Immunology Flashcards
(457 cards)
1
Q
What are SPUR infections?
A
Serious infections
Persistent infections
Unusual infections
Recurrent infections
2
Q
What would make you think a patient had a serious infection?
A
If they were unresponsive to oral antibiotics
3
Q
What two things would make you suspect persistent infections in a patient?
A
- Early structural damage
2. Chronic infections
4
Q
What two things would make you think a patient had an unusual infection?
A
- Unusualy organisms
2. Unusual sites
5
Q
What would you class as recurrent infections?
A
Two major or one major and recurrent minor infections in one year
6
Q
Give 6 features that may be suggestive of primary immune deficiency
A
- Weight loss or failure to thrive
- Severe skin rash (eczema)
- Chronic diarrhoea
- Mouth ulceration
- Unusual autoimmune disease
- Family history
7
Q
What can immunedeficiencies be classed into?
A
Secondary and primary
8
Q
What type of immunodeficiencies are common, often subtle and often involve more than one component of the immune system?
A
Secondary
9
Q
What type of immunodeficiencies are rare (1:10,000 live births)?
A
Primary
10
Q
Give 5 conditions associated with secondary immune deficiency
A
- Physiological immune deificency
- Infection
- Treatment interventions
- Malignancy
- Biochemical and nutritional disorders
11
Q
What two things can lead to physiological immune deficiency?
A
Ageing and prematurity
12
Q
What are HIV (human immunodeficiency virus) and measles associated with?
A
Secondary immune deficiency (infection)
13
Q
What three treatment interventions can lead to secondary immune deficiency?
A
- Immunosuppressive therapy
- Anti-cancer agents
- Corticosteroids
14
Q
What 2 malignancies are associated with secondary immune deficiency?
A
Cancer of immune system - lymphoma, leukaemia, myeloma
Metastatic tumours
15
Q
Give 4 biochemical and nutritional disorders associated with secondary immune deficiency
A
- Malnutrition
- Renal insufficiency/dialysis
- Type I and type II diabetes
- Specific mineral deficiencies e.g. iron and zinc
16
Q
Name 4 innate immune system cells
A
- Macrophages
- Neutrophils
- Mast cells
- Natural killer cells
17
Q
Name 3 innate immune system proteins
A
- Complement
- Acute phase proteins
- Cytokines
18
Q
Name two cells and one protein of the acquired immune system
A
T lymphocytes and B lymphocytes
Antibody
19
Q
What are macrophages and neutrophils?
A
Phagocytes
20
Q
What cells: initiate and amplify the inflammatory response, sscavenge cellular and infectious debris, ingest and kill microorganisms, produce inflammatory molecules which regulate other components of the immuen system and resolution and repair?
A
Phagocytes - macrophages/monocytes and neutrophils
21
Q
What is the main clinical feature of phagocyte deficiencies?
A
Recurrent infections
22
Q
Name three bacteria which can give recurrent infections in phagocyte deficient patients
A
- Staphylococcus aureus
- Burkholderia cepacia
- Mycobacteria both TB and atypical
23
Q
Name two fungi which can cause recurrent infections in phagocyte deficient patients
A
Candida
Aspergillus
24
Q
What disease is treated by chemotherapy or radiotherapy that kills bone-marrow derived cells, including neutrophils?
A
Leukaemia
25
Where are neutrophil precursors initially located?
In the bone
26
What three problems can cause phagocyte deficiency?
1. Defects of phagocyte production
2. Defects of phagocyte mobilisation
3. Defects of phagocyte recruitment
27
What does failure of stem cells to differentiate along myeloid lineage lead to?
Failure to produce neutrophils
28
Name a primary and secondary defect for failure of stem cells to differentiate along myeloid lineage
Primary defect: recticular dysgenesis
| Secondary defect: after stem cell transplantation
29
What can specific failure of neutrophil maturation lead to?
Failure to produce neutrophils
30
Give two diseases associated with specific failure of neutrophil maturation
Kostmann syndrome: severe congenital neutropaenia
| Cyclic neutropaenia: episodic neutropaenia every 4-6 weeks
31
What two features can ultimately lead to failure to produce neutrophils?
1. Failure of stem cells to differentiate along myeloid lineage
2. Specific failure of neutrophil maturation
32
At what point in the leukocyte lineage does recticular dysgenesis occur?
Before hematopoietic stem cell differentiation into common myeloid progenitor and common lymphoid progenitor
33
At what point of the leukocyte lineage does Kostmann syndrome occur?
Between the differentiation of granulocyte-monocyte progenitor into neutrophil
34
What is Kostmann syndrome?
A rare autosomal recessive disorder, severe chronic neutropenia
35
What is the normal neutrophil count, and what is the neutrophil count in a patient with Kostmann syndrome?
Normal > 3000/uL
| Kostmann syndrome < 200/uL
36
How do babies with Kostmann syndrome clinically present?
Infections, usually within 2 weeks after birth:
| Recurrent bacterial infection and systemic or localised infection
37
Name 4 non specific features of Kostmann syndrome
1. Fever
2. Irritability
3. Oral ulceration
4. Failure to thrive
38
What are 2 supportive treatments for Kostmann syndrome?
Prophylactic antibiotics
| Prophylactic antifungals
39
Give two definitive treatments for Kostmann syndrome
1. Stem cell transplantation - defect is in the neutrophil precursor, so strategy is to replace all precursors with allogeneic stem cells and start again
2. Granulocyte colony stimulating factor (G-CSF) - give specific growth factor to assist maturation of neutrophils
40
What would you expect to happen if a patients phagocytes were unable to recognise endothelial adhesion molecules?
Leukocyte adhesion deficiency
41
Give to general statements about leukocyte adhesion deficiency
1. Failure to recognise activation markers expressed on endothelial cells
2. Neutrophils are mobilised, but cannot exit bloodstream
42
Give a clinical feature of leukocyte adhesion deficiency
Recurrent bacterial and fungal infections
43
What is the blood count like in leukocyte adhesion deficiency?
Very high neutrophil counts
44
Where is the site of infection in leukocyte adhesion deficiency?
Deep tissues, N.B. no pus formation
45
What type of immunodeficiency is leukocyte adhesion deficiency?
Rare primary immunodeficiency
46
What type of genetic defect causes leukocyte adhesion deficiency?
Genetic defect in leuococyte integrins (CD18)
47
What does leucocyte adhesion deficiency result in?
Failure of neutrophil adhesion and migration
48
Name 3 direct recognition methods of the binding of a pathogen to a macrophage
1. Lectin receptors
2. TLRs
3. Scavenger receptors
49
Name 2 microbial-specific structures that pathogen recognition receptors recognise
1. Bacterial sugars
| 2. Lipopolysaccharide
50
What do pathogen recognition receptors exhibit?
Genetic polymorphism - some are associated with increased susceptibility to bacterial infection, but most do not cause significant disease
51
What is the name for molecules that act as binding enhancers for the process of phagocytosis?
Opsonins
52
Name 3 opsonins
1. Complement C3b
2. IgG
3. C-reactive protein
53
Where do opsonins bind to?
