Immuno Flashcards
1
Q
What do sebaceous glands produce that has antibacterial effects?
A
Hydrophobic oils – repels water and microorganisms
Lysozyme – destroys the structural integrity of the bacterial cell wall
Ammonia and defensins – anti-bacterial properties
2
Q
List the cells of the innate immune system.
A
Polymorphonuclear cells
Monocytes/macrophages
NK cells
Dendritic cells
3
Q
List the soluble components of the innate immune system.
A
Complement
Acute phase proteins
Cytokines and chemokines
4
Q
List some key features of cells of the innate immune system.
A
Identical responses in all individuals
Cells express genetically-encoded receptors (PRRs) that allow them to detect pathogens at the site of infection
Cells have phagocytic capacity
Cells secrete mediators (e.g. cytokines/chemokines) that regulate the immune response
5
Q
Name the resident macrophage in the liver
A
Kupffer cells
6
Q
Name the resident macrophage in the kidney
A
Mesangial cells
7
Q
Name the resident macrophage in the bone
A
Osteoclasts
8
Q
Name the resident macrophage in the spleen
A
Sinusoidal lining cells
9
Q
Name the resident macrophage in the neural tissue
A
Microglia
10
Q
Name the resident macrophage in the connective tissue
A
Histiocytes
11
Q
Name the resident macrophage in the skin
A
Langerhans cells
12
Q
How do macrophages differ from polymorphonuclear cells?
A
They can process antigens and present them to T cells
13
Q
Describe how cells of the innate immune system recognise pathogens.
A
Pattern-recognition receptors (e.g. TLR) recognise generic motifs called PAMPs (e.g. bacterial sugars, DNA and RNA)
Fc receptors on these cells allows binding to the Fc portion of immunoglobulins thereby allowing phagocytosis of immune complexes
14
Q
Which other factors can bind to phagocytes to facilitate phagocytosis?
A
Complement components (e.g. by binding to CR1)
Acute phase proteins (e.g. CRP)
Antibodies
15
Q
Why do neutrophils die after phagocytosis? What does this form?
A
Phagocytosis depletes the glycogen stores of the neutrophil resulting in neutrophil death
The accumulation of dying neutrophils forms pus
16
Q
How do NK cells determine whether to lyse cells or not?
A
They have inhibitory receptors which recognise self HLA and they have activating receptors that recognise heparan sulphate proteoglycans
The balance of these signals determines the response
They kill ‘altered self’ cells (e.g. malignancy or virus-infected cells)
17
Q
Describe the main features of dendritic cells.
A
Reside in peripheral tissues
Express receptors for cytokines/chemokines
Express pathogen recognition receptors
Express Fc receptors for immunoglobulin
Capable of phagocytosis
Present processed antigens to T cells in lymph nodes to prime the adaptive immune response
18
Q
Which receptor is involved in the migration of dendritic cells to lymph nodes?
A
CCR7
19
Q
What are the key features of cells of the adaptive immune response?
A
Wide repertoire of antigen receptors (NOTE: not entirely genetically encoded because of VDJ recombination)
Highly specific
Clonal expansion
Immunological memory
20
Q
Outline the selection of T cells in the thymus.
A
Cells with low and high affinity for HLA are deleted
Cells with intermediate affinity will survive (10%)
21
Q
Which class of HLA do CD4 and CD8 cell recognise?
A
CD4: HLA-II
CD8: HLA-I
22
Q
Outline the functions of CD4+ T helper cells.
A
Recognise peptides derived from extracellular proteins
These peptides are presented on HLA-II (HLA-DP, DQ, DR)
Provide help for the development of a full B cell response
Provide help for the development of some CD8+ T cell responses
23
Q
List the subsets of CD4+ T cell.
A
Th1
Th2
Th17
Follicular T cell
Treg
24
Q
Describe the function of CD8+ T cells.
A
Specialised cytotoxic cells
Recognise peptides derived from intracellular proteins presented on HLA class I (A, B and C)
Kills cell directly via perforin and granzyme or expression of Fas ligand
NOTE: particularly important against viral infections and tumours
25
In what form are B cells found in the periphery?
IgM B cells
26
What is the early IgM response of B cells?
If the B cell in the periphery engages an antigen it can cause an early IgM response where the cell differentiates into an IgM secreting plasma cell
27
What is a germinal centre reaction?
Dendritic cells present an antigen, thereby priming the CD4+ T helper cells
CD4+ T helper cells provide help for B cell differentiation via CD40L: CD40 interaction
This causes B cell proliferation
They undergo somatic hypermutation and isotype switching (from IgM to IgG/A/E)
They will become plasma cells and produce antibodies
NOTE: this process is dependent on CD4+ T helper cells
28
Which part of an antibody detects antigen and which part is responsible for its effector function?
Antigen is recognised by the antigen binding region (Fab) which is made up of the variable region of both heavy and light chains
Effector function is determined by the constant region (Fc) of the heavy chain
29
How is a secondary response to T-dependent antigens different from the primary response?
Lag time between antigen-exposure and antibody production is decreased (to 2-3 days)
Titres of antibody produced is increased
Response is dominated by IgG antibodies with high affinity
The response is independent of help from CD4+ cells
30
Where are pre-B cells found and what do they develop into?
Found in the bone marrow and develop into haematopoietic stem cells
31
In what form are complement proteins present in the circulation?
Inactive molecules
32
Outline the classical pathway of complement activation.
Activated by immune complexes
Formation of antibody-antigen complexes results in a conformational change exposing a binding site for C1 on the antibody
This binding results in activation of the cascade
NOTE: this is dependent on antibodies, therefore it requires prior activation of the adaptive immune response (i.e. it does NOT occur very early in the immune response)
33
Outline the mannose binding lectin pathway of complement activation.
Activated by the direct binding of MBL to microbial cell surface carbohydrates
This directly stimulates the classical pathway involving C4 and C2 (but NOT C1)
NOTE: this is NOT dependent on the adaptive immune response
34
Outline the alternative pathway of complement activation.
Directly triggered by the binding of C3 to bacterial cell wall components
This is NOT dependent on the adaptive immune response
Involves factors B, I and P
35
State an example of bacterial cell wall components that can activate complement in Gram-positive and Gram-negative organisms.
Gram-negative: lipopolysaccharide
Gram-positive: teichoic acid
36
What is the major amplification step of the complement cascade?
C3 convertase
37
What are the effects of complement fragments that are released during complement activation?
Increase vascular permeability
Opsonisation of immune complexes
Opsonisation of pathogens
Activation of phagocytes
Promotes mast cell/basophil degranulation
Punches holes in bacterial membranes
38
Give three examples of failure of neutrophil production and outline their mechanism.
