Hypersensitivity - Stiener-jones

Question 1

What is hypersensitivity?

Answer 1

Exaggerated or aberrant immune response to antigen resulting in inflammation and tissue damage.

Question 2

What is Type I hypersensitivity?

Answer 2

Referred to as Allergy, atopy or immediate hypersensitivity.

• occurs mixtures after reexposure to antigen/allergen.
• Rapid IgE and mast cell mediated vascular and smooth muscle reaction that is often followed by inflammation.
• Affects 20% of population.

Question 3

What is the basic sequence of events with Type I hypersensitivity?

Answer 3

1. Initial exposure to antigen and production of IgE = Sensitization.
   - Th2 cells secrete IL’s
   - Th2 cell Cd40L binds to B cell Cd40
2. Binding of IgE Ab to Fc receptor on mast cells
3. Cross-linking of bound IgE upon reexposure to allergen.
4. Release of mast cell mediators

Question 4

What are the immediate effects of Type I Hypersensitivity?

Answer 4

Dilation of blood vessels, increased vascular permeability, smooth muscle contraction.

Question 5

What is the late response of Type I hypersensitivity?

Answer 5

Inflammation

Question 6

What are the common allergens, Route of entry and response of Systemic anaphylaxis?

Answer 6

Common allergens: Drugs, venoms, peanuts & serum.

Route of entry: Intravenously or oral absorption

Response: Edema, increased vascular permeability, Tracheal occlusion, circulatory collapse, death.

Question 7

What are the common allergens, Route of entry and response of Acute urticaria?

Answer 7

Common allergens: Animal hair, insect bites, allergy testing

Route of entry: Through skin

Response: Local increase in blood flow and vascular permeability.

Question 8

What are the common allergens, Route of entry and response of Allergic Rhinitis?

Answer 8

Common allergens: Pollens & dust mite feces

Route of entry: inhalation

Response: Edema & irration of nasal mucosa

Question 9

What are the common allergens, Route of entry and response of Asthma?

Answer 9

Common allergens: Danders, pollens, dust mite feces

Route of entry: inhalation

Response: Bronchial constriction, increased mucous production and airway inflammation

Question 10

What are the common allergens, Route of entry and response of Food allergy?

Answer 10

Common allergens: Tree nuts, peanuts, shellfish, milk, eggs, fish.

Route of entry: oral

Response: vomiting, diarrhea, purtisis, urticaria (hives), anaphylaxis.

Question 11

What are the 2 lipid mediators?

Answer 11

Prostanglandins & Leukotrienes

Question 12

What are the 2 lipid mediators?

Answer 12

Prostaglandins & Leukotrienes

Question 13

What do Prostaglandins do?

Answer 13

*Made via cyclooxygenase pathway
VASOCONSTRICTION in the LUNGS or dilation in vascular smooth muscle.
- Cause aggregation or disaggregation of platelets.

Question 14

What do Leukotrienes do?

Answer 14

• Made in Lipoxygenase pathway
• Powerful inducer of BRONCHOCONSTRICTION, INCREASED VASCULAR PERMEABILITY.
• Refered to as slow reacting substance of anaphylaxis (SRS-A)

Question 15

What are the 2 lipid mediators of mast cell Degranulation?

Answer 15

Prostaglandins & Leukotrienes

Question 16

What is the immediate response of Mast Cell Degranulation?

Answer 16

Vasoactive amines (Histamine and serotonin) and proteases.
- synthesis and secretions of lipid mediators (prostaglandins and Leukotrienes made from arachidonic acid)

Question 17

What is the late–phase rxn of Mast cell Degranulation?

Answer 17

• Synthesis and secretion of cytokines and chemokine.

- Infiltration of Eosinophils, monocytes and neutrophils.

Question 18

What do ITAM’s do?

Answer 18

Activate map kinase

Question 19

Map kinases are important in the formation of what?

Answer 19

Cytokines

Question 20

What are the most common signs of asthma?

