Sem 1, hypersensitivity, atopy, IV
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| Why doesn't atopy follow Mendelian inheritance? | The development of these conditions is dependent upon many, multiple genes, and disease expression is influenced by environmental factors and exposures
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| Which regions of chromosomes are thought to be related to atopy? | 2q, 5q, 6p, 11q, 12q and 16q
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| What is filaggrin? | A protein that binds to aggregates the keratin cytoskeleton in the epidermis
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| What does a homozygous FLG mutation lead to? | Complete loss of filaggrin expression in the skin
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| What type of hypersensitivity is atopy? | Type 1
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| Where is atopic dermatitis common? | Folds of the arms, back of the knees, wrists, face and hands
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| What cycle often develops as a result of atopic dermatitis? | "itch-scratch cycle" -> extreme itchiness of skin causes the person to scratch, which in turn worsens the itch
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| What is lichenification? | A thick, leathery skin, resulting from constant scratching and itching
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| What are papules? | Small, raised bumps on the surface of the skin that may open when scratched, becoming itchy, crusty and infected
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| What are environmental irritants of atopic dermatitis? | Changes in temperature, low humidity, wool clothes, soaps and detergents, contact allergens, dietary factors, inhaled allergens
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| Which immunoglobulin increases with allergies, infections and immune conditions? | IgE
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| What scale is used to examine the severity of eczema? | Given a SCORAD score
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| What does atopy refer to? | A family tendency to develop certain allergic conditions, including eczema, asthma, and hayfever
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| What is atopic march? | When asthma progresses and another atopic disease develops
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| Which cytokine that induces the release of T cell-attracting chemokines from monocytes is produced by damaged skin cells? | Thymine stromal lymphopoietin (TSLP)
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| What are the effects of TSLP? | Induces the release of T cell-attracting chemokines from monocytes and enhances the maturation of myeloid (CD11c+) dendritic cells
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| When is the expression of TSLP enhanced? | When people have asthma
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| What psychologoical/psychosocial problems can result from eczema? | Lack of sleep, isolation as a result of embarrassment, financial strain, if the child's skin is rough it can adversely affect the sense of touch, treatment can be time consuming, children with eczema may need more attention than their siblings
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| What are the most common bacterial skin pathogens? | Staphylococcus aureus and group A beta-haemolytic streptococci
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| What is the most common viral skin disease? | Herpes simplex
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| What is the most common dermatophytic fungi? | Trichophyton rubrum
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| What is a secondary infection? | An infection that occurs during or after treatment of another pre-existing infection. It may result from the treatment itself, or from changes in the immune system
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| Is Staphylococcous aureus Gram positive or Gram negative? | Gram positive
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| How does S.A. exacerbate atopic dermatitis? | 1) Acting as superantigens by stimulating an augmented T-cell response, thereby leading to an exacerbation of the skin disease
2) Increasing production of IgE (in patients with atopic dermatitis these high IgE levels contribute to immune dysregulation)
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| What 3 groups of exotoxins can Staphylococcous aureus secrete? | Superantigens, exfoliative toxins and other toxins
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| Which group of toxins include enterotoxin type B? | Superantigens (enterotoxin type B causes TSS associated with tampon use)
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| What is usually used to treat Staphylococcus aureus? | Penicillinase resistant penicillins such as Flucloxacillin and dicloxacillin
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| How is Staphylococcal resistance to penicillin mediated? | By penicillinase (a form of beta-lactamase)
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| How is Staphylococcal resistance to methicillin mediated? | By the mec operon - part of the Staphylococcal cassette chromosome mec (SCCmec)
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| How is the mecAgene of S.A. code for resistance to all beta-;actam antibiotics? | It codes for an altered pernicillin-binding protein (PBP2a or PBP2') which has a lower affinity for beta-lactams
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| What is vancomycin and how does it act? | It is a glycopeptide that inhibits bacterial cell wall assembly
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| How does vancomycin affect the peptidoglycan matrix? | It prevents the incorporation of N-acetylmaramic acid (NANI) and N-acetylglucosamine (NAG) peptide subsunits from being incorporated into the peptidoglycan matrix
