Key facts Flashcards
1
Q
What does a type 1 Hypersensitivity reaction involve?
A
Allergy - IgE mediated mast cell activation to cause release of histamine
2
Q
What does a type 2 Hypersensitivity reaction involve?
A
Antibody mediated IgM and IgG reaction to cell-bound antigens
3
Q
What does a type 3 Hypersensitivity reaction involve?
A
Antibody mediated IgM and IgG response to soluble antigen complexes
4
Q
What does a type 4 Hypersensitivity reaction involve?
A
Macrophage and T-cell (cell-mediated) response to environmental antigens aka Delayed
5
Q
Name the first phase of hypersensitivity reactions and what happens
A
Sensitivity - first exposure, memory effector cells activated - no clinical manifestation
6
Q
What is the second phase of a hypersensitivity reaction?
A
Effector phase - second exposure leads to reaction
7
Q
Name 5 Type 2 Hypersensitivity diseases
A
- Pernicious anaemia
- Graves disease
- HDN
- Myasthenia gravis
- Goodpastures
- Transfusion reaction to blood
- Immune thrombocytopenic purpura
8
Q
What blood group is the universal donor?
A
O
9
Q
What blood group is the universal acceptor?
A
AB
10
Q
What does HDN lead to?
A
Jaundice - yellow sclera, skin, pale stools, dark urine
Mental retardation, seizures - “kernicterus”
11
Q
What is the treatment for HDN?
A
RhoGAM - given to mum during first birth
It is Anti-D - binds to the Rhesus D antigen, stops induction of an immune reaction and so no sensitisation can occur
12
Q
What antigen is Rhesus +ve?
A
D-antigen
13
Q
What is the diagnostic test for HDN and what does it involve?
A
Coombs test
Test either baby’s blood for antibodies attached to blood cells or mother’s serum for anti-D antibodies
14
Q
Describe the pathophysiology of Myasthenia Gravis
A
Antibodies bind AcH receptors - cannot be activated
15
Q
What are the symptoms of Myasthenia Gravis?
A
Muscular weakness + fatigue
Diplopia
Ptosis
Limited ocular movements
16
Q
Name a treatment for Myasthenia Gravis and its type
A
Pyridostigmine
AcHesterase inhibitor
17
Q
Name a side-effect of Pyridostigmine
A
SLUDGE
18
Q
What can happen to a baby if the mother has Myasthenia Gravis?
A
When born, can have IgG that passed through the placenta and so temporarily can have symptoms
19
Q
Name 3 treatments of Type 2 Hypersensitivity reactions
A
- Plasmapheresis
- AcHesterase inhibitor
- Splenectomy - ITP
- Correct metabolism eg. In Graves
20
Q
Describe the pathophysiology of Graves disease
A
TSH receptor antibody binding causes excess Thyroid hormone release
21
Q
Name 5 symptoms of Graves disease
A
- Lid lag
- Exophthalmos
- Pre-tibial Myxedema - non-pitting oedema of the skin
- Heat intolerance
- Tachycardia
- Weight loss
22
Q
Name 3 diseases that Plasmapheresis could help with and what it is
A
- Graves
- Goodpastures
- Myasthenia Gravis
Plasma separated from blood, containing IgG
23
Q
Describe Type 3 Hypersensitivity in detail
A
IgG and IgM form complexes with soluble antigens
Small complexes can be cleared by RE system and large by C3b
However, intermediate/low-affinity antigens cannot be sorted by either
These then deposit in organs and cause damage eg. RA
This can also occur if there is complement deficiency - cannot clear large either
24
Q
What can happen if there is complement (C3b) deficiency in a Type 3 Hypersensitivity reaction?
A
Cannot clear large immune complexes
25
Describe how damage occurs to an organ with an immune complex deposited within it
Immune complexes are deposited
C3b attaches
Neutrophils recruited, which cause degranulation
26
Name 3 diseases caused by Type 3 hypersensitivity reactions
- RA - Rheumatoid factor (IgG) deposited
- Glomerulonephritis (infectious cause) eg. Hepatitis B -> post-infection, bacteria form immune complexes
- SLE
27
Name an important feature about SLE and pregnancy
Commonly causes miscarriage
28
Why is a Type 4 hypersensitivity reaction referred to as "Delayed"?