Reticular dysgenesis
- Autosomal recessive severe SCID with no production of lymphoid or myeloid cells
- Caused by failure of stem cells to differentiate along lymphoid or myeloid lineage
Kostmann syndrome
- Autosomal recessive congenital neutropaenia
Cyclic neutropaenia
- Autosomal dominant episodic neutropaenia
- Occurs every 4-6 weeks
39
Name a phagocyte deficiency caused by failure of phagocyte migration.
Leucocyte adhesion deficiency
40
Describe the pathophysiology of leucocyte adhesion deficiency.
Caused by deficiency of CD18
CD18 normally combined with CD11a to produce LFA-1
LFA-1 normally binds to ICAM-1 on endothelial cells to mediate neutrophil adhesions and transmigration
A lack of CD18 means a lack of LFA-1, so neutrophils cannot enter tissues
During an infection, neutrophils will be mobilised from the bone marrow (HIGH neutrophils in the blood) but they will not be able to cross into the site of infection (NO pus formation)
41
Name a phagocyte deficiency caused by failure of oxidative killing mechanisms.
Chronic granulomatous disease
42
Outline the pathophysiology of chronic granulomatous disease.
Absent respiratory burst (deficiency of components of NADPH oxidase leads to inability to generate oxygen free radicals)
Excessive inflammation (persistent neutrophils and macrophage accumulation with failure to degrade antigens)
Granuloma formation
Lymphadenopathy and hepatosplenomegaly
43
What type of infection do patients with IL12/IL12R or IFN-gamma/IFN-gamma receptor deficiencies tend to present with?
Organisms that infect macrophages (usually atypical mycobacteria)
44
Name and describe the colour changes of two tests used to investigate chronic granulomatous disease.
Nitroblue Tetrazolium (NBT) – yellow to blue
Dihydrorhodamine (DHR) – fluorescent
NOTE: both of these tests are looking at the ability of neutrophils to produce hydrogen peroxide and oxidative stress
45
Which types of infection tend to occur in patients with phagocyte deficiency?
Recurrent skin and mouth infections
- Bacteria – Staphylococcus aureus, enteric bacteria
- Fungi – Candida albicans, Aspergillus fumigatus
Mycobacterial infections (particularly with IL12 deficiency)
- TB, atypical mycobacteria
46
state the expected neutrophil count, leucocyte adhesion markers, NBT/DHR test and presence of pus in Kostmann syndrome
Absent neutrophil count
Normal leucocyte adhesion markers
No neutrophils for NBT/DHR
No pus
47
state the expected neutrophil count, leucocyte adhesion markers, NBT/DHR test and presence of pus in leukocyte adhesion deficiency
High neutrophil count
Absent CD18
Normal NBT/DHR
No pus
48
state the expected neutrophil count, leucocyte adhesion markers, NBT/DHR test and presence of pus chronic granulomatous disease
Normal neutrophil count
Normal leucocyte adhesion markers
Abnormal NBT/DHR
Pus present
49
state the expected neutrophil count, leucocyte adhesion markers, NBT/DHR test and presence of pus in IL12/IFN-gamma deficiency
Normal neutrophil count
Normal leucocyte adhesion markers
Normal NBT/DHR
Pus present
50
Outline the treatment of phagocyte deficiencies.
Aggressive management of infection (infection prophylaxis and oral/IV antibiotics when needed)
Haematopoietic stem cell transplantation
Specific treatment for chronic granulomatous disease (e.g. IFN-gamma therapy
51
What is the main risk associated with NK cell deficiency?
Increased risk of viral infections (e.g. HSV, CMV, EBV, VZV)
52
Outline the treatment of NK cell deficiency.
Prophylactic antiviral drugs (e.g. aciclovir)
Cytokines (e.g. IFN-alpha to stimulate NK cytotoxic function)
Haematopoietic stem cell transplantation
53
What is the main clinical consequence of complement deficiency?
Increased susceptibility to infection by encapsulated bacteria
54
Which encapsulated bacteria are particularly problematic in patients with complement deficiency?
Neisseria meningitidis
Haemophilus influenzae
Streptococcus pneumoniae
NOTE: susceptibility to N. meningitidis is particularly common in properidin and C5-9 deficiency
55
What are the consequences of MBL deficiency?
Common but NOT associated with immunodeficiency
56
List some different complement deficiencies and state which is most common.
C1q
C1r
C1s
C2 – MOST COMMON
C4
57
Outline the clinical phenotype of complement deficiency.
Almost all patients with C2 deficiency have SLE
Usually have severe skin disease
Increased risk of infection
58
How does SLE lead to a functional complement deficiency?
Active lupus causes persistent production of immune complexes
This leads to consumption of complement components leading to a functional complement deficiency
C3 and C4 will be low
59
What are nephritic factors?
Autoantibodies that are directed against components of the complement pathway
They stabilise C3 convertases (break down C3) resulting in C3 activation and consumption
60
What disease is associated with the presence of nephritic factors?
Glomerulonephritis (usually membranoproliferative)
It may also be associated with partial lipodystrophy
61
Which complement components may be measured in assays and why?
C3 and C4 are measured routinely to monitor SLE (low in active lupus)
C1 esterase inhibitor – decreased in hereditary angio-oedema
62
Name two functional complement assays and describe what they are testing.
CH50 – test of classical pathway (C1, 2, 4, 3, 5-9)
AP50 – test of the alternative pathway (B, D, Properidin, C3, C5-9)
63
Outline the management of complement deficiencies.
Vaccination (especially against encapsulated organisms)
Prophylactic antibiotics
Treat infection aggressively
Screen family members
64
Describe the stereotypical presentation of C1q deficiency
Severe childhood-onset SLE with normal levels of C3 and C4
65
Describe the stereotypical presentation of C3 deficiency with nephritic factor
Membranoproliferative nephritis with abnormal fat distribution (partial lipodystrophy)
66
Describe the stereotypical presentation of C7 deficency
Meningococcus meningitis with a family history of a sibling dying aged 6
67
Describe the stereotypical presentation of MBL deficiency
Recurrent infections when neutropaenic following chemotherapy, but previously well
68
What is anisopoikilocytosis and which type of anaemia is it associated with?
Variations in size and shape of cells
Associated with iron deficiency anaemia (and thalassemia trait to a lesser degree)
69
What is basophilic stippling? List some causes.
Basophilic appearance of red blood cells caused by the presence of aggregated ribosomal material
Causes: beta-thalassemia trait, lead poisoning, alcoholism, sideroblastic anaemia
70
Which condition do hypersegmented neutrophils tend to be present in?
