Hypersensitivity Types III-IV - Hunter

Question 1

Type III Hypersensitivity is mediated by what antibody?

Answer 1

IgG

Question 2

Type III Hypersensitivity causes what kind of diseases?

Answer 2

Immune complex diseases

Question 3

What organs are particularly sensitive to build up of immune complexes?

Answer 3

The kidneys

Question 4

Name 4 categories of mechanisms leading to immune complex diseases.

Answer 4

1. persistent infections involving microbial antigens
2. injected antigen such as drugs or biologics
3. inhaled antigens such as molds, spores and chemicals
4. autoimmunity involving self antigens and chronic diseases

Question 5

Do immune complexes form in most infections?

Answer 5

yes

Question 6

Are immune complexes usually removed?

Answer 6

Yes, via complement but the removal system can become overwhelmed.

Question 7

What are the main determinants of pathology in immune complex diseases?

Answer 7

Route and dose of antigen delivery.

Question 8

If given a high dose of intravenous antigen what happens?

Answer 8

Immune complexes form and they can:

1. it can deposit in small vasculature and cause vasculitis.
2. it can deposit in the renal glomeruli and cause nephritis.
3. it can deposit in the vasculature of joint spaces and cause arthritis.

Question 9

When immune complexes deposit what can happen?

Answer 9

They can lead to the fixing of complement and inflammation causing vascular and tissue damage.

Question 10

Small areas of vascular damage caused by immune complexes result in what?

Answer 10

Petichiae hemmorhages

Question 11

When large areas of petichiae come together to form large bloody areas this is called what?

Answer 11

purpura

Question 12

Subcutaneous routes of antigen delivery can lead to what?

Answer 12

Deposit of immune complexes in perivascular spaces leading to the arthrus reaction.

Question 13

Inhaled routes of antigen delivery can lead to what?

Answer 13

Deposit of immune complexes at the alveolar/capillary interface causing Farmer’s lung.

Question 14

Immune complexes are formed over time. Describe this process.

Answer 14

Early in infection when there is antigen excess, small complexes form that do not fix complement and are not readily cleared. These deposit in the vasculature. During mid-infection large complexes form, these fix complement and are cleared rapidly. Late in infection when there is antibody excess, intermediate complexes form that can fix complement. These are cleared.

Question 15

What do immune complexes bind to and how are they cleared?

Answer 15

After complement has caused C3b and C4b to adhere to the antigen, these can be recognized by CR1 receptor on RBC’s. The RBC and complex travel to the spleen and liver where they are removed via splenic macrophages or liver Kupffer cells. The immune complexes are destroyed and the RBC returns to circulation.

Question 16

Where is CR1 located?

Answer 16

CR1 is a receptor that recognizes C3b and C4b on immune complexes. It is located on the surface of RBC’s.

Question 17

What is the type of receptor that is located on splenic macrophages and Liver Kupffer cells that binds to immune complexes?

Answer 17

The Fc receptor.

Question 18

The system of immune complex clearing normally works well but can break down in what situations?

Answer 18

Complement deficiency, overwhelming infections with large amounts of antigen, and persistent infections leading to complement depletion.

Question 19

What influences where immune complexes will deposit?

Answer 19

Hemodynamic factors that favor deposition such as you would find in the renal glomerulus and also can happen in arteries in spots of bifurcation where the bifurcation has caused turbulence and the immune complex can get to the basement membrane of the vasculature. Also, immune complexes tend to deposit in small vasculature.

Question 20

Describe the steps of immune complex deposition and how it leads to immunopathology.

Answer 20

1. immune complexes form and travel throughout the body in the blood stream
2. if it reaches small vasculature and/or if the hemodynamic conditions are right it may deposit and begin to aggregate
3. the complexes are recognized as foreign and complement is triggered
4. anaphylatoxins are released and they trigger inflammatory processes
5. neutrophils show up but cannot phagocytose the big, imbedded aggregates and instead they release their granules
6. the result is tissue destruction

Question 21

If immune complexes cause tissue destruction in the kidney what will result?

