Immuno pathology Flashcards
(132 cards)
1
Q
Bone marrow biopsy
A
Aspirate- cells
Trephine- tissues
2
Q
B symptoms
A
Weight loss > 10%
Fever >38.5
Night sweats
3
Q
Joske’s Law
A
The more of the three cell lineages that are numerically abnormal, the more likely it is to be an intrinsic marrow disorder
4
Q
Spectrum of haematological disorders
A
Aplasia –> Dys/Hypoplasia –> Hyperplasia –> Neoplasia
5
Q
Aplastic anaemia- causes and treatment
A
Pancytopaenia
Causes:
- Drugs
- Irradiation
- Viruses
- Thymoma
Treatment:
- Immunosuppression
- BM transplant
6
Q
Myelodysplasia- what is it and treatment
A
Low peripheral blood count
Abnormal cell morphology
5-20% blasts
Risk of progression to AML
Treatment:
- RBC Transfusion
- Antibiotics
AZACITIDINE (promotes myeloid differentiation)
LENALIDOMIDE
7
Q
Myeloproliferative disorders
A
Overproduction of blood cells- usually through one cell lineage- generally normal cellular morphology
Fatigue, headaches, weight loss, night sweats and can progress to AML
8
Q
Myeloproliferative disorders- three conditions
A
1) Polycythaemia vera
2) Essential thrombocythaemia
3) Myelofibrosis
9
Q
PV
A
Too many red cells
Either relative or true
Under true either primary or secondary
10
Q
Polycythaemia vera treatment
A
Venesection
Aspirin
Hydroxyurea
11
Q
Essential thrombocythaemia
A
Too many platelets
>1000 sometimes
Film has thrombocytosis and giant cells
Treatment:
Aspirin
Hydorxyurea
Anagleride
12
Q
Chronic myeloid leukaemia
A
Myeloproliferative disorder with high neutrophil count
Philadelphia chromosome
Imatinib treatment
13
Q
Acute leukaemia
A
Too many white cells in the blood (>20% blasts)
ALL more common in children
AML more common in adults
14
Q
Acute promyelocytic leukaemia
A
Abnormal myelocytes with excess granules
15
Q
Treatment of acute leukaemias
A
Acute myeloid
- Cytosine arabinoside
- Etoposide
Acute lymphoid
- Prednisolone
- MTX
16
Q
Which lymphoma type are chemo resistant?
A
T cell
17
Q
Which viral infection can increase the risk of NHL
A
EBV
18
Q
Investigations for lymphoma
A
Fine needle aspiration
Core biopsy
Open biopsy
And,
Blood tests
PET
Imaging
19
Q
Commonest lymphoma
A
Follicular B-cell lymphoma
20
Q
Follicular B-cell lymphoma
A
Commonest
Indolent relapsing course
Bcl-2 over-expression
21
Q
Diffuse large B-cell lymphoma
A
Commonest agressive lymphoma
22
Q
Burkitt’s lymphoma
A
EBV
Rapidly growing masses in the head, neck or abdomen
23
Q
Hodgkin’s lymphoma
A
“Reed-Sternberg cells”
B-cell lymphoma not over-expressing B cell surface antigens
Hallmark is high levels of cytokines produced eliciting a vigorous inflammatory response
24
Q
Multiple myeloma
A
Cancer of the immune system (plasma cells)
Plasma cells acquire a mutation that leads to them producing an abnormal protein that can lead to bone absorption, anaemia and renal impairment
25
Monoclonal gammopathy of uncertain significance
Plasma cells producing abnormal proteins
26
Multiple myeloma isotypes
IgG
IgA
Light chain
27
Renal disease is multiple myeloma
Light chain cast neuropathy
Dehydration
Hypercalcaemia
Amyloidosis
28
Amyloid light chain (AL) Amyloidosis
Abnormal folding of the light chain- produced by plasma cells in the bone marrow
Misfolded light chain --> Aggregation --> Direct tissue toxicity or organ damage due to fibril accumulation
29
Screening tests for multiple myeloma
Protein electrophoresis
Immunofixation
Serum free light chains
30
What can be used to differentiate clonal from reactive sybtypes of lymphoproliferative disorders
Flow cytometry
31
Chronic lymphocytic leukaemia
Clonal
Reactive
Accumulation of small, mature lymphocytes in the blood, lymph nodes and BM
32
Most common adult leukaemia
Chronic lymphocytic leukaemia
33
CLL vs SLL
CLL has more blood and BM involvement compared to SLL
CLL: B cell >5x10(9)
SLL B cell <5x10(9)
34
Monoclonal B cell lymphocytosis
B cell <5x10(9) in the peripheral blood
35
CLL sequelae
Impaired cell mediated and humoral responses leading to increased risk of infection
Risk of progression to a high grade lymphoma
36
Primary immunodeficiency
Inherent problems of the immune system
37
DiGeorge syndrome
Heterozygous chromosomal deletion affecting chromosome 22
Abnormal faces
Hypocalcaemia
Absence or partial thymus
Cardiac abnormalities
38
What problem is shared in B cell defects?
