Hypersensitivity Flashcards
What is hypersensitivity classify
It is an exagerrated and inappropriate immune response of tissue or body to an ag in a previously sensitized indivisual leading to gross tissue damage
Coomb and gels classification
Type 1- anaphylactic reaction ige mediated
Type 2 ab mediated cytotoxic hypersensitivity igm or igg
Type 3 immune complex mediated hypersensitivity
Type 4 delayed hyperensitivity
Cell mediated
On the basis of onset of action
Immediate type 123
Delayed type 4
On the basis of mechanism of action
Ab mediated type 123
Cell mediated type 4
Cells inv in hypersensitivity
Type 1
Mast cell basophil eosinophil
Type 2
Nk cell
Mq
Monocyte
Neutrophil
Eosinophil
Type 3
Neutrophil
Type 4
T cell
Explain type 1 hypersensitivity
It is also known as immediate hypersensitivity
ige mediated hypersensitivity Anaphylactic rxn
it is induced by certain types of antigens called allergen. type 1 hypersensitivity reaction also occurs through 2 phases: sensitivization phase
effector phase
both phases occur with an interval of 2 to 3 weeks
In the sensitivitization phase:
When an individual is exposed for the first time to the sensitizing or priming dose of an Antigen, the allergen is processed by the antigen presenting cells and the antigenic peptides are presented to the cd 4 helper tcells activated Tfh cells are differentiated into Th2 cells which in turn secretes IL4. IL4 induces the b cells to differentiate into ig producing plasma cells and memory cells. Secreted igE migrates to the target cells And coats on the surface of the mast cells and the basophils,
fc region of the ig binds to the high affinity fc receptors present on the mast cell surface
Such sensitized mast cells will be waiting for interaction with the subsequent antigenic challenge.
then we have the effector phase when the same allergen is introduced subsequently it directly encounters with the FAB region of the ige coated on mast cells. Ige cross linkage initiates degranuation.
allergens bound to ige triggers the mast cell and basophil activation and degranulation.
granules in turn release a number of pharmacologically active chemical mediators that lead to the various manifestations of type 1 reaction the memory B cells further differentiate into plasma cells and produce ige. granulation occurs in 2 phases primary mediators
secondary mediators
Phases of degranulation
Primary mediators:
histamine
Heparin
Serotonin
Eosinophil chemotactic factor A
Neutrophil chemotactic factor A
Proteases
Secondary
Paf
Prostaglandins
Leukotriens
Bradykinin
Cytokines IL 1 2 3 4 5 6 and
TNF a
Example of type 1 HR
Anaphylaxis
Atopic dermatitis
Asthma
Examples of type 2 HR
Transfusion reactions
Rh incompatibility
Hemolytic anaemia
Examples of type 3 HR
Arthus rxn
Serum sickness
Glomerulonephritis
Rheumatoid arthritis
Examples of type 4
Tuberculin test
Granuloma formation in tb leprosy
Contact dermatitis
What is atopy
It is an abnormal recurrent non-fatal local and ige
mediated response of an individual to common environmental antithaving a strong familial
Predisposition
Mechanism of type 2 HR
It is also known as cytotoxic hyperensensitivity.
It is an antibody mediated immune reaction
Reaction involves igg and igm antibody these are directed against cellular Antigen leading to cell damage.
igg and rarely igm interact with various types of Antigen such as
host cell surface Antigen
for example :rbc membrane ag
Ecm ag
After ag ab binding occurs the FC region of antibody initiate type 2 reactions by following 3 broad mechanisms
1. compliment dependent reactions
2.Antibody dependent cellular cytoxicity ADCC
3.antibody dependent cellular dysfunction ADCD
Adcc
IGG antibodies can coqt on the target cell by interacting with the surface Antigen through fab region.
the fc portion of igg in turn binds to fc receptor of various effector cells like
nk cells
Mq
Monocytes
Neutrophils
Adcc is involved in destruction of the target that are too large to be phagocitized for example parasites
tumours
graft rejection
although ADCC is typically mediated by igg but in certain instances igE are used for example eosinophil mediated killing of parasites
Type 3 HR
Also known as immune complex mediated hypersensitivity
It develops as a result of excess formation of immune complexes which initiate an inflammatory response through activated compliment system leading to tissue injury.
the immune complex stimulates the classical pathway of complement compliment by product C3A,C5A being anaphylatoxins ;induce localised mast cell degranulation with consequent increase in vascular permeability C3 a and C5A also act as chemo attractants and cause a recruitment of neutrophils to the site of immune complex deposition. Neutrophils release large number of lytic enzymes from secretory granules which causes extensive tissue damage
Types
Localised or arthus reaction
Systemic or serum sickness
Causes of type 3 HR
Following insect bites
During allergic desensitization treatment
In lungs following
Farmers lung
Cheese workers lung
Wood workers lung
Wheat millers lung
Mechanism of blood transfusion reaction
Type 2 adcc explain
Type 4 HR
Also known as delayed type of hypersitivity reaction.
it is a cell mediated hypersensitivity reaction
it occurs in 2 phases sensitization phase
effector phase
sensitization phase :
DTH response begins with an initial sensitization phase of 1 to 2 weeks after primary contact with Antigen
the Th cells are activated and clonally expanded by Antigen with class 2 MHC on APC.
langerhans cells and mq
Involve in activation of DTH response.
During sensitiization phase cd4 + tcells ,T helper 1 cell, and a few cd 8 + tcells have also been shown to induce dth response.
2.effector phase :
a subsequent exposure to an antigen inducing the effector phase.
Th1 secretes of variety of cytokines that activate microphages and other non-specific inflammatory cells at the site of delayed type of hyperensitivity reaction.
dth response occurs 24 hrs after second contact with Antigen and peaks 48 to 72 after second contact
Anaphylactoid reaction
This is similar to anaphylactic reaction clinically but are not ige mediated.
some drugs and iodinated contrast media directly induce the mast cells and basophils to release their mediators without involvement of igE.
