️ Autoimmune Diseases and Allergies
When the immune system turns against itself — or over-reacts to harmless triggers. This lesson examines the loss of self-tolerance behind autoimmune disease and the IgE-mediated hypersensitivity behind allergy and anaphylaxis, plus the treatments for each.
Practise this lesson
Four printable worksheets that build from the foundations up to exam-style questions — start at whatever level suits you.
Your immune system can distinguish self from non-self with remarkable accuracy — almost all the time.
Before you read: what do you think could go wrong with this recognition system? What would happen if immune cells attacked your own body, or triggered a response to harmless substances like pollen?
Come back to this at the end of the lesson.
Know
- Definition of autoimmune disease and allergy (Type I hypersensitivity)
- Key terms: self-tolerance, allergen, IgE, mast cell, histamine, anaphylaxis
- Examples of autoimmune diseases and their target tissues
Understand
- How loss of self-tolerance leads to autoimmune attack
- The two-stage mechanism of allergic response (sensitisation → re-exposure)
- Why anaphylaxis is a medical emergency
Can Do
- Compare autoimmune and allergic diseases using tissue targets and antibody classes
- Describe the mechanism of a named autoimmune disease
- Evaluate treatments — immunosuppressants, biologics, antihistamines, desensitisation
Core Content
Why the immune system normally leaves your own cells alone
The immune system must be both powerful enough to destroy pathogens and restrained enough not to destroy the body it protects. This balance is called self-tolerance.
During development, T lymphocytes undergo a screening process in the thymus called clonal deletion. T cells that react strongly to self-antigens (proteins on the body's own cells) are destroyed before they can circulate. This normally prevents autoimmune attack.
How Self-Tolerance Can Break Down
Several mechanisms have been identified:
- Molecular mimicry — a pathogen antigen resembles a self-antigen; antibodies raised against the pathogen accidentally attack host tissue (e.g. rheumatic fever)
- Defective regulatory T cells (T-reg) — T-reg cells normally suppress self-reactive lymphocytes; if they malfunction, self-reactive clones proliferate
- Exposure of hidden antigens — cell damage releases intracellular proteins the immune system has never encountered; these can be treated as foreign
- Genetic predisposition — certain HLA (human leukocyte antigen) alleles increase risk; many autoimmune diseases cluster in families
What to write in your book
- Self-tolerance = immune system distinguishes self from non-self; maintained by clonal deletion of self-reactive T cells in the thymus.
- Breakdown mechanisms: molecular mimicry, defective T-reg cells, exposure of hidden antigens, genetic (HLA) predisposition.
- Autoimmune disease = immune attack on self-tissues (antibodies or cytotoxic T cells) → chronic inflammation/organ damage.
- ~1 in 20 Australians affected; MS rises with distance from equator (vitamin D link).
The immune system's ability to distinguish self from non-self, maintained by clonal deletion of self-reactive T cells, is called self-_____.
Target tissues, antibodies and clinical consequences
Autoimmune diseases are classified by the tissue attacked. In organ-specific diseases, a single organ is targeted. In systemic diseases, antibodies attack antigens found throughout the body.
Type 1 Diabetes
Target: Beta cells in pancreatic islets of Langerhans. T cells destroy insulin-producing cells → absolute insulin deficiency → hyperglycaemia.
Rheumatoid Arthritis
Target: Synovial membrane of joints. Antibodies (including rheumatoid factor, an anti-IgG antibody) cause joint inflammation, cartilage erosion and deformity.
Multiple Sclerosis
Target: Myelin sheath of neurons in CNS. Demyelination disrupts nerve conduction → progressive neurological dysfunction (vision, balance, motor control).
Systemic Lupus Erythematosus (SLE)
Target: DNA, nuclear proteins, red blood cells and kidneys. Anti-nuclear antibodies form immune complexes that deposit in tissues → inflammation. Classic butterfly facial rash.
