Respiratory Immunology Flashcards
(174 cards)
1
Q
What features other than SPUR can be suggestive of a primary immune deficiency?
A
Weight loss, failure to thrive, severe skin rash, mouth ulceration, family history and unusual autoimmune disease.
2
Q
What are the two classifications of immunodeficiencys?
How common are they?
A
Primary - rare.
Secondary - common and often subtle, involving more than one component of the immune system. Those over the age of 85 are particularly at risk.
3
Q
What two types of immune deficiencies do we get?
What cells do these involve.
A
Either innate immune system deficiency of phagocytes.
Acquired immune system T and B lymphocytes.
4
Q
What are the clinical features of phagocyte deficiencies?
A
May affect common and unusual sites e.g. Deep muscle infection.
5
Q
What is the common infection for someone with CF?
A
Burkholderia cepacia.
6
Q
What is the differential diagnosis of someone with a burkholderia cepacia infection?
A
It is an extremely rare infection.
So they must already have CF, chronic granulomatous disease or a neutrophil defect.
7
Q
What different mechanisms of phagocyte deficiency are there?
A
Failure to produce phagocytes, mobilisation and recruitment.
8
Q
How can the body fail to make neutrophils?
What two types of defects cause this?
A
Failure of stem cells to initiate the myeloid lineage.
Primary defect: reticular dysgensis.
Secondary defect: after stem cell transplantion.
9
Q
What is reticular dysgensis?
A
Failure to mature stem cells or make platelets. Children with this die in a few days.
10
Q
What two syndromes cause specific failure to mature neutrophils?
What happens?
A
Kostmann syndrome - rare autosomal recessive disorder causing severe congenital neutropenia. Children don’t grow properly and don’t regain their birth weight.
Cyclic neutropenia - episodic neutropenia every 4-6 weeks.
11
Q
What lineage to phagocytes come from?
A
The leukocyte lineage.
12
Q
What is the clinical presentation of kostmann syndrome?
A
Infections, usually within 2 weeks after birth. Then recurrent bacterial infections which can be systemic or localised.
13
Q
What is the management of Kostmann syndrome?
A
Supportive treatment: prophylactic antibiotics and antifungals.
Definitive treatment: stem cell transplantation.
Granulocytes colony stimulating factor - assists with maturation of neutrophils.
14
Q
What is leukocyte adhesion deficiency?
A
Rare primary immunodeficiency.
Caused by defect in leukocyte integrins CD18.
15
Q
What does leukocyte adhesion deficiency result in and what is the clinical presentation of it?
A
Results in failure of neutrophil migration and adhesion.
Clinical picture is characterised by marked leukocytosis and localised bacterial infections that are difficult to detect.
16
Q
What is the word we remember for features suggesting immunodeficiency and what do the letters mean?
A
SPUR
Serious infection that are unresponsive to oral antibiotics.
Persistent infections
Unusual infections
Recurrent infections - two or more major ones in one year.
17
Q
What two ways do phagocytes recognise pathogens?
A
By direct recognition - binding directly to pathogen
or indirect recognition - binding to opsonins on pathogen.
18
Q
What different types of PRRs do we get on the surface of phagocytes?
A
Toll like receptors, scavenger receptors and lectin receptors.
19
Q
What kind of microbial structures do PRRs recognise?
A
Bacterial sugars and lipopolysaccharides.
20
Q
What can go wrong with PRRs causing disease?
What is the result of this?
A
They can exhibit genetic polymorphisms. Some are associated with increased susceptibility to bacterial infection, but most do not cause disease.
21
Q
What opsonins receptors to phagocytes display?
A
Fc receptors that bind to antibodies attached to antigens. Complement receptor (CR1) which binds to complement fractions bound to antigens.
22
Q
What does a defect in phagocyte opsonin receptors cause?
A
May cause defective phagocytosis but significant redundancy means this normally doesn’t cause disease.
23
Q
What are the FAB and Fc ends of antibodies?
A
The FAB end is at the top of the Y prongs.