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| What type of antibiotic is Flucloxacillin? | A penicillin beta-lactam
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| How does Flucloxacillin act? | It inhibits cell wall synthesis and is mediated by binding to specific penicillin binding proteins
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| What are the 2 types of autoimmune disease? | Organ specific and organ non-specific
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| What cells to both T and B cells differentiate from? | Common lymphoid progenitor cells
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| What happens to T cells in the Thymus? | Immature T cells undergo 2 rounds of selection in the Thymus; - Positive selection for MHC1 and MHC2 recognition
-negative selection to remove self reactive T antigens
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| How many T cells survive in the whole process? | ~2%
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| What is the mediator of a type 1 hypersensitivity reaction? | IgE
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| What is the effector mechanism of a type 1 hypersensitivity reaction? | Mast cells, eopsinophils
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| What are some examples of type 1 hypersensitivity reactions? | Food allergy, allergic rhinitis and asthma
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| Which class of hypersensitivity reaction does not use a soluble antigen? | Type 2; it uses cell/matrix
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| Which class of hypersensitivity reaction has an immediate response? | Type 1
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| Which class of hypersensitivity reaction has a delayed response? | Type 4
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| What mediator does a type 2 hypersensitivity reaction use? | IgG
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| What is the effector mechanism of a type 2 hypersensitivity reaction? | Complement, FcR+ cells
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| What is the mediator of a type 3 hypersensitivity reaction? | T cells
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| What effector mechanisms do type 3 hypersensitivity reactions use? | Macrophages
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| Give an example of a type 3 hypersensitivity reaction? | Contact dermatitis, poison ivy
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| In what two stages do allergic reactions occur in? | 1) Induction/Sensitisation (first exposure an individual is primed)
2) Elicitation (subsequent exposure to same allergen, a sensitised individual shows clinical manifestations)
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| In a type 1 hypersensitivity reaction what does the cross-linking of 2 IgE portions by the antigen result in? | 1)Release of pre-formed contents from the mast granules into the surroundings.
2)The synthesis of metabolites of arachidonic acid which have powerful pharmacological effects, notably in relation to smooth muscle tone
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| What happens when serine proesterase is activated in a type 1 hypersensitivity reaction? | Causes changes in the fluidity of the cell membrane through methylation of phospholipids which results in an influx of calcium ions through the membrane
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| When more calcium ions pass through the membrane in a type 1 hypersensitivity reaction, what are the two effects? | Increases the concentration of cyclic nucleotides, and activates phospholipase A2 and releases arachidonic acid
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| What is desensitisation? | Giving repeated injections of small doses of the allergen to reduce the tendency of an allergic reaction
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| What chemical can be injected to prevent the entry of Ca2+ ions in a type 1 hypersensitivity reaction? | Disodium comoglycate
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| In type 2 hypersensitivity reactions, when an antibody binds to its epitope it causes damage to, and death of the affected cells in 3 mechanisms. What are they? | 1)Lysis of the cell membrane may occur as a result of activation of the complement system
2) The cell to which the antibody is bound may be phagocytosed by macrophages
3)Antibody-coated cells may be killed by natural killer cells
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| What happens to large antibody-antigen complexes? Are they soluble? | Usually phagocytised, and soluble
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| In what 3 situations are type 3 hypersensitivity reactions common? | Elicited by microbial agent, rejection of tissue or organ grafts, or contact dermatitis
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| Which cells produce histamine? | Basophils and mast cells
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| How is histamine derived? | Decarboxylation of the amino acid histadine
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| What enzyme catalyses this reaction? | L-histidine decarboxylase
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| Where is the H1 (histamine receptor subtype 1) found? | Smooth muscle, endothelium and CNS tissue
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| What is the effect of H1? | Causes bronchodilation bronchial smooth muscle contraction, separation of endothelial cells and pain and itching due to insect bites
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| What receptor coupling does H1 use? | G-protein coupled receptors
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| Where are H2 (histamine subunit 2) found? | On parietal cells and vascular smooth muscle cells
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| What is the receptor coupling of H2? | Receptor activation causes increase in cAMP production