Coeliac Disease
Target: Small intestine villi. IgA antibodies attack gluten-modified tissue transglutaminase → villous atrophy → malabsorption of nutrients.
Hashimoto's Thyroiditis
Target: Thyroid gland follicular cells. Antibodies against thyroid peroxidase destroy thyroid tissue → hypothyroidism (inadequate thyroid hormone).
Organ-specific
- Tissue-specific protein
- Type 1 Diabetes, Hashimoto's, Multiple Sclerosis
- Localised to one organ/tissue
- Cytotoxic T cells or organ-specific antibodies
Systemic
- Widespread antigens (e.g. DNA)
- SLE, Rheumatoid Arthritis
- Multi-organ inflammation
- Immune complex deposition, complement activation
Treatment of Autoimmune Diseases
Treatment aims to suppress the misguided immune response while minimising susceptibility to infection:
- Corticosteroids (e.g. prednisolone) — broad immunosuppression, reduce inflammation rapidly; long-term use causes significant side effects
- Disease-modifying antirheumatic drugs (DMARDs) — e.g. methotrexate; slow disease progression in RA
- Biologic therapies — monoclonal antibodies targeting specific immune mediators:
- Anti-TNF-α (e.g. adalimumab) — blocks inflammatory cytokine in RA, Crohn's
- Anti-CD20 (rituximab) — depletes B cells; used in SLE, MS
- Anti-IL-17 — blocks interleukin-17 in psoriasis, ankylosing spondylitis
- Hormone replacement — e.g. insulin in Type 1 Diabetes, thyroxine in Hashimoto's — replaces the missing product rather than treating the immune cause
What to write in your book
- Organ-specific (T1D, Hashimoto's, MS) vs systemic (SLE, RA — widespread antigens like DNA).
- Examples + targets: T1D (beta cells), RA (synovium), MS (myelin), SLE (DNA/nuclei), coeliac (villi), Hashimoto's (thyroid).
- Treatments: corticosteroids, DMARDs (methotrexate), biologics (anti-TNF-α, anti-CD20), hormone replacement.
- Most treatments are immunosuppressive — manage, not cure (loss of self-tolerance remains).
An autoimmune disease occurs because the immune system is:
IgE-mediated hypersensitivity to harmless environmental antigens
An allergy is an exaggerated immune response to a normally harmless substance (allergen). Unlike autoimmunity — which involves self-attack — allergies direct the immune response outward, but towards the wrong target.
The Two-Stage Mechanism
Sensitisation (first exposure)
The allergen (e.g. pollen, bee venom, peanut protein) is processed by antigen-presenting cells. Helper T cells (Th2 subset) stimulate B cells to produce IgE antibodies specific to the allergen. IgE binds to high-affinity receptors on the surface of mast cells in tissues and basophils in the blood. No symptoms occur at this stage — the individual is now sensitised.
Re-exposure (subsequent exposure)
The same allergen enters the body again and cross-links two adjacent IgE antibodies on the surface of mast cells. This cross-linking triggers mast cell degranulation — the rapid release of pre-formed chemical mediators stored in granules inside the cell.
Release of mediators → symptoms
Key mediators released include:
• Histamine — increases vascular permeability (fluid leaks into tissues → swelling), causes vasodilation (redness, heat), stimulates mucus secretion, and causes smooth muscle contraction (bronchoconstriction, gut cramps)
• Prostaglandins and leukotrienes — sustain and amplify the inflammatory response; leukotrienes are potent bronchoconstrictors
• Heparin — prevents local clotting
Common Allergens and Associated Conditions
Hayfever (Allergic rhinitis)
Allergen: airborne pollen, dust mite faeces. Affects nasal mucosa → sneezing, itchy/watery eyes, congestion.
Asthma (allergic)
Allergens: pollen, pet dander, mould. Mast cells in bronchioles degranulate → bronchoconstriction, mucus hypersecretion, wheeze.
Food Allergy
Common: peanuts, tree nuts, shellfish, milk. IgE-mediated reaction → hives, vomiting, potential anaphylaxis.
