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 1 (antibody-mediated)
Hypersensitivity Type 1 is antibody-mediated.
It is known as an ‘allergy’
Pathophysiology;
* Mediated by IgE antibodies (produced by plasma cells)that bind to mast cells, causing degranulation
Aetiology;
* Reactions can be systemic, i.e. anaphylaxis or localised, e.g. hay fever, eczema, irritant contact dermatitis
Signs and symptoms:
* Onset is immediate / rapid (within minutes)
Hypersensitivity Type 2 (antibody-mediated)
Hypersensitivity Type 2 1 is antibody-mediated and involve blood transfusion reactions (problems with donations of certain blood groups to a patient)
Pathophysiology;
* IgG antibodies produced by the immune response bind to antigens to the cells surface to activate the complement system
Aetiology;
* As seen in haemolytic disease of the newborn and blood transfusion reactions)
Main signs and symptoms;
* Rapid onset
Hypersensitivity Type 3 (antibody-mediated)
Hypersensitivity Type 3 is antibody-mediated and occurs when antibody-antigen complexes form and are deposited in capiliaries, skin, kidney, joints, triggering an immune response. They activate the complement system
Pathophysiology;
* Reactions can involve different antibodies - IgG, IgM, IgA mediated.
* Immune complex deposition is common in the glomeruli due to the higher B.P (compared to system system = 4 x higher)
Aetiology;
* As seen in glomerulonephritis, rheumatoid arthritis and systemic lupus erythematosus
Signs and symptoms;
* Onset in 4-8 hours
Hypersensitivity Type 4 (cell-mediated)
Hypersensitivity Type 4 is cell-mediated and involves cytoctoxic T- cells. It is associated with over-reaction of T- lymphocytes to an antigen.
Pathophysiology;
Large numbers of cytotoxic T-cells activated and cytokines released that can damage normal tissues
Aetiology;
* As seen in skin graft rejection, allergen contact dermatitis and in multiple sclerosis (MS)
Signs and symptoms;
* Delayed type hypersensitivity – 48-72 hours
Allergy (vs. intolerance)
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
Pathophysiology;
* Initial exposure causes sensitization – 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
Aetiology;
Examples of common allergens inc:
* Certain foods
* Animal dander
* Mites
* Dust
* Chemicals / detergents / perfumes / soaps
* Latex
* Pollen
Signs and symptoms;
* Can range from mild presentation, such as runny nose and streaming eyes, to anaphylaxis which can be fatal (swelling of airway mucosa)
Other;
* 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
Anaphylactic shock
Severe, systemic, allergic response within 5-10 minutes of antigen exposure
Pathophysiology;
* Exposure to allergen causes IgE to activate mast cells and basophils, causing the release off histamine
Aetiology;
* Allergens might include common allergens, e.g. peanuts
Signs and symptoms;
* Causes bronchoconstriction, vasodilation and oedema of tissue
* Dangerous because it can cause occlusion of the airways
Allopathic treatment;
* Epinephrine (Epipen)
Autoimmunity
Autoimmune disorders are conditions associated with an immune response against the body’s own tissues
Pathophysiology;
* Can be defined as a breakdown of mechanisms responsible for self-tolerance
* Auto-antibodies, cytotoxic T-cells are formed against self-antigens.
* The antibody-antigen reaction leads to complement activation, inflammation and tissue damage
Aetiology;
* Autoimmunity often has a genetic link. There is 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, multisystem disorder in which auto-antibodies are formed against nuclear antigens
SLE follows a relapsing-remitting course
Pathophysiology;
SLE involves:
* 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 = complements is activated causing inflammation
* Impaired T-cell regulation
Aetiology;
* 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
* Common bacterial infections are common pre-diagnosis. Also links to viral infections, e.g. EBV
* Smoking and silica dust may increase risk
* Flare ups can be induced / exacerbated by the oral contraceptive pill, HRT, stress, UV light, pesticides
Signs and symptoms:
* Non-specific symptoms malaise, fatigue
* Butterfly rash, photosensitivity, vasculitis, Raynaud’s syndrome
* Joint pains- usually peripheral joints (symmetrical or asymmetrical). The pain is often disproportionate to the swelling. Hand, knees and elbows commonly affected.
