Immune Flashcards
Hypersensitivity
antigen sensitive responses that result in inappropriate or excessive immune response, leading to harm to host
exogenous antigens
non-infective substances
e.g. peanuts, infectious microbes or drugs e.g. penicillin
intrinsic antigens
infectious microbes (mimicry) or self antigens (auto immunity)
properties of all hypersensitivity reactions
sensitisation phase (1st encounter, triggers APC activation + memory cells, no clinical effects) effector phase (pathological reaction upon re-exposure to antigen, memory cells and AB production, notable clinical manifestation)
Type 1 hypersensitivity
allergy
IgE
immediate response (<30 mins), local or systemic
Type 1 hypersensitivity mechanism
activation of TH2
activation of IgE
1st exposure - memory cell production
2nd exposure - IgE cross linking -> mast cell degranulation -> mediators released
Type 1 HS
Mediators
Tryptase
histamine
leukotrienes
platelet activating factor
Type 1 HS
tryptase
remodels CT matrix
type 1 HS
histamine
toxic to parasites
increases vascular permeability + smooth muscle contraction
type 1 HS
leukotrienes
(C4/D4/E5)
increases smooth muscle contraction, vascular permeability + mucus production
type 1 HS
platelet activating factor
attracts leucocytes
increases lipid mediator production (leukotrienes) + activates neutrophils, eosinophils + platelets
type 1 HS
characterised by
increased vascular permeability
vasodilation
bronchial constriction
type 1 HS
presentation
urticaria - rash (activation of mast cells in epidermis)
angioedema - mast cell activation in deep dermis
anaphylaxis
type 1 HS systemic mast cell activation hypotension CVS collapse generalised urticaria angioedema breathing problems
anaphylaxis treatment
IM adrenaline (epipen) multiple doses may be required
(reverses peripheral vasodilation, airway obstruction and mast cell activation, alleviates hypotension, reduces oedema, +ve inotropic effect)
allergen desensitisation / immunotherapy
increasing doses of allergen extracts over years by injection / sublingual drops
very effective in bee + wasp anaphylaxis
Xoliar
anti-IgE monoclonal antibody
to control severe asthma
type 2 HS
antibody mediated (IgG/IgM
develops in 5-12 hours
IgG/IgM antibodies target cell bound antigens
exogenous - blood group / Rhesus D antigens
endogenous - self antigens (autoimmunity)
type 2 HS
mechanism
IgG/IgM -> tissue damage by complement activation ->
cell lysis ->
opsonisation + neutrophil activation + natural killer cell activation
also cause physiological change by receptor stimulation/blockade
type 2 HS
treatment
anti-inflammatory drugs
splenectomy (prevents opsonisation/phagocytosis)
plasmapheresis (filters blood to remove ABs, myasthenia gravis/Graves)
IV immunoglobulin (causes IgG degradation)
replacement therapy (e.g. pyridostigmine inhibits ACh esterase in MG)
Myasthenia gravis
autoimmune destruction of nicotinic ACh receptors at NMJ
weakness of skeletal muscle + fatigue
treatment -> pyridostigmine (acetylcholinesterase inhibiotr) with immunosupressants e.g. prednisone
Haemolytic disease of the newborn (HDN)
occurs in newborn
Rhesus -ve mother has a 2nd Rhesus +ve baby
IgG antibodies cross placenta to fetus -> haemolysis
HDN
1st vs 2nd baby
1st Rh+ baby - sensitisation
maternal and foetal blood don’t mix until birth -> triggers IgG
2nd Rh+ baby - effector phase
ABs present in mother’s blood against Rh+, cross placenta
HDN
treatment
RhoGAM (anti-Rhesus D antibody)
given to all Rh- mothers to prevent HDN (after birth of Rh+ child)
binds to + removes Rh+ blood cells in blood stream -> mother doesn’t make ABs to Rh+ cells
blood types
\+/- = Rhesus D antigen O = no antigen / A + B antibodies A = A antigen / B antibody B = B antigen / A antibody AB = A + B antigens / no antibodies - must have - cannot give the antigen if they have the antibody
universal blood donor
O-
type 3 HS
immune complex (IgG/IgM)
develops 3-8 hrs
IgG/IgM forms immune complexes with soluble antigens
damages tissues by deposition in joints, kidney, small vessels, skin
type 3 HS
factors affecting level of damage
complex size - large cleared by opsonisation, small complexes cleared by reticuloendothelial system, intermediate complexes not cleared