Megaloblastic anaemia
71
In which conditions might you see target cells (codocytes)?
Iron deficiency
Thalassemia
Hyposplenism
Liver disease
NOTE: target cells have a high SA: V ratio
72
What are Howell-Jolly bodies? Which condition are they associated with?
Nuclear remnants present within red blood cells
Present in hyposplenism
73
Why might a patient with coeliac disease have a low calcium and high ALP?
Reduced absorption of vitamin D leads to vitamin D deficiency which causes a secondary hyperparathyroidism
74
Which investigations are typically performed in Coeliac disease?
CRP and ESR
Serological tests
Upper GI endoscopy and distal duodenal biopsy (GOLD STANDARD)
75
Which HLA alleles are particularly common in patients with coeliac disease?
HLA-DQ2 (80%) – DQA1*0501 and DQB1*02 alleles
HLA-DQ8
76
Which type of anti-gliadin antibodies may be tested when investigating coeliac disease?
IgA antibodies
NOTE: it is not a very sensitive test and is outdated
77
What important test should be performed before checking anti-tTG and anti-endomysial antibody levels?
gA levels
IgA deficiency can produce false-negative results
78
What are the characteristic histological features of coeliac disease?
Subtotal villous atrophy with crypt hyperplasia
Intra-epithelial lymphocytes
79
List some other causes of villous atrophy.
Giardiasis
Tropical sprue
Crohn’s disease
Radiation/chemotherapy
Nutritional deficiencies
Graft-versus-host disease
Microvillous inclusion disease
Common variable immunodeficiency
80
How many intraepithelial lymphocytes would you expect to see in coeliac disease?
More than 20 IELs/100 epithelial cells
NOTE: normal would be < 20
81
List some other causes of high intraepithelial lymphocytes.
Dermatitis herpetiformis
Giardiasis
Cows’ milk protein sensitivity
IgA deficiency
Tropical sprue
Post-infective malabsorption
Drugs (NSAIDs)
Lymphoma
82
List some complications of coeliac disease.
Malabsorption
Osteomalacia and osteoporosis
Neurological disease (epilepsy and cerebral calcification)
Lymphoma (causes multi-focal T cell lymphoma)
Hyposplenism
83
How often should a DEXA scan be performed in coeliac patients?
Every 3-5 years
84
List some conditions that are frequently associated with coeliac disease.
Dermatitis herpetiformis
Type 1 diabetes mellitus
Autoimmune thyroid disease
Down syndrome
SLE
Autoimmune hepatitis
85
Name a defect in stem cells that causes SCID and name the gene that is mutated.
Reticular dysgenesis – adenylate kinase 2 (AK2)
NOTE: this is a mitochondrial energy metabolism enzyme
86
What is the most common type of SCID?
X-linked SCID
87
Describe the typical cell counts you would expect to see in X-linked SCID.
Very low T cells
Very low NK cells
Normal or increased B cells
Low immunoglobulin
88
Describe the pathophysiology of ADA deficiency.
ADA – adenosine deaminase
This is an enzyme required by lymphocytes for cell metabolism
ADA deficiency leads to failure of maturation along any lineage
89
Describe the typical cell counts you would expect to see in ADA deficiency.
Very low T cells
Very low B cells
Very low NK cells
90
Describe the clinical phenotype of SCID.
Unwell by 3 months age (once protection by maternal IgG dissipates)
Infections of all types
Failure to thrive
Persistent diarrhoea
Unusual skin disease (colonisation of infant’s empty bone marrow by maternal lymphocytes can cause a graft-versus-host disease-like condition)
Family history of early death
91
Which cellular insults are CD8+ T cells particularly important in protecting against?
Viral infections
Tumour
92
Outline the immunoregulatory functions of CD4+ T cells.
Provide help to mount a full B cell response
Provide help for some CD8+ T cell responses
93
In which group of syndromes does the thymus gland fail to develop properly?
22q11.2 deletion syndromes (e.g. Di George syndrome)
This is characterised by failure of development of the pharyngeal pouch
94
What are the main clinical features of 22q11.2 deletion syndromes?
Facial abnormalities (high forehead, low set ears, cleft palate, small mouth and jaw)
Underdeveloped parathyroid gland (resulting in hypocalcaemia)
Oesophageal atresia
Underdeveloped thymus
Complex congenital heart disease
95
What are the immunological consequences of an underdeveloped thymus gland?
Normal B cell count
Low T cell count
Homeostatic proliferation with age (T cell numbers increase with age)
Immune function is mildly impaired and tends to improve with age
96
What condition is caused by a deficiency of MHC Class II? Briefly outline its pathophysiology.
Bare lymphocyte syndrome (BLS) type 2
Deficiency of MHC Class II means that CD4+ T cells cannot be selected in the thymus leading to CD4+ T cell deficiency
97
Describe the typical cell counts that you would expect to see in Bare Lymphocyte syndrome type 2.
Normal CD8+
Very low CD4+
Normal B cell count
Low IgG
NOTE: BLS Type 1 is a similar condition caused by failure of expression of HLA Class I
98
Outline the clinical phenotype of bare lymphocyte syndrome.
Unwell by 3 months of age
Infections of all types
Failure to thrive
Family history of early death
99
What are the common clinical features of T lymphocyte deficiencies?
Viral infections (e.g. CMV)
Fungal infections (e.g. PCP)
Some bacterial infections (e.g. TB, salmonella)
Early malignancy
NOTE: disorders of T cell effector function include defects in cytokine production, cytokine receptors and T-B cell communicatio
100
List some investigations that may be used for suspected T cell deficiencies.
Total white cell count and differentials
Lymphocyte subsets
Immunoglobulins
Functional tests of T cell activation and proliferation
HIV test
101
How are lymphocyte counts different in children compared to adults?
Higher in children compared to adults
102
Outline some management approaches for immunodeficiency involving T cells.
Aggressive prophylaxis/treatment of infection
Haematopoietic stem cell transplantation
Enzyme replacement therapy (e.g. PEG-ADA for ADA deficiency)
Gene therapy
Thymic transplantation (in Di George syndrome)
103
What determines the class of immunoglobulin?
Heavy chain
104
What determines the effector function of immunoglobulin?
Constant region of the heavy chain
105
Outline the pathophysiology of Bruton’s X-linked hypogammaglobulinaemia.
Prevents the maturation of B cells at that point at which they emerge from the bone marrow
Caused by an abnormal B cell tyrosine kinase (BTK) gene
This results in the absence of mature B cells and, hence, an absence of antibodies
106
Outline the clinical phenotype of Bruton’s X-linked hypogammaglobulinaemia.