Receptors on phagocyte surface
54
What do Fc receptors of phagocytes allow?
Binding of antibody that is also bound to antigen
55
What do phagocytes express which binds to complement fragments which are also bound to antigens?
Complement receptor 1 (CR1)
56
What may cause defective phagocytosis?
Defect in opsonin receptors
57
What type of defect will also result in decreased efficiency of opsonisation, as well as defect in opsonin receptors?
Any defect of complement or antibody production
58
When the complement or antibody production have defects, what type of defect of recognition is this classed as?
Functional defect of phagocytosis
59
What type of failure is involved in chronic granulomatous disease?
Failure of oxidative killing mechanisms
60
What three features lead to absent respiratory burst, which leads to failure of oxidative killing mechanisms?
1. Deficiency of the intracellular killing mechanism of phagocytes
2. Inability to generate oxygen free radicals
3. Imparied killing of intracellular micro-organisms
61
What is the inability to clear organisms caused by in chronic granulomatous disease?
Excessive inflammation
62
What two features lead to excessive inflammation in chronic granulomatous disease?
1. Failure to degrade chemoattractants and antigens
| 2. Persistent accumulation of neutrophils, activated macrophages and lymphocytes
63
In chronic granulomatous disease: failure of oxidative killing mechanisms - what does the inability to clear organisms ultimately result in?
Granuloma formation
64
Give 5 features of chronic granulomatous disease
1. Recurrent deep bacterial infections
2. Recurrent fungal infections
3. Failure to thrive
4. Lymphadenopathy and hepatosplenomegaly
5. Granuloma formation
65
What 4 recurrent deep bacterial infections are especially prominent in chronic granulomatous disease?
Staphylococcus
Aspergillus
Pseudomonas cepacia
Mycobacteria, atypical mycobacteria
66
What investigation would you do for chronic granulomatous disease?
NBT ("nitroblue tetrazolium") test
67
Give the three steps in the method for NBT testing in chronic granulomatous disease
1. Feed patient neutrophils source of E.coli
2. Add dye that is sensitive to H2O2
3. If hydrogen peroxide is produced by neutrophils, due changes colour
68
Give two supportive treatment options for chronic granulomatous disease?
Prohpylactic antibiotics
| Prophylactic antifungals
69
Give two definitive treatments for chronic granulomatous disease?
Stem cell transplantation
| Gene therapy
70
What is special about these three intracellular organisms - Salmonella, Chlamydia, Rickettsia?
They hide from immune system by locating within cells
71
What is clever about the way mycobacteria species hide in the body?
They are intracellular organisms and hide within immune cells
72
What does an infection with mycobacteria (TB) activate?
IL-12 - gIFN network
73
What is the first step in IL-12 - gIFN network?
Infected macrophages stimulated to produce IL-12
74
IL-12 - gIFN network: after IL-12 has been produced by infected macrophages, what occurs?
IL-12 induces T cells to secrete gamma interferon (gIFN)
75
During IL-12 - g-IFN network - what occurs after T cells have secreted gIFN?
gIFN feeds back to macrophages and neutrophils
76
During IL-12 - gIFN network: what occurs after gIFN has fed back to macrophages and neutrophils?
It stimulates the production of TNF
77
During IL-12 - gIFN network: what occurs after the production of TNF?
TNF activates NADPH oxidase which stimulates oxidative pathways
78
Give 3 single gene defects in the IL-12 - gIFN axis?
gIFN receptor deficiency
IL-12 deficiency
IL-12 receptor deficiency
79
Name an important side effect of anti-TNF therapy?
Reactivation of latent tuberculosis
80
Name the two phagocyte recruitments
1. Mobilisation from bone marrow
| 2. Migration to site of infection
81
How would you investigate the phagocyte recruitment: mobilisation from bone marrow?
Full blood count and differential
82
How would you investigate phagocyte recruitment: migration to site of infection?
Presence of pus, expression of neutrophil adhesion molecules
83
How would you investigate chemotaxis and endocytosis in phagocyte function?
Chemotactic assays
84
How would you investigate the formation of phagolysosomes in phagocyte function?
Phagocytosis assays
85
How would you investigate oxidative killing in phagocyte function?
NBT test of oxidative killing
86
What are is the neutrophil count, pus formation, leukocyte adhesion markers and nitroblue test of oxidative killing (NBT) like in congenital neutropaenia?
Neutrophil count - absent
Pus formation - No
Leukocyte adhesion markers - Normal
NBT - usually absent (because no neutrophils)
87
What are is the neutrophil count, pus formation, leukocyte adhesion markers and nitroblue test of oxidative killing (NBT) like in leukocyte adhesion defect?
Neutrophil count - Increased during infection
Pus formation - No
Leukocyte adhesion markers - Absent
NBT - Normal
88
What are is the neutrophil count, pus formation, leukocyte adhesion markers and nitroblue test of oxidative killing (NBT) like in chronic granulomatous disease?
Neutrophil count - normal
Pus formation - yes
Leukocyte adhesion markers - normal
NBT - abnormal
89
What two ways can phagocyte deficienceies be treated?
Aggressive management of infection
| Definitive therapy
90
In aggressive management of phagocyte deficiencies, what two drugs are used in infection prohpylaxis?
Septrin
| Itraconazole - antifungal
91
In the aggressive management of infection in phagocyte deficiencies, what other than infection prophylaxis, can be used for treatment?
Oral/intravenous antibiotics
| Surgical draning of abscesses
92
Give two definitive therapies for treatment of phagocyte deficiencies?
Bone marrow transplantation
| Specific treatment for Chronic granulomatous disease - gamma interferon therapy/gene therapy
93
What is severe congenital neutropaenia and cyclic neutropaenia caused by?
Failure of neutrophil differentiation
94
What does failure to express leukocyte adhesion markers give rise to?
Leukocyte adhesion deficiencies
95
What disease results from failure of oxidative killing?
Chronic granulomatous disease
96
What does a failure of cytokine production lead to?
gIFN and IL-12 deficiency
97
What type of response is the recognition by preformed, non-specific effectors via pattern recognition molecules. Recruitment and activation of phagocytes and complement?
Innate immune response
98
What do migrating dendritic cells initiate?
Adaptive immunity
99
What immunity is responsive to an unlimited number of molecules, has specificity and memory and its repertoire is not genetically encoded?
Acquired
100
What two organs beginning with 'a' are involved in the aquired immune response?
1. Adenoid
| 2. Appendix
101
What three anatomical parts are involved in the aquired immune response, beginning with "t"?
Tonsil
Thymus
thoracic duct
102
Which two veins are involved in the squired immune response?
Subclavian vein (left and right)
103
Which three anatomical parts beginning with "L" are involved in the adaptive immune response?
Lymph nodes
Lymphatics
Large intestine
104
Is bone marrow part of the anatomy of the acquired immune response?
Yes
105
Which anatomical part beginning with "p", "k", "h" and "s" are involved in the acquired immune response?
Peyer's patch in the small intestine
Kidneys
Heart
Spleen
106
Where do T lymphocytes arise from?
