Hypersensitivity Reactions

Question 1

Define Allergy and anaphylaxis (Type I)

Answer 1

Rapidly progressing immune reaction through antigen binding to surface of IgE-coated basophils or mast cells

• -> “immediate hypersensitivity”
• -> e.g. respiratory allergies, allergic asthma, hives, food allergies, anaphylaxis

Question 2

Define Anaphylaxis

Answer 2

Induced by insect venoms, penicillin, seafood, nuts, etc

–> Allergens - directly into bloodstream or rapidly absorbed fro gut (systemic mast cell activation

Question 3

Define Atopy

Answer 3

Atopic = increased tendency to develop allergies

• -> usually IgE response to parasites, but atopic individuals make IgE to allergens
• -> Th2 responses = absence of inflammation (which allergens DONT elicit)
• -> physiologic responses to parasites usually in skin, airways and gut are the same places as most allergic responses

Question 4

Define Hygiene hypothesis

Answer 4

deceases exposure to pathogens early in life leads to Th2-mediated immunity and IgE

Question 5

Define Respiratory allergen

Answer 5

small molecules carried on larger particles (pollen grains or mite feces)

• -> soluble allergen elutes and diffuses into the mucosa at very small doses
• -> transmucuosal delivery in very low doses = effective at eliciting Th-2 mediated IgE response

Question 6

Describe Basophils

Answer 6

• contain basophilic granules that contain lots of histamine
• NON-phagocytic
• related to tissue mast cells
• -> PROMINENT role in allergies and anaphylaxis

Question 7

Describe the development of anaphylaxis

Answer 7

• 1st exposure to allergen –> IgE (no anaphylaxis on 1st exposure)
• Penicillin is hapten –> must couple to self proteins to stimulate IgE
• IgE binds to Fc receptors on basophils + mast cells
• Subsequent exposure to allergen binds to surface-bound Ige –> cells release granule contents (histamine)
• Granule contents contain vasoactive compounds –> edema and smooth muscle contraction –> symptoms and possibly death (trouble breathing, and lungs filling up with fluid)

Question 8

Describe the effects of Histamine

Answer 8

Bronchial smooth muscle contraction + increased vascular permeability

Question 9

Describe Leukotrienes (LT)

Answer 9

Most potent substances known that cause smooth muscle contraction and increased vascular permeability

• -> released more slowly (synthesized) + longer effect
• -> in contrst: histamine = released quickly + shorter effect

Question 10

Describe eosinophils

Answer 10

Accumulate in nasal and bronchial mucosa in respiratory allergies and in intestinal mucosa during certain worm infestations:
–> attach to worms and release granules containg hydrolytic enzymes

Question 11

Describe Late phase response

Answer 11

2nd phase of smooth muscle contraction
–> sustained edema
–> recruitment of eosinophils and Th2 Cells
Remodeling of tissue –> eg smooth muscle hypertrophy + hyperplasia

May lead to chronic asthma and associated airways hyperactivity

Question 12

Describe treatments of type I

Answer 12

• Enjections of epinephrine
• repeated subcutaneous allergen injections –> IgE levels decrease and IgG levels increase
• Humanized mouse anti-IgE antibodies –> binds IgE to prevent binding to IgE receptors

Question 13

Describe Non-cytotoxic reactions (both are autoimmune diseases)

Answer 13

Graves disease = antibodies to TSH receptor causes overproduction of thyroid hormones –> hyperthyroidism

Myasthenia gravis = antibodies to acetylcholine receptor blocks nerve impulse transmission to muscles

Question 14

Describe Type III - immune complex diseases

Answer 14

Pathogenesis: Antigen + antibody = immune complexs

• -> antigen must persist for long periods for disease to develop
• -> optimal proportions of antibody and antigen are required

Pathogenic process:

• immune coplexes lodge in tissues (skin/kidney etc)
• complement activation –> C5a –> neutrophil accumulation
• lysosomal enzymes damage tissue

Question 15

Define Serum sickness

Answer 15

Protoype immune complex disease = serum sickness
–> occurs as a consequence of repeat injection of foreign serum

Foreign serum = horse anti-tetanus serum etc

Question 16

Describe Delayed type hypersensitivity (Type Iv)

Answer 16

Manifests 24-72 hours after exposure to antigen

• -> tuberculin reaction, contract dermatitis, delayed graft rejection
• -> cell mediated immune response, therefore mediated by Th1 cells
• -> memory response: requires prior sensitization to antigen

Question 17

Define Contact dermatitis

Answer 17

skin exposure to nickel, chromium, cosmetics, hair dye, poison oak, etc

• -> small molecules complexed with skin proteins are presented on antigen presenting cells to T helper cells
• -> ex: poison ivey leaf oil is lipid soluble and crosses cel membrane to modify intracellular proteins that are experssed on class I MHC for recognition by CTL’s
• -> CD4 and CD8 cells secrete inflammatory cytokins, including IFN-gamma

Question 18

Describe granuloma formation in Typic IV

Answer 18

Antigen not eradicted –> DTH –> granuloma (walled off bacteria)

• -> small basic DTH mechanism, but different outcome
• -> macrophages ingest organism, surrounded by other macrophages
• -> CD4 lymphocytes surround macrophages to maintain macrophage activation + structural integrity of the granuloma

Question 19

Describe type I immunity

Answer 19

Immediate
Immune mechanism = IgE and Th2 cells
–> Mast cells, eosinophils and their mediators involved

Question 20

Describe type II immuity

Answer 20

Antibody mediated
Immune mechanism = IgM and IgG antibodies against cell surface or ECM antigens

• -> Osonization, Phagocytosis of cells
• -> complement- and Fc Receptor mediated recruitment and activation of leukocytes

Question 21

Describe Type III immunity

Answer 21

Immune complex mediated
Immune mechanism = immune complexes of circulating antigens and IgM or IgG antibodies

–> complement and Fc receptor mediated recruitment and activation of leukocytes

Question 22

Describe Type IV immunity

Answer 22

T-cell mediated

Immune mechanism = CD4 T cells and CD8 CTL’s

• -> cytokine-mediated inflammation
• -> direct target cell killing