Answer 20

coughing, wheezing, shortness of breath

Question 21

What causes the narrowing of airways with asthma?

Answer 21

Inflamed muscle wall.

Question 22

Treatment strategies for asthma?

Answer 22

• inhaled Corticosteroids (dampen inflammatory response)
• Leukotriene modifiers (block chain of reaction)
• Chromolyn =inhaled; prevents mast cell degranulation
• Theophylline = opens airways.

Question 23

Treatment strategies for asthma?

Answer 23

• inhaled Corticosteroids (dampen inflammatory response)
• inhaled long acting beta2 agonists = receive inflammation.
• Leukotriene modifiers (block chain of reaction)
• Chromolyn =inhaled; prevents mast cell degranulation
• Theophylline = opens airways.

Question 24

Intravenous antigen (gets into blood) causes what?

Answer 24

mast cell degranulation = systemic response = systemic anaphylaxis

Question 25

Low does inhalation of antigen leads to what?

Answer 25

Hay fever symptoms

Question 26

Low dose inhalation of antigen leads to what?

Answer 26

Hay fever symptoms

Question 27

Enzymes released from mast cells cause what?

Answer 27

Tissue damgage

Question 28

Cytokine & Lipid mediators released from mast cells cause what?

Answer 28

inflamation

Question 29

Cytokine & Lipid mediators released from mast cells cause what?

Answer 29

inflammation

Question 30

All clinical and pathological features of immediate hypersensitivity reactions are driven by ________.

Answer 30

Mediators produced by mast cells.

Question 31

The most severe from of immediate hypersensitivity is _____.

Answer 31

Anaphylaxis

Question 32

What 3 events occur as a result of mast cell activation?

Answer 32

1. mast cell degranulation 2. Synthesis and secretion of lipid mediators 3. Cytokine release

Question 33

What is Type II hypersensitivity?

Answer 33

Antibodies produced by the immune response that bind to antigens on our own cell surfaces. - primarily IgG and IgM isotypes. - Host Ab binds to foreign Antigen on cell surfaces or binds self antigen.

Question 34

Type II hypersensivity can activate complement resulting in _________.

Answer 34

Membrane attack complex formation.

Question 35

Type II hypersensivity can activate complement resulting in _________.

Answer 35

Membrane attack complex formation. | *Leads to destruction of cells, inflammation, or interfere with normal cellular function.

Question 36

What is the Target antigen, Mechanism of disease and clinical/pathological manifestations of Autoimmune hemolytic anemia?

Answer 36

Target antigen: Erythrocyte membrane proteins Mechanism of disease: opsonization and phagocytosis of erythrocytes. Clinical manifestations: Hemolysis, anemia

Question 37

What is the Target antigen, Mechanism of disease and clinical/pathological manifestations of Myasthenia

Answer 37

Target antigen: Acetylcholine receptor Mechanism of disease: Ab inhibits acetylcholine binding, down modulate receptors. Clinical manifestations: Muscle weakness, paralysis

Question 38

What is the Target antigen, Mechanism of disease and clinical/pathological manifestations of

Answer 38

Target antigen: Thyroid stimulating hormone receptor Mechanism of disease: Ab-mediated stimulation of TSH receptors Clinical manifestations: Hyperthyroidism

Question 39

Type II Hypersensitivity is also known as _____.

Answer 39

Cytotoxic Hypersensitivity

Question 40

What happens in Hemolytic disease of the Newborn?

Answer 40

Maternal Ab's target fetal RBC's for destruction.

Question 41

Type II Hypersensitivity is also known as _____.

Answer 41

Cytotoxic Hypersensitivity - Hemolytic newborn - hemolytic anemia - Blood transaction reaction - Graves disease - Myasthenia gravis

Question 42

What happens in Blood transfusion reactions?

Answer 42

Hose anti-blood group Ab's target transfused RBC's fro destruction

Question 43

What happens in Myasthenia Gravis?

Answer 43

At receptor Ab's bind to block the Ach receptor

Question 44

What happens in Graves Disease?