Haematopoetic stem cells in bone marrow
107
Where are immature T cells exported to from the bone marrow?
To the thymus for proliferation and maturation
108
What percentage of T cells survive selection in the thymus?
10%
109
Once mature T lymphocytes have entered the circulation, where do they reside?
In lymph nodes and secondary lymphoid follicles
110
What cells provide defence against intracellular pathogens and viruses and immunoregulation?
T lymphocytes
111
What are the two main groups of T cells?
CD4 and CD8 (each with different function and different expression of cell surface proteins
112
Which type of T cells have immunoregulatory functions and provide costimulatory signals?
CD4+
113
What two roles do the costimulatory signals from CD4 T cells have?
1. Necessary for activation of CD8 T lymphocytes nad naive B cells
2. Also influence phagocyte function
114
Other than providing costimulatory signals, what do CD4 T lymphocytes produce and regulate?
Produce cytokines
| Regulate other lymphocytes and phagocytes
115
Which type of T cell recognises peptides presented on HLA class II molecules?
CD4+ T lymphocytes
116
Which thee peptides in association with HLA class I do CD8+ cells recognise?
HLA-A
HLA-B
HLA-C
117
In what three ways do cytotoxic T cells kill other cells directly?
Production of pore-forming molecules: perforin
Triggering apoptosis of the target
Secrete cytokines e.g. IFNgamma
118
Name a production of pore-forming molecules used by T cells to kill cells?
Perforin
119
Where do B cells arise from?
Haemopoetic stem cells in bone marrow
120
Where are mature B lymphocytes mainly found?
In bone marrow, lymphoid tissue, spleen
121
What two functions fo B cells have?
Antibody production
| Antigen presentation
122
What are the 4 changes of B cell in development in the bone marrow?
1. Stem cells
2. Lymphoid progenitors
3. Pro B cells
4. Pre B cells
123
What do Pro B cells express?
IgM
124
What do pre B cells express?
IgM and IgD
125
What four other cells can IgM B cells go on to mature into?
IgM plasma cells
IgA
IgE
IgG
126
Where do antigen encounters with B cells occur?
Within lymph nodes
127
What do B cells within the lymph nodes need to rapidly proliferate?
Appropriate signals from T lymphocytes
128
What is meant by B cells undergoing highly complex genetic rearrangements?
Generate B cells that express receptors of greater affinity than the original
129
What two cells can T cell stimulated B cells further differentiate into?
Long-lived memory cells
| Plasma cells which produce antibody
130
Give four functions of antibodies
1. Identification of pathogens
2. Rcruitment of other componenets of immune response to remove pathogens
3. Neutrilisation of toxins
4. Particularly important in defence agaisnt bacteria of all kinds
131
What three componenets of immune response can antibodies recruit?
Complement
Phagocytes
NK cells
132
What is a defect of haemopoetic stem cells called, that makes the adaptive immune response go wrong?
Reticular dysgenesis
133
What leads to the failure of production of Neutrophils, Lymphocytes, Monocytes/macrophages, platelets and is fatal unless corrected with bone marrow transplantation?
Recticular dysgenesis
134
What disease is associated with failure of production of lymphocytes?
Severe combined immunodeficiency
135
How long before a patient with severe combined immunedeficiency becomes unwell?
3 months of age
136
Do you get persistent diarrhoea with severe combined immunodeficiency?
Yes
137
What significant clinical feature is present in severe combined immunodeficiency?
Graft versus host disease (skin disease)
138
What does colonisation of infants "empty" bone marrow by maternal lymphocytes cause?
Graft versus host disease
139
Which antibody can cross the placenta?
IgG
140
Between 0 months and 6 months, where does the neonate get IgG from?
Colostrum and breast milk
141
What is SCID?
Severe Combined Immuno Deficiency
142
What protects the SCID neonate in the first 3 months of life?
Maternal IgG
143
What is the term for normal babies getting infections at 3-4 months if their immune systems are slow to mature?
Transient hypogammaglobulinaemia of infancy
144
Name 4 pathways which can cause severe combined immunodeficiency
1. Deficiency of cytokine receptors
2. Deficiency of signalling molecules
3. Metabolic defects
4. Defective receptor arrangements
145
What is the commonest form of Severe combined immunodeficiency?
X-linked SCID
146
What is the mutation in X-linked SCID?
Mutation of componenet of IL-2 receptor
147
What receptor is shared by many other cytokine receptors?
IL-2 receptor
148
Which mutation in X-linked SCID results in inability to respond to cytokines and what two things does this lead to?
Mutation of componenet of IL-2- receptor
Failure of T cell and NK cell development
Production of immature B cells
149
What can be said about the T cell number, B cell number and development of lymphoid tissue and thymus in X-linked SCID?
T cells - very low or absent
B cells - normal or increased
Poorly developed lymphoid tissue and thymus
150
What are 3 methods of prophylactic treatment for SCID?
1. Prophylactic antibiotics and antifungals
2. Aggressive treatment of exisiting infections
3. Antibody replacement - IV immunogloblin
151
Give two definitive treatments for SCID involving stem cells
1. Stem cell transplant from HLA identical sibling if possible
2. Stem cell transplant from other sibling or parent, or from matched unrelated donor
152
In gene therapy for SCID: can Stem cells be treated ex vivo to express the missing component?
Yes
153
What is DiGeorge syndrome?
Developmental defect of 3rd/4th pharyngeal pouch
154
What chromosome is deleted in DiGeorge syndrome?
22q11
155
What is CATCH-22 for DiGeorge syndrome?
```
C - Cardiac defects
A - Abnormal facial features
T - Thymus underdevelopment
C - Cleft palate
H - Hypocalcemia
22 - Deletion of several genes in chromosome 22
```
156
What disease does a funny looking kid with: low set ears, abnormally folded ears, high forehead, cleft palate, small mouth and jaw, hypocalacemia, oesophageal atresia, T cell lymphopenia and complex congenital heart disease have?
DiGeorge Syndome
157
What does failure of thymic development in DiGeorge syndrome result in?
T cell immunodeficiency (nowhere for T cells to mature)
158
In DiGeorge syndrome, what comes before Hypocalcaemia?
Hypoparathyroidism
159
Which two developmental disorders can DiGeorge sybndrome cause?
Obsessive compulsive disorder
| Schizophrenia
160
Which gene is responsible for embryonic development of the pharyngeal pouch?
TBX1
161
Name three types of infections someone with DiGeorge will get?
Recurrent viral infections
Recurrnet bacterial infections
Frequent fungalo infecitons
162
In a laboratory investigation of DiGeorge syndrome - what can be said about: T cell number and activation response, B cell numbers and antibody responses and NK cell numbers?
T cells - absent or decreased, defective T cell activation response
B cells - normal or increased, low IgG, IgA, IgE, poor antibody responses to specific pathogens
Normal NK numbers
163
With DiGeorge syndrome, what happens to T cell function through ageing?
Improves
164
What 4 things can be done as management for DiGeorge syndrome?
