ALLERGIES AND ANTI-HISTAMINES

Question 1

What is the definition of hypersensitivity?

Answer 1

Harmful immune response in which tissue damage is induced by exaggerated or inappropriate immune responses in a sensitized individual on re-exposure to the same antigen

Question 2

What is central tolerance and how is it related to negative selection?

Answer 2

• Central tolerance - a developing lymphocyte interacts with a self-antigen
• Negative selection - the process of eliminating any developing T or B lymphocytes that are reactive to self

Question 3

What is peripheral tolerance?

Answer 3

The removal of mature T cell that interacts with a self-antigen in peripheral tissues.

Question 4

What are the 4 types of hypersensitivity reactions?

Answer 4

1. Type I = IgE-mediated Hypersensitivity
2. Type II = IgG-Mediated Cytotoxic Hypersensitivity
3. Type III = Immune Complex-Mediated Hypersensitivity
4. Type IV = Cell-Mediated Hypersensitivity

Question 5

What is the meaning of immediate hypersensitivity reactions and what type of hypersensitivity reactions are included?

Answer 5

• Antibody-mediated
• Involves I,II, and III

Question 6

What antibodies are involved in Type I hypersensitivity reaction?

Answer 6

IgE

Question 7

Why are Type I hypersensitivity reactions rapid?

Answer 7

Because of the presence of performed mediators (histamine and vasoactive mediators) in the mast cells

Question 8

What happens during a Type I hypersensitivity reaction?

Answer 8

• On exposure to the antigen, TH₂ cells specific to the antigen are activated
• This stimulates B cells to produce IgE antibodies
• IgE antibodies bind strongly to the Fc portion of mast and basophils cells
• This stimulates the degranulation of granules of mast cells

Question 9

What are the three types of responses that result from activation of mast cells in type I hypersensitivity?

Answer 9

• Rapid degranulation (release of histamine and vasoactive mediators)
• Synthesis and secretion of lipid mediators
• Synthesis and secretion of cytokines

Question 10

What do histamines do?

Answer 10

Dilate the small blood vessels, this increases vascular permeability and stimulates the contraction of smooth muscles

Question 11

What does sensitisation mean? (in reference to cells)?

Answer 11

The mast cells have been coated with IgE antibodies

Question 12

What are some examples of Type I hypersensitivity reactions?

Answer 12

Allergic rhinitis, allergic asthma, atopic dermatitis, and systemic anaphylaxis

Question 13

Why are some people allergic to penicillin?

Answer 13

• The β lactam ring of penicillin can be produce covalent conjugates with proteins of the body creating new foreign epitope
• The TH₂ cells recognise this epitote as foreign and activate B cells producing IgE antibodies and mast cells are degranulated

Question 14

What drugs have been linked to Type II hypersensitivity and what can they cause?

Answer 14

• Penicillin, quinidine, and methyldopa
• haemolytic anaemia (destruction of red blood cells) thrombocytopenia (destruction of platelets)

Question 15

Which antibodies are involved in type II hypersensitivity?

Answer 15

IgG and IgM

Question 16

What happens during type II hypersensitivity?

Answer 16

• IgM and IgG antibodies bind to the surface antigen, these antigens are structural components of cell surfaces
  
  • Antigen–antibody reaction leads to complement activation or ADCC (opsonisation)

Question 17

What are some examples of antibody mediated - complement dependent reactions? (3)

Answer 17

Transfusion reactions, reactions to certain drugs and autoimmune haemolytic anaemia

Question 18

How are the drugs cromlyn and ketotifin used in treatment of type I and II hypersensitivity?

Answer 18

They prevent mast cell degranulation, preventing allergic cascade from happening

Question 19

Which antibodies are involved in type III hypersensitivity?

Answer 19

IgA, IgE, IgG and IgM

Question 20

What happens during type III hypersensitivity reaction?

Answer 20

• Accumulation of immune complexes (antibody-antigen complex),
  
  • immune complex isn’t removed by phagocytes
• Immune complexes are deposited on blood vessel walls and joints
• When IgG binds antigen, complement is activated
• C5a (attracts neutrophils) and C3b (potent opsonin) are generated
• This leads to phagocytosis and this leads to the release of enzymes and formation of oxygen radicals, resulting in tissue damage.

Question 21

How long does type IV hypersensitivity take to develop?

Answer 21

12 hours or more

Question 22

What happens during a Type IV hypersensitivity reaction?

Answer 22

• First encounter: antigen is present on the surface of antigen-presenting cells, this activates the production of the TH₁ cells.
• At this point the immune system is said to be sensitised
• Second contact with same antigen = sensitized TH₁ cells react with antigen release cytokines that activate macrophages or Tc which can cause cellular damage

Question 23

Mycobacterium Tb can induce which type of hypersensitivity?

Answer 23

Type IV

Question 24

Which type of hypersensitivity does herpes simplex virus cause?

Answer 24

Type IV

Question 25

All four of histamine receptors subtypes are ligand gated ion channels. True or false?

Answer 25

False - GPC receptors

Question 26

Only H1 and H4 are of clinical interest. True or false?

Answer 26

False - H1 and H2

Question 27

What are the histamine physiological effects that are mediated by H1 receptors? (5)

Answer 27

1. Contraction of bronchial smooth muscle 2. Contraction of intestinal smooth muscle 3. Stimulation of sensory nerve endings 4. Enhancement of Ca2+ influx into cardiac myocytes leading to minor increases in force of contraction and rate of contraction 5. Increased production of nasal mucus

Question 28

What effect does activation of H2 receptors have?

Answer 28

Signals for the stomach to make acid

Question 29

What are glucocorticoids?

Answer 29

Steroids synthesised in the adrenal cortex

Question 30

What are the cytokines that are inhibited by glucorticoids?

Answer 30

IL1 to IL6 and IL8

Question 31

Glucorticoids inhibit cell-mediated immunity. True or false?

Answer 31

True

Question 32

Inhibition of which cytokine by glucorticoids has the most crucial effect in immunosuppression?

Answer 32

IL2 - inhibits proliferation of Tcells and activation of cytotoxic T cells

Question 33

What is the definition of immunological tolerance?

Answer 33

Specific unresponsiveness to an antigen induced by exposure of lymphocytes to that antigen

Question 34

What is an auto-antibody?

Answer 34

* An antibody produced to attack the host's own cell or tissue components.

Question 35

What are the important stages in embryonic development (to prevent auto-immunity)? (2)

Answer 35

* Isolation/removal of auto-antigens from the immune system * Deletion of auto-reactive TH-cell clones during development

Question 36

What is Myasthenia gravis and what is it an example of?

Answer 36

Example of autoimmune diseas * The patient with this disease produces autoantibodies that bind the acetylcholine receptors * These antibodies block the normal binding of acetylcholine and also induce complement-mediated lysis of the cells (reduction in number) * Na can't enter cell = no muscle contraction

Question 37

How does maturity-onset diabetes relate to autoimmunity and how can it be treated?

Answer 37

* Auto-antibody binds to insulin receptor site, so insulin cannot bind * This can be treated with injections of insulin = insulin outcompetes auto-antibodies

Question 38

How does insulin-dependent diabetes mellitus relate to auto-immunity?

Answer 38

* Beta cells of pancreas producing insulin are targeted by cytotoxic T-cells * They are recognised as being infectious * So, insulin isn't produced and this leads to increased glucose levels in blood

Question 39

How does multiple sclerosis relate to auto-immunity?

Answer 39

* Antibodies target myelin and degrade it = no protective substance to facilitate transmission of signal * Problems in transmitting signals neurone to neurone * CNS doesn't function normally = painful