Immunology (Respiratory) Flashcards
1
Q
What is the acronym which contains the clinical features suggestive of immunodeficiency?
A
SPUR
2
Q
What are all the parts of the SPUR acronym?
A
S - serous infection (unresponsive to oral antibiotics). P - persistent infections (early structural damage, chronic infections). U - unusual infections (unusual organisms, unusual sites). R - recurrent infections (two major or one major and recurrent minor infections in one year).
3
Q
What are the other features of immunodeficiencies?
A
Weight loss or failure to thrive, severe skin rash, chronic diarrhoea, mouth ulceration, unusual autoimmune disease, family history.
4
Q
What can lead to secondary immune deficiency?
A
Physiological immune deficiency (extremes of age), infection (HIV, measles), treatment interventions (immunosuppressive therapy, chemotheraphy, steroids), malignancy (cancers of immune system e.g. lymphoma, leukaemia, myeloma; metastatic tumours), biochemical and nutritional disorders (malnutrition, renal insufficiency/dialysis, type 1 and 2 diabetes, specific mineral deficiencies).
5
Q
What are the clinical features of phagocyte deficiencies?
A
Recurrent infections affecting common and unusual sites. Organisms include common (staph aureus) and unusual bacteria (burkholderia cepacian, mycobacteria, fungi).
6
Q
What is reticular dysgenesis and what will happen to babies with this inherited condition?
A
Where the haematopoetic stem cells can’t differentiate. They will die within a few days.
7
Q
What is the differentiation problem in Kostmann syndrome?
A
The granulocyte-monocyte progenitor can’t differentiate into neutrophils.
8
Q
What autosomal recessive disorder results in severe chronic neutropenia?
A
Kostmann Syndrome.
9
Q
What is the clinical presentation of Kostmann syndrome?
A
Infections usually within 2 weeks of birth (recurrent bacterial infection, systemic or localised). Non-specific: fever, irritability, oral ulceration, failure to thrive.
10
Q
What are the supportive treatments that can be used to manage Kostmann syndrome?
A
Prophylactic antibiotics, prophylactic antifungals (mortality 70% in first year without definitive treatment).
11
Q
What is the definitive treatment in Kostmann syndrome?
A
Stem cell transplantation with granulocyte colony stimulating factor (G-CSF, specific growth factor to assist maturation of neutrophils).
12
Q
What is leukocyte adhesion deficiency?
A
Failure to recognise activation markers expressed on endothelial cells. Neutrophils are mobilised but cannot exit bloodstream.
13
Q
What genetic defect is leukocyte adhesion deficiency caused by?
A
Defect in leukocyte integrins (CD18).
14
Q
What is the clinical presentation of leukocyte adhesion deficiency?
A
Leucocytosis (increase in white blood cells) and localised bacterial infections that are difficult to detect.
15
Q
What opsonins bind to receptors on the phagocyte surface in indirect recognition?
A
C3b, IgG and C-reactive protein.
16
Q
What are the different receptors on phagocytes for antibodies bound to antigens and complement fragments bound to antigens?
A
Fc receptors for antibody bound to antigen, complement receptor 1 (CR1) for complement fragments bound to antigen.
17
Q
What may a defect in opsonin receptors cause and why does this not generally cause significant disease?
A
Defective phagocytosis. Significant redundancy (think it means it is not that important a mechanism).
18
Q
What other type of defect may result in decreased efficiency of opsonisation?
A
Any defect of complement/antibody production.
19
Q
What is absent respiratory burst and what is the commonest form?
A
Deficiency of the intracellular killing mechanisms of phagocytes. Commonest form is deficiency of p47phox component of NADPH oxidase (X-linked), causes inability to generate oxygen free radicals (ROS/RNS).
20
Q
What can failure of oxidative killing mechanisms lead to?
A
Excessive inflammation, failure to degrade chemoattractants and antigens so persistent accumulation of neutrophils, activated macrophages and lymphocytes, granuloma formation.
21
Q
What is the disease name when there is failure of oxidative killing mechanisms?
A
Chronic granulomatous disease.
