The Immune System Flashcards
What is a hypersensitivity reaction? What are the classes of hypersensitivity response?
A tissue damaging immune response, which may be directed against self-antigens (autoimmunity) or harmless external antigens (allergy). There are 4 types of hypersensitivity reaction:
- Type 1 - IgE mediated (minutes)
- Type II - IgG / IgM mediated (hours)
- Type III - Immune complex deposition (hours)
- Type IV - Delatyed type hypersensitivity - T cell mediated (days / weeks)
What is atopy? What is the classic triad of atopic diseases?
Atopy is the inherited tendency to make large amounts of IgE in response to harmless external stimuli (i.e. patients are ‘hyperallergic’, presenting with regular type I hypersensitivity reactions). The classic atopic triad is:
- Eczema (atopic dermatitis)
- Allergic rhinitis
- Allergic asthma
What is allergy? What type of hypersensitivity reactions typically occur in allergic responses, and what are the risk factors for allergic disease?
Allergy is a tissue damaging response to an innocuous external stimulus. It is usually type I (IgE mediated) or type IV (T-cell mediated, delayed type hypersensitivity). Risk factors include:
- Atopy
- Age - commoner in children in adults
- Gender - commoner in boys than girls
- Family size - less common in large families
- Reduced microbial burden
- Smoking
- High levels of antigen exposure
What is anaphylaxis? What are the key clinical features?
Sudden, generalized cardiovascular collapse or bronchospasm, occurring when a patient reacts to a substance to which they are exquisitely sensitive. Clinical features tend to be of a more rapid onset when the antigen is introduced systemically (i.e. wasp sting) rather than absorbed (i.e. latex). Key clinical features:
- Cardiovascular - Cardiovascular collapse
- Respiratory - Bronchospasm / Laryngeal oedema
- Skin - Angioedema / Urticaria
- Gastrointestinal - Vomiting / Diarrhoea
What is an anaphylactoid reaction? How is it different from anaphylaxis?
Anaphyloid reactions produce a clinically similar result (circulatory collapse, angioedema etc), but are not mediated by IgE. They are caused by substances that induce degranulation of mast cells by direct activation or the alternative pathyway of complement activation (C3a, C5a)
The individual does not have to have been previously sensitized to the allergen
Agents include contrast medium, opioids and hot temperatures
What is allergic rhinitis? What are common causes of allergic rhinitis
An allergic inflammation of the nasal airway, causing mucosal oedema, itching and sneezing. Causes may be:
Seasonal
- Tree pollen (late March - mid-May)
- Grass pollen (mid-May - July)
- Weed pollen (end of June - September)
Perennial
- House dust mite
- Cat
- Dog
- Occupational antigens
What is asthma, and what are the presenting features of an asthmatic attack?
Asthma is a syndrome characterized by three cardinal features of:
- Generalized but reversible airways obstruction
- Bronchial hyper-responsiveness
- Airway inflammation
Presenting features are:
- Chest tightness
- Shortness of breath
- Wheeze
- Decreased peak flow measurement
Asthma may be defined as either extrinsic (atopic) or intrinsic (non-atopic). What are some important extrinsic and intrinsic factors?
Extrinsic:
- Pollens
- House dust mites
- Occupational allergens
Intrinsic
- Airway cooling - exercise / air temperature
- Emotional stress
- Irritants - smoking, fumes etc
What is Urticaria? What is the underlying cause?
Urticaria refers to transient episodes of demarcated, odematous, erythematous, pruritic lesions with a raised edge. It results from sudden fluid accumulation within the dermis due to increased local vascular permeability.
It may be acute, often caused by an IgE mediated reaction to an extrinsic antigen (as in food allergy). Chronic urticaria may also occur, which occurs often daily over a period of weeks.
What is angioedema?
Rapid swelling of the dermis and subcutaneous tissue. It is extremely similar to urticaria, except urticaria occurs in the upper dermis. Comonly occurs in allergic and anaphylactic reactions.
What is eczema (atopic dermatitis)? Which parts of the body does it commonly affect?
A common, chronic, severely pruritic, eczematous skin disease, usually occurring in individuals with a hereditary disposition to all atopic disorders, and frequently in association with high serum IgE levels.
