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Flashcards in Immunology Deck (280):
1

What are the 4 hallmarks of immune deficiency?

SPUR
Serious infections
Persistent infections
Unusual infections
Recurrent infections

2

what defines a serious infection?

unresponsive to oral antibiotics

3

what defines persistent infections?

early structural damage
chronic infections

4

what defines unusual infections?

unusual organisms
unusual sites

5

what defines recurrent infections?

two major or one major + recurrent minor infections in one year

6

what 6 features apart from SPURS may be surggestive of primary immune deficiency?

weight loss/ failure to thrive
severe skin rash
chronic diarrhoea
mouth ulceration
unusual autoimmune disease
family history

7

what 2 important infections lead to secondary immune deficiency?

HIV
measels

8

what 3 important treatment interventions lead to secondary immune deficiency?

immunosuppressive therapy
anti-cancer agents
corticosteriods

9

what type of malignancies can lead to secondary immune deficiency?

cancer of the immune system (lymphoma, myeloma, leukemia)
metastatic tumours

10

what biochemical/nutritional disorders can lead to secondary immune deficiency?

malnutrition
diabetes (Type 1 and 2)
dialysis

11

what is a major feature of phagocyte deficiencies?

recurrent infections
(which can affect either common or unusual sites)

12

what are the types of organisms typically infect patients with phagocyte deficiencies?

common bacteria (eg Staph sureus)
unusual bacteria (eg Burkholderia cepacia)
Mycobateria (TB and atypicals)
Fungi (candida, aspergillus)

13

what is the general life cycle of a phagocyte? (ie neutrophil

1. mobilisation of phagocytes and precursos from bone marrow or within tissues
2. upregulation of endothelial adhesion markers causing neutrophil adhesion and migration into tissues
3. phagocytosis and killing of organism
4. activation of other components of the immune system

14

what are the 2 reasons that can cause the failure of neutrophil production?
(and therefore neutropaenia and phacogyte deficiency)

failure of stem cells to differentiate along myeloid lineage
specific failure of neutrophil maturation

15

what is reticular dysgensis?

the failure of stem cells to differentiate along myeloid and lymphoid lineages. megakaryocyte-erythroid lineage is unaffected. most severe form of severe combined immunodeficiency (SCID)

16

when can the secondary defect which causes the failure of stem cells to differentiate along the myeloid lineage occur?

after stem cell transplantation

17

what are the 2 congenital causes of specific failure of neutrophil maturation? (and therefore cause neutropaenia)

Kostmanns syndrome
Cyclic neutropaenia

18

what is Kostmanns syndrome?

rare autosomal recessive disorder causing the specific failure of neutrophil maturation- leads to severe chronic neutropaenia

19

what is Cyclic Neutropaenia?

episodic neutropaenia every 4-6 weeks caused by the specific failure of neutrophil maturation

20

when do patients with Kostmanns syndrome usually present with recurrent infections?

within 2 weeks after birth

21

what is the supportive treatment of Kostmanns syndrome?

prophylactic antibiotics
prophylactic antifungals

22

what is the definitive treatment of Kostmanss syndrome?

stem cell transplantation
Granulocyte colony stimulating factor (G-CSF)

23

what is granulocyte colony stimulating factor (G-CSF)?

a growth factor which assists maturation of neutrophils

24

what rare, primary immunodeficiency is caused by the genetic defect in leukocyte integrins?

leukocyte adhesion deficiency

25

what does leukocyte adhesion deficiency result in?

failure of neutrophil adhesion and migration

26

what is the general clinical picture of leukocyte adhesion deficiency?

marked leukocytosis but with localised bacterial infections that are difficult to detect

27

what 2 receptors do phagocytes possess that bind to opsinons?

Fc receptors (for antibody Fc)
Complement receptor 1 (CR1- for binding to complement which are bound to the antigen)

28

what 2 defect can cause decreased efficiency of opsonisation? (and therefore a phagocyte deficiency)

defect of complement/antibody production
defect in opsonin receptor

29

what is chronic granulomatous disease?

a phagocyte deficiency due to failure of oxidative killing mechanisms

30

in chronic granulomatous disease what causes the failure of oxidative killing mechanisms?

inability to generate oxygen free radicals and so impaired killing of intracellular organisms

31

why are granulomas formed in chronic granulomatous disease?

inability to clear organisms leads to excessive inflammation and persistent accumulation of neutrophils, activated macrophages and lymphocytes. all leading to a granuloma

32

in chronic granulomatous disease what features would you find on an full abdominal exam?

lymphadenopathy
hepatosplenomegaly

33

how do you investigate chronic granulomatous disease?