22
Q
What are the clinical features of chronic granulomatous disease?
A
Recurrent deep bacterial infections (esp staph, aspergillus, pseudomonas, mycobacteria), recurrent fungal infections, failure to thrive, lymphadenopathy and hepatosplenomegaly (swelling of liver and spleen), granuloma formation.
23
Q
What is the lab investigation for chronic granulomatous disease?
A
NBT (nitroblue tetrazolium) test (shows whether neutrophils kill through production of oxidative free radicals).
24
Q
Describe the method of the NBT test.
A
Feed patient’s neutrophils source of E.coli, add dye sensitive to H2O2, if produced by neutrophils dye changes colour.
25
What are the supportive and definitive treatments for chronic granulomatous disease?
Supportive: prophylactic antibiotics and antifungals. Definitive: stem cell transplantation.
26
Give 3 examples of intracellular pathogens and 1 which hides within macrophages.
Salmonella, chlamydia, rickettsia. Mycobacteria.
27
Describe the pathway that allows defence against intracellular pathogens (specifically TB).
Infection with TB -> infected macrophages are stimulated to produce IL-12 -> IL-12 induces Th1 cells to secrete interferon gamma (INY) back to macrophages and neutrophils -> stimulates production of TNFA -> activates NADPH oxidase -> stimulates oxidative pathways.
28
Single gene defects in what are associated with susceptibility to intracellular bacteria?
IFNY receptor deficiency, IL-12 deficiency, IL-12 receptor deficiency.
29
How would you investigate how each stage of phagocyte function was occurring correctly?
Mobilisation from bone marrow (full blood count and differential), migration to site of infection (presence of pus, expression of neutrophil adhesion molecules), chemotaxis (chemotactic assays), formation of phagolysosome (phagocytosis assays), oxidative killing (NBT test).
30
Describe the 2 parts of treatment for phagocyte deficiencies.
Aggressive management of infection: infection prophylaxis (septrin, itraconazole [anti-fungal]), oral/IV antibiotics, surgical draining of abscesses.
Definitive therapy: bone marrow transplantation, specific treatment for CGD (gamma interferon therapy).
31
Describe the life cycle of a T lymphocyte.
Arise from haematopoetic stem cells in bone marrow -> undergo selection in thymus (10% survive) -> mature T lymphocytes enter circulation and reside in lymph nodes and secondary lymphoid follicles (approximately 10^7-10^9 clones).
32
Describe the development of a B lymphocyte.
Stem cells -> lymphoid progenitors -> pro B cells (IgM antibody) -> pre B cells (IgM and IgD) -> IgM B cells -> can differentiate into IgM plasma cells or other Ig producing cells which can then go on to form plasma cells.
33
When B cells are undergoing highly complex genetic rearrangements in the germinal centres, what is the Ig isotype switch influenced by?
Cytokines derived from Th1 and Th2 effector cells.
34
What are the functions of antibodies?
Identification of pathogens, recruitment of other components of immune response to remove pathogens (complement, phagocytes, NK cells), neutralisation of toxins, particularly important in defence against bacteria of all kinds.
35
What does defects of lymphoid precursors cause?
Severe combined immunodeficiency and failure of production of lymphocytes.
36
What is the clinical presentation of severe combined immunodeficiency?`
Unwell by 3 months of age, persistent diarrhoea, failure to thrive, infections of all types, unusual skin disease (graft versus host disease - colonisation of infant;s empty bone marrow by maternal lymphocytes), family history of early infant death.
37
What are some of the causes of severe combined immunodeficiency?
Deficiency of cytokine receptors, deficiency of signalling molecules, metabolic defects, defective receptor rearrangements.
38
What is the commonest form of severe combined immunodeficiency?
X-linked SCID (severe combined immunodeficiency).
39
What is the mutation in X-linked SCID and what does it cause?
Mutation of a component of IL-2 receptor. Results in inability to respond to cytokines so failure of T and NK cell development and production of immature B cells.
40
What is the clinical phenotype of X-linked SCID?
Very low or absent T cells, normal or increased B cells, poorly developed lymphoid tissues and thymus.