The Fc part is at the bottom on the Y body.
24
Q
What causes chronic granulomatous disease?
A
Absent respiratory burst meaning the phagocytes have deficient intracellular killing mechanisms.
25
What's the commonest form of deficiency causing chronic granulomatous disease?
Deficiency of p47phox component of NADPH oxidase which is X linked.
Gives an inability to form oxygen free radicals.
26
Why do the granulomas for in chronic granulomatous disease?
Excessive inflammation fails to degrade chemoattractants and antigens and there is a persistent build up of neutrophils, activated macrophages and lymphocytes forming the granuloma.
27
What are the features of chronic granulomatous disease?
```
Recurrent deep bacterial infections.
Recurrent fungal infections
Failure to thrive
Lymphadenopathy and hepatomegaly.
Granuloma formation.
```
28
What bacterial infections do we commonly see with chronic granulomatous disease?
Staphylococcus, aspergillus, pseudomonas cepacia, mycobacteria and atypical mycobacteria.
29
What test do we do for chronic granulomatous disease?
```
NBT test (nitroblue tetrazolium) test.
Feed neutrophils ecoli. Add a dye that is sensitive to H2O2. If neutrophils can use oxidative killing the dye will be activated.
```
30
What is the treatment of chronic granulomatous disease?
Supportive treatment: prophylactic antibiotics and antifungals.
Definitive treatment: stem cell transplantation.
31
Which bacteria hide inside normal cells and what ones hide inside immune cells?
Normal - salmonella, chlamydia and rickettsia.
| Immune - mycobacteria.
32
How is mycobacteria detected and killed by the body?
Infected macrophages produce IL-12
This induces T cells to make gamma interferon (gIFN).
gIFN feeds back to macrophages and neutrophils.
This stimulates production of TNF which activates NADPH oxidase and stimulates oxidative pathways.
33
What defects can cause susceptibility to mycobacteria?
Ones affecting gIFN or IL-12.
34
What do anti TNF drugs treat?
| What is an important side effect?
Used to treat inflammatory disease.
| Can reactivate latent TB.
35
What is congenital neutropenia?
What does it cause?
What happens during an NBT test?
Absent neutrophil count, no pus formation, normal leukocyte adhesion markers and NBT test usually absent.
36
What is leukocyte adhesion defect?
What does it cause?
What happen in an NBT test?
Absent leukocyte adhesion markers.
Increased neutrophil count during infection and no pus formation.
NBT test usually normal.
37
What do we find in investigation for chronic granulomatous disease?
Normal neutrophil count, pus formation, normal leukocyte adhesion markers.
Abnormal NBT test.
38
After what length of time does the acquired immune response initiate?
After 96 hours.
39
How do T cells develop and where?
Armies form haematopoietic stem cells.
exported as immature cells to the thymus.
Only 10% survive selection process in the thymus.
Mature lymphocytes enter the blood stream.
40
What are the two main groups of T cells?
CD4+ and CD8+
41
What do CD4+ cells do?
Activate CD8+ and naive B cells.
Influence phagocyte function.
Produce cytokines.
Recognise peptides presented on HLA class II molecules.
42
What do CD8+ cells do?
```
Recognise peptides associated with HLA class I molecules.
Kill by production of perforins and cytokines.
Particularly important in defence against viral infections and tumours.
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43
How do B lymphocytes develop and where?
Arise from haemopoetic stem cells in bone marrow
| Mature cells are found mostly in bone marrow, lymphoid tissues and the spleen.
44
What are the functions of antibodies?
Identification of pathogens.
Recruitment of other immune components.
Neutralisation of toxins
Particularly important in defence against bacteria.
45
What happens to patients with severe combined immunodeficiency?
Unwell by the age of three months.
Persistent diarrhoea, failure to thrive, infections of all types.
Unusual skin diseases.
Colonisation of infants empty bone marrow by maternal lymphocytes.
Usually a family history of early infant death.
46
What is severe combined immunodeficiency?
Failure of production of lymphocytes.