Answer 44

TSH receptor Ab's stimulate TSH Receptor to over produce TSH.

Question 45

What happens in Hemolytic anemia?

Answer 45

Auto-Ab's are produced against self antigens on the surface of RBC's. This triggers rapid destruction of RBC's, leading to anemia.

Question 46

Tx of Hemolytic anemia?

Answer 46

Prednisone or blood transfusion

Question 47

Tx of Newborn Hemolytic disease?

Answer 47

anti-Rh Ab

Question 48

Tx of Graves Disease?

Answer 48

radioactive iodine, anti-thyroid drugs or thyroid removal.

Question 49

Tx of Myasthenia Gravis?

Answer 49

Cholinesterase inhibitors and corticosteroids

Question 50

Summarize Type II....

Answer 50

Host Ab binds foreign Ag on cell surfaces or binds self Ag. | *IgG

Question 51

What is Type III Hypersensitivity?

Answer 51

Ag-Ab complexes clump and despot in blood vessels or tissues attracting an acute inflammation response.

Question 52

What happens to larger aggregates in Type III?

Answer 52

they fix complements and are cleared from circulation by phagocytes.

Question 53

What do small complexes in Type III do?

Answer 53

deposit in vessels or tissue.

Question 54

What are examples of Type III?

Answer 54

Systemic lupus, Arthus reaction, serum sickness, lupus nephritis and rheumatoid arthritis.

Question 55

Type III occurs within ______ after exposure to antigen.

Answer 55

3-10 hours

Question 56

In Type III, immune complexes trigger inflammation via 3 mechanisms, what are they?

Answer 56

1. Mast cell activation 2. Macrophage release TNF-Alpha and IL-1 that induce inflammatory cascade. 3. C3a, C4a and C5a

Question 57

The Arthus rx (type III) is triggered in the ____ by _____.

Answer 57

Skin by IgG

Question 58

What are the symptoms of Arthus?

Answer 58

Swelling, induration, severe pain, edema, hemorrhage, (gangrene in extreme cases)

Question 59

Tx of arthus?

Answer 59

anti-inflammatory agents

Question 60

Serum sickness is example of ________.

Answer 60

transient systemic immune complex-mediated syndrome.

Question 61

What causes serum sickness?

Answer 61

Injection of a foreign protein or proteins which leads to antibody response.

Question 62

Symptoms of serum sickness?

Answer 62

Fever, chills, rash, nephritis, lymphadenopathy.

Question 63

_____ is self limiting and follows kinetics of secondary Ab response.

Answer 63

Serum sickness (Type III)

Question 64

Most severe Type III hypersensitivity disease?

Answer 64

SLE = IgG Ab against ubiquitous self antigen in all nucleated cells. Damage can lead to death.

Question 65

Type III summary?

Answer 65

Ag-Ab complexes clump and aggregate in or near blood vessels attracting an acute inflammatory reaction. - Primarily IgG (possibly IgM or IgE) - Immune complex - Ex. arthus, serum sickness & SLE

Question 66

Tx of lupus?

Answer 66

avoidance or anti-inflammatory agents

Question 67

Tx of serum sickness?

Answer 67

don't get shots. (avoid anti-venom, antihistamines, corticosteroids)

Question 68

Tx of Arthus?

Answer 68

avoidance or anti-inflammatory agents

Question 69

Tx of lupus?

Answer 69

NSAID, corticosteroids, immunosuppressive agents.

Question 70

What is Type IV hypersensitivity?

Answer 70

Its a cell mediated reaction, mediated by Ag specific T cells which induce macrophage infiltration in a sensitized individual. * DTH response to injected ir absorbed Ab * 2-3 days - Ex. TB test, contact dermatitis, chronic asthma, crohn's disease.

Question 71

Type IV is generally initiated by ____>

Answer 71

Happens (small molecules that must become bound to a larger carrier molecule in order illicit an immune response.

Question 72

Tb test is example of _______.

Answer 72

Type IV