Occurs only 24-72 hours after exposure
29
Describe the pathophysiology of a Type 4 immune reaction
Sensitisation phase: TH1 cells developed to antigen by APC presentation
Effector phase: Macrophages activate and try to attack antigen - however, they cannot clear it eg. Tb - leads to massive interferon/cytokine release
Cytotoxic as recruits TH2 (T killer cells)
30
Name 5 diseases caused by Type 4 hypersensitivity reactions
- Contact: Nickel
- Granulomatous: Tb/Sarcoidosis
- Tuberculin: Mantoux test for Tb epithelial reaction
- Diabetes mellitus type 1 - attack of pancreatic B cells
- Hashimoto's
31
Name 2 treatments for Type 3 and 4 hypersensitivity reactions
Corticosteroids - Prednisolone
| Steroid-sparing agents: Azothioprine
32
What antibody type can pass across the placenta?
IgG
33
Why does an ABO mismatch between mother and child not cause HDN?
ABO antibodies are IgM
34
What is the treatment for a type 1 hypersensitivity reaction?
Adrenaline injection to prevent systemic mast cell activation
35
Give an example of a seasonal and perennial allergen
Seasonal: Pollen
Perennial: Dust mites
36
Describe the pathophysiology of Type 1 Hypersensitivity reactions in relation to antibody response
TH2 response via IL-4, 5, 13
IgE production by B cells that then binds to mast cells, which then migrate to cell surface
These then degranulate and release histamine etc. on SECOND EXPOSURE ONLY
Leads to IgE cross linking and histamine release
37
What interleukins are involved in a Type 1 Hypersensitivity reaction?
IL-4, 5, 13
38
Name 3 factors of western culture leading to the Hygiene hypothesis/ Microbial dysbiosis - what do these lead to?
Small family sizes, high antibiotic use, good sanitation
| Alters body microbiome diversity
39
Where are mast cells most commonly found?
At mucosal surfaces eg. in GI tract, skin etc.
40
Name 3 mast cell mediators
Histamine, leukotrienes, platelet-activating factor
41
Name 2 skin manifestations of allergic reactions
- Urticaria
| - Angioedema
42
Describe Urticaria
Reddening of the skin caused by mast cell activation in the epidermis - histamine/cytokine activation
43
Describe Angioedema
Swelling of lip/eyes/tongue/URT due to activation of mast cells within the deep dermis - histamine and bardykinin
44
What is anaphylaxis?
Systemic activation of mast cells
45
What are the symptoms of anaphylaxis? (5)
```
Hypotension
CVS collapse
Generalised urticaria
Angioedema
Breathing problems
```
46
Describe how adrenaline acts as a treatment for anaphylaxis
Timesaver, not lifesaver
- Reverses vasodilation and reduces oedema
- Reverses airway obstruction
- Increases CO
- Inhibits mast cell activation
47
Name 4 treatments for Type 1 Hypersensitivity reaction other than adrenaline
- Oral desensitisation immunotherapy
- Anti-IgE
- Anti-histamine
- Corticosteroids
48
Define food allergy
Hypersensitivity to food that can lead to disease
49
What is the definition of an allergen?
Any substance that can stimulate an IgE immune response or a cellular immune response (either)
50
What is the definition of Atopy?
Tendency to produce IgE antibodies in response to ordinary exposure to potential allergens
51
Name 5 presentations of allergy
- Allergic rhinitis
- Allergic conjunctivitis
- Asthma
- Eczema
- Urticaria
52
Describe the allergic march
Early age: Food allergy and eczema most dominant
School age: Asthma
Later age: Rhinitis most common allergy (pollen food allergy)
53
What is important to note about milk allergy?
It can present many weeks after first ingested
54
Name the two types of milk allergy presentation
- Immediate IgE mediated onset - anaphylaxis symptoms
| - Delayed onset (more common) - mostly GI symptoms
55
Name 3 major allergens
Celery
Crustaceans
Gluten
56
What is the difference between food allergy and intolerance?