NBT test
(nitroblue tetrazolium)

34

how does a NBT test work?

you feed patients neutrophils a source of E-coli
add a dye sensitive to H202
if hydrogen peroxide is produced by neutrophils (meaning oxidative killing is function) the dye will change colour showing patient doesn't have chronic granulomatous disease

35

what is the supportive treatment for chronic granulomatous disease?

prophylactic antibiotics
prophylactic antifungals

36

what type of cells do mycobacteria reside within?

macrophages

37

what network is activated when a macrophage becomes infected with mycobacteria?

IL12-gIFN network

38

what are the 6 steps in the IL12-gIFN network?

1. infected macrophages stimulated to produce IL 12
2. IL 12 induces T cells to secrete gIFN
3. gIFN feeds back to macrophages and neutrophils
4. stimulation of TNF within the infected macrophage
5. activation of NADPH oxidase within the macrophage
6. TNF and NADPH oxidase stimulate oxidative pathways

39

what is the definitive treatment for chronic granulomatous disease?

stem cell transplantation
(gene therapy)
gIFN therapy

40

what 3 single gene defects are associated with suscpetibility to intracellular bacteria such as mycobacteria infection and salmonella?

gIFN receptor deficiency
IL 12 deficiency
IL 12 receptor deficiency

41

what can happen when anti-TNF drugs are used in the treatment of inflammatory diseases?

reactivation of latent intracellular bacteria such as tuberculosis

42

compare congenital neutropaenia, leukocyte adhesion deficiency and chronic granulomatous disease with regards to neutrophil count?

conginital neutropaenia: absent
leukocyte adhesion defect: increased during infection
chronic granulomatous: normal

43

compare congenital neutropaenia, leukocyte adhesion deficiency and chronic granulomatous disease with regards to the ability to form pus?

congenital neutropaenia- no
leukocyte adhesion defect- no
chronic granulomatous- yes

44

compare congenital neutropaenia, leukocyte adhesion deficiency and chronic granulomatous disease with regards to leukocyte adhesion markers?

congenital neutropaenia- normal
leukocyte adhesion defect- abnormal
chronic granulomatous- normal

45

compare congenital neutropaenia, leukocyte adhesion deficiency and chronic granulomatous disease with regards to oxidative killing?

congenital neutropaenia- absent
leukocyte adhesion defect- normal
chronic granulomatous- absent

46

how is reticular dysgenesis treated?

fatal unless corrected with bone marrow transplantation

47

what is severe combined immunodeficiency?

failure of lymphocyte production (failure of lymphocyte precursors)

48

what are the 6 typical features of a child with severe combined immunodeficiency?

unwell by 3 months of age
persistent diarrhoea
failure to thrive
infections of all types
unusual skin disease
family history of early infant death

49

what is the unusual skin disease usually present in a child with severe combined immunodeficiency?

graft versus host disease
caused by colonisation of the infants empty bone marrow by maternal lymphocytes

50

what is the period of time called where even normal babies get infections (3-4 months) if there immune system is slow to mature?

transient hypogammaglobulinaemia of infancy

51

how long does maternal IgG protect any neonate?

3 months

52

what is the most common form of severe combined immunodeficiency?

X-linked SCID

53

what is the mutation in X-linked SCID?

mutation of component of IL 2 receptor
(IL2 is very important for T cell development

54

what are the levels of T and B cells in a child with SCID?

very low or absent T cells
normal or increased B cells (but poor response)

55

why do children with SCID have poorly developed lymphoid tissue and thymus?

not being stimulated by T cells

56

what is the prophylactic treatment of children with SCID?

hospitalised
avoid infections (prophylactic antibiotics, fungals, no vaccines)
aggressive treatment of existing infections
antibody replacement- IV Ig

57

what is the definitive treatment options of a child with SCID?

