Hypersensitivity

Question 1

What are hypersensitivities?

Answer 1

Maladaptive immune responses toward harmless foreign substances or self antigens that occur after tissue sensitisation:

• Immediate
• Delayed
• Autoimmunity

Question 2

Mechanism of allergies?

Answer 2

1. Exposure to allergen
2. APCs present processed allergen to Th cells
3. Th cells stimulate B cells to produce IgE antibodies
4. IgE interacts with mast cells
5. Upon subsequent exposure to the same allergen, IgE molecules on mast cells bind the antigen and stimulate the mast cell to release histamine and serotonin
6. These chemical mediators then recruit eosinophils which mediate allergic responses.

Question 3

What do Type I hypersensitivity reactions involve?

Answer 3

IgE antibody against soluble antigen, triggering mast cell degranulation.

Question 4

For susceptible individuals, describe the first exposure to an allergen in a Type I hypersensitivity reaction?

Answer 4

A first exposure to an allergen activates a strong TH2 cell response. APCs process allergen and present it to Th2 cells.

1. Th2 cells release cytokines interleukin (IL)-4 and IL-13 which activate B cells specific to the same allergen
2. This results in clonal proliferation, differentiation into plasma cells, and antibody-class switch from production of IgM to production of IgE.
3. IgE binds to mast cells by Fc regions mast cells
4. Mast cells are primed or a subsequent exposure and the individual is sensitised to the allergen.

Question 5

During subsequent exposures to allergens in Type I reactions, what happens?

Answer 5

1. Allergens bind to multiple IgE molecules on mast cells, cross-linking the IgE molecules.
2. This cross-linking of IgE activates the mast cells and triggers degranulation (histamine, serotonin and bradykinin)
3. The chemical mediators released by mast cells collectively causing allergy symptoms

Question 6

What is the effect of histamine?

Answer 6

• Mucus secretion in nasal passages
• Tear formation from lacrimal glands, promoting the runny nose and watery eyes of allergies.
• Itching and sneezing
• Smooth muscle contraction
• Increases vascular permeability

Etc etc

Question 7

Examples of localised type I hypersensitivity reactions?

Answer 7

Hay fever rhinitis, hives, asthma

Question 8

Examples of systemic type I hypersensitivity reactions?

Answer 8

anaphylaxis or anaphylactic shock.

Question 9

What are late-phase reactions in Type I hypersensitivities?

Answer 9

may develop 4–12 hours after the early phase

Question 10

What are late-phase reactions in type I mediated by?

Answer 10

eosinophils, neutrophils, and lymphocytes that have been recruited by chemotactic factors released from mast cells

Question 11

What does activation of eosinophils, neutrophils, and lymphocytes in late-phase type I reactions lead to?

Answer 11

Leads to the release of more chemical mediators that cause tissue damage and late-phase symptoms

Question 12

What are late-phase symptoms?

Answer 12

swelling and redness of the skin, coughing, wheezing, and nasal discharge.

Question 13

There is evidence that the IgE produced during type I hypersensitivity reactions is actually meant to counter what?

Answer 13

helminth infections

Question 14

Allergy-induced asthma:

a) Cause?
b) Signs and symptoms?

Answer 14

a) Inhalation of allergens

b) Constriction of bronchi, laboured breathing, coughing, chills, body aches

Question 15

Anaphylaxis:

a) Cause?
b) Signs and symptoms?

Answer 15

a) Systemic reaction to allergens

b) Hives, itching, swelling of tongue and throat, nausea, vomiting, low blood pressure, shock

Question 16

Hay fever:

a) Cause?
b) Signs and symptoms?

Answer 16

a) Inhalation of mould or pollen

b) Runny nose, watery eyes, sneezing

Question 17

Hives:

a) cause?
b) signs and symptoms?

Answer 17

Raised, bumpy skin rash with itching; bumps may converge into large raised areas

Question 18

Depending on the cytokines they synthesise and secrete, what can CD4+ helper T cells (Th) be divided into?

Answer 18

Type I helper T lymphocytes (Thl) and type II helper T cells (Th2).

Both derived from Th

Question 19

What are the most effective regulators of Th cell differentiation?

