Hypersensitivity

Question 1

Hypersenstivity

Answer 1

Exaggerated immune responses that cause inflammation and tissue damage

Question 2

The 4 types of hypersensitivity reactions are classified by thier ____

Answer 2

Effector mechanisms

Question 3

Type 1 Overview

Answer 3

IgE mediated hypersensitivity to harmless antigens (soluble)

• mas cell activation
• allergic rhinitis, asthma, systemic anaphylaxis

Question 4

Type 2 Overview

Answer 4

Antibody mediated destruction of cells

• IgG
• self antigen
• FcR+ cells, phagocytosis by NK cells
• autoimmune diseases

Question 5

Type 3 Overview

Answer 5

Immune complex mediated

• IgG
• soluble antigen
• FcR+ cells, complement
• serum sickness, arthus reaction

Question 6

Type 4 Overview

Answer 6

T cell mediated

• Th1 cells –> soluble antigen, macrophage activation, DTH
• CTL –> cell- associated antigen, cytotoxicity, contact dermatitis

Question 7

Type 1 mechanism

Answer 7

Allergic response to harmless environmental antigen

• sensitization
• germinal center formation in 2nd week of primary response
• isotype switching to IgE
• memory B cells and long lived plasma cells
• mast cells express high-affinity Fc receptor for IgE and bind free IgE from blood

Question 8

Sensitization

Answer 8

Initial exposure generates a primary immune response

Question 9

Allergy

Answer 9

State of hypersensitivity to a non-harmful antigen

Question 10

Type 1 what happens with a second exposure to the original allergen?

Answer 10

Early phase: immediate
- effector function of IgE-mediated activation of mast cells = degranulation and release of histamine and TNF-alpha, leading to an inflammatory response at the site of allergy exposure

Question 11

Allergen specific IgE

Answer 11

Mast cells express Fc-receptors for IgE

- found in connective tissues surrounding blood vessels and in the mucosa of the gut and airways

Question 12

Mast cell degranulation effect on tissues

Answer 12

GIT: increased fluid secretion, increased peristalsis = expulsion of GIT contents
Airways: decreased diameter, increased mucus secretion = expulsion of airway contents
Blood vessels: increased blood flow, increased permeability = edema, inflammation, increased lymph flow and carriage of antigen to lymph nodes

Question 13

Late phase (6-8 hours)

Answer 13

Mast cell synthesis

• prostaglandins and leukotrienes = vasodilation and vascular permeabiltiy
• cytokines and chemokines = leukocyte recruitments
• eosinophils: respond to mast cell derived cytokines, release damaging proteases
• basophils: IgE mediated activation or respond to mast cell derived cytokines= histamine release

Question 14

What is the goal of the late phase response?

Answer 14

Recruit leukocytes with anti-parasite effector functions (eosinophils and basophils)
- could result in narrowing of airway or sustained edema

Question 15

Type 1 systemic response

Answer 15

Allergen enters blood stream

- IgE mediated activation of mast cells (CT mast cells associated with blood vessels throughout the body

Question 16

Anaphylaxis

Answer 16

Immediate type 1 hypersensitive reaction causing circulatory shock and suffocation due to bronchiole constriction

Question 17

Histamine release by mast cells

Answer 17

• vasodilation and vascular permeability = decrease in blood pressure
• bronchial smooth muscle contraction
• intestinal smooth muscle contraction

Question 18

Examples of allergens

Answer 18

• drugs
• insect venom
• foods

Question 19

Heart/vascular system systemic response

Answer 19

• increased capillary permeabilty and entry of fluid into tissues
• swelling of tissues including tongue
• loss of blood pressure
• reduced oxygen to tissues
• irregular heartbeat
• anaphylactic shock
• loss of consciousness

Question 20

Respiratory tract systemic response

Answer 20

• contraction of smooth muscle and constriction of throat and airways
• difficulty in swallowing
• difficulty in breathing, wheezing

Question 21

GIT systemic response

Answer 21

• contraction of smooth muscle
• stomach cramps
• vomiting
• fluid outflow into gut
• diarrhea

Question 22

Type 2 drug-induced hemolytic anemia

Answer 22

• sensitization
• some drugs can bind to self proteins and induce a primary immune response in allergic individuals
• ex: antibiotics (penicillin)

Question 23

Type 2 mechanism

Answer 23

• drug binds to self proteins to generate a new epitope (could include proteins expressed on surface of RBCs)
• activation of a primary response to a new epitope
• germinal center formation results in high affinity IgG

Question 24

Type 2 second exposure

Answer 24

• antibiotics bind to self proteins expressed on RBCs
• drug induced IgG binds to the surface of RBCs
• drug induced hemolytic anemia: RBCs are opsonized by IgG and activated complement (C3b) = removal of opsonized RBCs by macrophages in the spleen

Question 25

Is there a type 1 hypersensitivity to penicillin in some people?

