Hypersensitivity Flashcards
What is the definition of hypersensitivity?
Excessive, undesirable reactions produced by the normal immune system
Who made the 4 types of hypersensitivity classification?
Coombs-Gell
Which one is an immediate hypersensitivity?
1
Which one is a distinct/delayed hypersensitivity?
4
Which hypersensitivity is triggered by antibody molecules (humoral immune response)?
1,2,3
Which hypersensitivity is triggered by T cells (cell immune response)?
4
Which antibody is most in type 1 hypersensitivity?
IgE (allergic)
What is the process of hypersensitivity 1?
Antigen met -> make IgE (instead of IgG)
crosslinking antigen w/ receptor and mast cell
mast cell + basophil make histamines + leukotrienes
What are the 4 phases of hypersensitivity 1?
Sensitization phase -> activation phase -> effector phase -> late stage phase
What is atopy? What is it caused by? Which exposure do you feel symptoms? best example?
- Allergies
- caused by: family tendencies + genetic predisposition
- second exposure
- hay fever
How do allergens enter?
Skin, Ingestion, Injection + Inhalation
What is the sensitization stage?
1st time: inject guinea pig -> make IgE but no primary response
2nd time: inject guinea pig -> allergen cross link IgE on cell surface -> neutrophil -> anaphylaxis + vasodilation (low BP) + bronchoconstriction
What is activation stage?
- Allergen internalized by APC
- APC breaks it down –> presents it with MHC class 2
- this will then be recognized by T cell receptor
- clonal expansion + differentiation (make TH0 -> TH2)
- TH2 produce IL4,5,9,13
- These Cytokines makes IgM to IgE
- IgE will then bind to mast cell to Fc receptors
- the allergen bind to IgE through antigen binding site (2 Ab bound to 1 antigen must happen)
- binding= degranulation of mass cell
In activation stage- how many IgE should bind to an antigen molecule?
2
What is effector stage dependent on?
Method of allergy entry
Effector stage- what happens if it is in GI? lung? blood vessels?
If it enters GI… diarrhea + vomiting
If it enters lung… airway constriction + mucus hypersecretion + coughing + wheezing + phlegm
If it enters blood vessel… edema + > blood flow + > vascular permeability
What are preformed mediators + new molecules made in effector stage?
preformed: Histamine + eosinophilic chemotactic factors + IL8
new molecules: Leukotrienes + Prostaglandins + Platelet-activating factor
What is late stage?
24-48 hours later. (can last a few days)
Recruitment of eosinophils and neutrophils
How to stop anaphylaxis?
Epi-pen
What do these cytokines do in hypersensitivity 1: IL 4,5,6,13 + TNF
IL 4 + 13: Make TH2 cell + switching to make IgE
IL 5: Maturation, chemotaxis, activation + survival of eosinophil (prepare basophil for histamine + leukotriene release)
IL6: Mucus production
TNF: Pro-inflammatory cytokine= activate neutrophil + eosinophil + > monocyte chemotaxis
What is clinical aspect of allergies?
- Allergic rhinitis
- Asthma
- Atopic dermatitis
- Food allergies
How to detect allergies? Which way is qualitative and which is quantitative?
ELISA – checks IgE (quantitative)
SKIN PRICK TEST- wheal + flare reaction (arm or back) -> prick individual with all different allergens -> then you see erythema + edema (qualitative)
What is the 4 ways to help to type 1 hypersensitivity?
Desensitization: instead of making IgE we teach it to make IgG -> you do this by therapy by small doses of allergen -> not 100% effective (should be controlled)
Monoclonal antibodies IgE (so we make an Ab to stop IgE so no cross linking occurs)
Bronchodilators
Avoid allergens
What is the hygiene hypothesis?
- The dirtier you are -> the less allergies you get
* You are exposed CONSTANTLY -> so you teach immune system to not react at everything
What is Th1 vs Th2 balance in type 1 hypersensitivity?
> Th2
What is type 2 hypersensitivity antibody?
IgG (can cross placenta)
What is type 2 example?
hemolytic disease of newborn
What is type 2 mechanism?
o Antibodies bind to self antigen on cell membrane
o This activates cascade (classical)
o Cell undergoes lysis
o Opsonization occurs by macrophage + C3b
o This leads to severe damage
What is type 2 transfusion reaction?
Type O blood has anti a and anti B
If a type O is transfused with type A blood
IgM in blood of type O recognize donor blood -> activate complement -> lysis of RBC
What Rh incompatibility/ Erythroblastosis fitalis or hemolytic disease of the newborn?
