Core Immunology - Part 1 Flashcards
1
Q
What makes you more likely to get an autoimmune disease
A
Women
Elderly
Sequestered antigens
Environemntal triggers - infection, trauma-tissue damage, smoking
2
Q
What is the most common genetic susceptibility in autoimmune diseases
A
In the HLA region aka the MHC protein
3
Q
What does the ACPA antibody in rheumatoid arthritis attach to
A
MHC
4
Q
Where is MHC I found
A
on all cells
5
Q
Where is MHCII found
A
On T cells and APCs
6
Q
Failures in what can cause autoimmune disease
A
Central tolerance (where self-recognises T cells are destroyed in the thymus) Peripheral tolerance (where sclf-recogniseing T cells are removed in the lymph nodes by T-reg cells)
7
Q
How do T cells cause inflammation
A
Inflammatory Cytokines
Helping B cells make autoantibodies
8
Q
How do auto reactive T cells cause clinical disease
A
Directly cytotoxic
Inflammatory cytokines
9
Q
How do auto reactive B cells cause clinical disease
A
Directly cytotoxic
Activate the complement system (antibodies bind to C1q)
Interfere with normal physiological function
10
Q
What is organ specific autoimmune disaese
A
Auto-immunity restricted to that organ
Overlap with other organ specific diseases
Typically autoimmune thyroid
11
Q
What are non organ specific autoimmune diseases
A
Affects several organs
Auto-immunity assocaited with antigens found on most cells in the body
Overlap with non-organ specific diseases
Typically connective tissues disaeses
12
Q
What is Hashimotos Thyroiditis
A
Destruction of thyroid follicles
Auto-antibodies to thyroid peroxidase and thyroglobulin
Results in hypothyroidism
13
Q
What is Grave’s diseases
A
Anti-TSH autoantibodies
Cause hyperthyroidism
14
Q
What is myasthenia gravis
A
Auto antibodies to the ACh receptor in the NMJ
Quickly fatigued muscles, difficulty keeping eyes open, speaking, swallowing
15
Q
What is pernicious anaemia
A
Antibodies to parietal cells or intrinsic factor
Cant absorb B12
Get pernicious anaemia (macrocytic anaemia), decreases Hb levels
16
Q
Example of sequestered angtigens
A
The nuclei of cells
17
Q
How does the nuclei of cells becomes in contact with the immune system
A
Defective apoptosis or necrosis means the DNA is not destroyed
18
Q
How does SLE occur
A
Get anti-nuclear antibodies (ANA) due the sequestered nuclei being exposed
The ANA and their antigens form immune complex that bind to complement factors and cause inflammation in any tissue
19
Q
How do ANA cause inflammation
A
Bind to complement factors causing inflammation in any tissue
20
Q
Common features of SLE
A
Photosensitivity, malar rash, mouth ulcers, arthralgia, arthritis, fatigue, alopecia
Organ invovlement
21
Q
Organ involvement of SLE
A
Kidneys - Lupus Nephritis
Lungs - pleural effusion/pleurisy
CNS - Cerebral lupus, seizures, comas
22
Q
Testing for SLE
A
ANA
23
Q
Treatment of SLE
A
Immunosuppression
24
Q
What are ANCAs
A
Anti-neutrophil cytoplasmic antibodies
25
What are the 3 forms of vasculitis
Microscopic Polyangiitis
Granumaltosis with polyangiitis (wegeners granulomatosis)
Eosinophilic granulomatosis with polyangiitis
26
What is a granuloma
mass of inflamed tissued - often get lesion in the URT dance an be destructive leaving cavities
27
What is polyangiitis
Inflammation of many small vessels in the skin, kidney, lungs and gut
28
Treatment of ANCA Vasculitis
Immunosuppression
29
Test for ANCA Vasculities
ANCA antibodies
30
What is primary Raynauds
Common in young women
Runs in family
ANA negative
31
What is secondary Raynaud's
ANA positive
| May be associated with scleroderma, SLE and other diseasesa
32
What is scleroderms
Autoimmunity leading to ischaemia and fibrosis
ANA antibodies - particular anti-centromere and anti Scl-70 (look for these in diagnosis)
33
What does scleroderma affect
Raynaud's phenomenon
Skin thickening and tightening in fingers and face
Fibrosis may affect lungs, gut and kidneys
34
How to treat myasthenia gravis
Acetycholinesterase inhibitors
35
How to treat pernicious aneamia
Replace B12
36
How to treat Hashimotos Thyroiditis
Give thryoxine
37
How to treat Grave;s diseases
block thyroid function
38
How to treat SLE and ANCA Vasculitis
Immunosuppresions