Boys present in the first few years of life
Recurrent bacterial infections (e.g. otitis media, pneumonia)
Viral, fungal and parasitic infections
Failure to thrive
107
Outline the pathophysiology of X-linked hyper IgM syndrome.
Blocks the maturation of IgM B cells through germinal centres into B cells that produce other classes of immunoglobulin (i.e. prevents germinal centre reactions)
Caused by a mutation in the CD40 ligand gene
This is technically a T cell problem, however, it means that CD4+ T helper cells cannot provide help to B cells so they cannot undergo germinal centre reactions
NOTE: CD40 ligand is encoded on Xq26
108
Describe the typical biochemical results you would expect to see in X-linked hyper IgM syndrome.
Normal B cells
Normal T cells
No germinal centre reactions
High IgM
Absent IgG, IgA and IgE (failure of isotype switching)
109
Outline the clinical phenotype of X-linked hyper IgM syndrome.
Boys present in the first few years of life
Recurrent infections (mainly bacterial)
Subtle abnormality in T cell function (predisposes to PCP, autoimmunity and malignancy)
Failure to thrive
110
What is common variable immunodeficiency and what are the main features?
A group of disorders caused by some form of failure of differentiation of B lymphocytes
Defined by:
· Marked reduction in IgG, IgA and IgE
· Poor/absent response to immunisation
· Absence of other defined immunodeficiency
111
Outline the clinical phenotype of common variable immunodeficiency.
May present in adults or children
Recurrent bacterial infection (often severe)
Pulmonary disease (e.g. interstitial lung disease)
GI disease (e.g. IBD-like disease)
Autoimmune disease (e.g. AIHA)
Malignancy (e.g. NHL)
112
What are the clinical features of antibody deficiency?
Bacterial infections (e.g. Staphylococcus)
Toxins (e.g. tetanus)
Some viral infections (e.g. enterovirus)
113
List some investigations that may be used for suspected B cell deficiencies.
Total white cell count and differential
Lymphocyte subsets
Serum immunoglobulins and protein electrophoresis
Functional tests of B cell function (e.g. measure IgG antibody against a specific pathogen (e.g. S. pneumoniae), if this is low, vaccinate using a killed vaccine and check levels again in 6-8 weeks)
NOTE: IgG production is a surrogate marker for CD4+ T helper cell function
114
Which peak represents immunoglobulin in protein electrophoresis?
Gamma peak
115
What is the difference between autoinflammatory and autoimmune diseases?
Autoinflammatory – driven by components of the innate immune system
Autoimmune – driven by components of the adaptive immune system
116
Mutations in which pathways are implicated in monogenic autoinflammatory disease?
Innate immune cell function – abnormal signalling via key cytokine pathways involving TNF-alpha or IL-1
117
Which protein is upregulated in autoinflammatory diseases caused by a gain-of-function mutation in NLRP3? Name 3 diseases that are caused by this mutation.
Cryopyrin (NALP3)
Muckle Wells syndrome
Familial cold autoinflammatory syndrome
Chronic infantile neurological cutaneous articular syndrome
All of these are autosomal dominant
NOTE other examples of monogenic autoinflammatory conditions: TNF receptor associated periodic syndrome (TNF receptor mutation), Hyper IgD with periodic fever syndrome (mevalonate kinase mutation)
118
Which gene mutation causes Familial Mediterranean Fever and which protein does this gene encode?
MEFV gene
Encodes pyrin-marenostrin which is a negative regulator of the inflammatory pathway
119
Which mutations can lead to hyperactivity of the inflammasome complex?
Loss of function of pyrin-marenostrin
Gain of function of cryopyrin
120
What is the inheritance pattern of Familial Mediterranean Fever?
Autosomal recessive
121
Which cells contain pyrin-maronestrin?
Neutrophils
122
Outline the clinical presentation of Familial Mediterranean Fever.
Periodic fevers lasting 48-96 hours associated with
· Abdominal pain (peritonitis)
· Chest pain (pleurisy, pericarditis)
· Arthritis
· Rash
123
What is a complication of Familial Mediterranean Fever?
AA amyloidosis (due to chronic elevation of serum amyloid A)
This can deposit in the kidneys causing nephrotic syndrome and renal failure
124
Outline the treatment of Familial Mediterranean Fever.
Colchicine 500 µg BD (binds to tubulin and disrupt neutrophil migration and chemokine secretion)
2nd line: blocking cytokines
· Anakinra – IL1 receptor blocker
· Etanercept – TNF-alpha blocker
125
What does APECED stand for?
Autoimmune polyendocrinolpathy candidiasis ectodermal dystrophy
NOTE: it is autosomal recessive
126
What mutation causes APECED? What is the role of this gene?
AIRE – this is a transcription factor that is responsible for the expression of self-antigens in the thymus and promotes apoptosis of self-reactive T cells
Defects in AIRE leads to a failure of central tolerance and the release of auto-reactive T cells
127
Which autoimmune conditions tend to occur in APECED?
Hypoparathyroidism (COMMON)
Addison’s disease (COMMON)
Hypothyroidism
Diabetes mellitus
Vitiligo
128
Why are patients with APECED prone to Candida infections?
They produce antibodies against IL17 and IL22
129
What does IPEX stand for?
Immune dysregulation polyendocrinopathy enteropathy X-linked syndrome
130
What mutation causes IPEX? What is the role of this gene?
FoxP3 – required for the development of Treg cells
A lack of Tregs leads to autoantibody formation
131
Which autoimmune conditions are often seen in IPEX?
Enteropathy
Diabetes mellitus
Hypothyroidism
Dermatitis
132
What does ALPS stand for?
Autoimmune lymphoproliferative syndrome
133
Which mutations cause ALPS?
Mutations in the FAS pathway leading to defects in apoptosis of lymphocytes
This leads to a failure of lymphocyte tolerance (as autoreactive lymphocytes don’t die by apoptosis) and failure of lymphocyte homeostasis (you keep producing lymphocytes)
134
Describe the clinical phenotype of ALPS.
High lymphocyte count
Large spleen and lymph nodes
Autoimmune disease (usually cytopaenias)
Lymphoma
135
What is the best known chromosomal region that is implicated in Crohn’s disease?
IBD1 on chromosome 16
136
Outline the treatment approaches to Crohn’s disease.
Corticosteroids
Azathioprine
Anti-TNF-alpha antibodies
Anti-IL12/23 antibodies
137
What is the strongest genetic association of ankylosing spondylitis?
HLA-B27
NOTE: others include IL23R, ERAP1, ANTXR2 and ILR2
138
Where does ankylosing spondylitis tend to manifest?
At sites with high shear forces (i.e. entheses)
139
What are the treatment options for ankylosing spondylitis?