Correct metabolic/cardiac abnormalities
Prophylactic antibiotics
Early and aggressive treatment of infection
Some patients require immunoglobulin replacement
165
What three features can disorders of T cell effector function affect?
Cytokine production
Cytotoxicity
T-B cell communication
166
What does deficiency of any componenet of cytokine production (T cell effector function) result in?
Susceptibility to infection such as TB, BCG, Aspergillus
167
What disease is failure of lymphocyte precursors?
SCID
168
What disease involves failure of thymic development?
DiGeorge syndrome
169
What disease involves failure of expression of HLA molecules?
Bare lymphocyte syndromes
170
What two deficiencies are associated with failure of signalling, cytokine production and effector functions?
gIFN deficiency and IL-12 deficiency
171
What disease is associated with failure of normal apoptosis?
Autoimmune lymphoproliferative syndromes
172
What are recurrent infections (viral, fungal, bacterial, intracellular), opportunistic infections, malignancies young and autoimmune disease all clinical features of?
T cell deficiencies
173
What are the 3 first line investigations for T cell deficiencies?
1. Total WCC and differential
2. Serum immunoglobulins and protein electrophoresis - surrogate marker of functional T cells
3. Quantification of lymphocyte subpopulations
174
What are the 3 second line investigations for T cell deficiencies?
1. Functional tests of t cell activation and proliferation - may be useful if signalling or activation defects are suspected
2. Additional tests of lymphocyte lineage
3. An HIV test is essential
175
Are lymphocyte counts higher in children or adults?
Children
176
If a patient is getting recurrent upper and lower respiratory tract infections, recurrent GI infections, often common organisms what is going on?
Antibody deficiency
177
Name 2 antibody mediated autoimmune diseases?
1. Idiopathic thrombocytopaenia
| 2. Autoimmune haemolytic anaemia
178
What occurs when there is failure to produce mature B cells (Pro B cells cannot make Pre B cells)?
Bruton's X-linked hypogammaglobulinaemia
179
What disease is there no circulating B cells, no plasma cells and no circulating antibody after the first 6 months?
Bruton's X-linked hypogammaglobulinaemia
180
What is the prevelance for selective IgA deficiency?
1:600
181
What disease has low IgG, IgA and IgE, recurrent bacterial infections, cause and mechanism is unknown and often associated with autoimmune disease?
Common variable immuno deficiency
182
In common variable immune deficiency - what three immunoglobulins are low?
IgG, IgA, IgE
183
What are 3 clinical features of common variable immune deficiency?
1. Recurrent bacterial infections
2. AAutoimmune disease
3. Granulomatous disease
184
What disease is failure of B cell maturation?
X-linked agammaglobulinaemia
185
What disease is failure of T cell costimulation?
X-linked hyper IgM syndrome
186
What disease is failure of IgA production?
Selective IgA deficiency
187
Which two diseases involve failure of production of IgG antibodies?
Common variable immuen deficiency
| Selective antibody deficiency
188
What are the 3 first line investigations for B cell deficiencies?
1. Total white cell count and differential
2. Serum immunoglobulins
3. Serum and urine protein electrophoresis
189
What are 2 second line investigations for B cell deficiencies?
Quantification of B and T lymphocytes
| Specific antibody responses to known pathogens
190
What is one method of investigating specific antibody responses to known pathogens in B cell deficiencies?
Measure IgG antibodies agaisnt tetanus, Haemophilus influenzae B and S. pneumoniae
191
What are the three management methods for B cell deficiencies?
1. Aggressive treatment of infection
2. Immunoglobulin replacement
3. Stem cell transplantation in some situations
192
Name 3 lymphoproliferative disease?
Chronic lymphocytic leukaemia
Myeloma
Non-Hodgkins lymphoma
193
What two diseases can lead to protein loss?
Protein losing enteropathy
| Nephrotic syndrome
194
What investigation strategy would you use for hypogammaglobulinaemia (4 steps)?
1. Lymphocyte subsets
2. Repeat immunoglobulins, serum and urine electrophoresis and total proteins
3. CT
4. Check sepcific antibodies and consider test immunisation
195
In selective IgA deficiency: what are the serum immunoglobulins and lymphocyte subpopulations like?
```
IgM - no
IgG - often raised
IgA /
IgE - No
B cells - no
T cells - no
```
196
What are the serum immunoglobulins and lymphocyte subpopulations for Common variable immune deficiency?
```
IgM - decreased
IgG - decreased
IgA - decreased
IgE - decreased
B cell - variable
T cell - variable
```
197
What other investigation would you do for common variable immune deficiency?
Failrue to produce specific antibodies after test immunisation
198
What would the serum immunoglobulins and lymphocyte subpopulations be like for specific antibody deficiency?
All N, IgA N decreased
199
What are immune responses that result in bystander damage to the self?
Hypersensitivity reactions
200
What are the 4 classifications of hypersensitivity reactions?
Type I - Immediate hypersensitivity
Type II - Direct cell killing
Type III - Immune complex mediated
Type IV - Delayed type hypersensitivity
201
What type of hypersensitivity do allergic diseases come under?
Immediate (Type I)
202
What is the definition of an allergy?
IgE-mediated antibody response to external antigen
203
Name 3 non-IgE mediated reactions
1. Coeliac disease
2. Eosinophilic gastroenteritis
3. Protein induced enteropathy
204
Why is the prevalence of allergy increasing?
Hygiene hypothesis
205
How quickly do type I allergic diseases occur after exposure to allergen?
minutes - 1-2 hours
206
What can the threshold for type I allergic disease be influenced by?
Cofactors such as exercise, alcohol and infection
207
What are asthma, urticaria, angioedema, allergic rhinitis, allergic conjunctivitis, diarrhoea and vomiting and anaphylaxis all a type of?
Type I (immediate hypersensitivity) allergic disease
208
Name 6 allergens
1. House dust mite
2. Pollen and animal dander
3. Foods
4. Drugs
5. Latex
6. Bee and wasp venom
209
What are many allergens?
Soluble proteins that function as enzymes
210
Name 3 types of cells involved in allergic disease
1. B cells
2. T cells
3. Mast cells
211
What type of cells in allergic disease recognise the antigen and produce antigen-specific IgE antibodies?
B lymphocytes
212
What cells in allergic disease provide help for B lymphocytes to make IgE antibody?
T lymphocytes
213
What are mast cells
Inflammatory cells that release vasoactive substances
214
Where are mast cells found?
Resident in tissues, especially at interface with external environment
215
What two classes of vasoactive substances do mast cells produce?
Preformed
| Synthesised on demand
216
Name 3 preformed vasoactive substances produced from mast cells?
Histamine
Tryptase
Heparin
217
Name 3 synthesised on demand vasoactive substances produced by mast cells
1. Leukotrienes
2. Prostaglandins
3. Cytokines including IL-4 and TNF
218
What 4 steps do mast cells do in the orchestration of the inflammatory cascade?
Increase blood flow
contraction of smooth muscle
increase vascular permeability
increase secretions at mucosal surface
219
What are mast cells important in the defense against?
