rejected a
skin graft is regrafted with skin from the same donor

What happens if a graft from a third party is added

A

the graft is rejected more rapidly in a second set reaction

3rd party graft will be rejected the same as for the 1st set reaction

132
Q

How do we know second set reactions in transplantation is caused by a memory immune response from clonally expanded and primed T cells specific for the donor skin?

A

The rapid second set rejection course can be transferred to normal or irradiated recipients by T cells from the
original recipient

133
Q

Why is the second set reaction in transplant rejection faster?

A

Memory T cells are produced alongside
effector T cells in a primary immune response.

Upon a second exposure to the same antigens memory T cells promote a more rapid, more effective response.

This is because memory T cells to a specific antigen are
more numerous than naïve T cells and they are more readily activated.

134
Q

Which cells are important in recognition of transplants

A

A central role for recognition of transplanted tissue is played by T cells but other cells may be involved
in rejection, including NK. However, in some cases antibodies are important, although their production may be
initiated by T cells.

135
Q

How can T cells recognize antigens on transplanted tissue

A

through direct recognition of the donor MHC or indirect recognition, of
an antigen presented by self MHC molecules.

136
Q

What are the 3 types of rejection following an allotransplant

A
  1. Hyperacute rejection
  2. Acute rejection
  3. Chronic rejection
137
Q

What are hyperacute rejections

A

occurs very rapidly, within minutes or a few hours. It results from pre-existing
antibody, such as in ABO incompatible transplants

138
Q

Give 3 examples of hyperacute rejection occurring

What type of Ab is involved in all of these

A

y:
1. From previous organ transplants (e.g. children who have multiple transplants)
2. From pregnancy – at childbirth fetal cells enter maternal circulation and stimulate adaptive
response to paternal HLA
3. From blood transfusion (matched for ABO but not HLA)

anti-HLA

139
Q

Why are tissues rejected rapidly in hyperacute rejection

A

ABO and HLA antigens are expressed on the endothelial cells lining blood vessels

140
Q

How is the tissue damaged in hyperacute rejection

A

by complement activation, coagulation and leakage of fluids, as well as
by aggregation of platelets that block the microvasculature

141
Q

What is the issue facing companies who hope to use pig organs to transplant into humans

What are the problems that need to be overcome

A

Hyperacute rejection also takes place in Xenotransplants

First, we make
natural IgM and IgG antibody to modified sugars on pig tissue. These transplants are said to be discordant.
Second, complement does not function well across species. Normally complement is disabled on self tissues by the action of regulatory proteins such as decay accelerating factor (DAF). This does not work on pig
tissue and the graft is attacked by the human complement.

142
Q

What is the main immunological barrier to allotransplantation

A

acute graft rejection

143
Q

What is acute graft rejection caused by

What can it be compared to

A

T cell recognition of the transplanted tissue.

Acute rejection can be thought of as a type of Type IV hypersensitivity reaction as it involves the response of CD8 T cells to HLA class I differences and CD4 T cells to HLA class II differences.

144
Q

Why does blood transfusion not result in acute graft rejection

A

RBCs do not carry MHC antigens

145
Q

Why does the polymorphic nature of the MHC genetic region make transplants problematic

A

and it is highly polymorphic. In
spite of attempts at matching, most organ transplants are
performed across some HLA class I and/or class II
differences. The recipient’s naïve T cell population contains
clones of so-called alloreactive T cells that recognise HLA
allotypes that are not shared with the recipient. Some of
these clones are of the memory type and were initially
stimulated and expanded in response to pathogens but
cross-react with allogeneic HLA

BoD (11 decks)

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