41
Describe the prophylactic and definitive treatment of SCID.
Prophylactic: avoid infections (prophylactic antibiotics/antifungals, no live attenuated vaccines), aggressive treatment of existing infections, antibody-replacement (IV immunoglobulin).
Definitive: stem cell transplant from HLA identical sibling if possible; other sibling or parent, or from matched unrelated donor.
42
What is the potential gene therapy for SCID?
Stem cells can be treated ex vivo to express the missing component, these cells have a survival advantage in vivo.
43
What syndrome is a developmental defect of the 3rd/4th pharyngeal pouch?
DiGeorge syndrome.
44
What does DiGeorge syndrome cause?
Low set ears that are abnormally folded, high forehead, cleft palate, small mouth and jaw, hypocalcaemia, oesophageal atresia (absence or closure), T cell lymphopenia and complex congenital heart disease.
45
What kind of infections do people with DiGeorge syndrome get and why?
Recurrent viral infections (CD8+ T cells are essential in killing virally-infected host cells), recurrent bacterial infections (effector CD4+ Tfh cells are essential for helping B cells make antibodies), frequent fungal infections (effector CD4+ Th cells are essential for defence against fungal pathogens).
46
What would the white cell count look like in Di George syndrome?
Absent or decreased number of T cells, normal or increased B cells, normal NK cell numbers.
47
Are recurrent bacterial or viral infections more common in immune deficiencies affecting B lymphocytes?
Bacterial.
48
What is the B cell maturation defect in Bruton's X-linked hypogammaglobulinaemia?
Pro B cells do not differentiate into pre B cells, so no circulating B cells.
49
What can a selective IgA deficiency cause?
1/3rd of people get recurrent respiratory tract infections.
50
What types of antibodies are low in common variable immune deficiency?
IgG, IgA and IgE.
51
What are the clinical features of common variable immune deficiency?
Recurrent bacterial infection (often with severe end-organ damage e.g. bronchiectasis, persistent sinusitis, recurrent GI infection), autoimmune disease, granulomatous disease.
52
What is the genetic defect in X-linked hyper IgM syndrome (HIGM syndrome)?
Defective CD40 signalling via B cells affecting Ig class switch recombination (CSR) and somatic hypermutation.
53
What co-stimulatory signal is essential for full B cell activation/differentiation and the germinal centre reaction?
Interaction between CD40 ligand (antigen-activated B cells) and CD40 (effector Tfh cells).
54
What are the clinical features of B cell deficiencies?
Recurrent infections (often very common bacteria), opportunistic infections, antibody-mediated autoimmune disease.
55
What are the first line investigations of B cell deficiencies?
Total white cell count and differential, serum/urine immunoglobulins.
56
What are the second line investigations of B cell deficiencies?
Quantitation of B and T lymphocytes, specific antibody responses to host pathogens (measure IgG antibodies against pathogens, if low immunise with killed vaccine then test again 6-8 weeks later to see if antibody response has been mounted).
57
What are the management options for B cell deficiencies?
Aggressive treatment of infection, Ig replacement, stem cell transplantation in some situations.
58
What is hypersensitivity reaction?
Immune response that results in bystander damage to the self. Usually exaggeration of normal immune mechanisms.
59
What are Gel and Coomb's classification of hypersensitivity reactions?
Type I - immediate hypersensitivity. Type II - direct cell killing. Type III - immune complex mediated. Type IV - delayed type hypersensitivity.
60
.What is an allergy?
IgE mediated response to external antigen (allergen).
61
Describe the hygiene hypothesis.
Changes in microbial stimuli influences the maturation of the immune response e.g. general decrease in infectious burden in early life (resp infections in particular), variations in GI flora, results in increased predisposition to allergic conditions during early childhood.
62
Describe some Th1 differentiation stimuli.
Older siblings, early daycare oxposure, rural environment, childhood infections, microbial exposure.
63
Describe some lack of Th1 stimuli.
Only child, widespread use of antibiotics, urban environment with allergen sensitisation e.g. dust mites, cockroaches.