Food allergy = immune response causing an adverse health effect
Food intolerance = adverse health effect not involving an immune response
57
Name two types of adverse reaction to foods
- Non-immune mediated - intolerance
| - Immune mediated - allergy
58
Name two types of immune mediated reactions to food (allergies)
IgE and non-IgE
59
Give 2 examples of food intolerances
Lactose intolerance
| Caffeine (overdose)
60
Describe the differences between IgE mediated and non-IgE mediated allergies
IgE = immediate onset, Non-IgE = delayed (days)
IgE = Presentation - based on age of onset, Non-IgE = early childhood
IgE will often resolve later than non-IgE
61
Name 4 IgE mediated allergy symptoms
```
Pruritus, erythema
Urticaria
Angioedema
Respiratory - blocked/rhinitis
Hypotensive
```
62
Name 4 non-IgE mediated allergy symptoms
Eczema
Mostly GI:
GORD, loose stools, constipation, blood in stools, abdominal pain
63
What is the most common IgE food allergy in adults?
Pollen food syndrome - pruritus and mild oedema in the oral cavity associated with raw fruit and vegetables
64
Describe the food allergy march (not the allergic march)
Infancy: Milk, eggs, peanuts
Childhood: Wheat, fish
Adults: Food pollen syndrome
65
Describe how food can be processed to reduce allergic-ness
- Heat it - milk, egg, apples
| - Processing to destroy epitopes
66
Describe "cross-reactivity"
Can be allergic to cows milk and also to goat's milk
| Also with pollen and fruit and vegetables
67
What is acute viral urticaria?
A non-allergic cause of urticaria - usually children
| Caused by flu and leads to excess histamine release
68
Name the food allergy tests
- Skin-prick test
| - IgE serum test
69
Describe the skin-prick test
Allergen injected into skin layer - becomes red and swollen
| Will have a control for normal reaction based on width - can test multiple allergens at the same time
70
Describe the IgE serum allergy test
Serum taken from patient and added to allergen - check IgE reaction
71
Name 3 types of replacement milk in infants for milk allergy
- Extensively hydrolysed formula
- Amino acid formula
- Soya
72
How would you tell the difference between non-IgE mediated milk allergy and lactose intolerance?
- Non-IgE = constipation, abdo pain, food refusal
| - Lactose intolerance = explosive diarrhoea, bloating, flatulence
73
Describe the 4 steps of management of food allergies
Allergy testing
Diet advice - avoid foods
Desensitisation therapy
Oral food challenge form
74
Describe Sjorgens syndrome
Autoantibody Type 4 disease causing dry eyes, mouth and arthritis
75
Name the two classifications of autoimmune disease
- Organ specific - Type 2
| - Non Organ-specific - Type 3
76
Describe 5 diagnosis criteria for autoantibodies
- Presence of autoantibodies that correlate with disease severity
- Autoantibodies at tissue area
- Transfer of autoantibodies to a healthy host causes disease
- Clinical benefit from immunotherapy
- Family history
77
What is a primary autoantibody?
The primary antibody is one that binds directly to the antigen.
78
What is a secondary autoantibody?
A secondary antibody binds with a primary antibody that is directly attached to the target antigen.
79
Name 3 examples of primary antibodies
- Anti-TSHR antibodies in Graves
- Anti-AcH in Myasthenia
- Anti-GBM in Goodpastures - affects both lung and kidney
80
Name 4 examples of secondary antibodies
- Anti-nuclear in SLE
- Anti-parietal in Pernicious - reliable diagnostic tool
- Anti-thyroid peroxidase in Hashimotos
- Anti-RF in RA - only useful in females below 30
81
Define the "specificity" of an autoantibody
% of people who do not have the disease that the test excludes
82
Define the "sensitivity" of an autoantibody
% of people with the disease the test identifies
83
Name 4 IgGs that can be passed to babies in pregnancy
Myasthenia gravis
Graves
ITP
SLE
84
How does autoimmunity become an autoimmune disease?
