17-11-22 – Hypersensitivity Flashcards
Learning outcomes
- Describe the main features of type II, III and IV hypersensitivity reactions
- Describe the main sites if immune complex deposition in type III reactions
- To understand that many autoimmune diseases can be classified in the same way as hypersensitivity reactions
For the 4 types of hypersensitivity reactions, what is the:
* Immune reactant
* Antigen
* Effector mechanism
* An example
What are type 2 hypersensitivity reactions a result of?
What can cause type 2 hypersensitivity reactions?
What is an example of each cause?
- Type 2 hypersensitivity reactions are a result of antibodies, usually IgG, binding to components of cell membranes or extracellular matrix.
- Type 2 hypersensitivity reactions can be cause by self-components, or exogenous components (from outside the body)
- An example of a self-cause of type 2 hypersensitivity reactions is Goodpasture’s syndrome
- An example of an exogenous cause of type 2 hypersensitivity reactions is penicillin allergy
What occurs in good pastures syndrome?
What structures does it affect and not affect?
- 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
What are 2 potential effects of penicillin?
Describe 7 the steps that lead to a type 2 hypersensitivity reaction from penicillin
- 2 potential effects of penicillin:
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)
* If the 2nd occurs this can lead to type 2 hypersensitivity reactions occurring, which can lead to anaemia
- 7 Steps that lead to a type 2 hypersensitivity reaction from penicillin:
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
Penicillin mechanism extension
What are type 3 hypersensitivity reactions caused by?
What are type 3 antibodies directed to?
When are antibody-antigen complexes formed?
What are they usually cleared by?
What can excess concentrations of antibody-antigen complexes cause?
- Type 3 hypersensitivity reactions caused by antibodies, usually IgG, but also sometimes IgM
- 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)
- The formation of antibody-antigen complexes is a normal part of immune response.
- They are usually cleared by reticuloendothelial system (RES): macrophages, neutrophils in liver spleen and bone marrow that ingest and degrade immune complexes
- Excess immune antigen-antibody complex deposition in tissues leads to pathology
Describe the 3 steps in the normal process of antibody response fighting off pathogens
- 3 steps in the normal process of antibody response fighting off pathogens:
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
Describe the 4 steps in a type 3 hypersensitivity reaction
- 4 steps in a type 3 hypersensitivity reaction:
1) Locally injected antigen in immune individual with IgG antibody
2) Local immune-complex formation which can activate complement
3) Activation of complement in the wrong context releases inflammatory mediators, which also induces mast cell degranulation
4) Local inflammation, movement of fluid and protein into tissue, and blood vessel occlusion causes damage to local environment
Where are the sites of immune complex deposition in type 3 reactions?
What are 5 locations of immune complex disposition?
- Sites of immune complex (IC) deposition in type 3 reactions are not necessarily the sites from where the antigen is derived.
- 5 locations of immune complex disposition:
1) Glomeruli
* Most common location for deposition of immune complex
* Kidney filtration process makes it very common site in IC deposition, damage driven by complement activation
* Excess immune complexes get caught in the normal filtration of the kidney
2) Blood vessel walls
* IC accumulate on veins and arteries, causes vasculitis, often seen as skin lesions if close to surface
3) Synovial membranes
* Rheumatoid arthritis, in which the IgG of the immune complexes can become an antigen itself, and IgM Rheumatoid Factor antibodies develop.
4) Skin
* Common site for IC deposition, causes rashes.
5) Systemic sites
* In the case of Systemic Lupus Erythematosus (SLE) IC deposits in kidney, joints, skin, vasculature, muscle and other organs
How does Type 4 hypersensitivity differ from the other 3?
What doesn’t play a role in type 4 reactions?
What are most type 4 reactions caused by?
What do CD4+ TH1 helper cells have their activity driven by?
What tissue is affected by type 4 reactions?
- Unlike hypersensitivity reactions 1, 2, and 3, the type 4 reactions are entirely cell-mediated
- Complement does not play a role in type 4 reactions as there is very little involvement of antibodies to activated the complement cascade (driven almost exclusively by t cells)
- Most Type 4 reactions are caused by CD4+ TH1 helper cells (T cells) in delayed type hypersensitivity (DTH) reactions.
- ‘Delayed’ refers to reaction occurring 2 to 4 days after antigen exposure
- CD4+ TH1 helper cells have their activity driven by releasing cytokines that drives the activation of other cells
- Macrophages that cause damage in type 4 reactions are not specific, so there will be harm in infected and non-infected tissue (primary site and distant sites)
What are the 3 steps in delayed type hypersensitivity (DTH) reactions?
- 3 steps in delayed type hypersensitivity (DTH) reactions:
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
What are classic DTH (delayed type hypersensitivity) reactions driven by?
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?
- Classic DTH (delayed type hypersensitivity) reactions are driven by bacterial infections
- 4 examples of microorganisms that can cause this:
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 (classic of chronic inflammatory response)
- Remnants of granulomas are tubercles seen in long-term TB
What are contact sensitivities?
What 2 things can they be caused by?
- 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
How are autoimmune diseases be classified?
How are autoimmune condition and hypersensitivity reactions be linked?
- 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
5 Autoimmune diseases can be classified in same way as Hypersensitivity reactions: Type II
5 Autoimmune diseases can be classified in same way as Hypersensitivity reactions: Type II
3 Autoimmune diseases can be classified in same way as Hypersensitivity reactions: Type III
3 Autoimmune diseases can be classified in same way as Hypersensitivity reactions: Type III
3 Autoimmune diseases can be classified in same way as Hypersensitivity reactions: Type IV
3 Autoimmune diseases can be classified in same way as Hypersensitivity reactions: Type IV