Contact Dermatitis (Type IV)
Allergen: nickel, latex. T cell-mediated (not IgE); delayed reaction 24–72 h → localised redness, blistering.
What to write in your book
- Allergy = Type I hypersensitivity, IgE-mediated, to a harmless allergen.
- Sensitisation (1st exposure): Th2 → B cells → IgE → IgE binds mast cells (no symptoms).
- Re-exposure: allergen cross-links IgE → mast cell degranulation → histamine, leukotrienes, prostaglandins.
- Symptoms: vasodilation, oedema, bronchoconstriction, mucus, itching. Contact dermatitis = Type IV (not IgE).
Which antibody class binds to mast cells and mediates Type I allergic reactions?
Mechanism, recognition and immediate management
Anaphylaxis occurs when a Type I allergic response becomes systemic — mast cells and basophils throughout the body degranulate simultaneously, causing life-threatening cardiovascular and respiratory collapse.
Pathophysiology
Massive histamine release from widespread mast cell degranulation causes:
- Systemic vasodilation → sudden drop in blood pressure (anaphylactic shock) — blood pools in peripheral vessels, organs are underperfused
- Increased vascular permeability → plasma leaks into tissues → angioedema (swelling of face, throat, tongue) — can obstruct the airway
- Severe bronchoconstriction → respiratory distress, inability to breathe
- Cardiac effects — reduced cardiac output due to low circulating blood volume
Emergency Management
Intramuscular adrenaline (epinephrine)
First-line and life-saving. Adrenaline acts via alpha-adrenergic receptors to cause vasoconstriction (reversing vasodilation) and via beta-receptors to cause bronchodilation and increase cardiac output. Auto-injectors (EpiPen) allow self-administration. Delivered into the lateral thigh for fastest absorption.
Call emergency services (000)
Adrenaline wears off in 15–20 minutes; a second dose may be needed and medical monitoring is essential. The individual should lie down with legs elevated unless breathing is compromised.
Antihistamines and corticosteroids (secondary)
IV antihistamines (H1 blockers) and corticosteroids may be administered in hospital to prevent a biphasic reaction (second wave of symptoms 4–12 hours later), but they act too slowly to treat the acute crisis.
What to write in your book
- Anaphylaxis = systemic mast cell degranulation → cardiovascular + respiratory collapse.
- Massive histamine → vasodilation (↓BP/shock), angioedema (airway obstruction), bronchoconstriction.
- 1st-line: IM adrenaline (α → vasoconstriction; β → bronchodilation + ↑cardiac output) + call 000.
- Antihistamines/steroids are secondary (too slow for the acute crisis; prevent biphasic reaction).
A person can suffer anaphylaxis the very first time they are exposed to an allergen.
In autoimmune diseases, the immune system produces antibodies and T cells that target the body's own tissues.
Allergies are autoimmune diseases because they involve the immune system attacking harmless environmental substances.
Antihistamines, corticosteroids, biologics and immunotherapy
Antihistamines
Nasal corticosteroids
Bronchodilators
Anti-IgE biologic
Allergen immunotherapy (desensitisation)
Comparing Autoimmune Disease and Allergy
| Feature | Autoimmune Disease | Allergy (Type I) |
|---|---|---|
| Target | Self-antigens (body's own tissues) | Non-self allergen (harmless foreign substance) |
| Antibody class | IgG, IgM (or cytotoxic T cells) | IgE (bound to mast cells) |
| Mechanism | Loss of self-tolerance → attack on host tissue | Sensitisation → mast cell degranulation |
| Time course | Chronic, progressive | Immediate (minutes after re-exposure) |
| Key mediator | Cytokines, complement, antibody-dependent cytotoxicity | Histamine, leukotrienes, prostaglandins |
| Example treatment | Immunosuppressants, biologics | Antihistamines, desensitisation, adrenaline (anaphylaxis) |
Autoimmune disease and allergy both involve immune dysfunction, but differ in target, antibody class, speed of onset and treatment approach.
