Lecture #10 Flashcards
Fc gamma RI
On macrophages, neutrophils, dendritic cells and eosinophils
Phagocytosis and activation
Fc gamma RIIA
On macrophages, neutrophils, eosinophils and platelets
Phagocytosis and degranulation
Fc gamma RIIB
On B cells
Negative feedback
Fc gamma RIIIA
On NKC
Activation
Fc epsilon RI
On mast cells, basophils and eosinophils
Degranulation
What is the time required for sensitization in allergic reactions?
14 days
In the activation of mast cells upon second exposure to an allergan how many receptors should be cativated?
At least 2
What are the first line of molecules secreted from mast cells upon activation?
Preformed granules with:
Histamine, heparin, serotonin, tryptase, chimase, carboxypeptidase
What are the second line of molecules secreted from mast cells upon activation?
PLA releases AA and activating COX, LOX:
PGD2, LTC4, LTD4, LTE4, PAF
What are the third line of molecules secreted from mast cells upon activation?
Activation of cytokine gene expression (2-4h)
IL3, IL4, IL5, IL6, TNFalpha
Upon allergan binding to an IgE on a mast cell intracellular _________ motif activates signal transduction pathway
ITAM
Explain the “late phase reaction” events during allergic reaction
Delayed secretion of IL5 from mast cells along with IL5 secretion from Th2 will activate eosinophils degranulation (occurs about 8h after the first phase reaction)
2 types of mast cells
Mucosal- react to inhaed or ingested allergan
Connective tissue- reat to skin or intravenous allergan
What are the main symptoms of anaphylactic shock?
- Increased HR
- Increased vascular permeability
- Hypotension and decreased tissue perfusion
- Broncospasm
- Respiratory or circulatory collapse
- Death
In which cases can anaphylactic shock occur?
- Intra venous allregan (animal toxin/ drug)
2. Quick absorbtion through the gut mucosa to the blood (peanut)
Atopy?
Genetic predesposition to high IgE levels (it doesnt mean that the person will have any allergic reaction in his life)
Atopic triad?
- Atopic eczema
- Hay fever
- Bronchial asthma
Often associated with food allergies
Properties of allergic asthma
- Multifactorial: genetic + environmental factors
2. Genetic hetrogenicity (many different alleles on different genes will have the same phentoypic appearance)
Hygenic theory
In endemic regions where the rate of microbial infections are high there was less allergic incidances.
The explanation is that microbial infections such as viral infection activate the cellular immunity hence activating Th1 which in turn inhibits Th2 by producing IFN gamma
Antibody mediated glomerulo nephritis can occur in 2 hyper sensitivity reactions explain
- Hypersensitivity type 2- due to autoreactive IgGs against the BM of glomeruli (linear deposits)
- Hypersensitivity type 3- Immune complex deposition along the BM (granular deposits)
What is the mechanism of tissue damage and IC deposition in type 3 hypersensitivity reactions?
IC formation
- Mast cell degranulation (Fc gamma RIIIB) release of vasoactive mediators and increase permeability
- Complement activation release of C3a C5a further causing mast cell degranulation and chemotaxis of neutrophils which by frustrated phagocytosis will release hydrolytic enzymes and ROS leading to tissue damage
- Platelet activation and release of vasoactive mediators
- deposition of immune complexes and platelets at the site of injury.
What are the 3 typesof type 4 hypesensitivity reaction?
- Th1 activation by soluble antigen - macrophages are activated by IFN gamma - release pro inflammatory cytokines and chemokines - recruit more lymphocytes and macrophages- granuloma formation
Ex: contact dermatitis, TB infection - Th2 activation by soluble antigen - IgE production - similarily to allergic reaction but chronic
Ex: chronic asthma, chronic rhinitis - CTL activation by cell associated antigen - cytotoxicity
Ex: contact dermatitis
The major difference between type 1, 2 and 4 hypersersenitivity reactions?
Type 1,2 are antibody mediated responses and type 4 is cell mediated
Poison Ivy type of hypersensitivity reaction, give another example
Type 4 causind contact dermatitis
NIckle induced contact dermatitis
The effects of activated Th1 (4)
- MCP1 secretion - macrophages chamotaxis
- TNF alpha TNF beta secretion - local tissue damage and expression of adhesion molecules on endothalial cells
- INF gamma secretion - macrophage activation which in turn release IL1 IL6 TNF alpha
- IL3 / GM-CSF secretion - monocyte production in the bone marrow
