Immunology Flashcards
(280 cards)
1
Q
What are the 4 hallmarks of immune deficiency?
A
SPUR Serious infections Persistent infections Unusual infections Recurrent infections
2
Q
what defines a serious infection?
A
unresponsive to oral antibiotics
3
Q
what defines persistent infections?
A
early structural damage
chronic infections
4
Q
what defines unusual infections?
A
unusual organisms
unusual sites
5
Q
what defines recurrent infections?
A
two major or one major + recurrent minor infections in one year
6
Q
what 6 features apart from SPURS may be surggestive of primary immune deficiency?
A
weight loss/ failure to thrive severe skin rash chronic diarrhoea mouth ulceration unusual autoimmune disease family history
7
Q
what 2 important infections lead to secondary immune deficiency?
A
HIV
measels
8
Q
what 3 important treatment interventions lead to secondary immune deficiency?
A
immunosuppressive therapy
anti-cancer agents
corticosteriods
9
Q
what type of malignancies can lead to secondary immune deficiency?
A
cancer of the immune system (lymphoma, myeloma, leukemia)
metastatic tumours
10
Q
what biochemical/nutritional disorders can lead to secondary immune deficiency?
A
malnutrition
diabetes (Type 1 and 2)
dialysis
11
Q
what is a major feature of phagocyte deficiencies?
A
recurrent infections
which can affect either common or unusual sites
12
Q
what are the types of organisms typically infect patients with phagocyte deficiencies?
A
common bacteria (eg Staph sureus)
unusual bacteria (eg Burkholderia cepacia)
Mycobateria (TB and atypicals)
Fungi (candida, aspergillus)
13
Q
what is the general life cycle of a phagocyte? (ie neutrophil
A
- mobilisation of phagocytes and precursos from bone marrow or within tissues
- upregulation of endothelial adhesion markers causing neutrophil adhesion and migration into tissues
- phagocytosis and killing of organism
- activation of other components of the immune system
14
Q
what are the 2 reasons that can cause the failure of neutrophil production?
(and therefore neutropaenia and phacogyte deficiency)
A
failure of stem cells to differentiate along myeloid lineage
specific failure of neutrophil maturation
15
Q
what is reticular dysgensis?
A
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
Q
when can the secondary defect which causes the failure of stem cells to differentiate along the myeloid lineage occur?
A
after stem cell transplantation
17
Q
what are the 2 congenital causes of specific failure of neutrophil maturation? (and therefore cause neutropaenia)
A
Kostmanns syndrome
Cyclic neutropaenia
18
Q
what is Kostmanns syndrome?
A
rare autosomal recessive disorder causing the specific failure of neutrophil maturation- leads to severe chronic neutropaenia
19
Q
what is Cyclic Neutropaenia?
A
episodic neutropaenia every 4-6 weeks caused by the specific failure of neutrophil maturation
20
Q
when do patients with Kostmanns syndrome usually present with recurrent infections?
A
within 2 weeks after birth
21
Q
what is the supportive treatment of Kostmanns syndrome?
A
prophylactic antibiotics
prophylactic antifungals
22
Q
what is the definitive treatment of Kostmanss syndrome?
A
stem cell transplantation
Granulocyte colony stimulating factor (G-CSF)
23
Q
what is granulocyte colony stimulating factor (G-CSF)?
A
a growth factor which assists maturation of neutrophils
24
Q
what rare, primary immunodeficiency is caused by the genetic defect in leukocyte integrins?
A
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
