15. Immune System Pathologies Flashcards
Hypersensitivity Reactions
A hypersensitivity refers to an excessive immune response produced by the normal immune system.
• Hypersensitivity is divided into four types.
• Hypersensitivity Type I, II and III are antibody-mediated.
• Hypersensitivity Type IV is cell-mediated
Type I Hypersensitivity
Known as an ‘allergy’.
• Mediated by IgE antibodies (produced by plasma cells) that bind to mast cells, causing degranulation.
• Type I hypersensitivity reactions can be systemic, i.e. anaphylaxis or localised, e.g. hay fever, eczema, irritant contact dermatitis.
• Onset is immediate / rapid (within minutes of exposure).
Type II Hypersensitivity
As seen in haemolytic disease of the newborn and blood transfusion reactions. Rhesus
• IgG antibodies produced by the immune response bind to antigens on the cell surface to activate the complement system.
• Rapid onset.
Type III Hypersensitivity
As seen in glomerulonephritis, rheumatoid arthritis and systemic lupus erythematosus.
• Immune complex deposition is common in the glomeruli due to the higher blood pressure (compared to sysemic circulation = four x higher).
• Antibody-antigen complexes form and are deposited in capillaries, skin, kidney, joints, triggering an immune response. They activate the complement system.
• IgG, IgM, IgA mediated. Onset in
four–eight hours.
Type IV Hypersensitivity
Skin graft rejection, allergen contact
dermatitis and in multiple sclerosis (MS).
• Cell-mediated, not antibody-mediated. Associated with over-reaction of T-lymphocytes to an antigen.
• Large numbers of cytotoxic T-cells activated and cytokines released that can damage normal tissues.
• Delayed type hypersensitivity — 48–72 hours.
Allergy
A powerful immune response to an allergen.
• An allergen is an antigen that generates allergy.
• The allergen itself is usually harmless, it is the immune response that causes damage.
Examples of common allergens:
• Certain foods.
• Animal dander.
• Mites.
• Dust.
• Chemicals / detergents / perfumes / soaps.
• Latex.
• Pollen.
Allergy Response
- Initial exposure causes sensitisation — a slow response as not many cells have the correct specificity to respond to the antigen (allergen) as they have not been activated.
- The body produces IgE specifically for that allergen (B-cell -> plasma cells -> antibodies targeted to specific antigen).
- Subsequent exposure is an exaggerated immune response. The full immune response has been developed and antibodies are readily available.
- IgE cross-links mast cells and the allergen.
- Symptoms can range from mild presentation, such as runny nose and streaming eyes, to anaphylaxis which can be fatal (swelling of airway mucosa).
Allergy v. Intolerance
True food allergy only affects 2% of adults and 6% of children — it is an IgE-mediated immune response that can be triggered by even the smallest amount of food.
• Far more people have a food intolerance — symptoms which are triggered by eating a quantity of a particular food and lacking enzymes, probiotics, bile, HCl or other digestive factors needed to deal with the food.
• Food intolerance does not have a defined
immune response.
• An example of a food intolerance is lactose
intolerance, whereby there is lack of the
enzyme lactase being produced to digest
lactose — causing digestive disturbance.
Anaphylactic Shock
Severe, systemic, allergic response within five–10 mins of antigen exposure.
• Exposure to allergen causes IgE to activate mast cells and basophils, causing the release of histamine.
• Causes bronchoconstriction, vasodilation and oedema of tissue.
• It is dangerous because it can cause occlusion of the airways.
• Allergens might include common allergens, e.g. peanuts.
• Treatment: Epinephrine (EpiPen).
Autoimmunity
Autoimmune disorders are conditions associated with an immune response against the body’s own tissues.
• Autoimmunity can be defined as a breakdown of mechanisms responsible for self-tolerance.
• Autoantibodies, cytotoxic T-cells are formed against self-antigens.
• The antibody-antigen reaction leads to complement activation, inflammation and tissue damage.
• Autoimmunity often has a genetic link. There is an association between some human leukocyte antigens (HLAs) and autoimmune diseases e.g. HLA: B27, DR2, DR3, DR4, etc.
• Significant links with increased intestinal permeability (leaky gut), the ‘hygiene hypothesis’, exposure to certain pathogens. These factors can increase the risk in a genetically predisposed person.
Systemic Lupus Erythematosus (SLE)
A chronic inflammatory, autoimmune, multi-
system disorder in which autoantibodies are formed against nuclear antigens.
• SLE follows a relapsing-remitting course.
• SLE involves the following:
• B-cell activation, increasing IgG levels against components of cell nuclei (DNA, nucleic acids, etc.).
• Impaired immune regulatory mechanisms: Inability to remove immune complexes from tissue -> complement is activated causing inflammation.
• Impaired T-cell regulation.
Systemic Lupus Erythematosus (SLE): Causes
- SLE is caused by a multifactorial interaction between various genetic and environmental factors.
- Higher oestrogen levels have been linked to onset.
- Links with low vitamin D levels.
- Chronic bacterial infections are common pre-diagnosis. Also links to viral infections, e.g. Epstein-Barr virus (EBV).