Stem cell transplant from HLA identical sibling if possible
Stem cell transplant from other sibling or parent of from matched unrelated donor

58

What causes DiGeorges syndrome?

deletion of chromosome 22q11

59

what is the phenotype of a child with DiGeorge syndrome? (5 things)

Congenital heart defects
Abnormal facial features
Thymic hypoplasia
Cleft palate
Hypocalcaemia (due to hypoparathyroidism)

60

why is there a T cell deficiency in DiGeorges syndrome?

failure of thymic deveopment (nowhere for the T cells to mature)

61

what are the B cell, T cell and NK cell count like in DiGeorges Syndrome?

absent or very low T cells
normal or increased B cells (but poor response)
Normal NK cells

62

what is the management of DiGeorge Syndrome?

correct metabolic/cardiac abnormalities
prophylactic antibodies
early and aggressive treatment of infection
Ig replacement

63

why does T cell function improve with age in patients with DiGeorge syndrome?

extrathymic maturation of T cells

64

what type of disease happens when there is failure of normal apoptosis?

autoimmune syndromes

65

what are the 3 first line investigations of T cell deficiencies?

total white cell count differential
serum immunoglobulins and protein electrophoresis
quantitation of lymphocye subpopulation

66

what second line test is essential in investigating a T cell deficiency?

HIV test

67

what is the cause of Bruton's X linked hypogammaglobulinaemia?

failure to produce mature B cells

68

what are the B cell levels like in Bruton's X-linked hypogammaglobulinaemia?

no circulating B cells
no plasma calls
(no circulating antibody after first 6 months)

69

what is the name of the genetic condition in which IgM B cells can't differentiate into IgA cells?

selective IgA deficiency

70

what are the symptoms of IgA deficiency?

2/3 asymp
1/3 recurrent respiratory tract infections

71

what is the name of the genetic condition in which there is low IgG, IgA and IgE?

common variable immune deficiency

72

what is the name of the genetic condition in which there is a failure of T cell co-stimulation of B-lymphocytes?

X-linked hyper IgM syndrome

73

what are the 3 main features of B cell deficiencies?

recurrent infections
opportunistic infections
antibody-mediated autoimmune disease

74

what are the 1st line investigations if there is a suspected B cell deficiency?

total white cell count and differential
serum immunoglobulins
serum and urine protein electrophoresis

75

how do you manage a B cell deficiency?

aggressive treatment of infection
immunoglobulin replacement
stem cell transplantation

76

what is a hypersensitivity reaction?

immune response that results in bystander damage to the self

77

what are the 4 types of hypersensitivity reactions?

Type 1: immediate hypersensitivity
Type 2: direct cell killing
Type 3: immune complex mediated
Type 4: delayed type hypersensitivity

78

what type of hypersensitivity reaction is an allergic disease?

type 1: immediate hypersensitivity

79

what is causes an immediate hypersensitivity reaction (allergy)?

IgE-mediated antibody response to external antigen

80

explain the prevalence of allergies?

increasing prevalence

81

what 2 factors can account for the increased prevalence of allergic disease?

genetic
environmental (eg hygiene hypothesis)

82

explain the hygiene hypothesis?

over the years there has been a general decrease in infectious burden during early life, this resulted in an underdeveloped immune response which predisposes to allergic conditions

83

what type of helper T cells (Th) cells are involved in the allergic response?

Th2

84

how quickly does the allergic attack occur after exposure to the allergen? (type 1: immediate hypersensitivity)

very quickly (minutes to 1/2 hours after exposure)

85

how can thresholds for allergic reactions be lowered?

by co-factors eg exercise, alcohol, infection

86

what does it mean by 'type 1 immediate hypersensitivities are stereotyped'?

the same reaction occurs every time trigger is present
(ie always a rash on exposure)

87

name 6 common allergens?

dust mite
pollen/animal dander
foods
drugs
latex
bee + wasp venom

88

what are the main immune cells involved in the type 1 immediate hypersensitivity response?

B lymphocytes
T lymphocytes
mast cells

89

what are the 2 functions of B cells within the allergic response?

recognise antigen (allergen)
produce antigen-specific IgE antibody

90

what is the function of T cells within the allergic response?

provide help for B lymphocytes to make IgE antibody

91

what is the function of mast cells within the allergic response?

Fc receptors are binded to Fc of allergen specific IgE, when allergen antigen binds to variable part of the antibody, mast cells become active and release vasoactive substances

92

where are mast cells located?

resident in tissues, especially at interface with external environment

93

what vasoactive substances secreted by a mast cell are already preformed?

histamine
tryptase
heparin

94

what vasoactive substances secreted by a mast cell are synthesised on demand and aren't preformed?

leukotrienes
prostaglandins
cytokines (including IL4 and TNF)

95

what are the 4 functions of vasoactive substances produced by a mast cell in response to an allergen?

increased blood flow
contraction of smooth muscle
increased vascular permeability
increased secretions at mucosal surface

96

what are the main 2 functions of a mast cell?

defence against parasites
wound healing

97

mast cells express Fc receptors on their surface that correspond to the Fc of what type of antibody?