In infants, the dermatitis often appears on the face first, followed by the flexural aspects of the arms and legs (back of knee, front of elbow).
Spontaneous resolution occurs in many patients: half clear by the age of 7, 90% by teens. However, for some it persists into adult life
What is the management of atopic eczema?
Management directed at a reduction of cutaneous inflammation (e.g. emollients) and elimination of exacerbating factors including allergens, infection and irritants.
What is allergic contact dermatitis?
An inflammatory skin disease caused by Th1-cell-mediated (Type IV) hypersensitivity to external agents which come into contact with the skin. It is considered an archetypal T-cell mediated hypersensitivity, and therefore requires 48h to develop, a characteristic of cell-mediated but not antibody mediated hypersensitivity.
What is the classic history of allergic contact dermatitis?
Typical history is biphasic - there is an induction phase from the time of initial antigen contact to sensitization of T lymphocytes, and an elicitations phase, from antigen re-exposure to the apperance of dermatitis.
What is autoimmune thrombocytopenic purpura? What are the primary and secondary causes?
- An autoimmune condition characterised by IgG antibody to platelet antigens, leading to platelet destruction in the spleen.
- Often occurs idiopathically, however may be secondary to:
- SLE
- Infection
- Drug
What is the clinical presentation of autoimmune thrombocytopenia purpura? Who is most commonly affected?
Clinical presentation:
- Purpura / petechiae
- Increased bleeding e.g. epistaxis, menorrhagia
- Bleeding from gums whilst brushing teeth
Epidemiology
- Occurs in both children and adults. Most children will enter remission within 6 months, whereas adults are more likely to have chronic disease
- Affects women more commonly than men (2:1)
On what basis is the diagnosis of autoimmune thrombocytopenic purpura made? How is the condition managed?
Diagnosis of exclusion, ensuring that there are no secondary causes (SLE, HIV etc). Sustained low platelet count will be the predominant result of investigation.
Antibodies will be targeted against GpIIb/IIIa on the platelet surface.
First line of treatment is with steroids to reduce the autoimmunity.
What is pernicious anaemia? What is the underlying pathology?
A megaloblastic anaemia caused by the loss of gastric parietal cells. Anaemia results from reduced B12 uptake, as parietal cells secrete intrinsic factor required for B12 uptake in the ileum.
Disease is mediated by autoantibodies targeted against either gastric parietal cells themselves, or against intrinsic factor
What is autoimmune thyrotoxicosis (Grave’s disease)? What is the epidemiology, and what is the underlying cause?
- An autoimmune condition causing an overactive thyroid gland.
- It occurs much more frequently in women than in men, frequently presenting during adolescence or pregnancy. It has a powerful hereditary component.
- Underlying pathology is auto-antibodies targeted at the TSH receptor
What is Hashimoto’s thyroiditis? What is the most commonly used test for Hashimoto’s disease?
- An autoimmune condition in which the thryoid gland is attacked by a variety of cell mediated and antibody mediated responses. It produces clinical symptoms of hypothyroidism
- Antibodies to thyroid peroxidase (TPO) are present in virtually all patients, though they do not cause the disease and are not specific for it
What is type I diabetes mellitus? What is the underlying pathology and which autoantibodies may be detected during the course of the disease?
Destruction of beta-cells of the pancreas, mediated by auto-reactive cytotoxic T cells, leading to reduced insulin production and diabetes.
Antibodies to islet cells are present in early disease, and GAD (glutamic acid decarboxylase) are present in later disease. Note that the antibodies present are not responsible for the clinical course of the disease.
What is myasthenia gravis? What is the underlying pathology?
An autoimmune neuromuscular condition leading to fluctuating muscle weakness and fatigueability (muscles become weaker during periods of activity, and recover during rest). Most commonly presents in small muscles first, before symptoms are seen in larger muscles.
Caused by auto-antibodies targeted against acetylcholine receptors on the post-synaptic membrane of neuromuscular junctions
What other conditions is myasthenia gravis associated with?