47
What protects infants with severe combined immunodeficiency (SCID) in the first three months?
Maternal IgG.
48
What is transient hypogammaglobinaemia of infancy?
Infants immune system slow to mature so can get infections once the IgG from mothers colostrum has stopped but there production hasn't started properly.
49
What is SCID?
Severe combined immunodeficiency.
50
What is the commonest form of SCID?
X linked SCID.
| Is a mutation of a component of IL2 receptors. Resulting in an inability to respond to cytokines.
51
What kind of cell counts are found in X linked SCID?
| What happens to lymphoid tissue?
Very low or absent T cells (IL2 important for their development).
Normal or increased B cells.
Poorly developed lymphoid tissues and thymus.
52
What is the treatment of SCID?
Hospitalised to avoid infections.
Prophylactic drugs.
Aggressive treatment of existing infections.
Antibody replacement with IV Ig.
Definitive treatment: stem cell transplantation from HlA identical sibling if possible.
Gene therapy to express missing components, making functional lymphoid cells.
53
What is Digeorge syndrome?
Developmental defect of the 3rd/4th pharyngeal pouch. Caused by a deletion of chromosome 22q11
54
What do kids with DiGeorge syndrome look like?
Funny looking kid with low set ears, abnormally folded ears, high forehead, cleft palate, small mouth and jaw.
55
What syndromes do kids with DiGeorge syndrome have?
Hypocalcaemia
Oesophageal atresia
T cell lymphoma
Complex congenital heart disease.
56
What psychiatric issues can DiGeorge syndrome cause?
Developmental delay.
| Obsessive compulsive disorder and schizophrenia.
57
What does DiGeorge syndrome cause T cell deficiency?
T cells have nowhere to mature.
58
What infections do we get with DiGeorge syndrome?
Viral and fungal infections due to no CD8 cell to kill them
| Repeated bacterial infections as no T cells help B cells to make antibodies.
59
What cell counts will we find in lab investigations for DiGeorge syndrome?
Absent or decreased T cells.
Normal or increased B cells, but low antibodies levels and poor responses to invaders.
Normal NK cells.
60
What is the management of DiGeorge syndrome?
Correct metabolic and cardiac abnormalities.
Prophylactic antibiotics and aggressive treatment of infections.
Some require immunoglobulins.
61
What types of infection do you get when there is a deficiency of T cell cytokine production?
TB, atypical mycobacteria, BCG infection after immunisation and deep fungal e.g. Aspergillus.
62
What are the clinical features of T cell deficiencies?
Recurrent infections, viral, fungal, bacterial and intracellular pathogens e.g. Mycobacteria. Opportunistic infections, malignancies at a young age and autoimmune disease.
63
What investigations do we do for suspected T cell deficiencies?
First line : White cell counts and differential.
Serum immunoglobulins and protein electrophoresis.
Flow cytometry for quantitation of lymphocyte subpopulations.
Second line: HIV test etc.
64
How do patients with antibody deficiencies present?
Recurrent bacterial infections of upper and lower resp and GI tract.
Often common organisms.
Viral infection less frequent.
Antibody mediated autoimmune diseases e.g. Haemolytic anaemia.
65
What is Brutons Xlinked hypogammaglobinaemia?
Failure to produce mature B cells.
| Results in: no circulating B cells, no plasma cells and no circulating antibody after the first 6 months.
66
How common is selective IgA deficiency?
| What does it cause?
1:600
Two thirds of people Asymptomatic.
Rest get recurrent respiratory tract infections.
67
What is common variable immune deficiency and what does it cause?
Low IgG, IgA and IgE.
| Causes recurrent bacterial infections often with severe end organ damage e.g. Bronchiectasis and GI infection.
68
What are the clinical features of B cell deficiencies?
Recurrent infections usually very common bacteria.
| Opportunistic infections and antibody mediated autoimmune disease.
69
What are the first line investigations for B cell deficiencies?
Total white cell count and differential.
Serum IGs
Serum and urine protein electrophoresis.