If mother is Rh- + fetus is Rh+
At first birth mother will make Ab that is against Rh antigen -> make IgG
In second pregnancy -> IgG cross placenta
IgG coat fetal cell -> opsonize it.
Destoy fetus + new RBC + hemoglobin
What is cure for Rh incompatibility/ Erythroblastosis fitalis or hemolytic disease of the newborn?
Pregnancy: Inject mother with Anti-Rh Ab shortly before delivery (26-28 weeks)-> prevent sensitization (should be IgM)
After birth: give for 72 hours after delivery
Therapy: Rhogam -> makes IgM instead of IgG + bind to D antigen
What is ABO hemolytic disease of newborn? Is it as severe as Rh incompatibility?
Less severe than Rh incompatibility
Fetal RBCs express less ABO antigens compared to adult
ABO antigens are expressed on a variety of fetal cells reducing the chance of antibodies binding to antigens
What is type 3 hypersensitivity? is it systemic/localized? is it endogenous/ exogenous? At what time does the reaction start? What is the treatment? Which antibodies found here?
- Fc of antibody binds to phagocytic cells + RBC -> go to liver and get phagocytosed and destroyed
- is both systemic + localized
- both endogenous (SLE) + exogenous
- 3-8 hours after exposure (arthus reaction)
- anti-inflammatory agents
- IgG + IgM
Where is immune complex deposited in type 3? What do lesions contain?
kidneys, joint, skin + blood vessels
PMN (macrophage), deposits of immune complex and complement
What is the mechanism of hypersensitivity 3?
- Immune complex formed
- C3a + C5a made (classical pathway)
- > vascular permeability -> neutrophil come
- Autolysis of neutrophil -> lysosomal enzymes release -> damage to the glomerular basement membrane
- Immune complex activates complement cascade which activates basophils or mast cells
- Mast cell + basophil -> Histamine + leukotrienes made -> activate platelet
- vasoactomines released -> retraction of endothelial cells -> increase in permeability
- Immune complexes get deposited on sites such as kidney or joints
- Persistent inflammation
What is problem with hypersensitivity 3 in size and in Integrity of mononuclear phagocytic complex?
Size of complex
o If big = easily removed by phagocytes
o If small = bind less avidity
Integrity of mononuclear phagocytic complex= Overload
What is serum sickness? The process? The symptoms?
injection of foreign protein/ serum (Treatment of diphtheria and tetanus with antisera from horses)
Process: antibodies made for foreign Ig
Symptoms: Fever, pain in joint (arthralgia) + skin eruption
What is arthus reaction? due to? process?
- What: due to moldy hay -> respiratory distress
- Due to occupation.
- Process: IgG made against spores -> complex + inflammation in lung
What is activated in type 4 hypersensitivity/delayed type hypersensitivity ? how long is this hypersensitivity?
T cell + chemokine + cytokine
48-72 hours
What are the stages in type 4 hypersensitivity?
SENSITIZATION STAGE:
o Antigen enter -> recognized by T cell -> make TH1
ELICTION STAGE:
o TH17 + TH1 -> Pro-inflammatory cytokine made
o Recruit plasma cell + macrophage (non specific leukocytes)
What is contact dermatitis target organ? characterized by? example + symptoms?
- Target organ: skin
- Characterized by: eczema
- Example: Poison ivy dermatitis -> Urushiol penetrates the skin and form hapten-carrier conjugates -> Persists on the initial site of contact
- Symptom: Blister formation + Mononuclear infiltrates + Separation of epidermal cells
What is treatment for type 4 hypersensitivity?
Corticosteroids: topical or systemic
Why do we have type 4 hypersensitivity?
Protective:
• Intracellular bacteria which does not respond to antibody production
• They grow inside macrophages
• Presented in association with MHC II
• Activate Th1 cells -> IFN-gamma, TNF, MAF
• Activate macrophages
Damaging:
• Chronic infection (tuberculosis, leprosy)
• Bacteria are slow growing (several years)
• Following inhalation, alveolar macrophages get activated
• Ag is presented and Th1 cells are activated
• Recruitment of macrophages
• Bacteria is not efficiently cleared which leads to granuloma
• Damage to the lung
What is leprosy caused by? What are the 3 responses- normal, no response + hyper response?
- Caused by: Mycobacterium leprae
- If individual mounts normal response then there is a small lesion and infection is well controlled
- If individual fails to mount response: a lot of bacterial growth, blebs are full of bacteria and can be transmitted
- Hyper response: Hardly any bacteria BUT the response is so strong that there is damage to the nerve endings -> loss of fingers