Glucocorticoids
B cell depletion
39
How to treat scleroderms
Vasodilating drugs
Stem cell transplant
Cyclophosphamide
40
What is positive predictive value
The proportion of people who test positive who have the disease
41
What is negative predictive value
the proportion of people who test negative who do not have the disease
42
What is the likelihood ratio
likelihood of finding in disease patient/likelihood of finding in healthy patient
tells us how discriminate the test can be between patients with the disease and healthy patients
43
What is CRP produced in response to
Produced by the liver in response to IL-6
44
ESR in infection
Longer due to the higher viscosity due to increased good proteins
45
What happens to albumin in chronic inflammation
decreases
46
How do we measure complement activation
Measure using C3 and C4 levels particlarly
47
What are the precise targets of ANA
Extractable Nuclear Antigens
48
What is destroyed in SLE
the nuclei of cells by neutrophils/macrophages due to the ANAs to the ENAs
49
How do we test for ANAs
Large fibrocyte cells with antigen On
Add FITC-conjugated antibody --> fluoresces showing positive result
BUT positive ANA doesn't necessarily mean you have lupus
50
What is a micro-bead immunoassay
Multiplex assessment of non-organ specific autoantibodies
Attach patients serum to bead - if autoantibody is present beads will fluoresce
Can test unto 20 at a time - but only measures diseases specific and only autoantibodies against the nucleus
51
What is rheumatoid factor
Autoantibody against the Fc portion of IgG
52
When if rheumatoid factor found
Often in rheumatoid arthritis
| But only 70% sensitivity/specificity
53
Where else is rheumatoid factor found
In other disease with high polyclonal B cell stimulation e.g. chronic infection
High levels can be pathogenic in vaculitis
54
What is a more specific way for rheumatoid arthritis
ACPA (Anti-CCP) antibody
95% speicific but similar sensitivity to rhuematoid factor
ACPA positive patients tend to have a more severe and erosive disaeses
55
When is CCP made
Made when cells die --> but in rheumatoid arthritis we make antibodies against it
56
Detection of dsDNA
Crithidia lucillae assay (protozoa)
Farr Assay
ELISA (enzyme linked immunosorbent assay)
57
Detection of ENA's
Immunoblots
| Individual ELISA
58
Cytoplasmic and perniculear targets of ANCA
Cytoplasmic - PR3
| Perinuclear - MPO (MPO is an enzyme used by neutrophils to kill bacteria)
59
What is MPO
MPO (MPO is an enzyme used by neutrophils to kill bacteria)
60
Is ANCA clinically useful
Positive ANCA good at positive diagnosis BUT histology is gold standard
Negative ANCA does not exclude it
61
Do we need to treat positive ANCA with no clinical conditions
No
62
What does the re-currence of ANCA in a patient who was ANCA negative in remission suggest
Risk of diseases flare
| But poor temporal correlation between ANCA return and disease flare
63
What do you have i primary biliary sclerosis
Anti-mitochondrial antibodies
64
What causes autoimmune hepatities
auto-antiboides to smooth muscle and to liver/kidney/microsomal (LKS) antiboides
Detect these by IF screening using rodent tissue block and antigen specific ELISA
65
Negative predictive value of ICA and IAA in type I diabetes
almost 99%
Increased risk of development of type 1 diabetes with greater number of different autoantibodies and younger age of patient
66
Where are blood group substances found
On the surface of all vascular endothelial cells and certain epithelial cells
67
What are MHC
Set of genes found in all vertebrate species
68
What do MHC have roles in
```
Immune function
Disease susceptibility
Reproductive success (females choose their partners based on their HLA profile)
```
69
What disease has a strong association with HLA
ankylosing spondylitis
70
What do MHC present to T cells
self or non self antigens
71
Where is the MHC on the chromosome
6p21.3
72
What is the role of Class I HLA
Found on all nucleated cells
Present endogenous antigens
Present antigens such as in viral infections
73
What is the role of Class II HLAs
Primarily expressed on B lymphocytes
| Expression can be induced on T lymphocytes and other cells