70
What are the second line investigations for B cell deficiencies?
Quantitation of B and T cells
Specific antibody response to known pathogens e.g. Tetanus. If response low, vaccinate with killed vaccine and retest 6-8 weeks later.
71
What is the management of B cell deficiencies?
Aggressive treatment to infection, stem cell transplants and immunoglobulin replacement.
72
What is immunoglobulin replacement?
IgG antibodies to a wide range of common organisms derived for pooled plasma of thousands of donors.
IV every 3-4 weeks.
Life long treatment required.
73
What happens prior to hypersensitivity reactions and then during them?
First encounter to antigen causes no reaction but the antibody created gets stuck to mast cells.
Second exposure causes cross linking of antibodies to the same allergen. Causes I mediated degranulation and release of vasoactive mediators causing a reaction.
74
What is gel and Coombs classification of hypersensitivity reactions?
Type I - immediate hypersensitivity - allergic disease.
Type II - direct cell killing
Type III - immune complex mediated.
Type IV - delayed type hypersensitivity.
75
What are the two types of immune mediated hypersensitivity reactions?
IgE mediated - classical allergy.
| Non IgE mediated e.g. Coeliac disease and eosinophilic gastroenteritis.
76
What are some examples of non immune mediated reactions?
Metabolic e.g. Lacoste intolerance.
Toxic e.g. Bacterial food poisoning.
Pharmacological e.g. Caffeine.
IBS and food aversion.
77
What are the generic features of a type 1 allergic disease?
Occurs quickly after exposure - mins to a few hours.
May be associated with more than one organ system.
Stereotyped response.
Presentation influenced by site of contact.
Threshold for reactions may be influenced by co factors such as exercise.
78
What are the specific features of a type 1 allergic disease?
Asthma, urticaria, angioedema, allergic rhinitis, allergic conjunctivitis, D and V and anaphylaxis.
79
What are some common triggers of a type 1 allergic disease?
House dust mite, pollen and animal dander, food, drugs, latex and insect venom.
80
What is the definition of the pathophysiology of allergic disease?
IgE mediated antibody reaction to an external antigen.
81
What do mast cells express that allows binding with antibodies?
Fc receptors binding with IgE Fc regions.
82
What are the two classifications of asthma?
Intrinsic and extrinsic.
83
What is extrinsic asthma?
Response to an external antigen which is IgE mediated.
84
What reaction do inflammatory mediators released from degranulation of mast cells cause in the lungs?
Muscle spasm and bronchoconstriction.
Mucosal inflammation, oedema and increased secretions.
Inflammatory cell infiltrate - lymphocytes and eosinophils into bronchioles.
85
Why is asthma sputum often yellow?
Due to eosinophils.
86
How long does urticaria normally last?
Lesions appear within an hour and normally last 2-6 hours. Very occasionally 24 hours.
87
What is angioedema?
Self limiting localised swelling of subcutaneous tissues or mucus membranes. Is non pitting, not normally associated with itching and often without clear demarcation.
88
What are the clinical features of anaphylaxis?
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Itchy palms, feet and genitalia.
Wheeze and bronchoconstriction.
Flushing and urticaria.
Conjunctiva, rhinorhea and urticaria.
Feeling of impending doom, loss of consciousness and death.
Swollen lips.
Laryngeal obstruction and Stridor.
Hypotension, cardiac arrhythmias and MI.
Oral itching, vomiting, diarrhoea and abdominal pain.
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89
What are some non allergic causes of mast cell degranulation?
Spontaneous degranulation (mast cells can become hyper charged and easy to set off).
Drugs such as morphine, opiates, aspirin and NSAIDS.
Thyroid disease.
Physical urticaria - urticaria in response to pressure or heat e.g. Writing on patients back with finger.
Exercise induced anaphylaxis.
90
How long does piritin take to work?
7 mins.
91
How common is aspirin induced asthma?
How long does it take?
What drugs trigger it?
What drugs don't?
Affects around 20% of asthmatics.