Impaired defence against encapsulated bacteria
39
Two main problems of B cell defects
1) X-agammaglobulinaemia
| 2) Common variable immunodeficiency disorder
40
XLA
No B cells are produced due to a defect in BTK gene
Problems arise after maternal antibodies fade
Scarring lung diseases are common
41
CVID
Problems with antibody production
IgA deficiency or other antibody deficiency
Diagnosis- deficiency of at least two isotypes
42
Defects with T and B cells
SCID- severe combined immunodeficiency disorder
43
Defects of phagocytes
Chronic granulomatous disease
44
Which infections are common with which defect
T and B cell- systemic
Antibodies- URTI, LRTI, GI
Phagocytes- Resp, skin
Complement- systemic, meningitis
45
Investigations for immune defects
FBC
Lymphocyte subsets
Functional Ab
Functional neutrophil
46
What is the most common cause of over-activity or underactivity in endocrine organs
Autoimmunity
47
Hallmarks of autoimmunity
1) Auto-antibodies in tissues
2) Auto-reactive T cells
3) Lymphocytes, plasma cells and macrophages in tissues
4) Germinal centres in tissues
48
Causes of thyroid toxicosis
Graves disease
Toxic hyper-functioning multi-nodular goitre
Toxic adenoma
49
How is iodine used to test for thyrotoxicosis
Greater uptake of iodine by the thyroid if there is an adenoma present as the rest of the gland is switched off
50
Graves disease
Autoantibodies to TSH receptor leading to hyperactivity and growth
51
Symptoms and signs of Graves disease
```
Weight loss
Loss of appetite
Nervousness
Loose stools
Sweating
```
Enlarged thyroid
Fast pulse rate
Tremor
**Basically, over-activation of sympathetic NS
52
Eye signs in Graves disease
Stare
Lid-lag
Proptosis
53
Lab diagnosis in Graves disease
High T4, low TSH
54
Therapy for Graves disease
```
Ablative therapy (surgical thyroidectomy)
Anti-thyroid drugs
```
55
Atrophic thyroiditis
Chronic autoimmune inflammation that results in thyroid failure
Most common cause of primary hypothyroidism
Antibodies to thyroid peroxidase and thyroglobulin
56
Which antibody is common in hypothyroidism
Thyroid peroxidase antibody
57
Addisonian pernicious anaemia
Malabsorption of vitamin B12 due to antibodies to gastric parietal cells leading to lack of intrinsic factor
58
Coeliac disease
Autoimmunity to tissue transglutaminase (hence, hypersensitivity to gluten)
59
Process of autoimmunity in coeliac disease
Gluten --> Gliadin (Glutamine and Proline) --> tissue transglutaminase removes amine from glutamine --> the remaining then goes and binds to HLADQ2 --> presented to T cells --> T cell and antibody response against gliadin as well as tissue transglutaminase
60
Coeliac disease effects
Diarrhoea
Weight loss
Nutritional deficiencies
Osteoporosis
61
What are the antibodies directed against in Autoimmune thyroiditis
Thyroglobulin
| Thyroid peroxidase
62
SLE pathological changes in different organs
Skin- Malar rash, discoid rash, oral ulcers
Joints- Arthritis
Lungs and Heart- Pleuritis and pericarditis
Kidney- glomerulonephritis
Blood- Low WBC, platelets, haemolytic anaemia
Immune system- Anti dsDNA
Immune system- ANA
63
Autoantigens in SLE
Cell surface
Cytoplasmic
Nuclear
Extra-cellular
64
Sjogren's syndrome
Systemic chronic inflammatory disorder characterised by lymphocytic infiltrates in exocrine organs
Produces Sicca symptoms- dry eyes, dry mouth and other connective tissue disorders
65
Scleroderma
Fibrous thickening of wall of blood vessels in the small intestine and elsewhere
Raynaud's phenomenon
66
Raynaud's phenomenon
Sharply demarcated digital artery spasm and narrowing
Blue- slow flow in dilated venules
Red- capillary dilation in anoxic tissue
67
Mixed connective tissue disease
Term used to describe features of SLE, polymyositis, systemic sclerosis, Raynaud's joint pain
68
Poly/Dermatomyositis
Symmetrical weakness of limb girdle muscles