74
Composition of class I HLA
45d heavy chain non-covalenently associated with a polymorhpic B2 microglobulin
75
Composition of class II HLA
31-34kd alpha chain non covalently association with beta chain
76
Peptide binding domain in Class I
alpha 1 and 2. alpha 3 is proximal
77
Peptide binding domain in class II
alpha 1 and beta 1
78
What is the expression type of HLA genes
Co-dominant - all of the inherited antigens are displayed on the cell surface
79
Why is HLA polymorphic
Survival advantage - means if there is a new infection it is likely that we have an MHC suitable to that antigen
80
DIrect recognition in transplantation
WBC's from the donor move to the T cells of the recipient
| These cells move back to the transplant causing damage
81
Indirect recognition in transplantation
Graft peptides recognised by recipient immune system
| T cells activated and migrate to the graft in a normal immune response
82
Semi-direct recognition
Recipient and donor APC interact - these form a new APC and migrate to the lymph node
T cells activated
Causes immune response to transplant
83
What is sensitisation
Any event that elicits a HLA directed immune response e.g. pregnancy, blood transfusion, transplantation
84
How to prevent transplant rejection
Serum screening and cross matching
85
What is sensitisation calculation
HLA antigens made into a cRF (calculated reaction frequency) --> describes the amount of time in the past 10000 that a donor would have been inaccessibly to the recepient
86
What would a cRF of 0% indicate
They can receive virtually any donor as you have not been sensitised against them
87
What is the likelihood of a transplant based on
Blood group
Rarity of HLA type
Extent to which they are sensitised
88
How does cross matching occur
T cell from donor - will express its HLA antigens
Add donor lymphocytes to patients serum
Add reporter molecules that bind to antibodies and fluoresce if they have minded
Add a lineage marker to tell the specific cell antibodies have bound to
Pass through a flow cytometer
89
What happens in hyper-acute rejection
Activation of complement and clotting casacde
Coagulation
Lose integrity of vascular endothelium --> organ become engorged with blood--> DIC--> tissue becomes necrotic
90
Antigen in type II allergy
Occurs at cell surface
91
What type of allergy does penicillin trigger
type II
92
Good pastures nephritis, erythroblastosis and fetalis associated with wchih type of allergy
type II
93
What is SLE associated with allergy wise
type III
94
Contact dermatitis is which type of allergy
type IV
95
Mould hay and farmers lung in which type of allergy
type III
96
Onset time of type III
3-8 hours
97
Onset time of type II allergy
minutes to hours
98
HIstology in type i allergy
basophils and eosinophils
99
Histology in type II allergy
Antibody and complement
100
Histology in type III allergy
Neutrophils and complement
101
Histology in type IV allergy
Monocytes and lymphocytes
102
What occurs in cytotoxic allergy
IgG/IgM response to self or foreign antigen at the cell surface
Get complement activation, phagocytosis
Can occur in pregnancy
103
Type III is a reaction against what type of antigens
soluble
104
Type IV is a reaction against what type of antigens
tissues or organs
105
Traditional cause of type III reaction
Serum sickness
106
Where does arthurs reaction occur
It is a type III reaction that affects the perivascular space when drugs given IV
107
Common antigens of type IV reaction
metals or tuberculin reaction
Antigen taken up by T cells
T cells produce cytokines and activate macrophages causing damage
108
Development of an allergy
Breakdown of barrier
Sensitisation
Changes in T cell substype - predominantly Th2 cells
T cells activated and produce IgE
109
Similarities between parasitic infections and allergiess
The same components of the immune system response to both
110
What has driven the rise in allergies
The lack of infectious drive
111
Immune response to parasites
Increased levels of IgE
| Tissue inflammation due to basophils, eosinophils and mastocytosis
112
Method of preventing autoimmuntiy
Probiotics given to pregnant women
Stimulation by microbes in protective!