Parasites and wound healing
220
What do mast cells express on their surface, that are relevant in allergic reactions?
Express receptors for Fc region of IgE antibody on their surface
221
On encounter with an allergen, what do B cells produce?
Antigen-specific IgE antibody
222
What is the antigen specific region of an antibody called, and where is it located?
Fab
| At top of antibody
223
Where is the Fc region of an antibody and what region is it?
Constant region
| Bottom of antibody
224
What occurs after re-encounter with an antigen?
Allergen binds to IgE-coated mast cells are disrupts cell membrane. The release of vasoactive mediators - histamine, tryptase, also increased cytokines nad leukotriene transcription.
225
Once the allergen is initially cleared, what do residual IgE antibodies do?
Bind to circulating mast cells via Fc receptors
226
Clinical features of allergic disease: within minutes of release of vasoactive mediators, clinical manifestations occur - name 5
1. Urticaria
2. Angioedema
3. Asthma
4. Allergic rhinitis and conjunctivitis
5. Anaphylaxis
227
What two types of asthma can you get?
Extrinsic and intrinsic
228
What type of asthma is a response to external allergen and IgE mediated?
Extrinsic asthma
229
What type of asthma is intrinisc asthma?
Non-allergic asthma and not IgE mediated
230
In extrinsic asthma - what occurs after re-encounter with antigen?
Allergen binds to IgE coated mast cells
Disrupts cell membrane
Causes release of vasoactive mediators from primary granules (histamine, tryptase)
Increases production of other cytokines and leukotrienes
231
What occurs in response to the release of histamine and other inflammatory mediators to muscle spasm, mucosal inflammation and inflammatory cell infiltrate?
Causes bronchoconstriction
Causes mucosal oedema and increases secretions
Infiltration of lymphocytes and eosinophils into bronchioles
232
What clinical manifestation does bronchoconstriction give?
Wheeze
233
What kind of clinical manifestation does mucosal oedema and increased secretions give?
Sputum production
234
What kind of clinical manifestation does infiltration of lymphocytes and eosinophils into bronchioles cause?
Sputum often yellow
235
Give another name for urticaria
Hives, wheals, nettle rash, blisters
236
What is angioedema?
Self-limited, localised swelling of subcutaneous tissues or mucous membranes
237
What changes can occur to breathing during anaphylaxis?
Wheeze
Bronchoconstriction
Laryngeal obstruction - stridor
238
What can happen to the lips and mucous membranes during anaphylaxis?
Angioedema
239
What 3 circulatory changes can occur during anaphylaxis?
1. Hypotension
2. Cardiac arrhythmias
3. MI
240
What can happen to the palsm and soles of feet during anaphylaxis?
Itchiness
241
What 3 GI changes can occur during anaphylaxis?
Vomiting
Diarrhoea
Abdominal pain
242
Give 4 non-allergic causes of mast cell degranulation?
Drugs
Thyroid disease
Idiopathic
Physical urticaria
243
What is aspirin induced asthma characterised by?
Wheeze 0.5-3 hours after ingestion
244
What two other NSAIDS can cause induced asthma other than aspirin?
Diclofenac
| Ibuprofen
245
What affects 2-3% of asthmatics?
Samter's triad
246
What is Samter's triad?
Asthma
Nasal polyps
Salicylate sensitivity
247
Give 3 elective investigations for allergiies?
Skin prick tests
Quantitive specific IgE to putative allergen
Challenge test - supervised exposure
248
What investigation can be done to diagnose allergic reactions during an acute anaphylactic episode?
Evidence of mast cell degranulation - serum mast cell trpytase levels
249
What is the gold standard for supporting diagnosis of allergy?
Skin prick test
250
What is a postiive reaction in a skin prick test?
Local wheal and flare response
251
Do corticosteroids influence skin prick tests?
No
252
Do antihistamines influence skin prick tests?
Yes - discontinued 48 hours before testing
253
What are RAST tests?
Specific IgE tests that measure amount of IgE in serum directed against specific allergen
254
What are the most common causes of an elevated IgE in industrial societies?
Allergic disorders = high total IgE
255
Can vasculitis cause elevated IgE?
yES
256
Is total IgE a useful routine test in the diagnosis/investigation of allergic disease?
No
257
What does widespread degranulation of mast cells during anaphylaxis result in?
Increase in serum tryptase
258
Management of IgE mediated allergic disorders: What is used to block mast cell activation?
Mast cell stabilisers - sodium cromoglycate
259
How are mast cell stabilisers like sodium cromoglycate administered?
Topical spray when allergen exposure is predictable
260
Management of IgE mediated allergic disorders: What drugs can be given to prevent the affect of mast cell activation?
Anti-histamines
| Leukotriene receptor antagonists
261
What are the mainstay of treatment of allergic disease?
Anti-histamines
262
How do leukotriene receptor anatonists work and give an example?
Blocks effects of leukotrienes which are synthesised by mast cells after activation
Montelukast
263
What do corticosteroids inhibit the formation of?
Many different inflammatory mediators
264
Give three inflamamtory mediators that corticosteroids inhibit the formation of?
Platelet activating factor
Prostaglandins
Cytokines
265
What drugs are often used in aspirin-sensitive individuals for asthma?
Leukotriene receptor antagonists
266
What drug would you use in exercise-induced asthma?
Mast cell stabiliser - sodium cromoglycate
267
What do you add on next as well as use of an inhalted short acting beta-2-adrenoceprot agonist?
Low dow inhaled corticosteroids
268
What is the primary management in anaphylaxis?
Self-injectable adrenalin
269
What does adrenaline act on and what does it cause?
B2 adrenergic receptors to constrict arterial smooth muscle
270
What two effects does the constriction of arterial smooth muscle by adrenaline cause?
1. Increases blood pressure thereby limiting vascular leakage
2. Dilates bronchial smooth muscle, thereby decreasing airflow obstruction
271
What is immunotherapy in terms of anaphylaxis management?
Controlled exposure to increasing amounts of allergen
272
What is hypersensitivity II?
Direct cell killing
273
What is the key feature of direct cell killing?
Antibody to cell surface antigens
274
In the pathophysiology of direct cell killing - what occurs once the antibody has binded to cell-surface antigen?
Activation of complement - cell lysis and opsonisation
| Antibody mediated phagocytosis
275
What immunoglobulins do B cells produce directed against cell membrane protein?
IgM or IgG
276
What do classical C1, C2, C4, lectin MBL pathway and alternative pathway all lead to?
C3
277
What is formed at the end of the complement cascade?
Membrane attack complex
278
What are the 4 effects of complement activation?
1. Chemotaxis
2. Solubilsation
3. Direct killing
4. Opsonisation
279
What is chemotaxis?
Stimulation of migration of macrophages and neutrophils to site of inflammation
280
What is solubilisation?
Solubilisation of immune complexes
281
What does direct killing do?
Direct killing of encapslated bacteria
282
What does opsonisation do?
Enhance phagocytosis by macrophages and neutrophils
283
What punches holes in bacterial membranes?
Membrane attack complex
284
What increases vascular permeability and increases cell trafficking to site of inflammation?
