Allergy + Hypersensitivity Flashcards
Types of hypersensitivity reactions
Type I – Allergic IgE-mediated
Type II - antibody-dependent
Type III - immune complex- mediated
Type IV - cell-mediated or delayed
Type 1 hypersensitivity reaction - IgE mediated
• CD4+ T helper cell activate B cells to produce IgE antibodies specific to an antigen
• IgE antibodies bind to Fc receptors on the surface of tissue resident mast cells and blood basophils
• Mast cells and basophils coated by IgE antibodies are ‘sensitised’
• Immediate response on re-exposure to same allergen
• Allergen cross-links the bound IgE on sensitised cells, resulting in anaphylactic degranulation
• Basophils and mast cells release chemical mediators such as histamine, proteases and cytokines
• Resulting in vasodilation and smooth muscle contraction
What is bronchial asthma
• Chronic inflammation
• Intermittent and reversible airway obstruction
• Chronic bronchial inflammation with eosinophil infiltration
• Bronchial smooth muscle hypertrophy and hyperreactivity • Dominated by the presence of eosinophils, CD4+ cells (Th2), and large proportion of CD4+ natural killer T cells expressing an invariant T cell receptor (iNKT cells) that recognizes glycolipid antigens
What is anaphylaxis
• Severe systemic reaction to allergens (nuts, bee stings or drugs) causing body-wide degranulation of mast cells leading to vasodilation and, if severe, life-threatening shock
• IgE-mediated reaction simultaneously in multiple organs
• Allergen is a drug, insect venom or food. It can be evoked by minute amounts of
an antigen
• Lacks genetic propensity of atopy (genetic trait to have a predisposition for localised anaphylaxis)
• Urticaria (hives) and angioedema are mild localised forms of anaphylaxis
diagnosis of anaphylaxis
Treatment of anaphylaxis
Type II hypersensitivity - IgM/IgG-mediated
• Antibody mediated process, IgG and IgM antibodies are directed against antigens on host cells (such as red blood cells; RBCs)
• This leads to cell lysis, tissue damage or loss of function by mechanisms:
• Complement dependent
• Complement independent
• The activation of the complement system results in opsonization,
the agglutination of red blood cells, cell lysis by MAC, and cell death
• Reactions take between 2 to 24 hours to develop
• Transfusions, Haemolytic Disease of the Newborn (HDN)
Type II hypersensitivity Antibody-dependent cell-mediated cytotoxicity (ADCC)
• Low concentrations of IgG coat target cells
• Inflammatory cells such as NK cells,monocytes, and granulocytes bind to the IgG via Fc receptors and lyse the target cells by cytoplasmic granules, perforins form pores in cell membrane
to inject granzymes (serine proteases)
• Transplant rejection
• Immune reactions against neoplasms • Immune reactions against parasites
Haemolytic Disease of the Newborn (HDN)
HDN occurs when the immune system of the mother sees a baby’s
RBCs as non-self. Antibodies develop against the
baby’s RBCs and attack baby’s RBC causing hemolysis
• Severe cases involve D antigen of the Rh system
(RhD). If mother is Rh- and carries Rh+ fetus (RhD), at
birth, miscarriage, abortion, trauma or medical
procedures the blood of the fetus exposes to mother
who responds by producing anti-Rh antibody which
are mostly IgG type antibodies (anti-D antibodies)
• During subsequent pregnancies maternal anti-D
antibodies cross the placental barrier, enter the fetal
circulation and lead to hemolysis
• Treatment of mother with antibody to Rh antigen after
the birth will result no anti-D antibody production by
the mother (not sensitised) hiding them from mother’s
immune response
Type III hypersensitivity - Immune complex- mediated
• Immune complexes form in the circulation • Complexes eventually deposit in tissues
• Activates complement anaphylatoxins; C3a and C5a to mediate
granule release from mast cells
• Recruit inflammatory cells with lysosomal enzymes
• Cause inflammation and tissue injury (necrotising vasculitis)
What is serum sickness
• Serum sickness occurs when patients are administered serum from healthy people (usually contains antibodies that are
beneficial to the patients)
• After around 5-10 days the patients produce antibodies against the antigens in the donor’s serum
• Deposition of antigen-antibody complexes in blood vessel in the kidneys and joints
• Symptoms are arthritis, vasculitis and glomerulonephritis
Type IV hypersensitivity - T cell mediated
• T cell-mediated: CD4+ and CD8+ T cells
• Delayed type hypersensitivity, the reaction takes several days to develop
• Increases 48 hours after the injection of antigen
• Th1 cells (helper) secrete cytokines which activate cytotoxic T cells
• Not antibody-mediated
Mechanism of type IV hypersensitivity
• CD4+ Th1 helper cells recognise antigen in a complex with the MHC class II on the surface of antigen presenting cells
• CD4+ T cells secrete IL-2 and IFN-g inducing further release of other
cytokines, thus mediating the immune response • Activated CD8+ T cells destroy target cells on contact
• Activated macrophages produce hydrolytic enzymes
• The overreaction of the helper T cells and overproduction of cytokines damage tissues, cause inflammation, and cell death
• Type IV hypersensitivity can usually be resolved with topical corticosteroids and trigger avoidance
What is Contact dermatitis
Inflammatory skin disease caused by T cell- mediated (type IV) hypersensitivity to external agents that come into contact with the skin
What is tuberculin skin test
Test for TB
