Immunology 3: Hypersensitivity and allergy Flashcards
What are appriate immune reaction?
Response to foreign harmful argents such as virus, bacteria, fungi, parasites
Eliminate pathogens
Can cause tissue damage as a side effect but if the patogen is elminated then can be repaired
Involves Ag recognition by immunesystem
What is appropriate immune tolerance?
Tolerance to self Ag, and foreign Ag that cause no harm-food, pollen, plant proteinsm animal, commensals bacterua
Involves Ag recognition and Treg and regulatory blocking IgG4 AB
antigen in context of danger (microbial signals) cause immune response, and absence of danger-tolerance (unsure how)
When do hypersensitivity responses happen?
When react to harmless foreign Ag-allergy
Autoantigens-AID
alloantigens-foreign from human-serum sickness, tranplsant,
What are the 4 types of hypersensitivty reaction?
Type 1-immeduate
II-Ab dependent
III-immune complex
IV-delayed cell
these are distincts but most disease involve more than one
When is type 1 hypersensitivity important?
Anaphylaxis, ashtma, rhinitis-seasonal and perennial
food allergy
How does type 1 hypersensitivity develop?
1st AG exposure-inital
Sensitisation and not tolerance
IgE production in response-IgE bind mast cells and basophils
2nd Ag exposure-more IgE produce
Ag cross link IgE on mast cell/baso-degranulation
What is type II hypersensitivity and how does it present? How do you test?
Depends of Ab against the AG
depends on which organ affected-mysternia gravis wiith Anti acetycholin AB, glomerulonephritis-glomerual BM
Pemphigus vulgaris-blistering of skin
Pernicious aneamia
OR Autoimmune cytopenias-AB mediated blood cell destruction
Heamolytic aneamia, thrombocytopenia, neutropenia
test by testing for specific AB=with immunofluorescnence and histology, or ELISA test
What is Type III hypersensitivity? What is made from?
Formation of Ag -Ab complexes
COmplex deposite in smaller vessels-complement and cell activation (monocytes, neutrophils), activation of cascades (clotting)-Tissue damage (kidneym skin, lungs
common in SLE, Vasculidities
What is type IV hypersensitivity? what mediated by? Main pathways?
delayed-cell mediated
Chronic graft rejection, graft vs host, coeliac, contact hyper, AID –th1 mediated
ashtma, thinitis, eczema-th2 mediated
Th1-produce INFgamma, cytotoxic cells, and th2
transiet/persitant Ag-activation of T cells+macrophages-CTL
Tissue damage dependent on TNF and CTL (th1 produce IL2 to activation of CTL) or IFNgamma to macrophage to make TNF
also activtion of fibroblast
typical in metal reaction-contact hypersensitivity
What is the role of inflammation in hypersensitivity?
present in all types-
Reaction of recruitment and activation of cells to site of injuery
Mediated by cytokines
cause vasodilation-complement (C3, histamine), vascular permeability, increase in mediator and cytokines (Il1, 6, 2, TNF, INFy), chemotaxis cytokine-IL* (neutrophils), IP 10 (lymphocytes)
inflam cells and tissue damage
cause 4ors-redness, heat, damage, pain
involve neutrophils, macrophagesm lymphocytes and mast cells
How common is allergy?
Atopy-50% in UK
severity varies-midl symtoms, severe chronic ashtma, anaphylaxis
risk factors are genetic and environemental
increasing prevalence in UK-from 4% in 69 to 20% in 2009-probably environemental
What is the role of genetics in allergy?
important-80% that have allergy have family history
but polygenic-100 identified
important-genes in IL4 cluster-raised IgE, asmta and atropy
IgE receptor genes-allergy and ashtma
Genes to structural cells linked to eczema (like filagrin
What is the role of environement in Allergy
Imporntant-increase with age-peak in teenage years
Gender-more common in males in childhood, adult-female
Family size-more common in small families (lots of other to exposure them)
Infection-early infections protect
Animals-early exposure protects
diet-breast feeding, antioxidants, fatty acid protect
What are the 3 types of inflammation in allergy>
Most common-anaphylaxis, urtucariam angioodemia-Type 1
Idiopathuc.chronic urticarua-type II
Ashma, rhinitis, eczema-mix of type 1 and type IV
Always requires sensitisation and then further exposure produce the response
Describe classical pathogenesis of allergy in lungs
Antigen taken up by DC-process into peptide and present to local T helper cells-either become Th1 , Treg or Th2-when sensitise instead of tolerate-Th2
Produce IL4/13–b cells then produce IgE-proliferate and differentiate–produce IgE to Ag
when Ag again-memory T cells from before produce more Il4/13-produce more IgE-and IL5, recruiting eosinophils-inflammation
Also mast cells and basophils
Which cells are the most important in allergy?