IgE

98

what happens the first type the body encounters the allergen?

no allergic response

99

why is there no allergic response on first encounter with allergen?

B cells produce antigen-specific IgE antibody and allergen is cleared

100

on first encounter with allergen, once allergen has been cleared what happens to the residual IgE antibodies?

they bind to circulating mast cells via Fc receptors

101

what happens on re-encounter with an allergen (antigen)?

allergen binds to the IgE which is coating mast cells and disrupts cell membrane causing a release of preformed and newly synthesised vasoactive mediators (degranulation)

102

what is the name for allergic disease in the lung?

atopic asthma

103

what type of airway disease is asthma?

obstructive

104

how do you classify asthma? (3 questions)

early or late onset?
atopic or non-atopic?
extrinsic or intrinsic?

105

what is intrinsic asthma?

non-allergic asthma
(not IgE mediated)

106

what is extrinsic asthma?

response to external allergen
(IgE mediated)

107

name 3 common triggers of atopic asthma?

dust mite
grass pollen
animal dander

108

what is the clinical manifestation of muscle spasm caused by release of vasoactive substances in the lung?

wheeze (caused by bronchoconstriction)

109

what is the clinical manifestation of mucosal inflammation caused by release of vasoactive substances/inflammatory mediators in the lung?

sputum production (caused by mucosal oedema and increased secretions)

110

what is the clinical manifestation of the inflammatory cell infiltrate caused by release of vasoactive substances/inflammatory mediators in the lung?

yellow sputum (caused by infiltration of lymphocytes and eosinophils into bronchioles)

111

what 2 factors caue the narrowing of the airways during an asthma attack?

excess mucus
contracted brochiole smooth muscle (in spasm)

112

what is the clinical name for 'hives'?

urticaria

113

what is angioedema?

self-limited, localised swelling of subcutaneous tissues or mucous membranes
(non pitting oedema)

114

what are the respiratory signs/symptoms of anaphylaxis?

bronchoconstriction causing wheeze
laryngeal obstruction causing stridor

115

what are the cardiovascular signs/symptoms of anaphylaxis?

hypotension
cardiac arrhythmias
MI

116

what are the GI signs/symptons of anaphylaxis?

oral itching
vomiting
diarrhoea
abdominal pain

117

what can occur in the eyes, nose, lips during anaphylaxis?

conjuctival injection
rhinnorrhea
angioedema of lips and mucous membranes

118

where can become itchy during anaphylaxis?

palms
soles of feet
genitalia
mouth

119

what is the pathophysiology of non-allergic mast cell degranulation?
(ie non IgE mediated allergic-type reactions)

spontaneous mast cell degranulation
(due to mast cells becoming twitchy)

120

what 2 types of drugs can cause spontaneous mast cell degranulation?

opiates
NSAIDS

121

what is physical urticaria?

urticaria in response to pressure or heat
(non IgE allergic-type reaction)

122

what type of drug can commonly cause spontaneous mast cell degranulation in the lungs? (induces asthma, but non IgE mediated)

aspirin induced asthma
(also other NSAIDs eg diclofenac,

123

what is samters triad?

a patient who has asthma, nasal polyps and salicylate sensitivity (very severe aspirin sensitivity)

124

how do you investigate a food allergy?

oral challenge

125

what 3 elective investigations can confirm an allergy?

skin prick tests
specific IgE test (RAST test)
challenge test

126

what is a challenge test?

supervised exposure to the putative antigen

127

during an acute allergic reaction, how do you confirm anaphylaxis?

check serum mast cell tryptase levels
(shows evidence of widespread mast cell degranulation)

128

what is the gold standard investigation for confirming an allergy?

skin-prick tests

129

what does a positive skin-prick test show?

local wheal and flare response

130

what type of drugs should be discontinued for at least 48 hours before a skin-prick test?

antihistaines
(corticosteriods do not influence skin prick tests)

131

what are the 4 advantages of skin prick testing?

cheap
quick (15 mins)
unrivalled sensitivity of most allergens
patient can see the result

132

what are the 2 disadvantages of skin prick testing?

requires experience for interpretation
very rarely may induce anaphylaxis

133

what is a RAST test?

a specific IgE test

134

how does a specific IgE test work?

you measure the amount of IgE in serum directed against specific allergen

135

when is a specific IgE test used over a skin -prick tests?

for patients who are on antihistamines

136

what is a better indicators of allergy? (total IgE or specific IgE)

specific IgE
(many other causes of an elevated IgE)

137

in what type of allergic reactions do tryptase levels rise in?

only anaphylaxis
(not in local levels)

138

what are the 6 ain ways to manage an IgE mediated allergic disorder?