Answer 25

Yes

Question 26

Is type 3 hypersensitivity due to an allergy?

Answer 26

No, its immune complex mediated

Question 27

Type 3 local response

Answer 27

Arthus reaction: immune complexes form in tissue, cause localized inflammation - ex: booster vaccine sometimes results in swelling and/or pain at injection site due to residual antibodies from previous vaccine forming immune complexes with vaccine antigen

Question 28

Immune complexes activate what pathway of complement?

Answer 28

Classical - complement activation is proinflammatory - mast cells degranulate in response to C5a and signals through the Fc recptor for IgG - activation of Fc-gamma-R3 on mast cell induces degranulation = local inflammation, increased fluid and protein release, phagocytosis, and blood vessel occlusion (within 2 hrs)

Question 29

Type 3 systemic response

Answer 29

Serum sickness: immune complexes form in the bloodstream in capillaries of various tissues and induce inflammation

Question 30

Type 3 systemic example

Answer 30

Snake bite treatment - antiserum from horses immunized with snake venom occurs with injection of a large amount of poorly catabolized foreign antigen (horse IgG) - excess of antigen will cause formation of small immune complexes which are depositied in blood vessel walls, leading to activation of complement in vessel wall and inflammation - later in immune response, large complexes are rapidly cleared form bloodstream by macrophages in liver and spleen

Question 31

Early in type 3 response there is little _____ and excess of _____

Answer 31

Antibody; antigen = small immune complex formation - do NOT fix complement and are not cleared

Question 32

Late in type 3 response there is large amount of ____ and little ____

Answer 32

Antibody; antigen | = medium-sized immune complexes that fix complement and are cleared from circulation

Question 33

Type 4 (delayed-type)

Answer 33

- sensitization phase: primary immune response | - elicitation phase: mediated by memory T cells

Question 34

Is type 4 in response to an allergy?

Answer 34

NO

Question 35

Type 4 mechanism

Answer 35

- antigen is introduced into sub q tissue and processed by local APCs - Th1 effector cell recognizes antigen and releases cytokines which act on vascular endothelium - recruitment of T cells, phagocytes, fluid, and protein to site of antigen injection causes visible lesion

Question 36

Type 4 example

Answer 36

Turberculin skin test - requires previous infection with Mycobacterium tuberculosis or vaccination with the attenuated M. bovis vaccine - mediated by memory Th1 T cells - Others: anthraxin test or candidin test

Question 37

Is type 4 contact hypersensitivity in response to an allergen?

Answer 37

Yes! | - T cell mediated, allergic response to chemically modified self proteins

Question 38

Contact hypersensitivity example

Answer 38

Poison ivy - chemical from leaf can form covalent bonds and modify extracellular skin proteins (presented by MHC2) or enter cell and modify intracellular proteins (MHC1)

Question 39

Allergic contact dermatitis

Answer 39

- activation of memory Th1 cells = proinflammatory cytokines | - activation of memory CTL = cellular cytotoxicity and IFN-gamma

Question 40

Contact hypersensitivity mechanism

Answer 40

- contact sensitizing agent penetrates skin and binds to self proteins, which are taken up by Langerhans cells --> Langerhan cells present self peptides haptenated with contact sensitizing agent to Th1, which secrete IFN-gamma --> activated keratinocytes secrete cytokines (IL-1, TNF-alpha) and chemokines (CXCL8, CXCL11, CXCL9) --> product of keratinocytes and Th1 cells activate macrophages to secrete mediators of inflammation

Question 41

2 types of contact dermatits

Answer 41

- allergic: immunological form, allergic response to antigen - irritant: non-immunological, response to chemicals that irritate or traumatize skin (no sensitizaiton, occurs immediately, chemicals activate keratinocytes to produce pro-inflammatory cyo/chemokines)