eosinohphils-low in blood but high in tissue-recruited in allergy-bilobbed nucleus + granules-toxic proteins-leads to tissue damage-very in asthma
mast cells-immediate/anaphylaxis-resident in tissue-IgE receptor-Cross linking of IgE on large Ag-mediator release of granules (histamine, cytokines, toxic proteins) and newly synthesises-leukotrienes, prostagrlandins
neutrophils-virus induces asthma attacts, crhonic eczema-common in blood-polymophonuclear cells-granules have digestive enzymes and synthesis ROS, Cytokine and leukotrienes
Describe the immonopathogensis of asthma>
Actue inflam of airway
Mast cell activation and degranulation-histamine, prostaglanding, leukotriens => acute narrowing (consquence of vascular leakage-swelling of tissue
lead to mucus secretion and filling of airway
and SMC constriction, all combined block airway
2 phase response-large, peak response immediate (early response-leukotriene, histamine), then 6h-smaller but longer resonse–consquence of cellular response-eosinohils, macrophages, neutrophils
Describe the chronic inflammations of airway in asthma?
Cellular infiltrates-SMC hypertrophy, mucus pluggingm epithelial shedding and sub epithalial fibrosis
What are the clinical features of asthma>
Revesribke generilsed aiway obstructuion-chronic episodic wheezze
bronchial hyperresponsitivity
Cough, mucus production
breathlessness, chest tightness
important-response to treatment, spontaneous variation and reduce/variable PEF –varies a LOT during day
What is allrergic rhinits?
seasonal-hayfeaverl, etc
Perinial-all year0pets
sneezing, rhinorrhoae, itchy nose, eyes
Nasal block, sinusitis, loss of smell taste, nasal polyps
What are features of allergic aczema-
Chronic itchy skin rash-usually at flexture of arm and legs
sensitisation and dry cracked skin
complicated rarely by infection
but usually clears away from small children -90% lose it by adulthood
What is food allergy?
infancy-eggs, milk
Adults-peanutsm shellfish, fruits, cereal, soya
mild-itchy lips, mouth, angiodeamiam urticaria
severe-nausea, abdopain, collapse, wheeze, anaphalaxics
What is anaphylaxis? How do treat it?
severe generalise reaction-uncommon
fatal–generalised degranulation of IGE sensitised mast cells
Cause itchy mouth lipds, mouth, parynx (swelling_
wheeze, dysnpnea, faitness, collapse, DnV
vasodilation, cardio collapse, bronchospasm, larygeal odema, vasodilation of skin, utricaria, angioodeamia, DnV
treat with epipen-adrenaline-
a kit-also antihistamines, steroids–rest is medical aid
Main in prevent-avoid allergen, carry epipen, inform people around u
What are the main diagnostic test for allergy?
careful hisotyr is main one Skin prick test RAST-blood specific IgE test Total IgE Lung function for ashtma
What is the main treatment for rhinitis and eczema>
If mild-antihistamines will do
steroid spray-for nasal blockage
Cromoglyctae (children eyes)-block degranulation of mast cells
eczema-emoliants-improve skin barrier, topical steroid cream
If severe-Anti IgE, AntiIl4, anti IL5, anti IgE mAB
What are the main treatment for asthma
B2 agonist-Salbutamol
Inhaled steroids-becolmethasone/budesonide
more=long acting bronchodilators(leukotriens antagonsit), more steroids
Oral steroids, immune therapy, arithromycin (Abx also anti inflam, and mAb vs IL4/5)
Immunotherapy-effective for single Ag hypersensitivty-
What is immunotheraoy for allergy>
Immunotherapy-effective for single Ag hypersensitivty-venoms, pollens, mites,
need subcutaneous immunitherapy-3 years to form reduce sensitivity-weekly/monthly-stay for 2h visits in case of response
Sublingual-can be taken at home for 3 years-doesnt cause massive response
teaches immune system tolerance