NSAIDs
Immunosuppression (Anti-TNF-alpha and ant-IL17)
140
List the autoimmune diseases associated with the following HLA polymorphisms:
a. DR3
Graves’ disease
SLE
b. DR3/4
Type 1 diabetes mellitus
c. DR4
Rheumatoid arthritis
d. DR15
Goodpasture’s syndrome
141
Name and state the function of 2 genes that are involved in T cell activation and are often mutated in polygenic autoimmune disease.
PTPN22 – suppresses T cell activation
CTLA4 – regulates T cell function (expressed by T cells)
142
Outline the Gel and Coombs effector mechanisms of immunopathology.
Type I: immediate hypersensitivity which is IgE-mediated
Type II: antibody reacts with cellular antigen
Type III: antibody reacts with soluble antigen to form an immune complex
Type IV: delayed-type hypersensitivity, T cell-mediated response
NOTE: autoimmunity is most common with type II hypersensitivity
143
Outline the pathophysiology of IgE-mediated type I responses.
gE binds to a foreign antigen (e.g. pollen)
The Fc portion binds to mast cells and basophils leading to degranulation
NOTE: this mechanism is implicated in eczema
144
What is a type V hypersensitivity reaction?
Antibodies activate or block cellular receptors (e.g. Graves’ disease, myasthenia gravis)
145
What are the consequences of immune complex formation in type III hypersensitivity reactions?
Immune complexes can deposit in blood vessels (especially in the kidneys, joints and skin)
They activate complement and inflammatory cells through their Fc portion
146
Give some examples of type IV hypersensitivity mediated diseases and state the autoantigen involved.
Insulin-dependent diabetes mellitus – pancreatic beta-cell antigen
Multiple sclerosis – myelin basic protein, proteolipid protein, myelin oligodendrocyte glycoprotein
147
Describe the relationship between Langerhans cells and Th2 cells.
Langerhans cells promote the secretion of Th2 cytokines
NOTE: skin defects (i.e. epithelial barrier issues) are a significant risk factor for the development of IgE antibodies via Th2 responses
148
How is oral allergen exposure different from respiratory or skin exposure with regards to developing an allergic response?
Oral exposure promotes immune tolerance whereas skin and respiratory exposure promotes IgE sensitisation
When an allergen is ingested orally, Tregs in the GI mucosa will inhibit IgE synthesis to keep the immune system in balance
149
List some clinical features of IgE-mediated allergic responses.
Angioedema
Urticaria
Flushing
Itching
Cough
SOB
Wheeze
150
List some elective investigations for allergic disease.
Skin prick and intradermal tests
Specific IgE measurement
Component resolved diagnostics
Basophil activation test
Challenge test
151
List some investigations that may be conducted during an acute allergic episode.
Serial mast cell tryptase
Blood/urine histamine
152
Does a positive specific IgE test demonstrate allergy?
No – it demonstrates sensitisation
153
What features of the specific IgE test are used to predict risk and likelihood of symptoms?
Concentration - higher levels means more symptoms
Affinity to the target – higher affinity means increased risk
Capacity of IgE antibody to induce mast cell degranulation
154
What are the advantages and disadvantages of skin prick testing?
Advantages
· Rapid (15-20 mins)
· Cheap
· High negative predictive value
· Increasing size of wheals correlates with higher probability of allergy
Disadvantages
· Operator-dependent
· Risk of anaphylaxis
· Poor positive predictive value
· Limited value in patients with dermatographism or extensive eczema
155
List some indications for specific IgE tests.
Patients who cannot stop antihistamines
Patients with dermatographism
Patients with extensive eczema
History of anaphylaxis
Borderline skin prick results
156
List some indications for allergy component testing.
Detect primary sensitisation
Confirm cross-reactivity
Define risk of serious reaction for stable allergens
157
What is mast cell tryptase used for?
it is a biomarker for anaphylaxis
158
When does mast cell tryptase reach peak levels and return to baseline levels?
Peak = 1-2 hours
Baseline = 6-12 hours
NOTE: if it fails to return to baseline, it may suggest systemic mastocytosis
159
What is the gold standard test for diagnosing food and drug allergy?
Challenge test
160
List some mechanisms of anaphylaxis.
IgE – mast cells and basophils – histamine and PAF (triggered by food, venom, ticks, penicillin)
IgG – macrophages and neutrophils – histamine and PAF (triggered by blood product transfusions)
Complement – mast cells and macrophages – histamine and PAF (triggered by lipid excipients, liposomes, dialysis membranes)
Pharmacological – mast cells – histamine and leukotrienes (triggered by NSAIDs)
161
List some reactions that can mimic anaphylaxis.
SKIN - Chronic urticaria and angioedema (ACE inhibitors)
THROAT SWELLING – C1 inhibitor deficiency
CVS – MI and PE
RESP – severe asthma, inhaled foreign body
NEUROPSYCH – anxiety/panic disorder
ENDOCRINE – carcinoid, phaeochromocytoma
TOXIC – scromboid toxicity (histamine poisoning)
IMMUNE – systemic mastocytosis
162
Which supportive treatments are given alongside adrenaline in the management of anaphylaxis?
Adjust body position
100% O2
Fluid replacement
Inhaled bronchodilators
Hydrocortisone 100 mg IV
Chlorpheniramine 10 mg IV
163
What is the key difference between food allergy and food intolerance?
The mechanism behind food intolerance is NOT immunological
164
List some types of food allergy.
IgE mediated – anaphylaxis
Mixed IgE and cell-mediated – atopic dermatitis
Non-IgE mediated – coeliac disease
Cell-mediated – contact dermatitis
165
Which organ is most commonly transplanted?
Kidneys
Followed by liver
166
What is the average half-life of a transplanted kidney?
12 years
167
What are the most relevant cellular proteins that can determine compatibility?
ABO
HLA
168
Which chromosome is HLA encoded on?
Chromosome 6
169
Which alleles encode HLA Class I and Class II?
Class I: A, B and C
Class II: DP, DQ, DR
170
Where are HLA Class I and Class II expressed?
Class I: all cells
Class II: antigen-presenting cells (can be upregulated at times of stress)
171
Which HLA alleles are most immunogenic?
A, B and DR
172
What are the actions of activated T cells?
Proliferation
Production of cytokines (IL2 is important)
Provide help for CD8+ T cells
Provide help for antibody production
Recruit phagocytes
173
Which test is used to give a definitive diagnosis of graft rejection?
Biopsy
174
Describe the effector phase of T-cell mediated graft rejection
T cells tether, roll and arrest on the endothelial cell surface
They will migrate across into the interstitium and start attacking the tubular epithelium
Macrophages (recruited by T cells) may also be seen in the interstitium
175
What are the typical histological features of T-cell mediated rejection?