- Smoking and silica dust may increase risk.
- Flare-ups can be induced / exacerbated by the oral contraceptive pill, HRT, stress, UV light, pesticides.
Systemic Lupus Erythematosus (SLE): Signs and Symptoms
- Non-specific symptoms: Fatigue, malaise.
- Butterfly rash, photosensitivity, vasculitis, Raynaud’s syndrome.
- Joint pains — usually peripheral joints (symmetrical or asymmetrical). The pain is often disproportionate to the swelling. Hands, knees and elbows commonly affected.
- Pleurisy (sharp chest pain, shortness of breath, etc.), pericarditis, hypertension.
- Nephritis (nephrotic syndrome).
- Lymphadenopathy, splenomegaly, anaemia, leukopenia (recurrent infections).
Systemic Lupus Erythematosus (SLE): Investigations
Blood tests: Anti-nuclear antibodies (ANAs), anaemia, elevated ESR and complement, anti-phospholipid antibodies.
Systemic Lupus Erythematosus (SLE): Treatment
•Immunosuppressants,
corticosteroids (adverse effects),
sunscreen (to reduce rash from UV light),
NSAIDs.
Rheumatoid Arthritis
Chronic, systemic inflammation of many tissues, primarily the synovium (potentially all organs except brain).
• Affects 1% of people worldwide, peak occurrence ages 30–50 years.
• Autoimmune. Rheumatoid factor (RF) is an auto-antibody which is directed against a portion of IgG (different RFs recognise different parts of the IgG).
• The resultant immune complexes activate complement proteins leading to inflammation.
• RF is present in the majority of sufferers (about 80%).
• Links with significant infection (e.g. EBV, SIBO) in a genetically predisposed (HLA–DR4 / DR1) individual
Rheumatoid Arthritis: Signs and Symptoms
- Symmetrical / bilateral arthritis of small joints (hands and feet mostly).
- Gradually spreads through more proximal structures.
- Progressive morning stiffness (>1 hour).
- Deformity of joints, e.g. swan neck, ulnar deviation.
- General malaise and fatigue.
- Subcutaneous nodules (around fingers and elbows).
- C1 / 2 subluxation and compression of the spinal cord leading to paralysis / neurological complications.
- Kidney problems.
Rheumatoid Arthritis: Treatment
- Anti-inflammatories and immunosuppressants (significant implications of immune suppression).
- Surgery.
Ankylosing Spondylitis
AS is a systemic autoimmune disease associated with chronic inflammation of the spine and sacroiliac joints, often leading to spinal fusion (‘ankylosis’) and stiffness.
• Age of onset is typically between 15–30 years of age, more commonly affecting males.
• Strong genetic association with HLA-B27 (present in 95% of AS patients).
• Links with inflammatory bowel diseases (and leaky gut), as well as urogenital or intestinal infections such as salmonella and shigella cross-reacting with HLA-B27.
Ankylosing Spondylitis: Signs and Symptoms
Typically begins with sacroiliac and low lumbar spine pain, before progressing up the spine. Associated with worsening morning stiffness.
• Lower back symptoms often improve with activity.
• The lumbar lordosis flattens and patients often become kyphotic.
• Hip and heel (Achilles) pain are common.
• 20% suffer acute iritis — (HLA-B27 diseases)
• Systemic symptoms: Fever, fatigue and malaise
Ankylosing Spondylitis: Diagnosis
- Elevated blood inflammatory markers (ESR / CRP), HLA-B27 positive.
- X-ray / MRI — identifies characteristic ‘bamboo spine’.
Ankylosing Spondylitis: Treatment
Surgery, anti-inflammatories (including non-steroidal and steroids).
Hashimoto’s Thyroiditis
An autoimmune condition causing ‘hypothyroidism’.
• The thyroid gland is gradually destroyed by a variety of cells and antibodies — mediated immune processes.
• Auto-antibodies develop that react with thyroglobulin and thyroid cells preventing the synthesis of thyroid hormones.
Hashimoto’s Thyroiditis: Signs and Symptoms
- Tiredness, malaise, weight gain, cold intolerance, constipation, depression.
- Slow cognition, poor memory, low libido, deep voice, menstrual changes, muscle cramps / aches, joint pains.
- Signs: Goitre. Dry, brittle skin. Slow tendon reflexes, bradycardia, loss of lateral third of eyebrows, puffiness around the eyes (myxoedema). High TSH, low thyroid hormones.
Graves’ Disease (Thyrotoxicosis)
An autoimmune condition whereby IgG antibodies bind to TSH receptors and stimulate production of thyroid hormones.
Graves’ Disease (Thyrotoxicosis): Signs and Symptoms
- Nervousness, irritability, hyperactivity, unexplained weight loss, insomnia, muscle weakness, diarrhoea, fatigue, heat sensitivity, increased sweating, palpitations.
- Signs: Goitre, exophthalmos, tachycardia, tremor, brisk tendon reflexes, lid lag.
Graves’ Disease (Thyrotoxicosis): Treatment
•Drugs: Carbimazole, radioactive iodine.