| Muscle fibre necrosis, phagocytosis and regeneration
69
Jo-1 syndrome
Major- myositis and pulmonary fibrosis
| Minor- Raynaud's tenosynovitis etc
70
Henoch-Schonlein purpura
Multi-system small vessel mediated vasculitis
71
What diagnostic test for small vessel vasculitis
Skin biopsy to diagnose fibrinoid necrosis
72
Diagnostic tests for small vessel vasculitis
Skin biopsy
Anti-neutrophil cytoplasmic antibody
Anti-proteinase 3
Anti-myeloperoxidase
73
Necrotising vasculitis of medium vessels
Medium arteriolies (
74
Pathophysiology of vasculitis
Immune complexes form and deposit in subendothelium, overwhelm the reticuloendothelial system, activate complement, recruit and degranulate neutrophils
75
Mixed cryoglobulinaemia
Immune complex mediated vasculitis
Small vessel vasculitis
Associated with cryoprecipitate
HCV infection (80%)
76
Treatment of mixed cryoglobulinaemia
Treatment of underlying HCV infection
| Immunosuppression
77
Anti-neutrophil cytoplasmic antibody
Antibodies directed against neutrophilic granules causing activation, sequesteration and degranulation in small vessels
78
Treatment of ANCA associated vasculitis
Prednisolone
Cyclophosphamide
Rituximab
Plasmapheresis
79
Examples of different types of vasculitis
Small vessel
- Henoch-Schonlein purpura
- Mixed cryoglobulinaemia
Medium vessel
- Polyarteritis nodosa
Large vessel
- Giant cell arteritis
80
Polyarteritis nodosa
Medium vessel vasculitis
| Primary or associated with HepB or HepC
81
Diagnosis of polyarteritis nodosa
Biopsy
| Angiography
82
Large cell primary vasculitis
Chronic, persistent inflammatory condition with infiltrates within arteries with 3 distinct layers and well developed elastic membranes
83
Histopathology of giant cell arteritis
Narrowed lumen
Intimal expansion
Pan-arteritis
Multi-nucleated giant cells
84
Treatment of giant cell arteritis
High dose corticosteroids tapered over 18-24 months
| Low dose aspirin
85
Secondary immunodeficiency disorders
Deficiency or dysfunction of immune cells caused by infection, disease or medical treatments
86
CMV disease
Can occur after solid organ transplantation
87
Progressive multifocal leukoencephalopathy
Reactivation of JC virus infection
Cause lesions on the myelin sheath leading to loss of coordination and weakness
Natalizumab therapy
88
Rarer causes of secondary cellular immunodeficiency
Idiopathic CD4 lymphopaenia
| Autoantibodies to IFNy
89
Six immune-related transfusion complications
1) Acute haemolytic transfusion reaction
2) Delayed haemolytic transfusion reaction
3) Hypersensitivity
4) Febrile non-transfusion related reaction
5) Graft-versus-host disease
6) Transfusion related acute lung injury
90
Secondary hypogammaglobulinaemia
After haematological malignancy or
| Solid organ transplantation
91
Treatment of secondary hypogammaglobulinaemia
Immunoglobin therapy
92
Causes of asplenia
Congenital asplenia
| Splenectomy
93
Causes of hyposplenia
Sickle cell disease
Coeliac disease
Lupus
94
Thymoma associated immune dysfunction
B cell deficiency
Cellular immunodeficiency
Autoimmune disease
Lichen planus
95
Allergy
Harmful, misguided and excessive immune response to antigens
96
Allergic rhinitis
Inflammation of the nasal mucose due to hypersensitivity to environmental antigens
97
Asthma
Chronic inflammatory disorder of the airways
98
Symptoms of asthma
Wheezing
Chest tightness
Breathlessness
Cough
99
Pathogenesis of asthma
Airflow limitation --> Chronic mucus plug formation --> Airway remodelling
Three components:
Infiltration of cells --> Change in resident cells --> Change in non-cellular components
100
Three hypotheses for raise in asthma
1) Hygiene hypothesis
2) Microbiota hypothesis
3) Biodiversity hypothesis
101
Which subset of T cells are produced in chronic allergic response
Th2 cells
102
What prevents default Type 2 immunity to environmental antigen at birth?