0.5-3 hours after ingestion.
Triggered by aspirin and other NSAIDS particularly diclofenac and ibuprofen.
Paracetamol and COX 2 inhibitors are usually ok.
92
What is samsters triad?
Gives asthma, nasal polyps and salicylate sensitivity.
93
What are elective investigations for allergy?
Skin prick tests.
Quantitate specific IgE to putative allergen.
Challenge test - supervised exposure to the putative agent.
94
What evidence of mast cell degranulation is present in the blood during acute anaphylaxis?
Increased serum mast cell tryptase levels.
| Peaks in 1-2 hours and returns to baseline by 6 hours.
95
What is the gold standard allergy test?
Skin prick test.
96
What is done during a skin prick test?
Skin prick of allergen to forearm.
| Local wheal and flare response is a positive reaction.
97
What drugs do and do not influence the results of a skin prick test?
Antihistamines must be discontinued for 48 hours prior to testing.
Corticosteroids don't affect it.
98
What are the advantages of a skin prick test?
Cheap, quick, patient can see results, very accurate.
99
What are the disadvantages of a skin prick test?
Requires experienced interpretation and can rarely cause anaphylaxis.
100
What is the fab region on an antibody?
The antibody specific region.
101
What is a RAST test?
A specific IgE test that measures the amount of IgE in serum directed at a specific allergen. Not as accurate as skin test but good when these aren't available.
102
Why is testing for increased tryptase levels a good test for anaphylaxis?
Only occurs in anaphylaxis not in local reactions. Good if the cause of hypotension and rash during anaesthesia for example is unknown.
103
What other allergy does a peanut allergy tend to coincide with?
Pea allergy.
104
What is the rise in tryptase levels often proportional to in anaphylaxis?
The drop in bp.
105
How do we manage IgE mediated allergic disorders?
```
Allergen avoidance.
Block mast cell activation.
Prevent effects of mast cell activation.
Anti-inflammatory agents.
Management of anaphylaxis.
Immunotherapy.
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106
What drug can we use to stabilise mast cells and what are its features?
Sodium chromoglycate.
Stabilises membranes.
Has a poor oral absorption, it is used as a topical spray when allergen exposure is predictable.
107
What are the mainstay drugs of treatment of allergic disease?
Anti histamines- H1 receptor antagonists.
108
When should we take antihistamines to make them more effective?
Early in the course of the reaction.
109
What drugs do we use to prevent the effects of mast cell activation?
Anti histamines.
Leukotriene receptor antagonists.
Corticosteroids.
Mast cell stabilisers.
110
What do leukotries receptor antagonists do and what is the name of one of these drugs?
Blocks effects of leukotrienes released from activated mast cells. Also blocks synthesis of other mast cells mediators.
Montelukast.
111
What do corticosteroids do?
Dampen down inflammation by inhibiting formation of many different inflammatory mediators e.g. Platelet activating factor and prostaglandins.
112
What is the management of anaphylaxis?
Adrenaline.
113
How does adrenaline help anaphylaxis?
Acts on beta 2 adrenergic receptors to constrict arterial smooth muscle. Increases the blood pressure thereby limiting vascular leakage and dilates bronchial smooth muscle.
114
How is immunotherapy carried out?
Controlled exposure to tiny amounts of allergen by subcut injection. Gradual increase of dose, may lead to inhibition of anaphylaxis by an unknown mechanism.
115
What is the major risk of immunotherapy?
Anaphylaxis.
116
What are the key features of type II hypersensitivity reactions?
Antibody to cell surface antigens.
117
What is the pathophysiology of a type II hypersensitivity reaction?
Antibody binds to cell surface antigen, resulting in activation if complement, cell lysis and opsonisation.
118
What are the complement fragments that increase vascular permeability called?
Anaphylotoxins
119
What are examples of blood based type II hypersensitivity reactions?
Transfusion reactions, autoimmune haemolytic anaemia and thrombocytopaenic purpura.
120
What are examples of kidney based type II hypersensitivity reactions?