Lymphocytic interstitial infiltration
Ruptured tubular basement membrane
Tubulitis (inflammatory cells within the tubular epithelium)
176
What other explanation might there be for graft failure other than rejection?
Immunosuppressive drugs may be nephrotoxic
177
What is a key difference between the production of anti-AB and anti-HLA antibodies?
Anti-AB antibodies are naturally occurring (pre-formed)
Anti-HLA antibodies are not naturally occurring but can be pre-formed due to previous exposure to epitopes (e.g. previous transplant, pregnancy) or post-formed (after transplantation)
178
What are the main histological features of antibody-mediated transplant rejection?
Presence of inflammatory cells within the capillaries of the graft (HALLMARK)
Immunohistochemistry can show fixation of complement fragments on the endothelial cell surface
179
What are the three main approaches to preventing graft rejection?
AB/HLA typing
Screening for antibodies
Overcoming organ mismatch issues
180
How can organ mismatch issues be overcome?
Improve transplantation across tissue barriers
More donors
Organ exchange programmes
Xenotransplantation and stem cell research
181
What T cell pathway is the main target for immunosuppressive drugs used in transplants?
The main signal is between MHC and TCR
Downstream, there are a number of pathways that involve calcineurin which result in cell proliferation
Once activated, T cells will release IL2 which has autocrine and paracrine effects on Th2 cells
These are all targets for immunosuppression
182
Name two calcineurin inhibitors.
Tacrolimus
Ciclosporin
183
Name two cell cycle inhibitors.
Mycofenolate mofetil
Azathioprine
184
Name two drugs that target TCR.
Anti-CD3 antibody (OKT3)
Anti-thymocyte globulin
185
Name an anti-CD52 antibody and state its effect.
Alemtuzumab – causes lysis of T cells
186
Name an anti-CD25 antibody and state its effect.
Daclizumab – targets cytokine signalling
187
What is rituximab?
Anti-CD20 – causes depletion of B cells
188
How to BAFF inhibitors work?
Target cytokines (BAFF) that promote B cell activation and growth
189
Name a proteasome inhibitor and describe how it works.
Bortezomib
Blocks the production of antibodies by plasma cells
190
Name a complement inhibitor.
Eculizumab
191
Outline the components of modern transplant immunosuppression regimes.
Induction agent (e.g. OXT3, anti-CD52, anti-CD25)
Baseline immunosuppression (e.g. calcineurin inhibitor, mycofenolate mofetil, azathioprine, steroids)
Treatment of acute rejection
· Cellular: steroids, OKT3
· Antibody-Mediated: IVIG, plasma exchange, anti-CD20
192
How can GVHD be prevented?
Methotrexate/ciclosporin
193
List some symptoms of GVHD.
Rash
Nausea and vomiting
Abdominal pain
Diarrhoea/bloody stools
Jaundice
194
List some opportunistic infections that are more common in transplant recipients.
CMV
BK virus
PCP
195
List some malignancies that are more common in transplant recipients.
Kaposi sarcoma (HHV8)
Lymphoproliferative disease (EBV)
Skin cancer
196
Describe how HIV affects CD8+ T cells.
CD4+ T cells are disabled by HIV which means that monocytes and dendritic cells are not activated by CD4+ cells and so cannot prime CD8+ T cells
Therefore, CD8+ T cell and B cell responses are diminished in HIV
197
List some advantageous features that HIV can acquire through mutation.
Escape from neutralising antibodies
Escape from HIV-1 specific T cells
Resistance and escape from antiretroviral drugs
198
List the steps in the life cycle of HIV.
Attachment and entry
Reverse transcription and DNA synthesis
Integration
Viral transcription
Viral protein synthesis
Assembly of virus and release of virus
Maturation
199
What are the screening and confirmatory tests for HIV?
Screening: HIV antibody ELISA
Confirmatory: HIV antibody Western blot
200
List some antigens that are found on T cells.
CD3
CD4
CD8
CD19
CD56
201
What are the effects of HAART?
Substantial control of viral replication
Increase in CD4+ count (initially because of memory cell redistribution, and later due to a rise in thymic naïve T cells)
Improvement in host defences
202
What are the limitations of HAART?
Does not eradicate latent HIV-1
Fails to restore HIV-specific T cell responses
Threat of drug resistance
Significant toxicities
High pill burden
Adherence
Quality of life
Cost
203
What are the two ways in which B cells can undergo clonal expansion once activated?
They can differentiate into T-cell independent IgM plasma cells
They can undergo a germinal centre reaction (with help from T helper cells) and become IgG memory and plasma cells
204
Which type of T cell undergoes a more pronounced proliferation following activation?
CD8 > CD4
205
List three types of antigen-presenting cell.
Dendritic cells
Macrophages
B lymphocytes
206
Which cell surface receptor is used in the influenza vaccine?
Haemagglutinin (HA) – this is a receptor-binding and membrane fusion glycoprotein
207
How long does protection from the influenza vaccine last?
Starts 7 days after the vaccine and protection lasts for 6 months
208
What agent is used in the BCG vaccine?
Attenuated strain of Mycobacterium bovis
209
Describe the protection that is achieved by using the BCG.
Some protection against primary infection
Mainly protects against progression to active TB
NOTE: T cell response is important in protection
NOTE: protection lasts for 10-15 years
210
What is the Mantoux test?
A small amount of liquid tuberculin (PPD) is injected intradermally
The area of injection is examined 48-72 hours after the injection
A reaction would appear as a wheal around the injection site (this is suggestive of latent TB, active TB or previous BCG)
211
What is a live attenuated virus vaccine? List some examples.
The organism is alive but modified to limit its pathogenesis
Examples: MMR, typhoid, BCG, yellow fever, polio (Sabin)
212
List some examples of toxoid vaccines
Diphtheria
Tetanus
213
List some examples of component/ subunit vaccines
Hep B (HBsAg)
HPV (capsid)
Influenza (HA)
214
List some examples of conjugate vaccines.
Haemophilus influenzae type B
Meningococcus
Pneumococcus
215
Describe how adjuvants work.
Increases the immune response without altering its specificity
They mimic the action of PAMPs on TLR and other PRRs
216
List some examples of adjuvants.
Aluminium salts (MOST COMMON)
Lipids (monophosphoryl lipid A)
217
What are dendritic cell vaccines?
Used against tumours
You collect some dendritic cells from the patient and load them with the antigen from the tumour to try and boost the immune response against tumour antigens
218
What are the main indications for haematopoietic stem cell transplantation?
Life-threatening immunodeficiency (SCID)
Haematological malignancy
219
List some indications for IVIG.
