hypersensitivity Flashcards
1
Q
what is a hypersensitivity reaction
A
excessive immune responses that cause damage
2
Q
what can a hypersensitivity reaction be in response to
A
different types of antigens:
infectious agens
environmental substances
self antigens
3
Q
hypersensitivity to infectious agents
- which infections
A
not all infections are capable of causing hypersensitivity reactions
infections that elicit hypersensitivity don’t do so in every case
influenza viruses can cause hypersensitivity
4
Q
how do influenza viruses cause hypersensitivity
A
damage to epithelial cells in resp tract
can sometimes elicit exaggerated immune response
can trigger high levels of cytokine secretion (cytokine storm)
cytokines attract leukocytes to lungs –> trigger vascular changes –> hypotension and coagulation
severe influenza: inflammatory cytokines spill out into the systemic circulation –> ill effects in remote parts of the body e.g. brain
5
Q
hypersensitivity to environmental substances - what substances
A
usually allergens that are available within the environment
e.g. dust, haptens, nickel, drugs
6
Q
hypersensitivity to dust
A
triggers response as it is able to enter the lower extremities of the resp tract - rich in adaptive immune response cells
dust can mimic parasites and may stimulate an antibody response
7
Q
dust - IgE resopnse
A
if the dominant antibody is IgE:
- may trigger immediate hypersensitivity
- manifests as allergy symptoms e.g. asthma, rhinitis
8
Q
dust - IgG response
A
if dust stimulates IgG antibodies:
- may trigger a different kind of hypersensitivity
- e.g. farmer’s lung
9
Q
hypersensitivity to environmental substances - smaller molecules
A
sometimes diffuse into the skin
may acts as haptens - trigger delayed hypersensitivity reaction
10
Q
what are haptens
A
small molecule irritants that bind to proteins and elicit an immune response
11
Q
hypersensitivity to environmental substances - reaction to nickel
A
contact dermatitis
12
Q
hypersensitivity to environmental substances - drugs
A
oral, topical or injected
can elicit hypersensitivity reactions
mediated by IgE or IgG antibodies or by T cells
immunologically mediated hypersensitivity reactions to drugs are quite common, even small doses can trigger life-threatening reactions (idiosyncratic adverse drug reactions)
13
Q
type I hypersensitivity: immediate hypersensitivity
- onset
- infectious trigger
- environmental trigger
- autoimmunity
- adaptive immune system mediators
- innate immune system mediators
A
- onset: seconds if IgE is preformed
- infectious trigger: schistosomiasis
- environmental trigger: house dust mite, peanut
- autoimmunity: NA
- adaptive immune system mediators: IgE
- innate immune system mediators: mast cells, eosinophils
14
Q
type II hypersensitivity: bound antigen
- onset
- infectious trigger
- environmental trigger
- autoimmunity
- adaptive immune system mediators
- innate immune system mediators
A
- onset: seconds, if IgG is preformed
- infectious trigger: immune haemolytic anaemias
- environmental trigger: immune haemolytic anaemias
- autoimmunity: immune haemolytic anaemias
- adaptive immune system mediators: IgG
- innate immune system mediators: complement, phagocytes
15
Q
type III hypersensitivity: immune complex
- onset
- infectious trigger
- environmental trigger
- autoimmunity
- adaptive immune system mediators
- innate immune system mediators
A
- onset: hours, if IgG is preformed
- infectious trigger: post streptococcal glomerulonephritis
- environmental trigger: Farmer’s lung
- autoimmunity: systematic lupus erythematosus
- adaptive immune system mediators: IgG
- innate immune system mediators: complement, neutrophils
16
Q
type IV hypersensitivity: delayed hypersensitivity
- onset
- infectious trigger
- environmental trigger
- autoimmunity
- adaptive immune system mediators
- innate immune system mediators
A
- onset: 2-3 days
- infectious trigger: hep B
- environmental trigger: contact dermatitis
- autoimmunity: insulin dependent DM, coeliac, MS, RA
- adaptive immune system mediators: T cells
- innate immune system mediators: macrophages
17
Q
how is type I hypersensitivity mediated
how quick are the effects
categories
A
through the degranulation of mast cells and eosinophils
within minutes of exposure
immediate hypersensitivity, allergy
18
Q
what is another name for type I hypersensitivity and what does it mean
A
atopy