64
Why is genetics unlikely to be the cause of increasing prevalence of allergic disease?
Genetic changes in stable populations do not occur in the time frame.
65
What are the generic clinical features of type 1 allergic disease?
Occurs quickly after exposure (minutes to 1-2 hours), responses are stereotyped, may be associated with more than one organ system, presentation is influenced by site of contact, threshold for reactions may be influenced by cofactors such as exercise, alcohol and infection.
66
What are the specific clinical features/diseases associated with type 1 allergic disease?
Asthma, urticaria (hives), angioedema, allergic rhinitis (hayfever), allergic conjunctivitis (eye inflammation), diarrhoea and vomiting, anaphylaxis.
67
What are the cells and molecules involved in an allergic reaction?
B lymphocytes (recognise antigen, produce IgE), T lymphocytes (Th2 cells provide help for B lymphocytes to make IgE), mast cells and eosinophils and basophils (release vasoactive substances).
68
Describe the cellular response to allergen exposure.
Dendritic cells present allergen-derived peptides in the context of class II MHC molecules -> CD4+ T cells differentiate into Th2 cytokine-producing cells -> Th2 cells produce IL-4, 5 and 13 -> regulate synthesis of IgE by B cells, stimulate differentiation and egress of eosinophils from bone marrow into blood, and help to activate mast cells and eosinophils at sites of allergen exposure.
69
What interleukins do what in the cellular allergic response?
Regulation of synthesis of IgE by B cells - 4, 5 and 13. Stimulation of differentiation and egress of eosinophils from bone marrow into blood - 5. Help to activate mast cells and eosinophils at sites of allergen exposure - 4 and 13.
70
Where are mast cells found?
In tissues, especially at interface with external environment.
71
What vasoactive substances do mast cells produce?
Histamine, tryptase, heparin, leukotrienes, prostaglandins, proinflammatory cytokines e.g. IL-4 and TNFalpha.
72
What do mast cells do?
Orchestrate inflammatory cascade: increase blood flow, contract smooth muscle, increase vascular permeability, increase secretions at mucosal surfaces.
73
What are mast cells important in?
Defence against parasites and in wound healing.
74
What is the role of mast cells in allergic reactions?
Express Fc receptors for IgE on furface (FcepsilonR1 receptors) -> first encounter will allergen, B cells produce IgE -> allergen cleared -> residual IgE bind to circulating mast cells via Fc receptors -> re-encountered allergen binds to IgE-coated mast cells and disrupts cell membrane -> release of vasoactive mediators -> also increased cytokine and leukotriene transcription.
75
What makes sputum yellow?
Eosinophils.
76
What are the other names for urticaria, when does it appear and how long does it last for?
Hives, wheals, nettle rash, blisters. Lesions appear within an hour and last 2-6 hours, sometimes 24.
77
What is angioedema?
Self-limited, localised swelling of subcutaneous tissue or mucous membranes. Is a non-pitting oedema often without clear demarcation. Generally not itchy unless associated with urticaria.
78
What are the key features of an allergic history?
What does the patient mean by allergy? Ask about specific features of IgE mediated reactions. What allergens are involved? History of allergic disease? Previous investigations for allergy? Has elimination of trigger made any difference to symptoms?
79
What are the elective specific investigations for allergic disease?
Skin prick tests, quantitate specific IgE to putative allergen, challenge test (supervised exposure to the putative antigen).
80
What do you test for during an acute anaphylactic episode?
Serum tryptase levels (evidence of mast cell degranulation).
81
Give an example of a mast cell stabiliser, how does it work and when is it used?
Sodium cromoglicate, stabilises mast cell membranes, used as topical spray for prophylaxis (allergic rhinitis, exercise induced asthma, allergic conjunctivitis).
82
What are H1 receptor antagonists?
Antihistamines.
83
Other than antihistamines, what other drug type can help prevent the effects of mast cell activation?
Leukotriene receptor antagonists.
84
How does self-injectable adrenaline help in anaphylaxis?
Acts on B2 adrenoceptors to constrict arterial smooth muscle (increases blood pressure thereby limiting vascular leakage) and relaxing bronchial smooth muscle (decreases airflow obstruction).