host response - low affinity antibody / complement deficiency
tissue factors - filtration / BP
Systemic lupus erythematous
autoimmune inflammation of connective tissue
affecting CNS, renal, joints, resp system, CNS
high risk of repeated miscarriage
opsonisation
makes a foreign cell more susceptible to phagocytosis
molecules chemically modified to have stronger interactions with cell surface receptors on phagocytes + antibodies
type 4 HS
cell mediated develops in 24-72 hrs (delayed) activation of TH1 sensitises body 2nd exposure - TH1 activates lymphocytes + macrophages to cause: contact hypersensitivity granulomatous hypersensitivity tuberculin hypersensitivity
contact hypersensitivity
type 4 HS
epidermal reaction to nickel/ivy/chemicals in 24-48 hrs
granulomatous hypersensitivity
type 4 HS
occurs in 21-48 days
post exposure e.g. TB, leprosy, schistosomiasis, sarcoidosis
tuberculin hypersensitivity
type 4 HS
Mantoux test
48-72 hrs
dermal reaction
Hashimoto’s disease
type 4 HS
autoimmune attack of thyroid gland
activation of TH1 -> lymphocyte + macrophage damage of thyroid
causes hypothyroidism
type 3 / 4 HS treatment
NSAIDs
corticosteroids - e.g. prednisolone
steroid sparing agents - e.g. aziathioprine/mycophenolate mofetil/cyclophosphamide
monoclonal antibiotics
TB antibiotics
6 months - rifampicin + isoniazid
2 months - pyrazinamide + ethambutol
allergen
any substance stimulating production of IgE or a cellular immune response
sensitisation
the production of IgE antibodies (detected by serum IgE assay) after repeated exposure to antigen
allergy
a hypersensitivity (type 1) reaction initiated by specific immunological mechanisms
IgE mediated - e.g. peanut allergy
non-IgE mediated - e.g. milk allergy
atopy
tendency to produce IgE antibodies in response to ordinary exposure to potential allergens
normally triad of asthma, eczema, allergic rhinitis (hayfever)
anaphylaxis
a serious allergic reaction with bronchial, laryngeal and cardiovascular involvement that is rapid in onset and can cause death
food allergy subdivisions
IgE mediated - immediate (5-30 min)
non-IgE mediated - delayed onset (hrs-days), occurs in infancy or early childhood
food allergy
IgE mediated presentation
skin - pruritis, erythema, acute urticaria, facial angioedema
GI - nausea + vomiting
resp - wheeze, dysponea
CVS (rare) - pallor, drowsiness, hypotension
food allergy
IgE mediated foods
milk + eggs (can resolve before adulthood) peanuts tree nuts fish shelfish fruit/vegetables pollen food syndrome
food allergy
non-IgE mediated presentation
skin - pruritis
GI - food refusal, abdo pain, diarrhoea/constipation, blood/mucus in stool
proctocolitis
enterocolitis
eosinophilic oesophagitis
food protein induced enterocolitis syndrome
proctocolitis
non-IgE mediated
mucus + blood stained stools in otherwise asymptomatic infants (breast milk allergy)
enterocolitis
non-IgE mediated
multiple GI symptoms (milk/egg/wheat allergy)
eosinophilic oesophagitis
non-IgE mediated
oesophageal inflammation and scarring, dysphagia, vomiting, reflux and food impaction (milk/egg/wheat allergy)
food protein induced enterocolitis syndrome
non-IgE mediated
infants
profuse vomiting leading to pallor, lethargy and possibly shock +/- diarrhoea (milk/soya/wheat/rice/meat allergy)
food allergy
non-IgE mediated foods
milk soya wheat rice oats can resolve by school age
milk allergy
presentation
always presents by 12 months old, symptoms can be present weeks after ingestion
immediate/IgE mediated (40%) - presents with typical allergy symptoms (wheeze, urticaria, diarrhoea, vomiting) but can cause anaphylaxis
delayed/non-IgE mediated (60%) - presents with mainly GI symptoms and can be misdiagnosed as GORD/colic
milk allergy
treatment
extensive hydrolysed formula (based on milk, can help tolerance)
2nd line - amino acid or soya formula, then at 9-12 months begin milk reintroduction
food allergy
diagnosis
serum specific IgE
skin prick tests (response of skin mast cells to allergens)
oral food challenge (small amounts of allergen ingested in controlled environment)
level of IgE in blood or response to skin prick test predicts likelihood of allergy, it DOESN’T correlate with severity of allergy
food allergy
management
dietary exclusion
