MCB Lecture 60 & 61 Immune Related Injury Flashcards
Broadly, what is hypersensitivity?
Too much of an immune response, or an immune response directed at the wrong thing
Which are the types of hyper sensitivities that involve antibody?
1, 2 and 3
What are the 4 different types of hypersensitivity?
Type I: allergic reaction
Type II: antibodies forming against self
Type III: deposition of immune complexes
Type IV: persistence of antigen specific T cells
Describe the process of an allergic reaction
- Allergen diffuses across mucosa
- Th2 cells activated by the allergen
- Th2 stimulates B cells to undergo class switching
- IgG -> IgE
- Plasma cells produce and secrete IgE
- Mast cells bind IgE with FceR, and patrol for next allergen
- More allergen diffuses, and mast cells bind it
- Degranulation of mast cells
What are the features of allergens?
Small
Airborne
Soluble
Low dose
What are some common allergens?
Dust mites Cat dander Milk Peanuts Pollen Spores
Differentiate between the physiological and pathological reactions of type I hypersensitivity
Physiological: this response is directed against multicellular parasites in the gut
Pathological: response directed against non harmful things such as allergens
What are the two causes for susceptibility to Type I sensitivity?
Genetic
Environmental
When doing genome wide scans of individuals who have allergies, which genes are different?
FceR
Cytokines that activate Th2
ADAM-33: tissue remodelling
HLA
What is the connection between geographical location and allergy?
Developed countries have a high, and increasing rate of allergy
What are the hypotheses about environmental factors on allergy?
Hygiene hypothesis: lack of expose during childhood –> increased sensitivity
Counter regulation hypothesis:
Infection during childhood –> stimulation of Treg
Lack of exposure early on –> Treg less efficiently produced
Where does IgE bind?
Mast cells in tissues
Basophils in circulation
Where are mast cells located?
Tissues
Where are basophils located?
Circulation
List the steps when IgE binds to mast cells
- IgE binds and the mast cell patrols for any more of the mitogen in the tissue
- Antigen binds and cross links
3a. Preformed toxic granules are released
3b. Synthesis of lipid mediators, cytokines and chemokines - Released products activate the immune response
What are the two phases of the allergic reaction?
Acute phase and Late phase
When does the acute phase of the allergic reaction occur?
5-30 minutes
When does the late phase of the allergic reaction occur?
2 hours after, persisting for days
What are the mediators of the acute and late phases of the allergic reaction?
Acute: histamine
Late: leukotrienes, cytokines, chemokines
What are the features of the acute phase reaction?
Vasodilation: redness Vascular leakage: swelling Smooth muscle contraction Mucus production Local tissue damage
What are the features of the late phase reaction?
Bronchospasm
Leukocytosis
Epithelial damage
What are the four areas where the allergic reaction is felt?
Gastrointestinal tract
Airways
Blood vessels
Skin
Describe the airway specific features of the allergic reaction
Contraction of muscle in bronchioles
Cellular infiltrate
Increase in permeability of small vessels –> oedema
Breathing becomes difficult
Describe the gastrointestinal specific features of the allergic reaction
Expulsion (vomiting and diarrhoea) due to increased fluid secretion and peristalsis
Describe the skin specific features of the allergic reaction
Redness, itching, hives and puffiness due to vasodilation and increased vascular permeability
Describe the blood vessel specific features of the allergic reaction
Vasodilation and increased permeability –>
Oedema and increased lymph draining
What happens in the systemic allergic reaction?
Widespread mast cell degranulation
Anaphalactic shock due to widespread vasodilation
What are the symptoms of systemic mast cells degranulation?
Itching
Respiratory difficulty
Gastrointestinal expulsion
Describe broadly type II hypersensitivity
This is the binding of antibodies to self, causing damage
In type II hypersensitivity, what are the two mechanisms of cell injury?
a. Complement activation: phagocytosis or lysis of host cells
b. Inflammation: antibody and complement binding to cells, neutrophil activation
What are the steps of Type II ?
- Antibodies bind to host cells, tissue antigens
- Complement activation, inflammation
- Cell injury and Interruption of cell function
What is myasthenia gravis? What is it an example of?
This is an example of Type II
This is when there are antibodies for the Acetyl choline receptors in the motor end plates.
The receptors are removed (phagocytosed), and there is muscle weakness due to the lack of muscle innervation
What is Rhesus disease of the newborn? What is it an example of?
This is when the mother is Rhesus negative and the baby is Rhesus positive.
When the baby’s blood crosses into the mother, she forms antibodies to the antigen on the RBC.
The mother launches an adaptive immune response agains the RBCs of the baby
The baby dies
This is an example of Type II hpersensitivity
What is rheumatic heart disease?
What is it an example of?
Rheumatic heart disease is an example of molecular mimicry, Type II
- Streptococcus infection, leaving behind antigen
- Host makes antibodies for this bacterially derived antigen
- Antigen is similar to that found in myocytes in the heart
- Host antigen directed against the heart valves, myocardium and pericardium
How can Rhesus disease of the newborn be treated?
Anti-D gamma globin given to mother
This destroys the RBCs of the baby before the mother can launch an immune response against them
Briefly describe type III hypersensitivity
This is the inappropriate formation and deposition of immune complexes
What are immune complexes?
These are antigen + antibody complexes
Describe the normal formation of immune complexes
Normally:
- Antibody and C3b binds to the antigen forming a large complex in circulation
- RBC binds the complex by CR to C3b
- Circulates to liver and spleen
- Phagocytes bind the complex by CR and FcR
- Phagocytosis and clearance of the immune complex
When do immune complexes cause disease?
When they are not properly cleared and are deposited in the vasculature or in the organs
What can cause an excess of antigen?
- Persistent infection
- Autoimmunity: thing can’t be gotten rid of
- Constant exposure
What can cause deposition of immune complexes?
a. If the complexes are too small
b. in adequately cleared
How can Type III cause systemic disease?
The complexes are in the circulation and can be deposited in any organ to which the blood circulates
What are lesions of Type III?
Give examples
These are accumulation of immune complexes in organs
Glomerulonephritis
Arthritis
Vasculitis
What is an example of Type III systemic disease?
Systemic lupus Erythematosis
What is vasculitis?
What causes it?
Vasculitis is inflammation of the vasculature
It is caused by immune complex deposition in the vasculature in Type III
What causes System Lupus Erythromatosis?
Caused by failure to maintain tolerance
What is the manifestation of systemic lupus erythromatosis?
Widespread deposition of immune complexes in the organs of the body