Primary antibody defect
· X-linked agammaglobulinaemia
· X-linked hyper IgM syndrome
· Common variable immunodeficiency
Secondary antibody defect
· CLL
· Multiple myeloma
· After bone marrow transplantation
220
Using an example, describe how virus-specific T cells are used.
Used for EBV in patients who are immunosuppressed to prevent the development of lymphoproliferative disease
Blood is taken from the patient or from a donor
Peripheral blood mononuclear cells are isolated and stimulated with EBV peptides
This creates an expansion of EBV-specific T cells which are then reinfused into the patient
NOTE: tumour infiltration T cell therapy follows the same principle but uses tumour antigens
221
What is ipilimumab and how does it work?
CTLA4 and CD28 are both expressed by T cells and they recognise antigens (CD80 and CD86) on APCs
Signalling through CD28 results in a stimulatory response
Signalling through CTLA4 results in an inhibitory response
Ipilimumab is a monoclonal antibody that blocks CTLA4 thereby removing this inhibitory response
It is used in advanced melanoma
222
Explain the use of antibodies against PD-1 in treating cancer.
PD-1 and PD-2 ligands are present on APCs and interact via PD-1 receptors on T cells to cause an inhibitory response
They can also be expressed by some tumour cells
Pembrolizumab and nivolumab are antibodies that are specific to PD-1, thereby blocking this effect
This is also used in advanced melanoma
223
List some examples of the therapeutic use of recombinant cytokines.
Interferon alpha – used as an adjunct in the treatment of Hep B, Hep C, Kaposi sarcoma, CML and multiple myeloma
Interferon beta – Behcet’s disease, relapsing MS
Interferon gamma – chronic granulomatous disease
224
List some side-effects of corticosteroids.
Central obesity
Moon face
Easy bruising
Thin skin
Osteoporosis
Diabetes
Cataracts
Glaucoma
Peptic ulceration
Immunosuppression
225
List some examples of anti-proliferative agents.
Cyclophosphamide
Mycophenolate
Azathioprine
Methotrexate
226
List some indications of cyclophosphamide.
Multisystem connective tissue disease
Vasculitis
Anti-cancer
227
List some side-effects of cyclophosphamide.
Toxic to proliferating cells – bone marrow suppression, sterility (mainly males), hair loss
Haemorrhagic cystitis – due to toxic metabolic (acrolein) in the urine
Malignancy – bladder cancer, haematological malignancy, non-melanoma skin cancer
Teratogenic
Infection (e.g. PCP)
228
List some indications for azathioprine.
Transplantation
Autoimmune
Autoinflammatory (e.g. Crohn’s)
229
List some side-effects of azathioprine.
Bone marrow suppression
Hepatoxicity
Infection
230
Which precaution must you take before starting a patient on azathioprine?
Check TPMT activity – 1 in 300 individuals have a TPMT polymorphism which means that they are unable to metabolise azathioprine leading to bone marrow suppression
231
List some indications for mycophenolate mofetil.
Transplantation
Autoimmune disease
Vasculitis
232
List some side-effects of mycophenolate mofetil.
Bone marrow suppression
Teratogenic
Infection (particularly HSV reactivation and PML (JC virus))
233
List some indications for plasmapheresis.
Severe antibody-mediated disease (e.g. Goodpasture’s, acute myasthenia gravis, severe transplant rejection)
234
What are the main side-effects of calcineurin inhibitors?
Hypertension and nephrotoxicity (also diabetes, nephrotoxic)
235
Give an example of a JAK inhibitor.
Tofacitinib (JAK1 and JAK2 inhibitor)
236
Give an example of a PDE4 inhibitor.
Apremilast
237
Which antigen does basiliximab target
Anti-CD25
238
WHich antigen does abatacept target
CTLA4-Ig
239
Which antigen does rituximab target
Anti-CD20
240
WHich antigen does natalizumab target
Anti-a4 integrin
241
WHich antigen does tocilizumab target
Anti-IL6 receptor
242
List some side-effects of anti-thymocyte globulin.
Infusion reactions
Leukopaenia
Infection
Malignancy
243
List some indications for rituximab.
Lymphoma
Rheumatoid arthritis
SLE
NOTE: it is given as two IV doses every 6-12 months
244
What is the main indication of natalizumab?
Multiple sclerosis
245
What are the main indications of tocilizumab?
Castleman’s disease (IL6-producing tumour)
Rheumatoid arthritis
246
List some anti-TNFa antibodies.
Infliximab
Adalimumab
Certolizumab
Golimumab
247
List some uses of anti-TNF alpha antibodies.
Rheumatoid arthritis
Ankylosing spondylitis
Psoriasis
IBD
248
List some side-effects of anti-TNF alpha antibodies.
Infusion reactions
Infection
Lupus-like conditions
Demyelination
Malignancy
249
Which antibodies is Hashimoto’s thyroiditis associated with?
Anti-TPO antibodies
Anti-thyroglobulin antibodies
NOTE: these can be present in normal people
250
List some autoantibodies that are found in type I diabetes mellitus.
Anti-GAD
Anti-IA2
Anti-islet cell
Anti-insulin
251
Outline the pathophysiology of pernicious anaemia.
Patients develop antibodies against intrinsic factor which leads to failure of absorption of vitamin B12
252
What is a major complication of vitamin B12 deficiency?
Subacute degeneration of the spinal cord (involved the posterior and lateral columns)
NOTE: other neurological features include peripheral neuropathy and optic neuropathy
253
Which antibodies are useful in the diagnosis of pernicious anaemia?
Anti-parietal cell antibodies
Anti-intrinsic factor antibodies
254
Which investigations may be used in the diagnosis of myasthenia gravis?
EMG studies are usually abnormal
Tensilon test – administer very short-acting acetylcholinesterase (e.g. edrophonium bromide) which causes a rapid improvement in symptoms
255
Which antibodies may be present in myasthenia gravis?
Anti-acetylcholine receptor antibodies
256
What type of hypersensitivity reaction is myasthenia gravis?
Type II hypersensitivity
257
List some genetic polymorphisms that predispose to rheumatoid arthritis.
HLA DR1
HLA DR4
PTPN22
PAD 2 and PAD 4 polymorphisms
Polymorphisms affecting TNF, IL1, IL6 and IL10
258
List some environmental factors that contribute to the pathogenesis of rheumatoid arthritis.
Smoking is associated with the development of erosive disease (due to increased citrullination)
Gum infection by Porphyromonas gingivalis is associated with rheumatoid arthritis as it expresses PAD, thereby promoting citrullination
259
Name and describe the antibodies that are often detected in the diagnosis of rheumatoid arthritis.