immediate hypersensitivity reaction to environmental antigens mediate by IgE
19
Q
atopy and Fhx
A
people w/ these allergies tend to have a Fhx w/ atopy traits
20
Q
features of atopy
A
anaphylaxis angioedema urticaria rhinitis asthma dermatitis eczema
manifestations differ according to the antigen
21
Q
what is the atopic march
A
the increase in risk of developing antigens over time if the patient develops allergies at a very young age
22
Q
what are allergens
A
antigens that trigger allergic reactions
gain access to the body through inhalation, ingestion, contact or drugs
23
Q
what is the most common cause of severe allergic reactions
A
peanut allergy
allergy to peanut protein Ara h2 - very stable protein (can’t have even a trace of peanut)
allergy to Ara h8 - cross reactivity w/ other foods, not very stable, can be eaten if cooked
other common allergies: latex, penicillin (beta-lactam)
24
Q
mechanism for type I hypersensitivity
A
IgE
produced by B cells when co-stimulated w/ IL-4 (from Th2 cells)
in pts w/ atopic genetic traits, they are more likely to have a polarisation of the immune system towards Th2 and produce more IL-3
25
what are degranulating cells
release of mediators that cause allergic symptoms
mast cells are resident in many tissues
eosinophils migrate to tissues where type I hypersensitivity reaction is
mast cells initiate allergic symptoms after allergen and IgE interact
mast cells have receptors for IgE and high affinity IgE receptors
26
how do mast cells initiate allergic symptoms in type I hypersensitivity reactions
mast cells already attached to abundant IgE if pt has had previous exposure to specific antigen
granules are filled w/ histamine, prostaglandin and leukotrienes
as soon as there is exposure to the antigen the mast cells degranulate their components and cause an immediate immune response
27
Systemic symptoms of allergies
ANAPHYLAXIS:
- low BP
- angioedema and airway obstruction can be fatal
28
airway symtptoms of allergies
ASTHMA:
- reversible airway obstruction in the bronchi
RHINITIS:
- discharge
- sneezing
- nasal obstruction
- often co-exist w/ allergic conjunctivitis
29
skin symptoms of allergies
URTICARIA:
- itchy oedema of the cutaneous tissues - short lived
- lesion is identical to that induced by skin prick testing
ANGIOEDEMA:
- short-lived, non-itchy oedema of the s/c tissues
- some forms e.g. lip swelling, may be manifestations of food allergy
ATOPIC ECZEMA:
- chronic, itchy inflammation of the skin
- some cases are caused by food allergy
30
epidemiology of allergies
very common, up to 40% of pop affected
runs in families
prevalence on the rise globally
31
genetics of allergies - skin
filaggrin is expressed by keratinocytes - involved in maintaining epithelial barriers and moisturising surfaces and controlling pH
polymorphisms in the gene encoding is established as a cause of allergy and implicated in 50% of severe eczema
exposure to environmental factors adds to the risk of developing allergies
32
risk of developing allergies - environmental exposure and timing
filaggrin variant and LPS receptor varient predispose to allergies
induction of Th2 - predispose to more IgE secretion by B cells
increased exposure to potential allergens - more Th polarisation, more IgE
increased exposure = increased likelihood of allergic reaction
33
effect of urbanisation and hygiene hypothesis
increase in allergies in the developed world is caused by reduced exposure to microorganisms in early life
BUT infections can increase or decrease the risk of allergies depending on the timing of exposure and the genetic makeup
34
how does anaphylaxis occur
mast cells produce prostaglandins and leukotrienes through the cyclooxygenase and lipoxygenase pathways
--> vasodilation and increased vascular permeability
--> shift of fluids from the vascular to extra-vascular space --> fall in vascular tone
severe drop in BP
in the skin: mast cells release histamine, further contributing to swelling and fluid shift
35
how does allergic rhinitis occur
inhaled allergens stimulate mast cells in nasal mucosa
subsequent vasodilation and oedema in the nose --> nasal stuffiness and sneezing
leukotrienes increase mucus secretion --> discharge
36
how does asthma occur in allergic reactions
increased mucus secretion contributes to airflow obstruction
in the lungs, leukotrienes cause smooth muscle contraction --> most dramatic effects on airflow reduction