85
Describe the immunotherapy for allergies.
Subcutaneous injections of tiny amount of allergen, followed by gradual increase in dose. Unknown mechanism of actions and may lead to inhibition of anaphylaxis. Risks: anaphylaxis.
86
What is a type II hypersensitivity reaction?
Direct cell killing (cell bound antigen). Antibody binds to cell surface antigens.
87
What does antibody binding result in in type II hypersensitivity reaction?
Complement activation and opsonisation.
88
What Ig is a good complement activator?
IgM.
89
What are the effects of complement activation?
Opsonisation, membrane attack complex (direct killing of bacteria esp encapsulated ones), solubilisation of immune complexes, chemotaxis (stimulate migration of macrophages and neutrophils).
90
What are the 3 pathways of activating complement?
Classical: antigen, antibody and C1 complex. Lectin pathway: MBL and mannose +ve pathogen. Alternative pathway: spontaneous C3 cleavage.
91
What are the main complement proteins that cause chemotaxis?
C3a and C5a.
92
Give some examples of opsonins.
C reactive protein (CRP), antibodies and complement C3b.
93
What can complement dissolve and what does this cause?
The immune complex which triggered them, switches off process of complement activation (negative feedback).
94
What is an immune complex?
An antigen and antibody bound together.
95
When does type II hypersensitivity occur?
When IgG or IgM binds to either self or foreign antigen on human cells.
96
What does type II hypersensitivity result in?
Phagocytosis, killer cell activity (ADCC, antibody dependent cellular cytotoxicity), or complement-mediated lysis.
97
What is a clinical example of type II hypersensitivity?
Immune haemolytic anaemias e.g. acute haemolytic transfusion reaction and drug-induced haemolysis.
98
What is acute haemolytic transfusion reaction (ATHR)?
When there is an antibody incompatibility with donor erythrocytes (RBCs) and recipient, leading to lysis of donor erythrocytes by pre-formed recipient antibodies.
99
In someone with ATHR, what will you detect in the urine?
Haemoglobin.
100
What should you do if someone has ATHR?
Stop the transfusion, monitor them, maybe give them fluids, do blood test on patient and blood in bag.
101
Give an example of drug-induced haemolysis.
Penicillin induced immune anaemia.
102
Describe the process of penicillin induced immune anaemia.
Penicillin is too small to induce antibodies, binds to protein on surface of red cells, penicillin acts as hapten and induces antibody production (IgG).
103
What could a suspected diagnosis of penicillin induced immune anaemia be confirmed by?
Tests showing presence of antibodies specific to RBC/penicillin complexes.
104
How are red cells destroyed in penicillin induced immune anaemia?
Antibody will bind to an FcR on a splenic macrophage and the red cell will be destroyed.
105
How would you manage type II hypersensitivity?
Plasmapheresis, immunosuppression (rebound antibody production limits efficacy of plasmapheresis, potent immunosuppressive given to switch of B cell production of antibody).
106
Describe the process of plasmapheresis.
Patient blood removed via cell separator (cellular constituents replaced, plasma replaced by plasma from someone else or pooled Ig, approx 50% of plasma removed each time).
107
What is type III hypersensitivity?
Immune complex mediated.
108
Describe the pathophysiology of type III hypersensitivity.
In presence of excess antigen, antibodies bind forming small immune complexes. These are trapped in small blood vessels, joints and glomeruli.
109
Describe how deposition of immune complexes causes cell damage.
1. Immune complexes are deposited in wall of blood vessel. 2. Presence of immune complexes activates complement and attracts inflammatory cells e.g. neutrophils. 3. Enzymes released from neutrophils cause damage to endothelial cells and basement membrane.
110
Describe the process of inflammation in farmer's lung (hypersensitivity pneumonitis).
Inhaled fungal particles deposited in lung -> stimulate antibody formation -> antibodies form immune complexes with antigen -> results in complement activation, inflammation and recruitment of other leukocytes.
111
What immunological response causes wheeze, breathlessness and malaise/pyrexia in hypersensitivity pneumonitis?