- Thyroid disease, including Hashimoto’s thyroiditis and Graves disease
- Insulin dependent diabetes
- Rheumatoid arthritis
- Lupus
- Demyelinating CNS diseases
What is pemphigus vulgaris? What is the underlying pathology?
A chronic blistering skin condition producing painful, flaccid blisters which are prone to scarring. It is due to disruption of the epidermal layers, and thus blisters are superficial and prone to rupture. They occur on both epidermal and mucosal surfaces
Due to autoantibodies targeted against desmosomes (desmoglein 1 and 3), disrupting the connections between squamous cells of the epidermis
What is bullous pemphigoid? What is the underlying pathology?
An acute or chronic autoimmune condition defined by tense, well defined blisters on an erythematous background. They are distributed on legs and arms, but not on mucosal surfaces. It is due to subepidermal disruption, and thus blisters are more tense and less prone to rupture.
Underlying pathology of is antibodies targeted against the skin basement membrane
Describe the common clinical presentation of SLE.
Has a diverse and variable presentation due to the potential multisystem pathology. Usual first presentation is with:
- Arthritis / arthralgia
- Skin rash - erythematous, raised, scaly, distributed across cheeks & nose in sun exposed areas. More common in summer due to UV exposure
- Fever / mailse
- Neuro-psychiatric problems
- Anaemia - commonly causes a haemolytic anaemia
What is Sjorgen’s syndrome? Who is commonly affected, and what is the aetiology?
A systemic autoimmune disease, in which immune cells attack and destroy exocrine glands, particularly those that produce tears and saliva.
Occurs much more commonly in women than men, and more frequently after the menopause. It may exist as both a primary or secondary disorder, in conjunction with rheumatoid artheritis, SLE, primary billiary cirrhosis, scleroderma etc.
The pathogenesis is not well understood. Although it is thought that viral infection may contribute.
What is Scleroderma? What are the two forms?
A chronic, systemic autoimmune disease, characterized by fibrosis, vascular alterations and autoantibodies. There are two forms:
Limited systemic scleroderma:
- Cutaneous manifestations mainly affecting hands, arms and face
- Previously called CREST syndrome - Calcinosis, Raynaud’s phenomenon, Esophagel dysfunction, Sclerodactyly, Telangiectasis
Diffuse systemic scleroderma
- Rapidly progressing and affects a large area of the skin and one or more internal organs, frequently the kidneys, oesophagus, heart and lungs.
Describe the clinical presentation of scleroderma.
- Scleroderma is characterized by the appearance of circumscribed or diffuse, hard, smooth, ivory colored areas that are immobile and give the appearance of hidebound skin.
- Typical scleroderma is classically defined as symmetrical skin thickening, with 90% also presenting with Raynaud’s phenomenon and nail-fold capilliary changes.
What is X-linked antibody deficiency (Bruton’s agammaglobinaemia)? What is the underlying genetic abnormality, and how is it carried?
- An X linked genetic disorder in which the inability to generate mature B cells manifests as a complete lack of antibodies in the blood stream. Patients are prone to developing serious and often fatal infections
- Due to defective B-tyrosine kinase, required for maturation of B cells. Mothers carry gene, sons are affected. Daughters may be carriers
What is selective IgA deficiency? How is it often identified?
A relatively mild genetic immunodeficiency in which individuals lack IgA, but have normal serum IgG and IgM. As IgA lines the mucous membranes of the mouth, airways and digestive tract, there is an increased tendancy for respiratory, digestive and genitourinary infections
It may have a similar presentation to CVID, however, it does not present with the same lymphocyte subpopulation abnormalities.
Often an incidental finding which investigation for coeliac disease
What is C1 inhibitor deficiency? How does it present, and how is it distinguised from other forms of angioedema?
C1 inhibitor is the main controller of bradykinin production, as well as inhibiting the activation of C1 in the classical pathway.
Deficienct leads to recurrent angioedema at any location, including the throat, which is potentially fatal. It is differentiated from other forms of angioedema by:
- Duration of swelling (days)
- Bowel wall angioedema with distension, severe pain, vomiting, diarrhoea
- Characteristic rash (similar to erythema marginatum - NOT urticarial)
- Family history (autosomal dominant)