Chemotaxis
285
What beginning with "c" can increase vascular permeability?
Complement
286
What are anaphylotoxins?
Fragments of complement proteins released after activation increase permeability of blood vessels
287
What fragments act to solublise immune complexes?
Complement
288
What is triggered by immune complexes?
Complement activation
289
How could fragments of complement switch off the process of complement activation?
They can dissolve the immune complexes which triggered them, switching off the process of complement activation
290
Which effect of complement activation causes regulation of pathway through negative feedback?
Solubilsation
291
In type II hypersensitivity reaction - what does the binding of IgG or IgM antibody to cell surface antigen result in?
Complement activation
292
Give a clinical example of type II hypersensitivity
Blood transfusion reactions (ABO reactions)
293
In an ABO reaction - what are the 5 steps?
1. Target is donor red cells
2. Anti-blood group antibodies bind to surface of circulating donor erythrocytes
3. Form antigen-antibody complexes
4. Activates complement
5. Stimulates phagocytosis
294
What is an overwhelming systemic inflammatory response including pyrexia and rigors, tachycardia/tachypnoea, hypotension/dizziness, headaches/chest or lumbar pain all part of?
Immediate haemolytic transfusion reaction
295
Give three reactions that are type II hypersensitivity blood cell reactions
1. Transfusion reactions
2. Autoimmiune haemolytic anaemia
3. Idiopathic thrombocytopaenic purpura
296
Name a type II hypersensitivity reaction to do with the kidney
Goodpastures sndrome (antibodies to glomerular basement membrane)
297
Give 2 diseases that are hypersensitivity type II and associated with the nervous system
1. Myasthenia gravis (antibodies to acetyl choline receptor)
| 2. Guillan Barre syndrome (antibodies to peripheral nerve glycoprotein)
298
Give a type II hypersensitivity reaction related to the endocrine system
Graves' disease (antibodies to TSH receptor)
299
Give a type II hypersensitivity reaction to do with the skin
Pemphigus vulgaris (antibodies to epithelial cell cement)
300
How could you prove that the disease is mediated by autoantibodies?
Demonstrate that serum causes disease when transferred into another host
301
Nmae 3 diseases that may be transferred to the neonate
1. Myasthenia gravis
2. Idiopathic thrombocytopaenic purpura
3. Rhesus disease
302
What are the two main managements for type II hypersensitivity?
Plasmapheresis
| Immunosuppresion
303
What is the aim of plasmopheresis?
Removal of pathogenic antibody
304
What management method involves: cellular constituents of blood replaced, plasma replaced by plasma from someone else (FFP) or pooled immunoglobulin approx 50% plasma removed each time?
Plasmapheresis
305
What does rebound antibody production limit the efficacy of?
Plasmapheresis
306
What type of hypersensitivity is type III?
Immune complex mediated
307
Where can immune complexes deposit?
In small vessels
308
Name a type III hypersensitivitry disease
Farmer's lung
309
What causes Farmer's lung?
Inhaled fungal particles from hay deposited in lung
310
In Farmer's lung - what happens after antibody formation has been stimulated by inhaled fungal particles?
Antibodies form immune complexes with antigen
| Results in complement activation, inflammation and recruitemnt of other cells
311
What clinical features does Farmer's lung cause?
Wheezing and malaise
312
Name two causes of hypersensitivity pneumonitis?
Farmer's lung - mouldy hay, aspergillus fumigatus
| Bird fancier's lung - avian excreta, avian serum proteins
313
What does immune complexes deposited in the walls of alveoli and bronchioles cause?
Acute hypersensitivity pneumonitis
314
What occurs within alveoli during acute hypersensitivity pneumonitis?
Cell accumulation and inflammation
315
What type of response is acute hypersensitivity pneumonitis mediated by?
Type III hypersensitivity
316
What does acute hypersensitiity pneumonitis cause after 4-8 hours after exposure to antigen, and what is it associated with?
Wheezing and malaise
| Associated with dry cough, pyrexia and breathlessness
317
What clinical feature does inflammation of terminal bronchioles and alveoli caused by activated phagocytes and copmplement cause?
Wheeze
318
What clinical feature does alveolitis, caused by activated phagfocytes and complement resulting in decreased efficiency of gas trasfer cause?
Breathlessness
319
What clinical feature does systemic manifestation of inflammatory response cause?
Malaise and pyrexia
320
What type of reaction is systemic lupus erythematosus (SLE)?
Type III hypersensitivity
321
What are the 4 stages in systemic lupus erythematosus (SLE)?
Antibodies produced against contents of cell nuclei
Form immune complexes
Depositied in small vessels in skin, joints, kidneys
Result in complement activation...iflammation and recruitment of other cells
322
What is small vessel vasculitis caused by?
Immune complex depososition
323
What does deposition of IgG immune complexes in glomeruli cause?
Renal dysfunction
324
What does immune complex deposition in joints cause?
Arthralgia
325
What does immune complex deposition in skin cause?
Vasculitic purpura
326
What is used to diagnose (SLE)?
Anti-DNA binding antibodies
327
What is used to diagnose Farmer's lung?
Antibodies to aspergillus
328
What two factors can you decrease to manage type III hypersensitivity reactions?
Decrease inflammation - corticosteroids
| Decrease production of antibody - immunosuppression
329
Can restrictive lung diseases such as sarcoid and pulmonary fibrosis be treated with corticosteroids?
Yes
330
Can sleep apnoea be treated with corticosteroids?
No
331
Can infective lung diseases be treated with corticosteroids?
Yes
332
Can uncomplicated infection be treated with corticosteroids?
No
333
What is hypersensitivity type IV?
Delayed type hypersensitivity
334
What cells mediate type IV hypersensitivity?
T cells
335
What hypersensitivity does this describe: Initial sensitisation to antigen generates "primed" T cells, subsequent exposure leads to activation of "primed" T cells, recruitment of macrophages, lymphocytes and neutrophils and release of proteolytic enzymes?
Delayed type hypersensitivity
336
Give an example of type IV hypersensitivity reaction?
Nickel hypersensitivity
337
What is a collection of activated macrophages and lymphocytes called?
Granuloma
338
What hypersensitivity reaction does a granuloma form in?
Type IV
339
What are the three steps in type IV hypersensitivity reaction?
1. Infiltration of activated T cells
2. Recruitment of macrophages - phagocytosis, production of inflamamtory cytokines
3. Granuloma formation
340
During a type IV hypersensitivity reaction: what 4 things do CD4 T cells do in the initial phase?
1. production of cytokines
2. Recruitment and activation of macrophages
3. Help for CD8 lymphocytes
4. Granuloma formation
341
Give 3 autoimmune diseases associated with delayed type hypersensitivity
1. Type 1 diabetes
2. Psoriasis
3. Rheumatoid arthritis
342
What type of reactions are: nickel hypersensitivity, TB, leprosy, sarcoidosis and cellular rejection of solid organ transplant?
Non autoimmune delayed type hypersensitivity reactions
343
What is sarcoidosis?