1. avoidance of allergen
2. block mast cell activation
3. prevent effects of mast cell activation
4. anti-inflammatory agents
5. management of anaphylaxis
6. immunotherapy

139

what is sodium cromoglycate?

a mast cell stabiliser

140

how does sodium cromoglycate work in the treatment of allergies?

stabilise mast cell membranes and so block mast cell activation and degranulation

141

how is sodium cromoglycate administered?

topical (nasal) spray
(poor oral absorption)

142

how do anti-histamines work in the treatment of allergies?

a H1 receptor antagonist which blocks effects of histamine to prevent the effects of mast cell activation and degranulation

143

how do leukotriene receptor antagonists work in the treatment of allergies?

a leukotriene receptor antagonist which blocks the effects of leukotrienes (which are synthesised by mast cells after activation) to prevent the effects of mast cell activation and degranulation

144

what type of drug is montelukast?

leukotriene receptor antagonist

145

how do corticosteriods work in the treatment of allergies?

anti-inflammatory effects
inhibits formation of many different inflammatory mediators (such as platelet activating factor, prostaglandins and cytokines)

146

what is the step up treatment protocol for asthma?

1. occasional use of inhaled short-acting B2 adrenoceptor agonist (SABA)
2. low dose inhaled corticosteriod
3. low/moderate dose inhaled corticosteroid and long-acting B2 adrenoceptor agonist (LABA)
4. high dose inhaled corticosteroids and regular bronchodilators and leukotriene receptor antagonist or theophylline
5. regular oral corticosteroids

147

what would you also give to a patient with atopic asthma if they can't avoid trigger?

anti-histamine

148

what is the treatment for anaphylaxis?

self-injectable adrenaline

149

how does adrenaline work in the treatment of anaphylaxis?

acts on B2 adrenergic receptors to constrict arterial smooth muscle (increases blood pressure and limits vascular leakage)
and to dilate bronchial smooth muscle (decreases airflow obstruction)

150

what is immunotherapy?

controlled exposure to increasing amounts of allergen

151

how is the allergen administered in immunotherapy?

subcutaneous injections

152

what is the main mechanism within direct cell killing? (type 2 hypersensitivity)

antibody binds to cell surface antigens

153

what results from the binding of the antibody to the cell surface antigens in direct cell killing? (type 2 hypersensitivity)

activation of complement (cell lysis, opsonisation)
antibody-mediated phagocytosis

154

what are the 3 ways of complement activation?

classical pathway
lectin pathway (MBL)
alternative pathway
(All result in C3 production which starts complement cascade)

155

what are the 4 effects of complement activation?

1. direct killing of encapsulated bacteria (with membrane attack complex)
2. opsonisation to enhance phagocytosis
3. solubilisation of immune complexes
4. chemotaxis (stimulates migration of neutrophils and macrophages)

156

what does the membrane attack complex (C5b, C6, C7, C8, C9) do?

punches holes in bacterial cell membranes

157

how does complement achieve chemotaxis? (which stimulates migration of neutrophils and macrophages)

increases vascular permeability to increase cell trafficking to the site of inflammation

158

specific fragments of complement proteins are released after activation and are the direct cause of the increased vascular permeability. what is the name of these fragments?

anaphylotoxins

159

what type of feedback is the process of complement fragments dissolving immune complexes (which triggered them in the fist place)?

negative feedback

160

by complement dissolving the immune-complexes, what occurs?

switching off of complement activation

161

what are the 2 main immunoglobulins involved in direct cell killing? (type 2 hypsensitivity)

IgM and IgG

162

what type of sensitivity is ABO blood transfusion reactions?

type 2 hypersensitivity

163

what 4 signs/symptoms shows the overwhelming systemic inflammatory response during a ABO blood transfusion haemolytic transfusion?

pyrexia and rigors
tachycardia/tachypnoea
hypotension (and therefore dizziness, headaches)
chest or lumbar pain

164

what type of immune hypersensitivity reaction are certain autoimmune diseases which causes cell lysis?

type 2: direct cell killing

165

what are the 2 ways to manage a type 2 hypersensitivity?

plasmapheresis
immunosuprresion

166

how does plasmapheresis work in the management of type 2 hypersensitivity? (direct cell killing)

removes the pathogenic antibody

167

how does immunosuppresion work in the management of type 2 hypersensitivity reactions? (direct cell killing)

switches off B cell production of antibody

168

which is more effective for the treatment of type 2 hypersensitivity reactions (autoimmune- direct cell killing), plasmapharesis or immunosuppresion?