allergy action plan
2 x EpiPens (carry)
autoimmunity
an immune response against the host due loss of immunological tolerance of self antigen
autoimmune disease
disease caused by tissue damage or disturbed physiological responses due to an autoimmune response
types of autoimmune disease
organ specific - one or multiple self antigens within one single organ or tissue
non organ specific - widely distributed self antigens throughout body
hypersensitivity is autoreactive T cell driven
cytotoxic T cells + macrophages
types of autoantibody driven
primary autoantibodies
secondary autoantibodies
IgG transfer
primary autoantibodies
rare/pathogenic
e.g. anti-TSHR in Graves / anti-acetylcholine receptor in myasthenia gravis / anti-anti-GBM antibodies in Goodpastures
secondary autoantibodies
appear later in disease
e.g. anti-nuclear antibodies in SLE / anti-gastric parietal cells in pernicious anaemia / anti-thyroid peroxidase in Hashimotos / anti-RF in rheumatoid arthritis
non-organ specific autoimmune diseases
autoimmune haemolytic anaemia - red blood cells antigens
rheumatoid arthritis - rheumatoid factor (Fc portion of the IgG antibody)
systemic lupus erythematosus (SLE) - double stranded DNA (dsDNA) + other nuclear proteins (histones)
Sjogren’s syndrome - nuclear antigens (Ro and La)
autoimmunity occurs due to
breakdown of central tolerance (thymus fails to delete autoreactive T cells)
breakdown of peripheral tolerance (regulatory T cell defects / altered self antigens / impaired immunoglobulin)
activation of autoreactive B cells
autoimmunity triggered by
genetics (increased risk with MHC variation)
hormonal factors = increased risk if female/post puberty
infection e.g. strep pyogenes to rheumatic fever
drugs e.g. D. pencillamine to myasthenia gravis, SLE + anti GBM
autoimmunity
treatments
plasmapheresis - myasthenia gravis / anti GBM / graves disease
immunosupressive drugs - e.g. ciclosporin / methotrexate
anti-inflammatory drugs
replacement therapy
surgery - e.g. thyroidectomy / splenectomy
monoclonal antibodies e.g. tocilizumab
Hashimoto’s thyroiditis
type IV hypersensitivity reaction
anti-thyroid peroxidase antibodies (secondary autoantibodies) lead to hypothyroidism
presentation - fatigue, bradycardia, constipation, weight gain, hoarse voice
diagnosis - low T3/T4, high TSH, presence of anti-thyroid peroxidase antibodies
treatment - levothyroxine (yearly TSH monitoring)
Graves disease
type II hypersensitivity
thyroid stimulating immunoglobulin bind to TSH receptor
hyperthyroidism
presentation - fatigue, weight gain, exophthalmos, heat intolerance
diagnosis - high T3/T4, low TSH, presence of thyroid stimulating immunoglobulin (TSI)
treatment - antithyroid drugs, plasmapheresis or radioactive iodine/surgery
Addison’s disease
type II-IV hypersensitivity reaction (involving antibody + cell mediated destruction)
steroid-21-hydroxylase antibodies alongside cytotoxic T cells attack adrenal cortex -> adrenal insufficiency
presentation - fatigue, hyperpigmentation, depression, sexual dysfunction, hypoglycaemia
diagnosis - high ACTH, presence of steroid-21-hydroxylase antibodies
treatment - lifelong glucocorticoid replacement
(ACTH triggers cortisol release from adrenal cortex)
Myasthenia gravis
type II hypersensitivity reaction
ACh receptor antibodies attack ACh receptors at NMJ
skeletal muscle weakness
treatment - acetylcholinesterase inhibitors, immunosupressants
Rheumatoid arthritis
type IV hypersensitivity reaction
rheumatoid factor antibodies -> inflammation and joint destruction
presentation:
joint - pain, stiffness, swelling (worse in morning)
malaise / weight loss
treatment - DMARDs + steroids
Systemic lupus erythematosus (SLE)
type III hypersensitivity reaction
antibodies to dsDNA and histones -> multisystem disease
RF - female, FHx, Afro-carribean>south Asian>caucasian
presentation:
hands - Raynauds, joint pain + swelling
head - alopecia, malor rash
trunk - myalgia, pericardial pain, pleuritic chest pain, photosensitivity
other - renal abnormalities, neurological symptoms (e.g. depression)
treatment - patient education + DMARDs (e.g. hydroxychloroquine) + steroids (e.g. prednisolone)
severe cases - IV cyclophosphamide (chemotherapy / suppress immune system)