What to write in your book
- Antihistamines block H1 receptors (symptom relief, don't stop release); nasal corticosteroids reduce local inflammation.
- Anti-IgE biologic (omalizumab) binds free IgE → prevents IgE binding mast cells.
- Desensitisation (immunotherapy): escalating allergen doses shift Th2→Th1/Treg — only disease-modifying treatment.
- Autoimmune vs allergy: self vs non-self target; IgG/IgM (or T cells) vs IgE; chronic vs immediate.
Which allergy treatment is the only one that modifies the underlying disease rather than just managing symptoms?
Autoimmune Disease
- Immune system attacks self-antigens due to loss of self-tolerance
- Effectors: IgG/IgM antibodies or cytotoxic T cells
- Organ-specific (T1D, MS) vs systemic (SLE)
- Tx: immunosuppressants, DMARDs, biologics (anti-TNF-α, anti-CD20)
Type I Hypersensitivity (Allergy)
- IgE-mediated response to allergen
- Sensitisation: B cells → IgE → IgE binds mast cells (no symptoms)
- Re-exposure: allergen cross-links IgE → degranulation → histamine
- Symptoms: vasodilation, oedema, bronchoconstriction, mucus
Anaphylaxis
- Systemic mast cell degranulation → anaphylactic shock
- Airway obstruction (angioedema) + cardiovascular collapse
- Tx: IM adrenaline → bronchodilation + vasoconstriction
- Requires second dose (EpiPen) + 000
Allergy Treatments
- Antihistamines — block H1 receptors; symptomatic relief only
- Corticosteroids — reduce local inflammation
- Anti-IgE (omalizumab) — prevents IgE binding to mast cells
- Desensitisation — shifts Th2→Th1; disease-modifying
Classify and Explain
For each condition listed below, identify whether it is an autoimmune disease or an allergy, name the target (tissue or allergen), and state the key antibody class involved.
| Condition | Type | Target | Antibody class |
|---|---|---|---|
| Hayfever | |||
| Multiple sclerosis | |||
| Peanut allergy | |||
| Systemic lupus erythematosus | |||
| Coeliac disease | |||
| Anaphylaxis to bee venom |
Anaphylaxis Scenario
- Explain why Jess did not react the very first time she ate peanuts.
- Describe the cellular and molecular events that occurred within seconds of eating the peanut oil at the school event.
- Explain why Jess's daily antihistamines did not prevent this reaction.
- Describe the mechanism by which adrenaline (epinephrine) reverses the key symptoms of anaphylaxis. (3 marks)
At the start of the lesson you were asked what could go wrong with the immune system's self/non-self recognition — what would happen if immune cells attacked your own body, or responded to harmless substances?
Now you can answer precisely — loss of self-tolerance causes autoimmune disease (immune attack on host tissue) and aberrant IgE production against harmless antigens causes Type I hypersensitivity (allergy). Both involve a fully functional immune system responding to the wrong target.
A fresh set drawn from this lesson's question bank — feedback shown immediately. +5 XP per correct · +25 XP all correct
Pick your answer, then rate your confidence — that tells the system what to drill next.
UnderstandBand 3(3 marks) 1. Using the concept of self-tolerance, explain why autoimmune diseases are classified as non-infectious diseases rather than immune deficiency disorders.
AnalyseBand 4(4 marks) 2. Compare the roles of IgE and IgG in the immune system, with reference to one condition involving each antibody class.
EvaluateBand 5–6(6 marks) 3. A new drug stabilises mast cells, preventing degranulation. Predict the drug's effectiveness for: (a) hayfever; (b) anaphylaxis first-aid; (c) multiple sclerosis. Justify each prediction.
Show all answers
Multiple choice
MC answers and full explanations are shown inline as you complete each question. Use the retry button to attempt a fresh set from the lesson bank.