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| What are the effects of H2? | Primarily involved in vasodilation, also stimulates gastric acid secretion
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| Where is H3 found? | On CNS, and, to a lesser extent, peripheral nervous system tissues
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| What receptor coupling does H3 use? | G-protein coupled receptors
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| What does H3 result in? | Decreased neurotransmitter release: histamine, acetylcholine, norepinephrine and serotonin
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| Where is H4 located? | Primarily in basophils and bone marrow. Also on the thymus, small intestine, spleen and colon
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| What receptor coupling does H4 use? | G-protein coupled receptors
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| What is the function of H4? | Plays a role in chemotaxis
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| Which histamine receptors do most antihistamines block? | H1 receptors
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| What do antihistamines do to capillaries? | Decrease their permeability (to help reduce redness)
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| What is the blood-brain barrier? | A separation of circulating blood from the brain extracellular fluid in the CNS
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| How are metabolic products, such as glucose, transported across the blood-brain barrier? | They are actively transported across the barrier by cells
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| How do drugs pass through the blood-brain barrier? | Via osmotic means; biochemically via the use of vasoactive substances, or by localised exposure to high-intensity focused ultrasound
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| Where do T cells mature? | Thymus
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| What name is given to T cells that haven't yet encountered their antigen? | Naïve T cells
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| What must antigens be bound to in order for them to be recognised by T cells? | Glycoproteins
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| What is filaggrin? | A filament associated protein that binds to keratin fibres in epithelial cells
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| What precursors is filaggrin clustered into? | Profilaggrin
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| What can happen to filaggrin monomers in the stratum corneum? | They can be incorporated into the lipid envelope or they can interact with keratin intermediate filaments
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| Where is the FLG gene situated? | 1q21
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| What is urticaria also called? | Hives
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| How long does acute urticaria last? | 6-8 weeks
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| How long does chronic urticaria last? | Longer than 6-8 weeks
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| What does idiopathic mean? | No cause is known
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| What are some common triggers of urticaria? | Food allergies, allergies to environmental factors e.g. pollen, allergic reaction to latex, infections, insect bites and stings, some medication
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| What might be prescribed for acute urticaria? | Antihistamines, corticosteroid tablets, or nothing
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| What might be prescribed for chronic urticaria? | Menthol cream or H2 antihistamines
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| What are the 4 main types of angioedema? | Allergic, Idiopathic, Drug Induced and Hereditary
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| Which tests are used to identify allergic angioedema? | Skin prick test or blood test
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| How can hereditary angioedema be identified? | Using a blood test to examine the proteins regulated by the C1-1NH gene. (Low level is probably hereditary)
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| How is angioedema usually treated? | A combination of antihistamines and corticosteroids
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| What type of condition is icthyosis vulgaris? | Autosomal dominant pattern
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| What are some symptoms of icthyosis vulgaris? | Severe dry skin, scaly skin, possible skin thickening, mild itching of the skin
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| What might cause acquired icthyosis? | Underactive thyroid, kidney disease, lymphoma, HIV infection, sarcoidosis
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| What are some treatments for icthyosis vulgaris? | -Moisturising and exfoliating the skin every
day
-Using a pumice stone to remove some thickened skin
-Prescribed retinoid tablets (Vit A) such as acitretin or isotretinorim
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| What are the benefits of breast feeding to a baby? | - Less chance of diarrhoea and vomiting
- Fewer chest and ear infections
- Less chance of constipation
-Less likelihood of becoming obese
-Less chance of developing eczema
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| What are the benefits of breast feeding for the mother? | -Lowers the risk of breast and ovarian cancer
-Naturally uses up to 500 calories a fay
-Saves money (formula and equipment may be expensive)
-Oxytocin is released which helps strengthen the mother-baby bond
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| What is colostrum? | The thick, yellow, first breast milk a woman makes
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| Wen is colostrum made? | During pregnancy and the first 3-5 days after birth
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