immunosuppresion as there is usually a rebound antibody production which limits the efficacy of plasmapheresis

169

what is the main feature of a type 3 hypersensitivity reaction? (immune-complex mediated)

the accumulation of immune complexes (in response to an antigen) in small vessels which causes complement activation and an infiltration of macrophages and neutrophils

170

what type of hypersensitivity is acute hypersensitivity pneumonitis? (farmers lung and bird fanciers lung etc)

type 3 hypersensitivity- immune complex mediated

171

what is the agent that causes acute bird fanciers lung? (type 3 hypersensitivity- immune complex mediated)

avian serum proteins

172

what are the organisms that causes acute farmers lung? (type 3 hypersensitivity-immune complex mediated)

aspergillus fumigatus
micropolyspora faeni
(2 types of fungi)

173

in a normal patient what can aspergillus cause?

aspergiloma
(a fungal ball in a pre-existing cavity- ie from prev TB or existing CF etc)

174

in an immunosuppressed patient what can aspergillus cause?

invasive aspergillosis

175

what is the main feature of acute hypersensitive pneumonitis?
(type 3 hypersensitivity- immune cell mediated)

immune complexes deposited in the walls of alveoli and bronchioles

176

what symptoms does acute hypersensitivity pneumonitis cause?

wheezing and malaise 4-8 hours after exposure to antigen
may be associated with dry cough, pyrexia, SOB

177

why does a wheeze occur with acute hypersensitivity pneumonitis?

inflammation of terminal bronchioles and alveoli caused by activated phagocytes and complement

178

why does breathlessness occur with acute hypersensitivity pneumonitis?

alveolitis- caused by activvated phagocyes and complement- results in decreased efficiency of gas transfer

179

why does malaise and pyrexia occur with acute hypersensitivity pneumonitis?

systemic manifestation of inflammatory response

180

what type of hypersensitivity reaction is SLE?

type 3- immune complex mediated

181

what type of autoantibodies are produced in SLE?

antibodies against contents of cell nuclei

182

what are the 3 ways to manage type 3 hypersensitivity reactions?
(immune complex mediated)

avoidance (not always an option)
corticosteroids (decrease inflammation)
immunosuppression (decrease antibody production)

183

are corticosteroids based on glucocorticoids or mineralocorticoids?

glucocorticoids

184

what is the key feature of type 4 hypersensitivity? (delayed type hypersensitivity)

T cell mediated hypersensitivity in response to an antigen
(infiltrate of activated T cells)

185

what is the pathophysiology of type 4 hypersensitivity reactions? delayed type hypersensitivity?

initial sensitisation to antigen generated primed T cells
subsequent exposure activated previously primed T cells, recruitment of macrophages, other lymphocytes, neutrophils and release of proteolytic enzymes
results in persistent inflammation

186

what forms because of the persistent inflammation and collection of activated macrophages and lymphocytes in a delayed type hypersensitivity reaction?

granuloma

187

what autoimmune conditions are associated with delayed type hypersensitivity reactions?

diabetes type 1
psoriasis
rheumatoid arthritis

188

what non-autoimune conditions are associated with delayed type hypersensitivity reactions?

nickely hypersensitivity
TB
leprosy
sarcoidosis
cellular rejection of solid organ transplant

189

what is a granuloma?

an organised collection of persistently activated macrophages and lymphocytes

190

what can trigger a granuloma?

diverse antigenic agents or inert foreign materials with failure to remove stimuli

191

what can granulomas n the lungs lead to?

tissue damage and fibrosis

192

what are the management options of sarcoidosis?

nothing (spontaneous remission)
NSAIDs (for acute onset of diease)
systemic corticosteroids (to block T cell and macrophage activation)

193

what type of hypersensitivity are dust diseases such as berylliosis and silicosis?

type 4- delayed type hypersensitivity

194

what type of hypersensitivity is the chronic stage of hypersensitivity pneumonitis?

type 4-delayed hypersensitivity

195

what has been the most effective public health intervention in the world?

clean water

196

what has been the 2nd most effectiv public health intervention in the worl?

vaccination

197

if a child who has had a Haemophilus Influenza B vaccine gets HIB what question should you ask?

is patient immunosuppressed?

198

compare first and second exposure to an antigen in terms of B cell maturation?

1st time: B cells need helper t cells to stimulate maturation
2nd time: only memory B cells needed

199

compare first and second exposures to an antigen in terms of IgG productions?