Activity 1 — Classify and Explain
Hayfever: allergy; target = airborne pollen/dust mite (nasal mucosa); IgE. Multiple sclerosis: autoimmune; target = myelin sheath (CNS neurons); cytotoxic T cells / autoantibodies. Peanut allergy: allergy; target = peanut protein allergen; IgE. SLE: autoimmune (systemic); target = DNA/nuclear proteins; anti-nuclear IgG. Coeliac disease: autoimmune; target = small intestine villi (tissue transglutaminase, gluten-modified); IgA. Anaphylaxis to bee venom: allergy (systemic Type I); target = bee venom allergen; IgE.
Activity 2 — Anaphylaxis Scenario
1. The first time Jess ate peanuts she was only sensitised — antigen-presenting cells processed the allergen, Th2 cells stimulated B cells to produce peanut-specific IgE, and that IgE bound to mast cell surfaces. No symptoms occur during sensitisation. 2. On re-exposure, peanut allergen cross-linked adjacent IgE molecules on her mast cells, triggering rapid degranulation and the release of pre-formed histamine (plus leukotrienes/prostaglandins). Histamine caused vasodilation and increased vascular permeability (hives, facial swelling/angioedema), bronchoconstriction (difficulty breathing), and a fall in blood pressure (feeling faint). 3. Antihistamines block H1 receptors on target cells — they do not prevent mast cell degranulation or histamine release, and they cannot counteract the massive, rapid systemic mediator release of anaphylaxis (they also act too slowly). 4 (3 marks): Adrenaline acts on α-adrenergic receptors to cause vasoconstriction (reversing vasodilation and restoring blood pressure) [1]; on β2-receptors to cause bronchodilation (relieving airway constriction) [1]; and increases cardiac output via β1-receptors, restoring perfusion — together rapidly reversing the life-threatening features of anaphylaxis [1].
Short Answer Model Answers
SA1 (3 marks): Self-tolerance is the mechanism by which the immune system avoids attacking its own cells, achieved through clonal deletion of self-reactive T cells in the thymus [1]. In autoimmune disease this tolerance breaks down — immune cells or antibodies attack host tissue rather than pathogens; the immune system is still functional and active, just misdirected, not deficient [1]. Immune deficiency involves an inability to mount an adequate response (e.g. HIV/AIDS), whereas autoimmune disease involves an excess or misdirected response causing tissue damage — hence it is classified as a non-infectious disease of immune dysregulation [1].
SA2 (4 marks): IgG is the most abundant serum antibody; it mediates long-term protective immunity, crosses the placenta, and activates complement — e.g. in rheumatoid arthritis IgG antibodies form immune complexes that deposit in joint synovial membranes [2]. IgE is produced in very small amounts normally; it binds mast cell and basophil surface receptors, sensitising cells to allergens, and on re-exposure IgE cross-linking triggers rapid degranulation — e.g. IgE against pollen mediates allergic rhinitis [2].
SA3 (6 marks): (a) Hayfever — highly effective: hayfever is a Type I hypersensitivity reaction mediated by mast cell degranulation in the nasal mucosa; preventing degranulation would stop histamine release and eliminate symptoms [2]. (b) Anaphylaxis first-aid — ineffective if given after exposure, because mast cell degranulation has already occurred; given prophylactically before a known exposure it could prevent the reaction, but adrenaline remains essential for treating an established anaphylactic response [2]. (c) Multiple sclerosis — ineffective: MS is an autoimmune disease mediated by cytotoxic T cells attacking myelin; mast cells are not the key effectors, so the drug's mechanism is irrelevant to MS pathology [2].
Five timed questions on self-tolerance, autoimmune diseases, IgE-mediated allergy and anaphylaxis. Beat the boss to bank a tier — gold (perfect + fast), silver (80%+), or bronze (cleared).
⚔ Enter the arenaAnswer questions on self-tolerance, autoimmune diseases, the IgE allergy pathway, anaphylaxis and treatments. Pool: lessons 1–16.
Look back at what you wrote at the start of this lesson. How has your thinking changed? What new connections can you make?