Mechanism: th1/2 deviation, antigenic competition and imunoregulation
113
Defect in FLG gene causes what
Eczema
| But genetic factors alone are not sufficient for the disease only makes you more susceptible
114
What is an allergen
Antigens that initiate an IgE mediated response
115
What does Th1 normally deal with
intracellular infections
116
Role of Th17
Thoguht to have a protective role
117
Role of Th2
These cells produce IL-4 that drives B cells to produce IgE
118
How does IgE cause an allergic response
Mast cell and basophil degranulation - released preformed mediators and de novo synthesised mediators that cause the late response
119
What causes the late response in type 1 reactions
Eosinophils and central role for th2 T cells
120
What are secondary mediators
leukotrienes and prostaglandings
121
Role of TH2 cells in allergy
Releases multiple cytokines
Drives immunoglobulin production
Activates the innate immune response
122
What type of allergic reaction is rhinitis
Type 1
123
What is rhinitis
Allergic response affecting upper airways
Blocked runny nose and eye symptoms
It is perennial/seasonal
124
Treatment of rhinitis
Antihistamines and nasal steroids
125
Causes of rhinitis
dust mite, animals, pollen
126
What is asthma
Inflammation and hyperactivity of the lower small airways
127
What is a key cause of asthma
house dust mite
128
How does damage to the airways occur in asthma
Due to the late phase response -> damaged air wards are hyperactive to non-allergic stimuli e.g. fumes
129
What types of dermatitis are there
Atopic e.g. eczema
| Contact e.g. allergic - type IV allergy
130
Features of dermatitis
Itching, blistering, weeping and cracking of skin
131
What is IL-31
A t cell derived itch mediator
132
Major trigger of contact dermatitis
House dust mite
133
What is anaphylaxis
IgE mediated systemic hypersensitivity response
| Can get hypotension, bradycardia, collapse and cardiac arrest
134
Basophil activation test to diagnose allergy
Measure basophils before and after allergen given
Measure the markers present on basophils (they are normally present in low levels which come out when they are activated)
135
Specific IgE tests for allergyn
Blood test, looks for specific IgE's, but lots of false negatives and positives
136
Skin prick test for allergy
Add 3 bits: Control e.g. water, histamine/poisitive control and allergen if over 3mm reaction you allergic
BUT risk of false/negatiev/ policies and need antihistamines as risk of major allergy
137
Treatments of allergic reaction
Antihistamines
Steroid for late phase
Adrenaline if anaphylaxis
Can sue immunotherapy too --> use if life/threatening reactions to wasp/bee stings
138
What is immunotherapy
Decreases tissue number and decreases mediator release and alters cytokines produced
139
What distinguishes anaphylaxis
Immediate onset diarrhoea
140
What its he gold standard test of allergies
Oral challenge test
141
IgE mediated food allergies
Anaphylaxis, urticaria, angioedema, oral allergy sydrome, acute rhinitis and asthma
142
Mixed food allergy
Atopic dermatitis, eosinophilic osephagitis, eosinophilic enteritis
143
Non-IgE mediated food allergies
contact dermatitis, dermatitis herpetiformis, proctocolitis, FPIES