1st time: IgG made over the course of the week
2nd time: due to memory B cells IgG can be made immediately

200

what does a secondary antibody response usually result in?

the ability to clear infection during incubation period, before the onset of clinical features

201

what cells does memory form in?

B and T cells

202

what is the meaning of immunisation?

the process through which an individual develops immunity/memory to a disease (includes natrual infection)

203

what is the meaning of vaccination?

the deliberate administration of antigenic material to produce immunity in to a disease

204

compare active immunity to passive immunity

active immunity: protection produced by the persons own immune system (vaccine or natrual infection)- usually permanent
passive immunity: protection transferred from another person or animal- temporary and wanes over time

205

how does an active vaccine work?

stimulates immune response and generation of immunological memory to antigen through same pathways as natural infection

206

are you increase the similarity between the vaccine to the disease what effect does it have on the 2nd exposure immune response to the disease?

improves the immune response to the disease

207

what is variolation?

a type of immunisation where the same organisms is being administered as the disease causing organism, but the route of administration is different

208

what are the 5 key features of an inactivated vaccine?

cannot replicate
generally not as effective as live vaccines
immune response primarily antibody based
antibody titer may diminish with time
require multiple doses

209

how do you make an inactivated vaccine?

expose pathogen to:
chemical fixatives
heat denaturation
irradiation

210

what are the problems you face with making an inactivated vaccine?

under inactivation (viable pathogens within organism) or over inactivation (loss of conformational antibody binding sites)

211

what was the problem with the Salk Polio vaccine?

under inactivation

212

what are the 4 advantages of an inactivated vaccine?

1. can be made quickly (to prevent epidemics)
2. may elicit good antibody responses
3. easy to store- no refrigeration required
4. usually safe (can be given to immunocompromised individuals)

213

what are the 3 disadvantages of an inactivated vaccine?

1. due to lack of replication may be hard to stimulate an immune response
2. poor at eliciting T cell responses
3. variable memory (boosters needed)

214

what are the 3 disadvantages of an inactivated vaccine?

1. due to lack of replication may be hard to stimulate an immune response
2. poor at eliciting T cell responses
3. variable memory (boosters needed)

215

what can be used to improve the immunogenicity of an inactivated vaccine?

adjuvant

216

what is an adjuvant?

a substance added to a vaccine which increases stimulation of immune response by creating an inflammatory environment

217

what are the 2 problems of adjuvants?

toxic
alter the immune response (immunity response is generated to vaccine:protein conjugate rather than the vaccine itself)

218

what 2 types of inactivated vaccines can you get?

whole cell vaccines
fractional vaccines

219

what is a whole cell vaccine?

whole organism used in the vaccine

220

what is a fractional vaccine?

only part of the organism used in the vaccine (subunit or toxoid or only polysaccharide)

221

what is the major positive of fractional vaccines compared to whole cell vaccine?

no risk of infection

222

what is a polysaccharide fractional inactivated vaccine?

only polysaccharides of outer capsule of bacteria used

223

what is the problem about a polysaccharide fractional inactivated vaccine?

polysaccharides are not good at stimulating response- antibodies are generated with less functional activity

224

what is a live attenuated vaccine?

exposure to a less virulent version (weakened) of the same pathoden

225

how do you weaken a pathogen to use for live attenuated vaccine?

passaging- growing attenuated strains through repeated subculturing (in other cells or animals)

226

what are the 3 advantages of a live attenuated vaccine?

1. v similar to natural infection, so relevant effector mechanisms elicited (antibody, activated T cells)
2. localised, strong response
3. memory good, therefore boosting not usually required

227

what are the 3 disadvantages of a live attenuated vaccines?

1. immune response can be interfered with by circulating antibody
2. safety issues
3. fragile- need to be stored and handled carefully

228

what are the safety issues that come with live attentuated vaccines?

may acquire new mutations and revert to virulence
may cause infection in immunocomprimosed host

229

what form of virus is the Sabin polio vaccine?

live attenuated virus
(subcultured in monkey kidney cells)

230

what are the naturally acquired sources of passive immunity?

transplacental transfer of antibody

231

what are the 4 therapeutic sources of passive immunity?