Answer 19

Cytokines

Question 20

Which cytokines are secreted by Th1?

Answer 20

IFN-γ，IL-2, IL-3, TNF-α, TNF-β

Question 21

Characteristic cytokine of Th1?

Answer 21

IFN-γ

Question 22

Which cytokines are secreted by Th2?

Answer 22

IL-4, IL-10, IL-5, IL-9, IL-13

Question 23

Characteristic cytokine of Th2?

Answer 23

IL-4

Question 24

Role of Th1 cells?

Answer 24

• Stimulate cellular immune response
• Participate in the inhibition of macrophage activation
• Stimulate B cells to produce IgM, IgG1

Question 25

Role of Th2 cells?

Answer 25

- Stimulates humoral immune response - Promotes B cell proliferation and induces antibody production (IL-4). - It can also induce the differentiation and proliferation of mast cells (IL-3, IL-4), and the differentiation and proliferation of eosinophilic leukocytes (IL-5).

Question 26

Effect of IL-4?

Answer 26

- Promotes B cell proliferation and induces antibody production - Induces differentiation and proliferation of mast cells

Question 27

Effect of IL-5?

Answer 27

differentiation and proliferation of eosinophilic leukocytes

Question 28

Under normal circumstances, describe the balance of Th1/Th2?

Answer 28

Are in a balanced state

Question 29

What happens once the Th1/Th2 balance is thrown off?

Answer 29

Diseases

Question 30

What can over expression of Th2 lead to?

Answer 30

inappropriate immune responses, leading to diseases such as allergies and asthma

Question 31

What can over expression of Th1 lead to?

Answer 31

autoimmune diseases such as rheumatoid arthritis and multiple sclerosis

Question 32

What does histamine (and other chemical mediators released by mast cells) recruit?

Answer 32

eosinophils, neutrophils, basophils and lymphocytes

Question 33

What do type II hypersensitivity reactions involve?

Answer 33

IgG and IgM antibodies directed against cellular antigens, leading to cell damage mediated by other immune system effectors.

Question 34

What are type II hypersensitivity reactions also known as?

Answer 34

cytotoxic hypersensitivities

Question 35

What are type II hypersensitivity reactions mediated by?

Answer 35

IgG and IgM

Question 36

In type II reactions, what i effect of antibodies binding to cell-surface antigens or matrix-associated antigens on basement membranes?

Answer 36

Either: 1) Activate complement, resulting in an inflammatory response and lysis of the targeted cells or 2) can be involved in antibody-dependent cell-mediated cytotoxicity (ADCC) with cytotoxic T cells.

Question 37

If the targeted antigen is a self-antigen in type II reactions, what is this known as?

Answer 37

autoimmune disease

Question 38

Antibodies may bind to naturally occurring, but exogenous, cell-surface molecules such as antigens associated with blood typing found on red blood cells (RBCs) in type II reactions. What does this lead to?

Answer 38

1) coating of the RBCs by antibodies 2) activation of the complement cascade 3) complement-mediated lysis of RBCs 4) opsonization of RBCs for phagocytosis

Question 39

What are 2 examples of type II hypersensitivity reactions involving RBCs?

Answer 39

1. haemolytic transfusion reaction (HTR) | 2) haemolytic disease of the newborn (HDN)

Question 40

What type of reactions are antibody-initiated responses against blood cells?

Answer 40

Type II

Question 41

What occurs during haemolytic transfusion reaction (HTR)?

Answer 41

IgG and IgM bind to antigens on transfused RBCs, targeting donor RBCs for destruction

Question 42

Signs and symptoms of haemolytic transfusion reaction (HTR)?

Answer 42

Fever, jaundice, hypotension, disseminated intravascular coagulation, possibly leading to kidney failure and death

Question 43

What occurs during haemolytic disease of the newborn (HDN)?

Answer 43

IgG from mother crosses the placenta, targeting the fetus’ RBCs for destruction

Question 44

Signs and symptoms of haemolytic disease of the newborn (HDN)?

Answer 44

Anaemia, oedema, enlarged liver or spleen, hydrops (fluid in body cavity), leading to death of newborn in severe cases

Question 45

What are the the four blood types based on?