upon exposure to allergen, the patient w/ asthma will develop airway obstruction characterised by wheezing seconds after exposure
symptoms improve after an hour or so as the immediate response dies down
37
delayed effect after antigen exposure in asthma
several hrs after the acute episode, the airflow in the bronchi may deteriorate again
reflects the migration of leukocytes into the bronchi in response to chemokines
late phase may last hrs
38
general treatment of allergies
tailored case by case
prevention
desensitisation - allergen immunotherapy
drug treatment
39
drugs used in the treatment of allergies
beta2-adrenergic agonists
epinephrine
antihistamines
specific receptor antagonists
corticosteroids
40
how do beta2-adrenergic agonists work
e.g. salbutamol
mimic the effects of the symp NS and work mainly by preventing smooth bronchial muscle contraction in asthma
41
how does epinephrine work
aka adrenaline
can be lifesaving in anaphylaxis
stimulates alpha and beta adrenergic receptors
decreases vascular permeability, increases BP, reverses airway obstruction
42
how to antihistamines work
block specific histamine receptors and have an important role in allergies that affect the skin, nose and mucous membranes
43
how do specific receptor antagonists work
block the effects of leukotrienes
e.g. montelukast - reduces the amount of airway inflammation in asthma
44
how do corticosteroids work
can prevent the immediate hypersensitivity reaction, the late phase and chronic allergic inflammation
45
skin prick testing
used to work out what the patient is allergic to
positive and negative control then allergens (histamine, saline, allergens)
46
what mediates type II hypersensitivity
antibody
IgG or IgM reacting w/ antigen present on the surface of eclls
bound Ig interacts w/ complement or w/ Fc receptor on macrophages
47
result of type II hypersensitivity
opsonisation of target cells
immune mediated haemolysis
takes several hours (if there is enough antibody in the system it could take seconds)
drug induced haemolysis
48
example of type II hypersensitivity
blood groups
different blood groups and rhesus factor
if a patient is rhesus negative, they will produce antibodies if they are exposed to the antigen
patients have naturally occurring antibodies against A/B - if they are A they have antibodies against B and vice versa
group O have antibodies against A and B
49
what happens if you mismatch blood groups during transfusion
haemolysis of blood
- transfused bloos is mainly blood cells and very little plasma
- usually haemolysis of the donor blood cells by the recipient antibodies
- the other way round could happen if you give plasma
50
what determines blood group
A and B blood group antigens are oligosaccharides on the surface of RBCs
similar to molecules expressed by bacteria
51
how does haemolysis occur during type II hypersensitivity reaction
polyvalent IgM causes agglutination of RBC and then IgM activates the complement system
IgG doesn't directly damage RBC but takes it to macrophages and binds to Fc receptor (either in the liver or spleen) and then the RBCs are destroyed
52
alloimmune haemolysis
rhesus -ve woman w/ rhesus +ve baby develops antibodies against rhesus +ve blood cells after cells are transferred to mother
2nd rhesus +ve baby, antibodies against rhesus +ve can cause haemolysis of the baby's RBCs
rhesus antigen (IgG develops during pregnancy and cross placenta and causes haemolytic disease)
incompatibility in the ABO system
53
how to prevent alloimmune haemolysis during pregnancy
rhesus -ve woman w/ rhesus +ve baby
anti-D injection to mother to inhibit the antibodies and prevent them from causing haemolysis in the baby
54
autoimmune haemolysis
can be either:
autoimmune haemolytic anaemia could be induced by infections or drugs
part of a systematic autoimmune disease (SLE)
autoantibodies produced by malignant B cells
55
type II autoimmune hypersensitivity against solid tissue
good pasture syndrome
IgG autoantibodies bind a glyocprotein in the basement membrane of the lung and glomeruli
anti-basement membrane antibody activates complement - triggers an inflammatory response
56
drug induced haemolysis
penicillin can bind to proteins on surface of RBC
this can induce antibody production
RBC will be marked for destruction by opsonisation either by complement system or through Fc receptor on macrophages