Good pastures syndrome - antibodies to glomerular basement membrane.
121
What are examples of nervous system based type II hypersensitivity reactions?
Myasthenia gravis - antibodies to acetylcholine receptor.
| Guillan barre disease - antibodies to peripheral nerve glycoprotein.
122
What are examples of endocrine based type II hypersensitivity reactions?
Graves' disease - antibodies to TSH receptor.
123
What are examples of skin based type II hypersensitivity reactions?
Pemphigus vulgaris.
124
What happens during ABO transfusion reactions?
Antibodies in serum bind to donor erythrocytes. They form antigen antibody complexes which stimulates complement. This also stimulates phagocytosis giving complement mediated lysis followed by haemolysis of the transfused cells.
125
What are the signs of immediate haemolytic transfusion reaction?
```
Pyrexia and rigors
Tachycardia and tachypnoea
Hypotension and dizziness.
Headaches and chest or lumbar pain.
Death.
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126
How do we manage type II hypersensitivity reactions?
Plasmapheresis and immunosuppression.
127
What is plasmapheresis?
Patients blood removed via cell separator, and cellular constituents are replaced in an attempt to remove pathogenic body.
Immunosuppression given with this to stop rebound antibody production messing with the results.
128
What are examples of type III hypersensitivity reactions?
Farmers lung (mould hay/straw), bird fanciers lung, malt workers lung, cheese workers lung and maple bark strippers lung.
129
What happens in bird fanciers lung?
Inhaled particles deposited by the lung, these stimulate antibody formation. Antibodies form immune complexes with antigen which results in complement activation. Inflammation and recruitment of other cells, causing wheezing and malaise after exposure to the antigen.
130
Why type of reaction is systemic lupus erythematosus?
| What happens?
SLE.
Type III hypersensitivity.
Antibodies produced against contents of the cell nuclei. They form immune come,exes which are deposited in small vessels in skin, joints and kidneys.
Results in complement activation, inflammation and recruitment of other cells.
131
What immune complex deposition in small vessels result in?
Small vessel vasculitis.
132
How do we diagnose type III hypersensitivity reactions?
Look for specific IgG to putative antigen e.g. Anti DNA binding antibodies in SLE.
133
What is the management of a type III hypersensitivity reaction?
Avoidance, corticosteroids for anti inflammatory properties. Decreases production of antibody with immunosuppression.
134
What cells mediate type IV hypersensitivity reactions?
T cells.
135
What is the pathophysiology of type IV hypersensitivity reactions?
Initial sensitisation to antigen gives primed T cells. Subsequent exposure activates them and causes recruitment of lymphocytes, neutrophils and inflammation etc.
136
What is a granuloma?
Collection of activated macrophages and lymphocytes.
137
What autoimmune disease are associated with type IV hypersensitivity reactions?
Type 1 diabetes, psoriasis and rheumatoid arthritis.
138
What non -autoimmune disease are associated with type IV hypersensitivity reactions?
Nickel hypersensitivity, TB, leprosy, sarcoidosis and cellular rejection of solid organ transplants.
139
What is sarcoidosis?
Multi system granulomatous disease characterised by a type IV hypersensitivity reaction to an unknown antigen
140
Where can sarcoid affect and where is it most common?
Anywhere in the body but 90% is in the lungs.
141
What happens in sarcoidosis in the lungs?
Inhalation of unknown antigen.
Stimulates alveolar macrophages, both T cells and B cells within lung parenchyma.
Failure to clear the antigen results in persistent stimulation and granuloma formation.
Persistent immune activation leads to tissue damage and fibrosis.
142
How do we manage sarcoid?
Watch and wait - may have spontaneous remission.
NSAIDS for acute onset.
Systemic corticosteroids.
143
What diseases are characterised by type IV hypersensitivity reactions?
Sarcoidosis, TB, leprosy and dust diseases.
144
What is vaccination?
Deliberate exposure to an antigen to induce immunological mediated resistance to disease through memory.