Thymic tolerance breaks down, Treg cells do not work, autoreactive B cells are activated
85
List some systemic causes of autoimmune diseases
- Hormones - women more affected
- Infectious factors post-infection - M protein from Strep Pyogenes causing rheumatic fever
- Drugs
- Genetic factors
86
Name 4 treatments for Type 4 Hypersensitivity reaction
```
Immunosuppressive drugs:
- Corticosteroids - prednisolone/hydrocortisone
- Anti-metabolites (methotrexate)
- Azothiaprine
Anti-inflammatory drugs
```
87
Describe the pathophysiology of SLE
Cellular remnants post-apoptosis end up in blebs.
These blebs are usually phagocytosed, but in SLE they are done so poorly. They are transferred to lymphoid tissues and presented by APCs and presented to T cells, which activate B cells to produce antibodies against self.
88
Describe the epidemiology of SLE
Female, black
89
Name 6 symptoms of SLE
Hands: Raynaud's, joint pains, swelling, hand rash
Sweater: Alopecia, proximal muscle weakness, mouth ulcers, rash, chest pain, photosensitivity
90
What is the autoantibody for Lupus called?
ANA positive
91
What would be visible on examination of a patient with SLE?
- Alopecia
- Malar rash
- Swelling of hands
92
Name 4 treatments for SLE
Education about sunscreen/lifestyle
DMARDs - Azothioprine, hydroxychloroquine
Steroids - prednisolone
Severe: IV cyclophosphamide
93
What is a common complication of Lupus?
Renal disease
| Systemic lupus erythematous nephritis - ESRD eventually
94
What type of renal damage does SLE cause?
Nephrotic syndrome
95
What type of immunoglobulin is Rheumatoid factor?
IgG
96
What causes damage in rheumatoid arthritis?
Overproduction of TNF-a following RF attack on the synovium of the joint
97
How is rheumatoid arthritis diagnosed?
X-ray, not RF test
98
What are the 4 signs that would be visible on an X-ray for RA?
- Loss of joint space
- Periarticular osteopenia
- Marginal bony erosions
- Subluxation
99
Name 4 treatments of RA
DMARDs - Hydroxychloroquine
| Steroids - prednisolone
100
How do the treatments for RA work to slow down RA?
Block TNF-a and IL-6
101
Name 3 non-articular manifestations of RA
Lungs: Rheumatoid nodules - scarring
Sjogren's: Dry eyes, dry mouth
Anaemia of chronic disease
102
Name 5 symptoms of Graves disease
- Exophthalmos
- Tibial Myxedema
- Lid lag
- Tachycardia
- Sweating
- Weight loss
- Heat intolerance
103
Name 2 treatments for Graves disease
- Carbimazole - anti-thyroid
| - Plasmapheresis
104
Name 5 symptoms of Hashimotos disease
- Alopecia
- Weight gain
- Weakness
- Cold intolerance
- Swollen thyroid (goitre)
105
How would Hashimoto's be diagnosed?
Raised TSH (since keeps trying to stimulate)
106
Name 1 treatment of Hashimoto's disease
Levothyroxine
107
How does Carbimazole work?
Inhibits thyroid peroxidase
108
Name the key enzyme of the Thyroid
Thyroid peroxidase
109
How is a hybridoma formed?
Immunise an animal, harvest B cells from spleen, immortalised (fused with myelomas)
110
How do MABs work?
Bind cell-surface receptor and activate or block signalling
Cause cell-death:
- Antibody dependent cell cytoxicity
- Complement dependent cytotoxicity
111
What is Lymphoma?
Cancer of the lymphocytes (b or t cells)
112
What are the B symptoms of Lymphoma?
Night sweats, weight loss
113
What receptor do lymph nodes express that is a target for Lymphoma treatment?
CD20
114
Name 3 monoclonal antibodies and what they treat
Rituximab - Lymphoma
Herceptin - inhibition of HER-2 signalling, breast cancer
Abciximab - glycoprotein 2/3a inhibitor - anti-platelet