Answer 45

the presence or absence of surface glycoproteins “A” and “B" (antigens)

Question 46

Describe the dominance of ABO blood types

Answer 46

The alleles for A and B blood types are codominant to each other, and both are dominant over blood type O.

Question 47

What antigens does a person with type AB blood express on the surface of RBCs?

Answer 47

Those with a genotype of AB have type AB blood and express both A and B glycoprotein antigens on the surface of their RBCs.

Question 48

What antigens does a person with type O blood express on the surface of RBCs?

Answer 48

lack A and B glycoproteins on the surface of their RBCs (none)

Question 49

Blood type A: a) what antibodies produced? b) What antigens on RBC?

Answer 49

a) Produces anti-B antibodies b) A antigen Can receive O and A blood

Question 50

Blood type B: a) what antibodies produced? b) What antigens on RBC?

Answer 50

a) produces anti-A antibodies b) B antigen Can receive O and B blood

Question 51

Blood type AB: a) what antibodies produced? b) What antigens on RBC?

Answer 51

a) no antibodies produced b) A and B antigens Can receive all blood types (universal recipient)

Question 52

Blood type O: a) what antibodies produced? b) What antigens on RBC?

Answer 52

a) Anti-A and Anti-B b) no antigens Can receive O

Question 53

What can a transfusion with an incompatible ABO blood type lead to?

Answer 53

a strong, potentially lethal type II hypersensitivity cytotoxic response called hemolytic transfusion reaction (HTR).

Question 54

Describe a hemolytic transfusion reaction (HTR)

Answer 54

If a person with type B blood receives a transfusion of type A blood, their anti-A antibodies will bind to and agglutinate the transfused RBCs. In addition, activation of the classical complement cascade will lead to a strong inflammatory response, and the complement membrane attack complex (MAC) will mediate massive hemolysis of the transfused RBCs. Leads to haemolytic anaemia.

Question 55

What are the second most frequently described RBC antigens?

Answer 55

Rh antigens Cells are classified as Rh+ or Rh-

Question 56

Which cells stimulate class switching from IgM to other antibody classes?

Answer 56

Th2 cells

Question 57

What type of reaction can Rh factor incompatibility between mother and fetus cause?

Answer 57

a type II hypersensitivity hemolytic reaction, referred to as hemolytic disease of the newborn (HDN)

Question 58

What are the only antibodies that can cross the placenta?

Answer 58

IgG

Question 59

Describe what happens during hemolytic disease of the newborn (HDN)

Answer 59

1. If an Rh− woman carries an Rh+ baby to term, the mother’s immune system can be exposed to Rh+ fetal red blood cells. 2. The Rh+ fetal RBCs will activate a primary adaptive immune response in the mother, and anti-Rh factor IgG antibodies will be produced and can cross placenta 3. In most cases, the first Rh+ baby is unaffected by these antibodies 4. If a subsequent pregnancy with an Rh+ fetus occurs, the mother’s second exposure to the Rh factor antigens causes a strong secondary antibody response that produces larger quantities of anti-Rh factor IgG. 5. These antibodies can cross the placenta from mother to fetus and cause HDN, a potentially lethal condition for the baby.

Question 60

Of what antibody class are anti-B and anti-A antibodies?

Answer 60

IgG or IgM

Question 61

What is an Fc region? What is an Fc receptor?

Answer 61

The tail region of an antibody that interacts with cell surface receptors called Fc receptors and some proteins of the complement system.

Question 62

Function of the Fc region?

Answer 62

This property allows antibodies to activate the immune system.

Question 63

Function of IFN-γ produced by Th1 cells?

Answer 63

Activates macrophages and DCs and thereby enhances their ability to kill intracellular microbes and to present antigens to T lymphocytes.

Question 64

What are the 3 major functions of antibodies?

Answer 64

1) Antibodies are secreted into the blood and mucosa, where they bind to and inactivate foreign substances such as pathogens and toxins (neutralisation). 2) Antibodies activate the complement system to destroy bacterial cells by lysis (punching holes in the cell wall). 3) Antibodies facilitate phagocytosis of foreign substances by phagocytic cells (opsonisation).