Multisystem granulomatous disease, characterised by presence of granulomas
344
What is a granuloma?
An organised collection of activated macrophages and lymphocytes
345
What are the 4 steps of sarcoidosis pathophysiology?
1. Inhalation of unknown antigen
2. Stimulates alveolar macrophages and CD4 and CD8 T cells, and B cells within lung parenchyma
3. Failure to clear the antigen results in persistent stimulation and granuloma formation
4. Persistent immune activation leads to tissue damage and fibrosis
346
What can be given for the management of acute onset of sarcoidosis?
NSAIDS
347
What do corticoisteroids block in the management of sarcoid?
T cell activation
| Macrophage activation
348
Give 5 diseases characterised by type IV hypersensitivity and granuloma formation
1. Sarcoidosis
2. TB
3. Leprosy
4. Berylliosis, silicosis and other dust diseases
5. Chronic stage of hypersensitivity pneumonitis
349
What is vaccination?
Deliberate exposure to an antigen
350
Why are vaccinations done?
In order to induce immunologically mediated resistance to disease
351
How do vaccinations work?
Through the induction of memory
352
What long-lived cells are generated during primary humoral immune responses?
Memory B cells
353
When do memory B cells undergo clonal expansion, differentiation into plasma cells and antibody production?
When they are rapidly reactivated to a second encounter with that specific antigen
354
During the secondary antibody response - what antibody blocks bacterial attachement to mucous membranes?
Preformed IgA
355
What is the name for: individual may clear toxin through anti-toxin antibodies, but remain a carrier of microorganism?
Diphtheria
356
What type of cells does vaccination stimulate?
Rare naive T cells
357
What are the two fates of effector T cells, induced by vaccination?
1. Mostly die by apoptosis in the absence of persisting antigen
2. Smaller number become memory cells and are maintained at low frequency
358
What are primed CD4 T cells able to do immediatly?
Produce cytokines
359
What are primed CD8 T cells able to do?
Kill immediatly without requirement of immunological help
360
What are two broad classes of vaccination?
Active and passive
361
What two classes can active vaccination be split into?
Live attenuated and inactive
362
Name three classes inactive vaccinations can be put into?
Killed
Subunit
Toxoid
363
What is the term for the process through which an individual develops immunity/memory to a disease, including natural infection?
Immunisation
364
What is the term for the delibrate administration of antigenic material to produce immunity to a disease?
Vaccination
365
What is the term of immunity: protection is produced by the persons own immune system, can be stimulated by vaccine or naturally acquired infection, usually permanent?
Active immunity
366
What type of immunity: protection is transferred from another person or animal, temporary protection that wanes with time?
Passive immunity
367
How does an active vaccination stimulate immune responses to antigens?
Through same pathways as natural infection
368
What is another name for the novel H1N1 flu virus?
Swine flu
369
Give two methods of exposing an individual to the infectious organism?
Variolation
| Swine flu parties
370
Give an example of exposure to a similar but less virulent pathogen?
Cowpox protects from smallpox
371
What is another term for inactivated vaccines?
Killed vaccines
372
What vaccines: cannot replicate, not as effective as live vaccines, immune response primarily antibody based, antibody titer may diminish with time, require multiple doses to stimulate immune response?
Inactivated vaccines
373
What are three ways to make an inactivated vaccine?
1. Chemical fixatives e.g. formalin
2. Heat denaturation
3. Irradiation
374
Give two problems with inactivated vaccines
1. Under-inactivation - leaves viable pathogens or toxins within organism
2. Over-inactivation - loss of tertiary structure and conformational antibody binding site
375
Do inactivated vaccines need refrigeration?
No
376
What vaccines require multiple injections and booster immunisation?
Inactivated vaccines
377
What are adjuvants?
Mixture of inflammatory substances required to stimulate immune responses to coadministered peptides, proteins or carbohydrates
378
Name 3 adjuvants
1. Aluminium hydroxide
Toxins e.g. tetanus toxoid
Bordetella pertussis
379
Why do adjuvants work?
Create inflammatory environment
380
In what two ways do adjuvants work by?
1. Bind to macrophages and signal the unequivocal presence of a microbial invader
2. Activate the innate immune system to stimulate development of antibody and T cell responses
381
Give two problems of adjuvants
Toxic
| Alter immune response
382
What are these three features a probelm of? Immune response is generated to vaccine:protein conjugates rather than vaccine itself, CD4 T cells may recognise the carrier only?
Adjuvants
383
What are inactivated vaccines called when they used the whole organism?
Whole cell vaccines
384
Give some examples of whole cell inactivated vaccines
```
Polio (Salk)
Hepatitis A
Rabies
Cholera
Plague
```
385
What is the name for inactivated vaccines where only part of the organism is used?
Fractional vaccines
386
What are the three subgroups of fractional inactivated vaccines?
Subunit vaccines
Toxoid
Pure polysaccharide vaccines
387
Give some examples of subunit vaccines?
```
Hepatitis B
Influenza
Acellular pertussis
HPV
Anthrax
```
388
Give two examples of toxoid fractional inactivated vaccines?
Diphtheria
| Tetanus
389
What do polysaccharides of outer capsules of some bacteria determine?
Their pathogenicity and antigenicity
390
Give three examples of polysaccharide only vaccines?
Pneumovax (pneumococcus)
Meningovax (MenC)
Salmonella Typhi (Vi)
391
Give two examples of polysaccharide conjugated to toxin, polysaccharide vaccines?
Haemophilus infleunze type B
| Prevenar (pneumococcus)
392
What do live attenuated vaccines contain?
Weakened form of the 'wild' virus or bacterium
393
What must the organism in a live attenuated vaccine do to be effective?
Replicate
394
What type of vaccines are these an example of: measles, mumps, rubella, chickenpox, yellow fever, rotavirus, smallpox and polio (Sabin)?
Live attenuated vaccines
395
Name two bacterial vaccines that are live attenuated?
BCG
| Oral typhoid
396
Do live attenuated vaccines need boosting?
No
397
Give three disadvantages of live attenuated vaccines?
Immune response can be interfered with by circulating antibody
Safety - immunocompromised hosts
Fragile - cold chain
398
Which is inactivated and which is live attenuated: Salk or Sabin?
Salk - inactivated
| Sabin - live attenuated
399
Give an example of passive immunity?
Maternal antibody
400
Name 4 sources of therapeutic passive immunisation
1. Pooled normal human immunoglobulin
2. Hyperimmune globulin
3. Heterologous hyperimmune serum
4. Monoclonal antibody agaisnt specific pathogen
401
When is hyperimmune globulin adminsitered?
After specific exposure
402
What is the name of a monoclonal antibody produced against a single determinant of the Respiratory Syncitial Virus (RSV)?
Palivizumab
403
How is palivizumab administered?
Intramuscular
404
What are the two types of cancer vaccines?
Preventative vaccines and therpeutic vaccines
405
What do preventative cancer vaccines do?
Immunise agaisnt viruses known to cause cancer
406
Name two viruses known to cause cancer?
