Autoimmune Diseases and Allergies
When the immune system turns against itself — or over-reacts to harmless triggers
Try this: Switch between Normal Tolerance, Autoimmune Failure, and Allergic Response to see how immune cells interact with self cells and pathogens.
This simulator visualises the difference between healthy self-tolerance, failed tolerance (autoimmunity), and exaggerated responses (allergy).
Self-tolerance depends on clonal deletion and regulatory T cells. When tolerance breaks down, the immune system attacks self cells (autoimmunity) or overreacts to harmless antigens (allergy).
Download this lesson's worksheet
Use the PDF for classwork, homework or revision. It includes key ideas, activities, questions, an extend task and success-criteria proof.
Try this: Read each disease description and classify it as autoimmune, allergic, immune deficiency, or infectious.
This activity tests your ability to distinguish between different types of immune dysfunction based on mechanism and trigger.
Autoimmune diseases involve self-attack, allergies involve hypersensitivity to harmless antigens, immune deficiencies involve inadequate response, and infectious diseases are caused by pathogens.
Think First
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
Understand the core concepts in this lesson.
Apply knowledge to explain biological phenomena.
Evaluate evidence and draw conclusions.
Misconceptions to Fix
Wrong: Bacteria and viruses are the same thing.
Right: Bacteria are living cells; viruses are non-living particles that require host cells to reproduce.
Self-Tolerance — The Immune System's Rule Book
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
Examples of Autoimmune Diseases
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).
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
Allergies — Type I Hypersensitivity
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.
Anaphylaxis — Systemic Allergic Emergency
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.
Managing Allergies Long-Term
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.
⚠ Common Misconceptions
✗ "An allergy is just a mild sensitivity — not a real immune response."
✓ Allergies are genuine immune responses involving B cells, IgE antibodies and mast cells. They can be fatal (anaphylaxis). The immune system is genuinely responding — it is just responding to the wrong target.
✗ "You can have an anaphylactic reaction the first time you encounter an allergen."
✓ Anaphylaxis requires prior sensitisation. The first exposure produces IgE; anaphylaxis can only occur on second or subsequent exposure when that IgE is already bound to mast cells.
✗ "Autoimmune diseases are caused by a weak immune system."
✓ Autoimmune diseases are caused by an overactive or misdirected immune system — one that has lost the ability to distinguish self from non-self. Immunosuppressant treatment can temporarily weaken the immune system, but the disease itself is not a sign of weakness.
✗ "Antihistamines stop mast cells from releasing histamine."
✓ Antihistamines block histamine receptors on target cells — they do not prevent mast cell degranulation or histamine release. Cromoglycate (sodium cromoglicate) stabilises mast cells and does prevent release, but is a different drug class.
📌 Autoimmune Disease
- Immune system attacks self-antigens due to loss of self-tolerance
- Effectors: IgG/IgM antibodies or cytotoxic T cells
- Organ-specific (e.g. Type 1 Diabetes, MS) vs systemic (e.g. 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 → mast cell 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
Try this: Step through the immune tolerance mechanism and observe what happens when self-tolerance breaks down.
This simulator shows how the immune system normally distinguishes self from non-self, and what goes wrong in autoimmune disease and allergy.
Immune tolerance is the immune system’s ability to recognise and not attack the body’s own cells. When tolerance fails, autoimmune diseases (Type 1 diabetes, multiple sclerosis) or allergic reactions occur. Understanding tolerance mechanisms is key to treating these disorders.
Try this: Read each case study and classify the immune disorder as autoimmune, immunodeficiency, or hypersensitivity.
This classifier helps you distinguish between three major categories of immune dysfunction.
Autoimmune disorders occur when the immune system attacks self-tissues (Type 1 diabetes, rheumatoid arthritis). Immunodeficiency disorders involve weakened immune responses (SCID, AIDS). Hypersensitivity involves exaggerated immune responses (allergies, anaphylaxis). Each requires different diagnostic and treatment approaches.
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)
Revisit Think First
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. Consider how your initial ideas compare to the detailed mechanisms you've now learned.
Multiple Choice
1. Which antibody class is responsible for mediating Type I hypersensitivity (allergic) reactions?
2. A student claims: "My first exposure to bee venom triggered anaphylaxis." This statement is incorrect because:
3. In multiple sclerosis, the immune system targets:
4. Mast cell degranulation during an allergic reaction releases histamine, which causes all of the following EXCEPT:
5. Which treatment for allergies is the only one that modifies the underlying disease rather than managing symptoms?
Short Answer Questions
Question 1 — Using the concept of self-tolerance, explain why autoimmune diseases are classified as non-infectious diseases rather than immune deficiency disorders. (3 marks)
Hint: Consider what self-tolerance does and what happens when it breaks down.
Question 2 — Compare the roles of IgE and IgG in the immune system, with reference to one condition involving each antibody class. (4 marks)
Question 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. (6 marks)
MC Answers: 1-B 2-A 3-D 4-C 5-B
SA 1 Model Answer (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; it is misdirected, not deficient. (1)
- Immune deficiency involves an inability to mount an adequate immune response (e.g. HIV/AIDS). Autoimmune disease involves an excess or misdirected response, causing tissue damage; hence it is classified as a non-infectious disease of immune dysregulation. (1)
SA 2 Model Answer (4 marks):
- IgG is the most abundant serum antibody; it mediates long-term protective immunity against pathogens, crosses the placenta, and activates complement. Example: IgG antibodies in rheumatoid arthritis form immune complexes that deposit in joint synovial membranes. (2)
- IgE is produced in very small amounts normally; it binds to mast cell and basophil surface receptors, sensitising cells to allergens. On re-exposure, IgE cross-linking triggers rapid degranulation. Example: IgE against pollen mediates allergic rhinitis. (2)
SA 3 Model Answer (6 marks):
- (a) Hayfever — highly effective. Hayfever is a Type I hypersensitivity reaction mediated by mast cell degranulation in nasal mucosa. Preventing degranulation would stop histamine release and eliminate symptoms. (2)
- (b) Anaphylaxis first-aid — ineffective if given after exposure, as mast cell degranulation has already occurred. If 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. The drug's mechanism is irrelevant to MS pathology. (2)
Look back at what you wrote at the start of this lesson. How has your thinking changed? What new connections can you make?