Anti-cyclic citrullinated peptide antibodies – bind to peptides where arginine has been converted to citrulline, 95% specific, 60-70% sensitive
Rheumatoid factor – IgM antibody directed against Fc region of human IgG
NOTE: there are IgA and IgG variants of RF
260
What happens to joints affected by rheumatoid arthritis?
The synovium becomes inflamed forming a pannus
This invades articular cartilage and adjacent bone
There is also an increased synovial fluid volume
261
What are antinuclear antibodies and how are they tested?
Group of antibodies against nuclear proteins
Tested by staining Hep-2 (human epidermoid cancer line) cells
NOTE: these are very common and are often present in healthy individuals
262
Which type of hypersensitivity reaction is SLE?
Type III hypersensitivity – antibodies bind to antigens forming immune complexes which deposit in tissues (e.g. skin, joints, kidneys) and activated complement via the classical pathway
These antibodies can also stimulate cells that express Fc receptors
263
What are the two types of ANA and how can they be distinguished?
Anti-dsDNA – homogenous staining pattern, they are highly specific for SLE and high titres are associated with severe disease (useful for disease monitoring)
Anti-ENA4 (extractable nuclear antigens such as ribonucleoproteins (e.g. Ro, La, Sm))
264
Which disease are anti-Ro and anti-La antibodies characteristically found in?
Sjogren’s syndrome
NOTE: these antibodies are not helpful in monitoring disease activity
265
List some other autoantibodies that are implicated in autoimmune disease.
Scl70, RNA polymerase, fibrillarin – diffuse cutaneous systemic sclerosis
Mi2, SRP – idiopathic inflammatory myopathies
266
Other than dsDNA, which other quantifiable component can be measured as a surrogate marker for disease activity in SLE?
C3 and C4 – C4 will decrease before C3
NOTE: we measure unactivated complement proteins
267
What triad defines antiphospholipid syndrome?
Recurrent venous or arterial thrombosis
Recurrent miscarriage
Thrombocytopaenia
268
Which antibodies are tested for in antiphospholipid syndrome?
Anti-cardiolipin antibody – immunoglobulins directed against phospholipids and b2 glycoprotein-1
Lupus anticoagulant – prolongation of phospholipid-dependent coagulation tests.
NOTE: cannot be assessed if the patient is on anticoagulant therapy
NOTE: both tests should be performed as 40% of patients have disconcordant antibodies
269
Which cells are particularly important in the pathophysiology of systemic sclerosis?
Th2 and Th17
270
What are the main features of limited cutaneous systemic sclerosis?
Skin involvement does not extend beyond the forearms
Calcinosis
Raynaud’s phenomenon
Esophageal dysmotility
Sclerodactyly
Telangiectasia
NOTE: also pulmonary hypertension
271
What are the main features of diffuse cutaneous systemic sclerosis?
Skin involvement extends beyond the forearms
CREST features
More extensive gastrointestinal disease
Interstitial pulmonary disease
Renal cysts
272
Which antibodies are seen in limited and diffuse cutaneous systemic sclerosis?
Limited – anti-centromere
Diffuse – anti-topoisomerase 2 (aka anti-Scl70)
273
Describe the differences between the histology of dermatomyositis and polymyositis.
Dermatomyositis – perivascular CD4+ T cell and B cells are seen, this can cause an immune complex-mediated vasculitis (type III response)
Polymyositis – CD8+ T cells surround HLA Class I expressing myofibres, CD8+ T cells kill these myofibres via granzyme/perforin (type IV response)
274
Which antibodies are seen in dermatomyositis
anti-aminoacyl tRNA synthetase (e.g. Jo-1), anti-Mi2
275
Which antibodies are seen in polymyositis
anti-signal recognition peptide antibody
276
Which classification system is used for systemic vasculitides?
Chapel Hill
277
Which small vessel vasculitides are associated with ANCA?
Microscopic polyangiitis (pANCA)
Churg-Strauss syndrome (pANCA)
Granulomatosis with polyangiitis (cANCA)
278
Outline the management of anaphylaxis.
ABCDE approach
Respiratory support if necessary
Oxygen by mask
IM adrenaline (0.5 mg)
IV antihistamine (10 mg chlorpheniramine)
IV corticosteroid (200 mg hydrocortisone)
IV fluids
Nebulised bronchodilators
NOTE: steroids take about 30 mins to start working but they are important in preventing rebound anaphylaxis
279
List some common causes of anaphylaxis.
Foods: peanuts, fish, shellfish, milk, eggs, soy
Insect stings: bee venom, wasp venom
Chemicals, drugs and other foreign proteins: penicillin, IV anaesthetic, latex
280
What can a type I hypersensitivity reaction to latex cross-react with?
Avocado
Apricot
Banana
Passion fruit
Papaya
NOTE: basically quite a lot of fruit
281
Describe the appearance of biopsy of urticarial tissue in anaphylaxis.
Infiltrating T cells
Granulomas
282
List some disorders associated with recurrent meningococcal meningitis.
Complement deficiency (increases risk of encapsulated organisms)
Antibody deficiency (causes recurrent bacterial infections)
Neurological (disturbance of blood-brain barrier (e.g. hydrocephalus, occult skull fracture))
283
Which investigation are typically used to investigate complement deficiency?
CH50 (classical pathway)
AP50 (alternative pathway)
C3 and C4
284
Which condition is characterised by a failure to produce any immunoglobulin?
X-linked agammaglobulinaemia – failure of pre-B cells to mature in the bone marrow leading to failure of production of antibodies
285
Which investigation is used to diagnose multiple myeloma?
Serum protein electrophoresis – shows a monoclonal band (this can be stained to check whether it is composed of heavy or light chains)
286
Which red blood cell abnormality may you see in the blood film of a patient with multiple myeloma?
Rouleaux formation
NOTE: you may also see Bence-Jones protein in the urine
287
What are the key clinical features of rheumatoid arthritis?
Peripheral, symmetrical polyarthritis with stiffness lasting > 6 weeks
288
When does rheumatoid arthritis commonly present and what is a possible explanation for this?
Post-partum – Th2 cells predominate during pregnancy and this switches back to Th1 post-partum
289
Describe how specific HLA alleles can predispose to the development of rheumatoid arthritis.
HLA-DR4 (60-70%) and HLA-DR1
290
Outline the management of rheumatoid arthritis.
First-line: methotrexate
Other options: TNF-alpha antagonists, rituximab, abatacept (CTLA4-Ig fusion protein), tocilizumab (antibody against IL6 receptor)
291
List some risks of biological therapy for rheumatoid arthritis.
TB
Opportunistic infections
Malignancy
