Hypersensitivity

Question 1

what is hypersensitivity?

Answer 1

Hypersensitivity is a group of disorders where the normally beneficial components of the immune response act in an exaggerated or inappropriate fashion to environmental antigens which do not normally cause tissue damage. The exaggerated response directed at the antigen rather than the antigen itself is responsible for the tissue damage which results.

Question 2

type 1 hypersensitivity =

Answer 2

allergy

Question 3

immunoglobulin in type 1 hypersensitivity

Answer 3

IgE

Question 4

phases of type 1 hypersensitivity

Answer 4

sensitisation

reaction

Question 5

treatment of type 1 hypersensitivity

Answer 5

antihistamines
corticosteroids
adrenaline
allergen avoidance

Question 6

atophy triad

Answer 6

eczema
asthma
hayfever

Question 7

what is atopy?

Answer 7

genetic tendency to develop allergic diseases

Question 8

describe atopic dermatitis

Answer 8

• Common in children
• Exposed and flexor surfaces
• Degranulation of basophils and mast cells in response to sensitised IgE
• “Leaky” skin allows more allergen in and water out
• Dry and itchy
• Itch leads to further infection/inflammation
• Itch worse at night

Question 9

type 2 hypersensitivity

Answer 9

cytoxic

Question 10

type 3 hypersensitivity

Answer 10

immune mediated

Question 11

type 4 hypersensitivity

Answer 11

cell mediated

Question 12

what is contact dermatitis

Answer 12

• Haptens cross stratum corneum
• Langerhans cells present to TH1 cells
• Langerhans cells are APC that site on cell surfaces
• TNF alfa and IL 1, 13 and 18
• LCs become differentiated Dendritic cells presenting allergenic epitope and multiply
• More aggressive response 2nd time
• Reexposure will not result in anaphylaxis
• Acquired immune response not innate

Question 13

effector mechanism in type 1 hypersensitivity

Answer 13

mast cell activation

eosinophil activation

Question 14

antibody in type 11 hypersensitivity

Answer 14

IgG

Question 15

type 2 hypersensitivity effector mechanism

Answer 15

cell or matrix associated complement
FcR+ cells

cell surface receptor
Ab alters signalling

Question 16

example of type 2 hypersensitivity

Answer 16

drugs

chronic urticaria

Question 17

immunoglobulin in type 3 hypersensitivity

Answer 17

IgG

Question 18

effector mechanism in type 3 hypersensitivity

Answer 18

complement

phagocytes

Question 19

example of type 3 hypersensitivity

Answer 19

arthus reaction

Question 20

type 4 hypersensitivity immune reactant

Answer 20

Th1 cells

Question 21

effector mechanism in type 4 hypersensitivity

Answer 21

macrophage activation

Question 22

example of type 4 hypersensitivity

Answer 22

contact dermatitis

tuberculin reaction

Question 23

describe the production of IgE

Answer 23

• IgE produced by plasma B cells in lymph nodes, or
locally at site of inflammation
• IgE located mostly in tissue (hence low serum
concentration), bound to Mast Cell surface
through high affinity IgE receptor Fc!RI
• Certain antigens and routes of delivery appear to
favour IgE production. Transmucosal at low doses
is often a common route.
• CD4+ T cells of the Th2 phenotype that produce
IL4 cytokines favour IgE responses
• Th2 T cells also force B cells to switch the
isotype of the Ig they secrete from IgM to IgE

Question 24

what do CD8 cytotoxic cells produce?

Answer 24

IFNgamma

TNF-a

Question 25

what are the functions of the things CD8 cells produce?

Answer 25

target cell lysis

Question 26

what do CD4 Th1 cells produce?

Answer 26

IFN-g GM-CSF TNF-a

Question 27

what are the functions of the things Th1 cells produce?

Answer 27

macrophage activation

Question 28

what do CD4 Th2 cells produce

Answer 28

IL4 | IL5

Question 29

what are the functions of the things Th2 cells produce?