145
What does a secondary antibody response do in relation to the incubation period of a pathogen?
Rapid antibody production means the pathogen can be cleared before the onset of clinical features during the incubation period.
146
What does preformed IgA do in a secondary antibody response?
Blocks bacterial attachment to muscles membranes.
147
What can happen in diphtheria?
Individual may clear toxin through anti toxin antibodies but remain a carrier of the microorganism.
148
How does vaccination affect T cells?
Stimulates naive T cells. Induces a strong response in 14-21 days. Some become effector T which die off in th absence of a pathogen. Sampler numbers become memory cells and are maintained at low frequency.
149
What two types of vaccination are there?
Active and passive.
150
What two types of active vaccination are there?
Live attenuated and inactive.
151
What three type of inactive vaccine are there?
Killed, subunit or toxoid.
152
What is immunisation?
Process through which an individual develops immunity/memory to a disease. Includes natural infection.
153
What are the two types of immunity?
| What are the features of both?
Active - protection produced by own immune system. Can be stimulated by a vaccine or an infection and is usually permanent.
Passive - protection transferred from another person or animal. Temporary and wanes with time.
154
How do active vaccines work?
Stimulates immune response to an antigen the same way as a natural infection would.
155
How do inactive vaccines work?
Killed vaccines that cannot replicate. Generally not as effective as live vaccines as response is primarily due to antibodies and not T cells. Antibody titre may diminish after time and so requires multiple doses.
156
How is an inactivated vaccine made?
Exposing pathogen to chemical fixatives, heat denaturation or irradiation.
157
What are the advantages of inactivated vaccines?
Made quickly, can elicit good antibody response. Easy to store are usually safe and can be given to the immunocompromised.
158
What are the disadvantages of activated vaccines?
May be difficult to stimulate an immune response. Poor at eliciting T cell response. boosters needed.
159
What are inflammatory adjuvants?
Added to an immunisation to stimulate an immune response. They activate the innate immune system. But are very toxic and may not elicit a secondary response to the actual pathogen.
160
What are sources of passive immunity?
Maternal antibodies or Igs from another being.
161
How do we minimise the chance of transplant rejection?
Minimise the stimulus - HLA matching (mostly used for stem cell and kidney transplants).
162
What organs do we not use HLA matching for?
Lungs, heart and liver.
163
What happens in acute cellular transplant rejection?
Recognition of donor antigens by CD4+ cells.
Activation of these cells to produce cytokines.
These stimulate other cells in a type IV sensitivity reaction.
164
What are the signs of acute cellular rejection?
Deteriorating graft function.
Pain and tenderness over graft.
Fever.
165
What signs do we get in kidney transplant rejection?
Rise in creatinine, fluid retention and hypertension.
166
What signs do we get in liver transplant rejection?
Rose in LFTs and coagulopathy.
167
What signs do we get in lung transplant rejection?
Breathlessness and pulmonary infiltrate.
168
What are the different types of transplant rejection?
Hyper acute.
Acute cellular rejection.
Acute vascular rejection.
Chronic allograft failure.
169
What happens in hyper acute rejection?
Rapid destruction of graft within mins to hours. Mediated by preformed antibodies that attack donor cells. E.g. From wrong blood group type or wrong HLA type.
170
How can we prevent hyperacute rejection?
ABO matching.
Screening for HLA antibodies in host.
Cross matching.
171
What happens in acute vascular rejection?
Mediated predominately by antibodies.
| Causes activation of B cells and antibodies produced against the graft initiating complement and phagocyte recruitment.
172
What causes chronic allograft rejection?
Major cause of graft loss. Can be caused by immune HLA mismatch.
Also can be caused by non compliance with medication, hypertension, hyperlipidaemia and older donor age.
173
What happens in chronic allograft rejection?
Cellular proliferation of smooth muscle of vessel wall. Occlusion of vessel lumen. Interstitial fibrosis and scarring is common.
174
What is the management of chronic allograft rejection?
Immunosuppression but this is usually to late.
| Try an avoid by managing BP etc.