Hep B - hepatocellular carcinoma
| HPV - genital warts and cervical cancer
407
In transplant rejection - which cells recognise foreign antigen?
T lymphocytes
408
What class do all nucleated cells express on the cell surface?
Class I (HLA-A, HLA-B, HLA-C)
409
What class do specialised antigen-presenting cells also express?
Class II (HLA-DR, HLA-DQ, HLA-DP)
410
What do polymorphisms in HLA molecules maintain?
Diversity
411
In preventing transplant rejection what is it good to maximise?
The similarity between recipient and donor HLA
412
What is the hierarchy of HLA-DR, HLA-A, HLA-B?
HLA-DR >> HLA-B > HLA-A
413
What is the difference between donor and recipient expressed as a number of?
Mismatches at HLA-A, HLA-B and HLA-DR
414
Name two organs where HLA matching is used to allocate donor?
1. Stem cell transplanatation - major preventable cause of graft versus host disease
2. Kidney transplantation
415
Give 3 organs where HLA matching is not used to allocate donor?
Lung
Heart
Liver
416
In transplant rejection - once the resting T cell has met an antigen presenting cell, what occurs?
Activation of T cell, release of IL-2 and proliferation
417
Give 4 effector functions of activated T cells?
Produce cytokines
Provide help to activate CD8 cells
Provide help for antibody production
Recruit phagocytic cells
418
In acute cellular rejection - what cells recognise fonor antigens?
CD4 cells
419
One CD4 cells have recognised donor antigens and become acitvated - what occurs?
Production of cytokines: help for CD8 cells, help fopr B cells and recruitment and activation of macrophages and neutrophils
420
What type of hypersensitivity response is acute cellualr rejection?
Type IV - delayed response
421
What are the three methods of killing - CD8+ lymphocytes?
Release of toxins to kill target
Punch holes in target cells
Apoptotic cell death
422
Name a toxin found in CD8 T cells that kills targets?
Granzyme B
423
During mobilsation of phagocytes by activated CD4+ cells, what four functions do they perform?
Phagocytosis
Release of proteolytic enzymes
Production of cytokines
Production of oxygen radicals and nitropgen radicals
424
What do T cells provide to activate B cells?
Costimulatory signals and cytokines
425
What cells produce antibodies agaisnt graft antigens?
B cells
426
What 4 things result form antibody production?
Complement activation
Opsonisation
Activation of NK cells
Recruitment of phagocytes
427
In acute cellular rejection, what do biopsies show?
Infiltration of phagocytes (60%), T cells (30-40%), B cells and NK cells
428
In acute cellular rejection - what activation markers do T cells express?
CD25
| CD69
429
In acute cellular rejection - what cytokines are increased?
IL-2 and gIFN
430
What 3 other substances can be sued to assist diagnosis of acute cellular rejection?
Fas L
Granzyme
Perforin
431
What are 3 broad symptoms of acute cellular rejection?
Deteriorating graft function
Pain and tenderness over graft
Fever
432
In relation to deteriorating graft function - what 3 clinical changes occur with a kidney transplant?
Increased creatinine
Fluid retention
Hypertension
433
In relation to deteriorating graft function - what 2 clinical changes occur with liver transplants?
Rise in LFTs
| Coagulopathy
434
In relation to lung transplants and deteriorating graft function - what 2 clinical changes occur?
Breathlessness
| Pulmonary infiltrate
435
What are the 4 types of transplant rejection?
1. Hyperacute rejection
2. Acute cellular rejection
3. Acute vascular rejection
4. Chronic allograft failure
436
Give the timeframe, pathology, mechanism and treatment for hyperacute rejection
Minutes to hours
Thrombosis and necrosis
Preformed antibody and complement fixation
None
437
Give the timeframe, pathology, mechanism and treatment for acute cellular rejection
5-30 days
Cellular infiltration, type IV hypersensitivity
CD4 and CD8 T cells
Immunosuppresion
438
Give the timeframe, pathology, mechanism and treatment for acute vascular rejection
5-30 days
Vasculitis
T lymphocytes and antibody
Immunosuppression
439
Give the timeframe, pathology, mechanism and treatment for chronic allograft failure
>30 days
Fibrosis, scarring
Immune and non-immune mechanisms
Minimise drug toxicity, hypertension, hyperlipidaemia
440
What is hyperacute rejection and what is it mediated by?
Rapid destruction of graft within minutes-hours
| Mediated by pre-formed antibodies that react with donor cells
441
Why would an individual have preformed antibodies agaisnt donor cells?
Blood group antigens - naturally occuring pre-formed antibodies, bind surface molecules found ubiquitously
HLA antigens - Arise through previous exposure (transplantation, transfusion, pregnancy), class I antibodies particularly important
442
Patient has red cells expressing A and serum with natural anti-B antibodies, Heart transplant from group B: Where do the circulating preformed recipient anti-B antibodies bind to B blood group antigens?
On donor epithelium
443
Patient has red cells expressing A and serum with natural anti-B antibodies, Heart transplant from group B: once antibodies have binded to antigens on donor epithelium complement is activated, what 3 things does complement activation cause?
Complement mediated lysis
Opsonisation
Increased permeability
444
Patient has red cells expressing A and serum with natural anti-B antibodies, Heart transplant from group B: As well as the antibodies activating complement, what 2 other things happen?
Other cells rapidly recruited - phagocytes
| Disruption of endothelium - platelets activated, infalmamtion, thrombosis
445
What will transplantation of any donor tissue across incompatible blood groups result int>?
Hyperacute rejection
446
As well as contradicting blood groups, what else can the recipient have that could cause a hyperacute rejection?
anti-donor HLA antibodies
447
What type of transplant rejection are thrombosis of graft, often with neutrophil infiltrate and widespread necrosis and irretrievable graft loss clinical features of?
Hyperactue rejection
448
In what two ways can hyperacute rejection be prevented?
1. ABO matching- standard ABO blood typing, blood group cross match
2. Identify if recipient has any anti-HLA antibodies - screening, HLA crossmatching
449
What directly tests if serum from recipient is able to bind and/or to kill donor lymphocytes?
Crossmatching between donor and recipient
450
What type of rejection is a rejection mediated predominantly by antibody?
Vascular rejection
451
What type of transplant rejection is a major cause of graft loss and affects 50% of heart transplants in hte first 12 months?
Chronic allograft failure
452
Give 5 non-immune risk factors for chronic allograft failure?
1. Non compliance with medication
2. hypertension
3. Hyperlipidaemia
4. Older donor age
5. Calcineurin inhibitors (Ciclosporin, Tacrolimus)
453
What are the three pathophysiological stages of chronic allograft failure?
1. Cellular proliferation of smooth muscle of vessel wall
2. Occlusion of vessel lumen
3. Interstitial fibrosis and scarring is common
454
Give three major complications of long-term immune suppression?
Infection
Malignancy
Atherosclerosis
455
What in relation to the gums is a complication of ciclosporin?
Gingival hypertrophy
456
What vaccines should never be given to immunosuppressed individuals?
Live vaccines
457
What encourages you to think about immune deficiency?
SPUR infections