Answer 29

b cell activation

Question 30

features of allergic asthma

Answer 30

``` • Bronchial constriction • Increased secretion of fluid and mucus, trapping inhaled air • Chronic inflammation may ensue with continued presence of Th2 T cells, eosinophils, neutrophils. • Chronic asthma driven originally by specific allergen, but may then result in hyperreactive airways to other irritants such as cigarette smoke and other pollutants ```

Question 31

describe the effects of ingested allergens

Answer 31

• Ingested allergens leads to two main symptoms • Activation of GI Mast cells results in transepithelial fluid loss and smooth muscle contraction: diarrhea and vomiting • If allergen enters bloodstream, generalised disseminated rash, Urticaria, (hives). • In severe cases of food allergy, eg nuts and shellfish, life threatening generalised anaphylaxis and cardiovascular collapse may occur

Question 32

chemical mediators of allergic responses

Answer 32

``` • Mast cells granules contain a wide range of inflammatory mediators • Lipids • Toxic mediators • Cytokines • enzymes ```

Question 33

lipids in allergic response

Answer 33

• Prostaglandins, increase vascular permeability, increase body temperature. Platelet activating Factor, increase adhesion between endothelium and neutrophils. Leukotrienes, attract and activate neutrophils, increase vasc permeability

Question 34

toxic mediators in allergic response

Answer 34

Histamine, increase vascular permeability, and promotes movement of fluid from the vasculature by constricting vascular smooth muscle.

Question 35

cytokines in allergic respoonse

Answer 35

``` • IL-4, IL-13; amplify Th2 response • IL-3, IL-5, GM-CSF; promote eosinophil activation and production • TNF-#; pro-inflammatory, activates endothelium Chemokine MIP-1#; attracts macrophages and neutrophils ```

Question 36

enzymes in allergic response

Answer 36

* Tryptase * Chymase * Cathepsin G * Carbopeptidase * Remodel connective tissue matrix

Question 37

describe type 2 hypersensitivity

Answer 37

* Type II reactions are the result of antibodies, usually IgG, binding to components of cell membranes or extracellular matrix. * Can be self-components, or exogenous components

Question 38

give examples of type 2 hypersensitivty endogenous

Answer 38

• Self: Goodpasture’s syndrome, antibodies bind to basement membrane collagen type IV, glomerulonephritis in kidney, pulmonary haemorrhage in lung

Question 39

describe type 3 hypersensitivity

Answer 39

* As with Type II, Type III are caused by antibody, usually IgG, but also sometimes IgM. * Type III antibodies directed to soluble antigens * Formation of antibody-antigen complexes is a normal part of immune response. * Usually cleared by reticuloendothelial system (RES): macrophages, neutrophils in liver spleen and bone marrow that ingest and degrade immune complexes * Excess immune complex deposition in tissues leads to pathology

Question 40

sites of immune complex deposition in type 3 hypersensitivity

Answer 40

* Sites of immune complex (IC) deposition are not necessarily the sites from where the antigen is derived. * Glomeruli : kidney, filtration process makes it very common site in IC deposition, damage driven by complement activation * Blood vessel walls: IC accumulate on veins and arteries, causes vasculitis, often seen as skin lesions if close to surface * Synovial membranes: Rheumatoid arthritis, in which the IgG of the immune complexes can become an antigen itself, and IgM Rheumatoid Factor antibodies develop. * Skin: common site for IC deposition, causes rashes. * Systemic sites: in case of Systemic Lupus Erythematosus (SLE) IC deposits in kidney, joints, skin, vasculature, muscle and other organs.

Question 41

describe type 4 hypersensitivity

Answer 41

* Unlike I, II & III, Type IV reactions are entirely cell-mediated * Complement does not play a role in Type IV. * Most Type IV reactions are caused by CD4+ delayed type hypersensitivity (DTH) reactions. ‘Delayed’ refers to reaction occurring 2 to 4 days after antigen exposure * Macrophages that cause damage are not specific, harm infected and non-infected tissue