1. pooled normal human immunoglobulin
2. hyperimmune globulin
3. heterologous hyperimmune serum
4. monoclonal antibody against specific pathogen

232

what is palivizumab?

a monoclonal antibody produced against a single determinant of respiratroy syncitial virus (RSV)

233

what is palivizumab used in?

prevention of sever lower respiratory tract infections in high-risk infants

234

how often does palivizumab need to be administered?

monthly intramuscular injections during RSV season

235

what is an addiction vaccine?

aim to reduce drug levels in the brain by stimulating an antibody wihich binds to the drug before it enters the brain

236

what are the 3 reasons for improved outcome of transplant?

better understanding of immunology of rejection
better immunosuppressive agents
improved post-transplant monitoring

237

what is the human form of MHC?

HLA

238

what HLA class do all nucleated clles express?

HLA class I
(HLA-A, HLA-B, HLA-C)

239

what HLA class do antigen presenting cells also express?

HLA class II
(HLA-DR, HLA-DQ, HLA-DP)

240

how many variants of each HLA molecule do individuals express?

2

241

what is the purpose of HLA molecule polymorphism?

maintenance of diversity

242

in HLA matching in transplantation which class is more important to be matched?

HLA class II

243

which HLA is more important to be matched in transplantation? (HLA-A or HLA-B)

HLA-B > HLA-A

244

why dont lung and heart transplants use HLA matching to allocate donor?

because of limited donor pool and prolongation of cold ischaemic time

245

which organ is HLA macthing used in transplantation? (kidney or liver)

kidney

246

what cytokine do activated T cells make that causes T cel proliferation and maturation?

IL 2

247

what type of hypersensitivity response is acute cellular rejection?

type 4 hypersensitivity

248

how can you detect deteriorating graft function of a kidney transplant?

rise in creatinine, fluid retension, hypertension

249

how can you detect deteriorating graft function of a lung transplant?

breathlessness
pulmonary infiltrate

250

how can you detect deteriorating graft function of a liver transplant?

rise in LFTs
coagulopathy

251

what are the general symptoms of deterioration of graft function of an organ transplant?

pain and tenderness over graft
fever

252

what are the 4 types of transplant rejection?

hyperacute rejection
acute cellular rejection
acute vascular rejection
chronic allograft failure

253

when does hyperacute transplant rejection occur?

minutes to hours after transplant

254

what is the pathology of hyperacute transplant rejection?

thrombosis and necrosis

255

what is the mechanism behind hyperacute transplant rejection?

preformed antibody and complement fixation

256

when does acute cellular rejection occur?

5-30 days after transplant
(usually T cell response is 5-7 days, 5-30 because of the immunosuppressive therapy post op)

257

what is the pathology behind acute cellular rejection?

cellular infiltrate
(type 4 hypersensitivity)

258

what is the mechanism behind acute cellular rejection?

CD4 and CD8 T cells

259

what is the treatment for acute cellular rejection

immunosuprresion

260

when does acute vascular rejection occur?

5-30 days after transplant

261

what is the pathology behind acute vascular rejection?

vasculitis

262

what is the mechanism behind acute vascular rejection?

T lymphocytes and antibody

263

what is the treatment for acute vascular rejection?

immunosuppression

264

when does chronic allograft failure occur?

.30 days after organ transplant

265

what is the patholgy behind chronic allograft failure?

fibrosis, scarring

266

what types of mechanisms are behind chronic allograft failure?

immune and non-immune mechanisms

267

what is the treatment for chronic allograft failure?

minimse drug toxicity, hypertension, hyperlipidaemia

268

in hyper acute transplantation rejection, why would an individual have preformed antibodies against donor cells?

if patient has been exposed to someone elses white cells or HLA
(ie during pregnancy)

269

when are antibodies against blood group antigens formed?

naturally occuring pre-formed antibodies

270

when are antibodies against HLA antigens formed?

arrise through previous exposure

271

when are antibodies against HLA antigens formed?

arise through previous exposure

272

what will transplantation of any donor tissue across incompatible blood groups result in?

hyperacute rejection

273

what is the result of hyperacute rejection?

irretrievable graft loss

274

how do you prevent hyperacute rejection?

ABO matching
identify if recipient has any anti-HLA antibodies

275

what is crossmatching?

directly tests if serum from recipient is able to bind and/or kill donor lymphocytes

276

what are the immune mechanisms behind chronic allograft failure?

HLA mismatch

277

what are the non-immune mechanisms behind chronic allograft failure?

non-compliance with medication
hypertension
hyperlipiademia
older donor age
calcineurin inhibitors

278

what are the 3 major complications of long-term immune suppression

infection
malignancy
atheroclerosis

279

what immunosuppressant drug used for the prevention of transplant rejection is associated with gingival hypertrophy?

ciclosporin

280

what is the indication for a lung transplant?

advanced respiratory failure with life expectancy less than 2/3 years