Answer 21

Hematuria and proteinuria and possible scarring of the kidney.

Question 22

Name a persistent infection in which immune complexes can form and lead to kidney damage.

Answer 22

Chronic Hepatitis B.

Question 23

Can viral infections lead to immune complex deposition?

Answer 23

yes

Question 24

Local injection of antigen in idividuals with high levels of pre-existing antibodies can cause what?

Answer 24

An Arthus reaction.

Question 25

Describe the Arthus reaction.

Answer 25

1. locally injected antigen in individual with high levels of pre-existing antibodies to that antigen.
2. local immune complexes form.
3. the FcyRIII receptor on mast cells binds to the Fc region on the antibodies and releases its granules.
4. The degranulation leads to local inflammation, increased fluid and protein release, phagocytosis and blood vessel occlusion.

Question 26

Can mast cells be involved with both IgE and IgG mediated reactions?

Answer 26

Yes. Mast cells have both Fcepsilon receptor type I to bind to IgE and they have FcyRIII receptors that bind to IgG.

Question 27

Would IgE mediated reactions as in type I hypersensitivity reactions cause petichiael hemorrhages?

Answer 27

No

Question 28

What is extrinsic allergic alveolitis?

Answer 28

This is an immune complex disease. It is also called hypersensitivity pneumonitis and farmer’s lung. It result when small particles are breathed in and get into the alveoli. There they cause an IgG response where complexes are formed and are deposited. Inflammation is triggered via mast cells and one result if petichiael hemorrhage. If chronic it can lead to lung fibrosis.

Question 29

Type IV hypersensitivity reactions are mediated by what?

Answer 29

T-cells

Question 30

Name 3 types of Type IV hypersensitivity.

Answer 30

TH1 delayed type hypersensitivity, TH17 mediated reaction, and CD8 delayed type hypersensitivity.

Question 31

Describe the TH1 delayed type hypersensitivity.

Answer 31

1. An APC interacts with an antigen and releases IL-12.
2. IL-12 causes a deviation to TH1 differentiation.
3. The APC presents an antigen in MHCII and interacts with a CD4 TH1 cell.
4. the TH1 cell releases cytokines such as INF-y and TNF that further activate macrophages and lead to inflammation.

Question 32

Describe the TH17 mediated reaction.

Answer 32

1. An APC interacts with antigen and releases IL-23 and TGF-B.
2. the APC interacts with a TH17 cell which then releases cytokines such as IL-17 and IL-22.
3. This cytokine environment leads to recruitment and activation of neutrophils and to inflammation.

Question 33

What is the prototype of the delayed type hypersensitivity reaction?

Answer 33

The Tuburculin reaction.

Question 34

Describe the Tuburculin reaction.

Answer 34

1. antigen is injected into subcutaneous tissue and is processed by local APC’s like Langerhan’s or Dendritic cells.
2. A TH1 effector cell recognizes antigen and releases cytokines such as TNF-a that act on vascular epithelium.
3. The cytokines result in recruitment of phagocytes and plasma to the site of antigen injection and inflammatory processes occur.
4. this process takes time (24-72 hours) because the memory T-cells have to be activated and the process started.

Question 35

What is the hallmark of the DTH reaction.

Answer 35

The presence of infiltrate with mononuclear cells such as monocytes and macrophages.

Question 36

What is allergic contact dermatitis?

Answer 36

A DTH reaction involving CD4 or CD8 (rare) T cells.

Question 37

Describe the allergic contact dermatitis process.

Answer 37

1. small, highly reactive small molecules penetrate the skin and form a hapten/protein complex with a self protein.
2. Langerhan’s dendritic cells take up the complex and process it to happen/protein peptides that are then presented in MHCII molecules. You must have an MHCII that can recognize or bind to this peptide.
3. The dendritic cell migrates to a lymph node and interacts with T cells. Memory T cells are made.
4. Subsequent exposure activates these memory T cells and they release IFN-y and other mediators.
5. The IFN-y stimulates keratinocytes to release a variety of cytokines and chemokines that attract monocytes and macrophages and lead to inflammation.