57
type Ii hypersensitivity - antibodies that affect cell function
Graves disease
most common cause of hyperthyroidism
mainly young women, Fhx
HLA allele DR3
thyroid is stimulated w/ an autoantibody that binds to the THS receptor
58
what causes/mediates type III hypersensitivity
how long does it take to happen
immune complex disease
IgG is responsible
immune complex of antigen and antibody form and cause damage at the site of production or circulate and cause damage elsewhere
immune complexes take some time to form and to initiate tissue damage
59
what must the antigens be in a type III hypersensitivity reaction
antigens that form complexes must be polyvalent
present long enough to start an antibody response
60
what are the antigens in a type III hypersensitivity reaction
infectious agents
innocuous environmental antigens
autoantigens
61
antigen:antibody levels in type III hypersensitivity reaction
at low levels of antibody - each antigen molecule binds several immunoglobulin molecules
when antibody and antigen levels are approximately equal, or antibody levels are slightly in XS, large complexes can form
when antibody > antigen, small complexes form
62
clearance of complexes
complement breaks down large complexes
complement receptor 1 transfers complexes to phagocytes
failure of clearance leads to immune complex disease and activation of the innate immune system
63
innate immune response in type III hypersensitivity
due to failure of clearance of immune complexes
64
immune complex disease in the kidney
common cause of renal failure
glomerulonephritis
- nephrotic syndrome (protein in urine) w/ gradual development of renal failure
- nephritis w/ rapid onset renal failure, blood and protein in the urine and hypertension
- depends on rate of immune complex formation
65
farmer's lung
immune complex formation
hypersensitivity reaction to inhaled fungal spores
66
how long does a type IV hypersensitivity reaction take
what is it mediated by
T cells
slowest form of hypersensitivity
can take 2-3 days to develop
aka delayed hpersensitivity
67
describe the process in a type IV hypersensitivity reaction
initiated when tissue macrophages recognise danger signals and initiate inflammatory response
dendritic cells loaded w/ antigen migrate to local LNs - present antigen to T cells
specific T-cell clones proliferate in response to antigens - migrate to site of inflammation
tumour necrosis factor (TNF) is secreted by both macrophages and T cells and stimulates much of the damage in delayed hypersensitivity
68
what is rheumatoid arthritis
how common
where do symptoms arise
chronic disabling condition
affects up to 1% of pop
most symptoms arise in the joints and tendons
also affects the skin, lungs and eyes
69
immune processes in RA
many features of delayed hypersensitivity w/ persistent Th1 and Th17 reactions and TNF secretion
autoantibodies
antigens that drive RA are citrullinated proteins
autoreactive T and B cells can recognise citrullinated proteins --> production of antibodies against cirtrullinated proteins (anti-cyclic citrullinated peptide (CCP) antibodies - can be detected yrs before RA manifests
70
how do symptoms arise in RA
synovium becomes infiltrated by T cells and macrophages
TNF and IL-17 attract and activate neutrophils that cause damage to the synovium
osteoclasts are activated and destroy bone at the joint margins creating erosions
persistent IL-6 secretion triggers an acute phase response
71
risk factors for RA
FHx
association w/ HLA-DR4
more common in smokers ad those infected w/ porphyromonas
72
what is MS and how does it occur
chronic disabling neurological disease
acute attacks - inflammatory lesions consisting of Th1 and Th17 cells and macrophages develop in the affected nervous tissue
inflammatory lesions cause the reversible, relapsing disability typical of early MS - once the inflammation settles, disability improves (good recovery of function between attacks in the early stages)
active inflammation is present in the vicinity; myelin loss impairs the ability of neurons to conduct impulses --> neurological symptoms - chronic disability occurs later from axonal loss
73
treatment of delayed hypersensitivity
prevention through avoiding antigens
anti-inflammatory drugs:
- NSAID
- corticosteroid
- drugs that block TNF and IL-6
- antibodies against B cells
immunosuppressive drugs
