immunology Flashcards
(28 cards)
what does SPUR stand for in immune deficiency?
- Serious infections (unresponsive to oral antibiotics)
- Persistent infections (early structural damage, chronic infections)
- Unusual infections (organisms and sites)
- Recurrent infections (1 or 2 major and recurrent minor infections in a year
what features might suggest immune deficiency? (apart from SPUR)
- weight loss or failure to thrive
- severe skin rash
- chronic diarrhoea
- mouth ulceration
- unusual autoimmune disease
- lymphoproliferative disorders
- cancer
- family history
what are primary immunodeficiency disorders?
- respiratory diseases are the main and initial manifestation in most cases and the most common complication
- pulmonary complications cause significant morbidity and mortality in patients with PIDs
- early diagnosis and appropriate treatment can prevent or at least slow the development of respiratory complications
- e.g. sinusitis, ottis media, laryngeal angioedema, malignancies, interstitial lung disease, pneumonia, bronchitis, bronchiectasis.
what are secondary immunodeficiency disorders?
- this is the most common type, is often subtle and often involves more than one component of the immune system
what is the most frequent primary immunodeficiency associated with sinusitis and ottis media?
- Primary antibody deficiency (PAD)
- less common = selective IgA deficiency, common variable immunodeficiency, specific antibody deficiency, X-linked agammaglobulinemia
what primary immunodeficiency disorder should be considered in patients with laryngeal angioedema?
- complement system disorders
- angioedema is characterised by local swelling that is generally asymmetrical owing to increased vascular permeability with leakage of plasma (not allergic but can be life threatening)
what primary immunodeficiency might people with pneumonia have?
- primary antibody deficiency (PAD)
- complement system disorders
- congenital phagocytosis deficiency
- combined immunodeficiencies
Describe congenital neutropenias.
- congenital neutropenias (kostmann syndrome)
- neutropenia = abnormally low concentration of neutrophils in the blood.
- rare genetic disorder, SCN type 1 is the commonest form and is inherited in an autosomal dominant manner
- this leads to recurrent bacterial/ fungal infections within 2 weeks of birth
- treated with recombinant G-CSF
what is leukocyte adhesion deficiency?
- very rare autosomal recessive primary immunodeficiency
- caused by genetic defect in CD18 integrin gene
- results in failure of neutrophil adhesion and migration
- clinical picture marked by leucocytosis and localised bacterial infections.
- treatment is hematopoietic stem cell transplant and prophylactic antibiotics
- results in recurrent bacterial and fungal infections in deep tissues and a very high neutrophil count.
what Is chronic granulomatous disease?
- deficiency of the intracellular killing mechanism of phagocytes - absent respiratory burst
- commonest form is a deficiency in a gene that makes a component of the NADPH oxidase complex (X-linked)
- inability to generate oxygen/nitrogen free radicals.
- impaired killing of intracellular micro-organisms.
- clinical presentations; recurrent deep bacterial infections, failure to thrive, lymphadenopathy and hepatosplenomegaly (enlargement of spleen and liver), granuloma formation.
what is the treatment for phagocyte deficiencies?
-immunoglobulin reblacement theraoy
-aggressive management of infection (oral/ IV antibiotics and anti-fungals, drainage of abscesses)
- haematopoietic stem cell treatment
-gene therapy
SCN - recombinant G-CSF
what are important PIDs associated with respiratory complications in children?
- transient hypogammaglobulinemia of infancy
- severe combined immunodeficiency’s
- X-linked agammaglobulinemia.
- congenital neutropenia
what is transient hypogammaglobulinaemia?
when the foetus fail to produce its own IgG after using sIgA from breast milk.
what is severe combined immunodeficiency (SCID)?
- failure of production of lymphocytes
- clinical presentation; unwell by 3 months of age, persistent diarrhoea, failure to thrive, infections of all types, unusual skin disease and family history of early infant death.
- over 20 possible causes identified
- commonest form is X-linked (mutation of IL-2 receptor)
- treatment; avoid infections and aggressively treat them, antibody replacement therapy, stem cell transplant from HLA identical sibling if possible, stem cell transplant.
what is bruntons X-linked hypogammaglobulinaemia?
- no circulating B cells
- no plasma cells
- no circulating antibodies after 6 months
- Severe combined immunodeficiency
what are the classifications of hypersensitivity reactions?
- type 1 - immediate hypersensitivity (allergy)
- type 2 - direct cell effects (cytotoxic or stimulatory - cell surface antigens)
- type 3 - immune complex mediated (soluble antigens)
- type 4 - delayed type hypersensitivity
what factors are likely to make you produce Th1 and therefore not have allergies?
- older siblings
- early day care exposure
- rural environments
- childhood infections
- microbial exposure
- pets
what factors are likely to make a child lack TH1 differentiation and produces allergies and asthma?
- only child
- widespread use of ABX
- urban environment with allergen sensitization
- dust mites
- cockroaches
how do Th2 cells cause an allergic response?
- they produced IL-4, IL-13 and IL-5 which co-ordinate the allergic response.
They do this by;
1) regulating the synthesis and secretion of IgE antibodies by plasma cells
2) stimulating the differentiation of eosinophils from the bone marrow into the blood
3) helping to activate mast cells and eosinophils at sites of allergen exposure.
Describe the sensitisation stage and allergic stage of allergic disease.
sensitisation:
- mast cells and eosinophils express receptors for the Fc region on IgE antibodies > once they encounter each other cells produce an antigen specific IgE > allergen is cleared > residual IgE antibodies bind to circulating mast cells.
Allergic:
- the mast cells re-encounter the allergen and bind to it, disturbing the cell membrane > there is an immediate release of vasoactive mediators (histamine, tryptase) > increase expression of pro-inflammatory cytokines and leukotrienes.
what are the clinical features of allergic disease?
- muscle spasm
- mucosal inflammation
- inflammatory cell infiltrate.
- asthma, urticarial (hives), angioedema, allergic rhinitis, allergic conjunctivitis, diarrhoea and vomiting, anaphylaxis.
How are IgE mediated disorders mediated?
- avoidance of allergen
- block mast cell activation
- prevent effects of mast cell activation
- anti-inflammatory agents
- management of anaphylaxis
- immunotherapy.
Describe type 2 hypersensitivity disorders.
- involves IgM or IgG antibodies to cell surface antigens
- eg Goodpasture’s syndrome
what is Goodpasture’s syndrome?
- an autoimmune disease affecting the lungs and kidneys (pulmonary alveolar haemorrhage, kidney disease)
- defined by the presence of auto reactive antibodies to the a3 chain of type 4 collagen present in basement membranes of alveoli and glomeruli.
- treatment = corticosteroids, cyclophosphamide, plasmapheresis, smoking cessation.