* Pleurisy (sharp chest pain, shortness of breath, etc), pericarditis, hypertension
* Nephritis (nephritic syndrome)
* Lymphadenopathy, splenomegaly, anaemia, leucopenia (recurrent infections)
Diagnosis/investigations:
Blood tests: Anti-nuclear antibodies (ANAs), anaemia, elevated ESR and complement, anti-phospholipid antibodies
Allopathic treatment:
* Immunosuppressants, corticosteroids (adverse effects)
* Sunscreen (to reduce rash from UV light)
* NSAIDs
Alternative treatment:
* Anti-inflammatory diet and supplements, Vitamin D3, antioxidants, Alpha lipoic acid, EFAs
* Herbs, acupuncture and homeopathy
* Manual therapy for joint pain
* Stress reduction, e.g. meditation, breathing exercises, etc.
Rheumatoid Arthritis
(RA)
Chronic, systemic inflammation of many tissues, primarily the synovium (potentially all organs except the brain)
Pathiphysiology;
* Autoimmune, Rheumatoid factor (RF) is an auto-antibody which is directed against a portion of IgG (different RFs recognize different parts of the IgG)
* The resultant immune complexes activate compliment proteins leading to inflammation
* RF is present in the majority of sufferers (80%)
Aetiology;
* Links with significant infection (e.g. EBV, SIBO) in a genetically predisposed (HLA-DR4/ DR1) individual
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
* Systemic issues, e.g. kidney, pulmonary problems.
Allopathic treatment;
* Anti-inflammatories
* Immunosuppressants
* Surgery
Alternative treatment;
* Nutrition anti-inflammatory and reducing intestinal permeability: increase anti oxidants, Mediterranean diet / increase omega -3, Vit D3
* Herbs for pain and inflammation and immune modulation: Turmeric, Boswellia, Devil’s Claw
* Homeopathy (e.g. Rhus tox)
* Acupuncture
Other;
* Affects 1% of people worldwide
* Peak occurrence between 30-50 years
Ankylosing Spondylitis
A systemic autoimmune disease associated with chronic inflammation of the spine and sacroiliac joints, often leading to spinal fusion (‘ankylosis’) and stiffness
Aetiology:
* Age of onset is typically between 15-30 years of age, more commonly affecting males
* Strong genetic association with HLA-B27 (95%)
* 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
Signs and symptoms:
* Typically begins with sacroiliac and low lumbar spine pain, before progressing up the spine.
* Associated with worsening morning symptoms
* 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
Diagnosis/investigations:
* Elevated blood inflammatory markers (ESR / CRP), HLA-B27 positive
* X-ray / MRI – identifies characteristic ‘bamboo spine’
Allopathic treatment:
* Surgery
* Anti-inflammatories (inc. non-steroidal and steroids)
Alternative treatment:
* Nutrition (remove pathogenic organisms / elimination diet / increase vit. D3 and antioxidants)
* Herbs – anti-inflammatory
* Homeopathy
* Acupuncture
Hashimoto’s Thyroiditis
(Autoimmune Hypothyroidism)
- An autoimmune condition causing ‘Hypothyroidism’
pATHOPHYSIOLOGY;
Hashimoto’s Thyroiditis
(Autoimmune Hypothyroidism)
- An autoimmune condition causing ‘Hypothyroidism’
Pathophysiology;
* 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
Signs and symptoms:
* Tiredness, malaise, weigh gain, cold intolerance, constipation, depression
* Slow cognition, poor memory, low libido, deep voice, menstrual changes, muscle cramps / aches, joint pains
* Goitre, dry, brittle skins, slow tendon reflexes, bradycardia, loss of lateral third of eyebrows, puffiness around 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
Signs and symptoms;
* Nervousness, irritability, hyperactivity, unexplained weight loss, insomnia, muscle weakness, diarrhoea, fatigue, heat sensitivity, increased sweating, palpitations
* Goitre, exophthalmos (bulging eyes), tachycardia, tremor, brisk tendon reflexes, lid lag
Allopathic treatment;
* Drugs; Carbimazole, radioactive iodine
Alternative treatment;
* Herbs and nutrition to restore immune balance
* Homeopathy