Wheeze: inflammation of terminal bronchioles and alveoli caused by activated phagocytes and complement.
Breathlessness: alveolitis, caused by activated phagocytes and complement (decreased transfer efficiency). Malaise/pyrexia: systemic manifestation of inflammatory response.
112
How would you manage type III hypersensitivity reactions?
Avoidance, decrease inflammation (corticosteroids), decrease production of antibody (immunosuppression).
113
What is type IV hypersensitivity and what is it mediated by?
Delayed type hypersensitivity, mediated by T cells.
114
Give some autoimmune disease examples of type IV hypersensitivity.
Type 1 diabetes, psoriasis, rheumatoid arthritis.
115
Give some non-autoimmune disease examples of type IV hypersensitivity.
Contact dermatitis, TB, leprosy, sarcoidosis, cellular rejection of solid organ transplant.
116
Describe the 2 stages of a type IV hypersensitivity reaction.
Initial sensitisation to antigen (generation of primed effector Th1 cells and memory T cells). Subsequent exposure (activation of previously primed T cells, recruitment of macrophages, other lymphocytes and neutrophils, release of proteolytic enzymes, persistent inflammation).
117
Describe the cellular process of contact dermatitis (poison ivy).
Chemical antigens cause activation, proliferation and differentiation of effector Th1 cells and memory cells. Subsequent exposure results in activation of Th1 cells that initiate an inflammatory response .
118
What are the functions of the following cytokines released from Th1 cells? Chemokines, IFNY, TNFalpha and LT, IL-3/GM-CSF
Chemokines: macrophage recruitment to site of antigen.
IFNY: activates macrophages, increasing release of inflammatory mediators. TNFalpha and LT: local tissue destruction, increased expression of adhesion molecules on local blood vessels. IL-3/GM-CSF: monocyte production by bone marrow stem cells.
119
Describe the cellular response in sarcoidosis.
Inhalation of unknown antigen -> stimulated alveolar macrophages and CD4 and CD8 T cells, also B cells within lung parenchyma -> failure to clear antigen results in persistent stimulation and granuloma formation -> persistent immune activation leads to tissue damage and fibrosis.
120
What is autoimmunity?
The presence of immune responses against self-tissue/cells.
121
Describe the steps in autoimmune disease.
Genetic susceptibility -> initiating event -> breakdown of self-tolerance (loss of immune regulation, generation of autoreactive B and T cells) -> autoimmune phenomena/disease.
122
What are monogenic autoimmune disorders?
Single gene defects causing autoimmune diseases (rare, e.g. IPEX syndrome).
123
What genetically do most autoimmune diseases result from?
Complex genetic interplay (HLA/MHC [human leukocyte antigen] genes, genes determining sex, other immune response genes).
124
What does IPEX syndrome stand for?
Immune dysregulation, polyendocrinopathy, enteropathy and X-linked inheritance syndrome.
125
What is IPEX syndrome, when does it present and what is it characterised by?
Rare genetic disorder of immune dysregulation, presents early in childhood, characterised by overwhelming systemic autoimmunity.
126
What are the symptoms of IPEX?
Severe infections, intractable diarrhoea, eczema, very early onset insulin dependent diabetes mellitus, autoimmune manifestations.
127
What is the treatment for stem cell manifestations?
Haematopoetic stem cell transplantation (HSCT), immunosuppressive drugs, total parental nutrition.
128
What mutation causes IPEX and is it X-linked?
Mutation in FOXP3 gene, essential for development of regulatory T-cells. It is X-linked.
129
What cytokines to Treg cells secrete?
Anti-inflammatory cytokines e.g. TGFbeta, IL-10.
130
What are Treg cells crucial for?
Suppressing hyperreactive T cells.
131
What 2 specific tolerance mechanisms are required to prevent autoimmunity?
1. Deletion of self-reactive lymphocytes in primary lymphoid tissues (central tolerance). Antigen presenting cells express self-antigens, when developing lymphocytes bind to these they undergo apoptosis.
