Immunology - Hypersensitivity Reactions
Hypersensitivity Reactions are 1234 ABCD ACID
- A A = allergic and Atopic
- C B = cytotoxic and antiBody
- I C = immune complexes (IgG and IgM) --> SLE
- D D = Delayed (contact Dermititis = poision ivy)
*Type 1 Hypersensitivity Reaction
- immediate IgE allergic reaction
- mostly IgE mediated
*Type 2 Hypersensitivity Reaction
- Cytotoxic IgM and IgG
*Type 3 Hypersensitivity Reaction
- Immune Complex
Henoch-Schonlein Purpura
- IgA complexes --> systemic vasculitis
- remember the "HENOCH PAAAPacy" = pope Henoch-Schonlein German pope fictional
"HENOCH PAAAPacy" = pope Henoch-Schonlein German pope fictional
- PAAAP = purpura
- A = IgA complexes cause vasculitis systemicall
- arthralgia = from the IgA complexes collecting in joints
- Abdominal pain = again from the IgA
Henoch-Schonlein Purpura case
Notes:
- note that HS purpura present with PAAAP as in this case
Case presentation:
Acute Serum Sickness = ASS Type reaction
- FAP symptoms = fever arthralgias, Pruritic rash
- 1-2 wks post Mabs or Abx or venom
ASS example
Case presentation:
Notes:
- note that ASS = acute serum sickness is a common way people who are allergic to certain medications or venom
--> happens 1 wk - 2wks after being given them - type 3 hypersensitivity reaction
- immune complexes of IgM and IgG and also complement cytokine = C3 get depositied in tissues and cause pruritic rashes and fever and
- FAP symptoms = fever arthralgias, Pruritic rash
- note that because you get these depositions int he issue of the Imune complexes and the C3, you have less c3 total circulating in the blood
*Type 4 Hypersensitivity Reaction
- delayed type --> t cells (CD8 mostly) and macrophages
- contact dermitidis = poison ivy
- reactive skin testing (tuberculin TB skin test)
- take 48 -72 hours
*Antigen skin testing (Tuberculin TB)
- Type 4 Hypersensitivity Reaction
- also candida injection for general CD8 testing
- 3 key cells respond to the antigen skin test
--> macrophages
--> CD4 T cells
--> CD8 T cells
*Poison ivy Dermatitis
- Type 4 Hypersensitivity Reaction
Clinical Cases
Posion Ivy Dermatitis
Notes:
- note that Poison Ivy Dermatitis is a type 4 hypersensitivity reaction
--> think that it usually takes a few days for poison ivy dermatitis to actually appear
Case presentation:
Clinical Case
Clinical Case
Notes:
- note that
Clinical Cases
Clinical Case
Clinical Case
Notes:
- note that
Allergic Reaction example
Notes:
- note that in an allergic reaction, the first exposure ever to the antigen has a class switch from IgM to IgE antibodies that bind to the specific antigen
- these IgE are now ready in B cells to be released if the antigen = allergen ever enters again
- second exposure --> these IgE antibodies bind to basophils and mast cells = granulocytes
--> cause them to release granules, cytokines, and interleukins
--> histamine, leukotrienes, proteases, prostaglandins, etc.
Clinical Case
Allergic Reaction example 2
Notes:
- note that the IgE that are produced for people who have allergies, these are not just free floating antibodies in the tissues or blood,
- they are mostly IgE antibodies that are surface bound to granulocytes like basophils and mast cells
- once the antgien or allergen enters the tissue it binds to IgE on these granulocytes and they release histamine, etc.
Clinical Case
3 phases of Type 1 rxns
- 1 = Prephase = sensitization tot he antigen
--> makes IgE antibodies that attach to mast cells and antibodies - 2 = Immediate inflammation phase = release of preformed IgE and tryptase
--> tryptase levels used for diagnosis - 3 = Delayed inflammation phase = infiltration and inflammation from the cytokines left over from the early phase of type 1 rxn
--> proteases cause most of delayed phase
2 = Immediate inflammation phase
- 2 = Immediate inflammation phase = release of preformed IgE and tryptase
--> tryptase levels used for diagnosis
3 = Delayed inflammation phase
- 3 = Delayed inflammation phase = infiltration and inflammation from the cytokines left over from the early phase of type 1 rxn
--> proteases cause most of delayed phase
Prephase = sensitization to the antigen
- makes IgE antibodies that attach to mast cells and antibodies
- 2 = Immediate inflammation phase = release of preformed histamine and tryptase
--> tryptase levels used for diagnosis - 3 = Delayed inflammation phase = infiltration and inflammation from the cytokines left over from the early phase of type 1 rxn
--> proteases cause most of delayed phase - depends on also the prephase granules that are present inside of mast cells and basophils
*Preformed Granules of mast cells and basophils
- depends on also the prephase granules that are present inside of mast cells and basophils
*IgE Fc attachment to mast cells and basophiles
- important for prephase of hypersensitivity type 1 rxns
- high affinity FcER IgE recetors are specific binders to the Fc portions of antibodies
Binding of the antigen to IgE on
- antigen IgE binding
--> on high affinity FcER IgE recetors are specific binders to the Fc portions of antibodies
Aggregation of the high affinity FcER IgE recetors
- agregation of multiple receptors to one antigen is what causes the release of granules from the mast cells and basophils
- this makes sense since the level of reaction response depends on the sensitization to the antigen and how much IgE you have made
- thus more exposure
--> more IgE bound to high affinity receptors
--> more high affinity IgE receptors can aggregate and release more granules
*Tuberculin skin testing (Tuberculin TB)
- Type 4 Hypersensitivity Reaction
- also candida injection for general CD8 testing
Clinical Cases
Clinical Case
Clinical Case
Notes:
- note that
*Candida Antigen skin testing
- note that virtually all people react to the candida antigen so this is used as a control
- only people who would not rect to it are SCID or other immunodeficient people
*DIRTY USMLE
Cmooth depostion = Good Pasture = 2 words = type 2 reaction
Cmooth depostion = Good Pasture
lump-I bumby-I depostiion = Immune Complex Depostin = ICD = 3 words = TYPE 3 reaction
ICD = PSG = lump-I bumby-I depostiion
*TB test = type 4 DELAYED reaction
- classic example of type 4 reaction
- since for a TB test you have to wait 48-72 hours for there to be a reaction
- this means it is type 4 reaction and Macrophages peak at day 3 after inflammation
--> hence type 4
--> TH1 activating = macrophages and CD8+ cells
