hypersensitivity Flashcards
what is a hypersensitivity reaction
excessive immune responses that cause damage
what can a hypersensitivity reaction be in response to
different types of antigens:
infectious agens
environmental substances
self antigens
hypersensitivity to infectious agents
- which infections
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
how do influenza viruses cause hypersensitivity
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
hypersensitivity to environmental substances - what substances
usually allergens that are available within the environment
e.g. dust, haptens, nickel, drugs
hypersensitivity to dust
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
dust - IgE resopnse
if the dominant antibody is IgE:
- may trigger immediate hypersensitivity
- manifests as allergy symptoms e.g. asthma, rhinitis
dust - IgG response
if dust stimulates IgG antibodies:
- may trigger a different kind of hypersensitivity
- e.g. farmer’s lung
hypersensitivity to environmental substances - smaller molecules
sometimes diffuse into the skin
may acts as haptens - trigger delayed hypersensitivity reaction
what are haptens
small molecule irritants that bind to proteins and elicit an immune response
hypersensitivity to environmental substances - reaction to nickel
contact dermatitis
hypersensitivity to environmental substances - drugs
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)
type I hypersensitivity: immediate hypersensitivity
- onset
- infectious trigger
- environmental trigger
- autoimmunity
- adaptive immune system mediators
- innate immune system mediators
- 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
type II hypersensitivity: bound antigen
- onset
- infectious trigger
- environmental trigger
- autoimmunity
- adaptive immune system mediators
- innate immune system mediators
- 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
type III hypersensitivity: immune complex
- onset
- infectious trigger
- environmental trigger
- autoimmunity
- adaptive immune system mediators
- innate immune system mediators
- 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
type IV hypersensitivity: delayed hypersensitivity
- onset
- infectious trigger
- environmental trigger
- autoimmunity
- adaptive immune system mediators
- innate immune system mediators
- 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
how is type I hypersensitivity mediated
how quick are the effects
categories
through the degranulation of mast cells and eosinophils
within minutes of exposure
immediate hypersensitivity, allergy
what is another name for type I hypersensitivity and what does it mean
atopy
immediate hypersensitivity reaction to environmental antigens mediate by IgE
atopy and Fhx
people w/ these allergies tend to have a Fhx w/ atopy traits
features of atopy
anaphylaxis angioedema urticaria rhinitis asthma dermatitis eczema
manifestations differ according to the antigen
what is the atopic march
the increase in risk of developing antigens over time if the patient develops allergies at a very young age
what are allergens
antigens that trigger allergic reactions
gain access to the body through inhalation, ingestion, contact or drugs
what is the most common cause of severe allergic reactions
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)
mechanism for type I hypersensitivity
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
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
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
Systemic symptoms of allergies
ANAPHYLAXIS:
- low BP
- angioedema and airway obstruction can be fatal
airway symtptoms of allergies
ASTHMA:
- reversible airway obstruction in the bronchi
RHINITIS:
- discharge
- sneezing
- nasal obstruction
- often co-exist w/ allergic conjunctivitis
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
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
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
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
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
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
skin prick testing
used to work out what the patient is allergic to
positive and negative control then allergens (histamine, saline, allergens)
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
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
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
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
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
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
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
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
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
innate immune response in type III hypersensitivity
due to failure of clearance of immune complexes
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
farmer’s lung
immune complex formation
hypersensitivity reaction to inhaled fungal spores
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
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
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
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
