Hypersensitivity

Question 1

What is hypersensitivity?

Answer 1

Altered state of immune responsiveness which causes excess or inappropriate immune response, leading to tissue damage

Question 2

Which types of hypersensitivity are antibody mediated?

Answer 2

1-3, 4 is cell mediated

Question 3

Type 1 hypersensitivity

Answer 3

Allergic/immediate hypersensitivity
IgE antibodies in response to antigens
Exposure - inhalation, ingestion, injection, direct contact

Question 4

Systemic hypersensitivity

Answer 4

Anaphylaxis

Question 5

Localised hypersensitivity

Answer 5

Allergic rhinitis, asthma

Question 6

Sensitisation type 1 hypersensitivity

Answer 6

• Allergen enters body, recognised by antigen presenting cells, breaks up allergen and presents on MHC II to T helper cells which activate B lymphocytes to differentiate = IgE antibodies which enter through blood to find mast cells and stick to their surface on Fc receptors (Bind to constant region of antibody)
• IgE antibodies coat surface of mast cell = sensitised mast cell
• Next time encountered, allergen binds to IgE antibodies on mast cell
• When 2 antibodies bind to one antigen, cross linking occurs - signal activates mast cell to degranulate
• Smooth muscle contraction, blood vessel contraction, mucous gland secretion, platelets activated, infiltration of eosinophils
• Re-activating T cells which activates more B cells = more IgE cells = replenishes B cells
• Smooth muscle - bronchospasm, cramps, rhinitis, hypovolaemia, hypoxia

Question 7

Blood vessels

Answer 7

Erythema, oedema, pulmonary oedema

Question 8

Eosinophils

Answer 8

Eosinophilia - damage of tissue

Question 9

Pathophysiology type 1 hypersensitivity

Answer 9

IgE as a result of prior sensitisation
Subsequent encounter with antigens results in IgE-mediated reaction by preformed IgE antibodies
Free antigens binds to two adjacent IgE antibodies
Cells degranulate
Histamines and other mediators released

Question 10

Type 3 hypersensitivity

Answer 10

• Immune complex hypersensitivity
• Onset usually 2-6 hours
• Can be local or systemic
• Antigens causing injury can be exogenous or endogenous
• Resultant disease depends where complex forms and deposits

Question 11

Pathophysiology of type 3 hypersensitivity

Answer 11

Immune complexes formed when antibodies bind to soluble antigens
Immune complexes deposit in basement membrane of blood vessels
Complement system activated
Release of anaphylatoxins which increase vascular permeability - oedema
Chemokines attract neutrophils - degranulation and inflammation

Question 12

Examples of type 3 hypersensitivity

Answer 12

Lupus, polyarteritis nodosa, poststreptococcal glomerulonephritis, serum sickness

Question 13

Symptoms of lupus and antigens involved

Answer 13

Nephritis, arthritis, vasculitis

DNA, nucleoproteins

Question 14

Symptoms of polyarteritis nodosa and antigens

Answer 14

Vasculitis, hep B virus surface antigen

Question 15

Symptoms of post streptococcal glomerulonephritis and antigens

Answer 15

Nephritis and streptococcal wall antigens

Question 16

Symptoms of serum sickness and antigens

Answer 16

Arthritis, vasculitis, nephritis

Various antigens

Question 17

Type 4 hypersensitivity

Answer 17

• Delayed hypersensitivity reaction - inflammation by 2-6 hours, peaks by 24-48 hours
• Result from interaction of T-cell initiated inflammation and don’t involve antibodies
• Inflammatory response results from manner in which T cells encounter and respond to antigen
• Can be transferred by sensitised T cells but not serum

Question 18

Pathophysiology of type 4 hypersensitivity

Answer 18

T cell mediated
T helper cells: antigen penetrates skin - uptake by Langerhans cells - migration to lymph nodes and formation of sensitised T lymphocytes
Secretion of lymphokines and cytokines by sensitised T lymphocytes - macrophage activation and inflammatory reaction in tussle
Killer T cells release perforin and granzymes

Question 19

Examples of type 4 hypersensitivity

Answer 19

Rheumatoid arthritis
MS
Type 1 diabetes
IBD
Psoriasis

Question 20

Principle mechanism of tissue injury of rheumatoid arthritis

Answer 20

Inflammation mediated by TH1 and TH17 cytokines

Question 21

Principle mechanism of tissue injury for MS

Answer 21

Inflammation mediated bey TH1 and TH17 cytokines - myelin destruction by macrophages

Question 22

Principle mechanism of tissue injury for IBD

Answer 22

Inflammation mediated by TH1 and TH17 cytokines

Question 23

Principle mechanism of tissue injury for type 1 diabetes

Answer 23

T cell mediated inflammation - destruction of islet cells by CTLs

Question 24

Principle mechanism of tissue injury for psoriasis

Answer 24

Inflammation mediated by T cell derived cytokines

Question 25

Anaphylaxis

Answer 25

Type 1 - mast cells and IgE

Question 26

Grave's

Answer 26

Type 2 - antibody-antigen complex, IgM

Question 27

Lupus

Answer 27

Type 3 - IgG and IgM

Question 28

MS

Answer 28

Type 4 - T-cell mediated

Question 29

Rheumatoid arthritis

Answer 29

type 4/3 | T cell driven

Question 30

Farmer's lung

Answer 30

Type 3 | Soluble antigens inhaled - mold

Question 31

1) hypersensitivity 2

Answer 31

1) antigen on healthy cell IgG or IgM bind to antigen = antigen-antibody complex on host tissue Complement cascade activated and antibody dependent cell mediated toxicity Complement binds to Fc portion of antibody. Some of the cascade becomes cleaved and chemotaxic (attracts neutrophils). Neutrophils undergo degranulation and release enzymes e.g. peroxidase, myeloperoxidase and proteinase 3 which generates oxygen radicals (cytotoxic to cell)

Question 32

2) Hypersensitivity 2

Answer 32

Antigen on healthy cell IgG or IgM binds to antigen = antigen-antibody complex on host tissue Complement cascade activated and antibody dependent cell mediated cytotoxicity Opsonisation and phagocytosis, again due to complement cascade. Phagocytes engulf cells in spleen

Question 33

3) hypersensitivity 2

Answer 33

Antigen on healthy cell IgG or IgM bind to antigen = antigen-antibody complex on host tissue Complement cascade activated and antibody dependent cell mediated cytotoxicity Ag-AB complex recognised by NK cells and binds to AB. Release perforins (form pores in cell). Granzymes and granulysin enter = apoptosis

Question 34

4) hypersensitivity 2

Answer 34

antigen on healthy cell IgG or IgM bind to antigen = antigen-antibody complex on host tissue Complement cascade activated and antibody dependent cell mediated cytotoxicity AB mediated cellular dysfunction. AB bound to antigen blocks normal receptor activator from getting to receptor e.g. myasthenia. Or cause overactivatioj of receptor e.g. Graves