2. Inactivation of self-reactive lymphocytes in peripheral tissues by Treg cells that escape central tolerance.
132
In what syndrome is there failure of peripheral tolerance due to defective Treg cells?
IPEX syndrome.
133
In what gene are there predisposing and protective alleles for an autoimmune disease?
HLA.
134
What makes an allele a predisposing allele for an autoimmune disease?
Predisposing allele better at presenting disease associated self-peptide than the protective allele.
135
What class of MHC/HLA molecules do all nucleated cells express on their surface?
Class I (HLA-A, HLA-B, HLA-C).
136
What class MHC molecules do antigen-presenting cells express?
II (HLA-DR, DQ, DP).
137
How many variants of each HLA molecule type will each individual possess?
2.
138
What evolutionary advantage does the large amount of polymorphisms in HLA genes give?
The species as a whole will be more likely to survive a pandemic.
139
Why are women more likely to get autoimmune diseases?
There are different hormonal influences on lymphocyte function in males and females. There is alteration of the course of some autoimmune diseases during pregnancy.
140
What are the environmental factors contributing to autoimmune disease?
1. Infection - cross-reactivity between antigens expressed by pathogen and self. 2. Molecular mimicry.
141
What is molecular mimicry?
T cells with cross-reactive TCRs are activated by peptides donated by the pathogen that resemble or are identical to endogenous peptides.
142
What can molecular mimicry lead to?
Aberrant immune activation against self-antigen triggered by presence of foreign antigen that shares molecular or antigenic properties with self.
143
Describe the cause of acute rheumatic fever after streptococcal infection.
Molecular mimicry. Streptococcal cell wall stimulates antibody response. Some antibodies cross-react with heart tissue, causing rheumatic fever.
144
What is the treatment for acute rheumatic fever after streptococcal infection?
Plasmapheresis, may need valves replaced or heart transplant.
145
What is reactive arthritis following bacterial infection?
Sterile inflammation secondary to bacterial infection, usually develops several weeks after a GI or GU infection.
146
What is reactive arthritis following bacterial infection genetically associated with?
Inheritance of certain MHC class I alleles (HLA-B27).
147
Describe the 3 potential mechanisms of autoimmune disease.
Molecular mimicry. Antigen sequestration: trauma to eye, blood-brain barrier or testis opens up these areas to the immune system (not normally exposed), leads to hypersensitivity reaction. Super antigens: can activate any type of T cell, binds the T cell and MHC without antigen being necessary.
148
What are the 2 ways you can classify autoimmune diseases?
1. Clinical classification: organ-specific diseases, non-organ specific or multisystem autoimmune diseases.
2. Pathological classification: Gel and coombs classification.
149
What type of hypersensitivity disease is Grave's disease and what is the molecular mechanism of it?
Type II, auto-antibodies are generated that bind to the thyroid stimulating hormone (TSH) receptor.
150
What does Grave's disease cause and what are the associated symptoms?
Hyperthyroidism, has all the symptoms of hyperthyroidism.
151
Where do antibodies attack in Goodpasture's syndrome and what does this lead to?
Antibodies attack the basement membrane in lungs and kidneys, leading to bleeding from the lungs and kidney failure (glomerulonephritis and pulmonary haemorrhage).
152
What is the suspected self antigen in Goodpasture's syndrome?
Alpha-3 subunit of type IV collagen.
153
Give an example of an autoimmune disease mediated by type III mechanisms.
Systemic lupus erythematosus (SLE).
154
What population is SLE more common in?
Afro-caribbeans.
155
What is there an increased risk of in SLE?
Cardiovascular disease.
156
Is there are strong genetic predisposition for SLE and what gender gets it the most?
Yes and females.
157
What is the management of SLE?
Limit sun exposure, analgesia, hydroxychloroquinine, decrease inflammation (steroids), decrease production of autoantibodies (immunosuppressives/anti-proliferative agents e.g. azathioprine, mycophenolate, cyclophosphate), inhibit B cell proliferation e.g. belimumab.
158
What autoimmune diseases are mediated by type IV mechanisms?
Type 1 diabetes, coeliac disease, rheumatoid arthritis.
