Hypersensitivity Reactions Flashcards
What is hypersensitivity?
An inappropriate immune response to non-infectious antigens that results in tissue damage and disease
State the 4 types?
- Type 1: immediate hypersensitivity/allergy
- Type 2: cytotoxic hypersensitivity
- Type 3: serum sickness and Arthus reaction
- Type 4: delayed-type hypersensitivity, contact dermatitis
State the components required for a type I hypersensitivity reaction and state 3 examples?
- Immune reactant: IgE, Antigen: Soluble antigen (allergen), effector mechanism: Mast cell activation + degranulation via IR + A
- Example -> Allergic rhinitis, asthma, systemic anaphylaxis
Describe what occurs in the immediate hypersensitivity reaction?
- Antigen enters tissue -> if cross-reactive with mast cells (IgE) -> activation -> release of immune cells -> Activates wheal-flare reaction -> Vasolidation, oedema + swelling of tissue
Describe what type II HS reactions respond to and state the components involved, naming an example of what causes it?
- Respond to altered components of human cells
- Components -> Immune reaction: IgG (anti-drug ABs), Antigen: Platelet/BC coated with drug, effector mechanism: AB binds cells -> Cleared via macrophages (FcRs) + complement -> kills RBCs -> haemolytic anaemia
- Example -> drug allergies i.e penicillin
Describe a special type of type II response and state 2 conditions which this occurs in
- IgG antibodies directed at CS receptors -> Antibodies disrupt function via uncontrollable activation OR block receptor
- Grave’s diseases (TSHR), myasthenia gravis (nACHR)
Describe how haemolytic disease of the newborn is an example of a type lI hypersensitivity reaction?
- HD -> child dies in utero -> via severe haemolytic anaemia
- Occurs with rhesus (RHD) -ve mother + RHD + ve foetus - First child: Placenta separates from uterus -> exposed to foetal RBC RHD -> maternal sensitisation -> ABs against foetal RBCs produced -> first child unaffected
- 2nd child -> ABs cross placenta -> into foetal circulation -> Foetal RBCs killed -> haemolytic anaemia
- If you’re rhesus positive (RhD positive), it means that a (D antigen) protein found on the surface of your red blood cells
Describe the type of components inolved in type 3 hypersensitivity reactions and state 2 examples?
- Immune reactant: IgG, Antigen: Soluble antigen,
- effector mechanism: IgG + soluble antigen = immune complex -> activate macrophage, complement, mast cells -> MSC release IF mediators -> IF cells invade site -> increase blood vessel permeability + blood flow -> accumulation of platelets -> occlusion of small blood vessels, haemorrhage + apperance of purpura -> IC cleared via phagocytes
- Example -> serum sickness + arthus reaction (following diptheria/tetanus vaccine)
What is serum sickness caused by and state examples of these?
- Caused by large IV dose of soluble antigens (drugs) -> immune complex formation -> depositied in tissues (blood vessel walls) -> tissue damage caused via complement activation + IF responses
- Occurs via -> Antivenon, farmer’s lung (IF of lung -> fibrosis + damage of lungs), 3-HS pneumonitis (dust, bacteria, fungi)
What 2 factors determine the pathology observed in type III HS reactions?
Antigen dose + route of delivery
Describe the components involved within Type IV HS reactions and state examples? (PART 1)
- Delayed - Occurs from 24-72 hours - other take <24 hours
- Type I -> Immune reactant: Th1 (Ag-specific), Ag: Soluble Antigen, effector mechanism: Th1 activation via Ag recognition -> release of IFN-y -> macrophage activation -> release of chemokine, cytokine, cytotoxin -> lesion,
- Example: Tuberculin reaction (tuberculoid leprosy), Mantoux test
Describe the components involved within Type IV HS reactions and state examples? (PART 2)
- Type II - IR: Th2 (Ag-specific), Ag: soluble Ag, EM: Th2 activation via Ag -> Release of IL-4, IL-5 eotaxin -> eosinophil activation -> release of basic proteins, enzymes, cytokines,
- Example: Allergic contact dermatitis (nickel), poison ivy
Production of allergen-specific IgE
What is the type I HS reaction defined as?
Disease following a response by the immune system to an otherwise innocuous/not-harmful antigen
What is allergen-specific IgE + describe its production?
- First line of defence against worms -> Binds FceR1 on mast cells + preps them to react in presence of antigen
- Exposure to allergen -> antigen recognition -> DC migration to lymph node Th2 activation -> IL-4/IL-13 release -> activates B cell -> IgE produced -> binds mast cell
What causes allergic sensitisation?
- Exposure to allergen -> nature of allergen, dosage (Increase vs decrease), timing (age), location of priming (in body)
- Role of pro-allergic DC + cytokines -> convert Th into Th2 cells
- Genetic predisposition to allergy
State features about common allergens?
- allergens named systematically (after source organism + order discovered)
- All may have common functionality
- Received in decreased doses
- Increased dose exposure = tolerance
How does genetics play a role in allergy?
Multiple Complex traits + genetics -> contribute to allergy
Describe the role of filaggrin and state what condition if there is a lack of filaggrin?
- Maintains skin integrity
- Defective: Increased risk of Atopic dermatitis -> via increased access for allergen + sensitisation
What makes dendritic cells pro-allergic?
- Injury to skin -> induces cytokine production -> Thymic stromal lymphoprotein may switch DC to ‘pro-allergic’ state -> migrate to LN
Effector mechanisms of allergic immune response
Describe what happens in the 2nd exposure to the pollen?
Initial response -> Pollen-specific IgE binds mast cell -> 2nd exposure -> Acute release of mast-cell contents -> allergic rhinitis
Describe what happens to mast cells when activated?
- Resting -> has bound IgE - allergen-specific -> Contains granules (histamine + IF mediators)
- Activated -> Specific allergen crosslinks IgE -> Release of granule contents -> Different effects on different tissues (GI, airways, blood vessels)
Describe different phases in the allergic response with symptoms?
- Early: Mediated via mast cells -> Release of IF mediators -> whezzing, urticaria, sneezing, conjunctivitis
- Late -> mediated via T cells -> IL-5 (eosinophil activation) + IL-4 (mast cell) + basophils -> further wheezing, sustained blocked nose, eczema
State the effector mediators and their effect produced by mast cells in the early and late phase?
- Early: Histamine (Increased vascular permeability + Smooth muscle contraction), leukotrienes (increased VP, SMC, increased mucus secretion), prostaglandins (chemoattractants for T cells, eosinophils + basophils)
- Late: Cytokines - IL-4/IL-13 (increased Th2 + IgE) + TNF-alpha (increased tissue IF)
Describe the features of eosinophils + its 2 effector function?
- Features -> located in the tissues, recruited to allergic reaction sites, express FceRl upon activation
- Effector functions -> Release highly toxic granule proteins + free radicals upon activation to kill microorganisms/parasites + cause tissue damage
- Synthesise + release PGs, leukotrienes + cytokines -> amplify the IF response -> via activating epithelial cells + recruiting leukocytes
