hypersensitivity

Question 1

For the 4 types of hypersensitivity reactions, what is the:
* Immune reactant
* Antigen
* Effector mechanism
* An example

Answer 1

Question 2

what are type 2 hypersensitivity reactions a result from?

Answer 2

• they are a result of antibodies, usually IgG, binding to components of cell membranes or extracellular matrix ( can be self components of exogenous components)

Question 3

What occurs in good pastures syndrome?

What structures does it affect and not affect?

Answer 3

In Goodpasture’s syndrome, antibodies are generated against collagen IV in the basement membrane

This results in antibodies binding to this collagen, which will cause glomerulonephritis in the kidneys and potentially pulmonary haemorrhage in the lungs

Although collagen IV is also found in the ears, the antibodies cant reach this area, so cant induce type 2 hypersensitivity reactions

Question 4

what can haemolytic anemia be caused by?

Answer 4

penicillin

Question 5

What are 2 potential effects of penicillin?

Answer 5

1) Penicillin can bind to bacterial transpeptidase and inactivate it

2) Penicillin can modify proteins on the surface of human RBCs, leading to the creation of foreign proteins (antigens)

Question 6

Describe 7 the steps that lead to a type 2 hypersensitivity reaction from penicillin

Answer 6

1) The complement-coated penicillin modified RBC can be phagocytosed by macrophages using their complement receptors

2) The macrophages can present peptides form the penicillin protein and activate CD4 T cells to become TH2 cells

3) B cells are activated by antigens and from help of activated TH2 cells

4) Activated B cells can develop into plasma cells, which can produce penicillin specific IgG antibodies that recognise penicillin bound onto RBCs

5) The next time we give the patient penicillin, the antibodies made can recognise penicillin bound onto RBCs, bind onto it, and activate a complements cascade

6) This will either results in lysis of the RBCs or the IgG antibodies on the RBCs coated in penicillin will bind to Fc receptors on macrophages and cause the uptake of the RBC by the macrophage

7) This means the patient can get anaemia by either direct lysis of RBCs or by clearance of RBCs by macrophages

Question 7

What are type 3 hypersensitivity reactions caused by?

What are type 3 antibodies directed to?

Answer 7

• IgG

Type 3 antibodies are directed to soluble antigens in the blood, which is the key difference between type 2 and type 3 (type 2 antigens are membrane bound)

Question 8

where will the formation of antibody-antigen complexes be cleared?

what does excess immune complexes lead to?

Answer 8

• the formation of antibody - antigen complexes is a normal part of immune responses.
• usually cleared by reticuloendothelial system macrophages: macrophages, neutrophils in liver, spleen and bone marrow that ingest and degrade the immune complexes.

excess leads to pathology

Question 9

Describe the 3 steps in the normal process of antibody response fighting off pathogens

Answer 9

1) Early in the response, there is little antibodies and excess antigens
* We need time to expand B cell numbers to produce more antibodies
* Small immune complexes are formed than do not fix complement and are not cleared from circulation

2) At intermediate stages in the response, there are comparable amounts of antigens and antibodies
* Immune complexes are formed that can fix complement and are cleared from circulation

3) Late in the response, there are large amounts of antibody and little antigen
* Immune complexes of intermediate size are formed that can fix complement are cleared from cleared from circulation
* There are excess antibodies in the blood that can stay for months/years, which is why we might need a booster vaccine

Question 10

Describe the steps in a type 3 hypersensitivity reaction

Answer 10

Activation of complement in the wrong context releases inflammatory mediators, which also induces mast cell degranulation
Local inflammation, movement of fluid and protein into tissue, and blood vessel occlusion causes damage to local environment

Question 11

what are the 5 site of immune complex deposition

Answer 11

• glomeruli
• blood vessels walls
• synovial membranes
• skin
• systemic sites

Question 12

immune complex deposition in the glomeruli?

Answer 12

kidney, filtration process makes it very common site in immune complex deposition, damage driven by complement activation.

Question 13

immune deposition on the blood vessel walls?

Answer 13

immune complexes accumulate on veins and arteries, cause vasculitis, often seen as skin lesions if close to the surface.

Question 14

immune deposition in the synovial membranes?

Answer 14

rheumatoid arthritis, in which the IgG of the immune complexes can become an antigen itself, and IgM rheumatoid factor antibodies develop.

Question 15

immune deposition in the skin

Answer 15

common site for immune complex deposition, causing rashes

Question 16

immune deposition in the systemic sites

Answer 16

• in the case of systemic lupus erythematous, immune complexes deposit in the kidneys, joints and skin, vasculature, muscle and other organs.

Question 17

type 4 hypersensitivity is driven by what?

what are they caused by?

what does delayed refer too?

Answer 17

• cell mediated
• the complement does not play a role in type 4.
• most type 4 reactions are caused by CD4+ delayed type hypersensitivity reactions.
  ‘delayed’ refers to the reaction occurring 2 to 4 days after antigen exposure.
• macrophages that cause damage are not specific, harm infected and non-infected tissue.

Question 18

What are the 3 steps in delayed type hypersensitivity (DTH) reactions?

Answer 18

1) Antigen is introduced into subcutaneous tissue and processed by local antigen-presenting cells

2) A CD4+ TH1 effector cell recognises antigen and release cytokines which act on vascular endothelium

3) Recruitment of T cells, phagocytes, fluid, and protein to the site of antigen injection cause visible lesion

Question 19

What are 4 examples of microorganisms that can cause this?

How damaging is DTH?

What can DTH responses lead to?

What can be seen in long-term TB?

Answer 19

1) Listeria
2) Leishmania
3) M. tuberculosis
4) M. Leprae

DTH reactions can be prolonged and damaging

DTH responses can lead to walling off of infectious sites, which forms granulomas

Remnants of granulomas are tubercles seen in long-term TB

Question 20

What are contact sensitivities?

What 2 things can they be caused by?

Answer 20

Contact sensitivities are a special category of DTH reaction in which antigen is not an infectious agent, but a chemical that binds to cell surface.

They can be caused by heavy metal sensitivity or poison ivy, which is a reaction in the skin to catechols - causes severe skin blistering

Question 21

How are autoimmune diseases be classified?

How are autoimmune condition and hypersensitivity reactions be linked?

Answer 21

Autoimmune diseases can be classified in same way as hypersensitivity reactions

Reactions can be an autoimmune condition, but are also an example of a hypersensitivity reactions

Autoimmune disorders can be the same reactions that we see when fighting a pathogen, but they are misdirected at something in the body instead of the infectious agent

Question 22

5 Autoimmune diseases can be classified in same way as Hypersensitivity reactions: Type II

Answer 22

Question 23

3 Autoimmune diseases can be classified in same way as Hypersensitivity reactions: Type III

Answer 23

Question 24

3 Autoimmune diseases can be classified in same way as Hypersensitivity reactions: Type IV

Answer 24