APC maturation
103
Early and late allergic response
```
Early- B cells class switch
Late- Chemokines produced and migration of eosinophils
```
104
Urticaria
Red, raised, itchy rash resulting from vasodilation, increased blood flow and increased vascular permeability
105
Angioedema
Similar as urticaria but involves the submucosa, deeper reticular dermis and subcutaneous tissue
106
Difference between urticaria and angioedema
Urticaria swellings subside in 8-12 hours
| Angioedema swellings continue for days
107
Urticaria treatment
Anti-histamines
108
Allergen specific immunotherapy
Subcutaneous and Sublingual
Subcutaneous
- More evidence for asthma and allergic rhinitis
- Multi-allergens
Sub-lingual
- Effective for allergic rhinitis
- Single allergen
109
Allergic contact dermatitis
Allergen induced delayed hypersensitivity immune response
110
Pathogenesis of allergic contact dermatitis
Allergen --> engulfed by APCs --> Presented to naive T cells --> Sensitised CD4+ and CD8+ cells
Re-exposure --> (12-48 hours later) --> Causes reaction in sensitised individual
111
Diagnosis of allergic contact dermatitis
Patch testing
112
Three mediators released from mast cells
Histamine
Leukotrienes
Prostaglandins
113
Drug hypersensitivity
Type B drug reaction
Immediate (<1 hour), Accelerated (1-<72 hours) and Late (>72 hours)
Usually requires prior drug exposure or unsuspected cross-reactivity
114
Approaches to penicillin allergy
```
Amoxycillin
Skin testing (gold standard)
Penicillin challenge (administer a small dose)
```
115
Oral penicillin desensitisation protocol
Small doses of penicillin given every 15 minutes, patient observed for 30 minutes and then full therapeutic dose given
116
What do most cross-reactivity reactions occur with in terms of penicillin and cephalosporins
With 1st generation cephalosporins
117
Delayed drug hypersensitivity
Occurs after several days to weeks
| Often due to drug-viral interactions
118
DRESS, DIHS and SCAR
DRESS- Drug reaction with eosinophilia and systemic symptoms
DIHS- Drug induced hypersensitivity reaction
SCAR- Severe cutaneous adverse reaction
119
Sepsis cascade
Toxins produced --> Trigger the innate immune system --> inflammatory cascade --> systemic activation --> organ circulation --> multi-organ failure
120
What has nosocomial causative agents for bacteraemia shifted to?
Gram positives (MRSA)
121
Classic signs and symptoms of bacteraemia
```
Fever
Rigors
Chills
Hypothermia
Delirium, agitation
Acute renal failure
```
122
What score is used for sepsis
SOFA score
123
Sepsis, rapid identification is necessary- what methods are used?
MALDI-TOF
FISH
PCR
124
Treatment of sepsis
Antibiotics (identify the organism fast, start with broad spectrum)
Drainage of infected fluid
Support- IV fluid, glycaemic control
Glucocorticoids to curb inflammation
125
Toll-like receptors
Found on intracellular vesicles of dendritic cells and macrophages.
Activates NFkB to induce pro-inflammatory cytokines and chemotactic factors
126
NOD like receptors
Expressed in cytoplasm of the cells routinely exposed to bacteria
Have a NOD protein
Loss of the NOD protein- Crohn's disease
Also activate NFkB
**NAPL3 is an example
127
Muckel-Wells Familal Cold inflammatory syndrome
Two types of periodic fever syndrome
| Due to inappropriate expression of NAPL3 inflammasome
128
Corticosteroids
Act by increasing the expression of anti-inflammatory genes and suppression of pro-inflammatory genes
129
Complement function
Host defence against infection
Links innate to adaptive immune system
Disposal of waste
130
How can acute lupus flare be identified
Low C3 and C4
131
Two functions of T-reg cells
1) Inhibit T-cell activation
| 2) T-cell effector function
132
Four different types of angioedema
1) Allergy
2) Drug induced
3) Hereditary
4) C1 esterase inhibitor gene
