203 L13 Flashcards
Hypersensitivity
When you first encounter an antigen that’s called a ——– immune response. The response is fairly —– and —-. — and —- —– lymphocytes are produced.
If you see that antigen again it’s called a ——– immune response. The – and — —– lymphocytes enable much —— and —— protection.
Usually the immune response is helpful but sometimes the ——– immune response can be harmful to the —– which is what kind of underlies the ——— reaction.
When you first encounter an antigen that’s called a primary immune response. The response is fairly weak and short. B and T memory lymphocytes are produced.
If you see that antigen again it’s called a secondary immune response. The T and B memory lymphocytes enable much faster and stronger protection.
Usually the immune response is helpful but sometimes the secondary immune response can be harmful to the host which is what kind of underlies the hypersensitivity reaction.
Are the symptoms immediate for Type 1 hypersensitivity reaction or type 2?
Type 1
An allergic reaction is like an overzealous ——- response to a normally innocuous ——- called ——–.
——– are involved in these reactions
In individuals that have a predisposition to having —– they have this abnormal response to an ——–. The individual becomes ———- as part of their ——– immune response. If they see that —— again they have a ——– immune response that gives rise to all of the features associated with the —— reaction.
An allergic reaction is like an overzealous immune response to a normally innocuous antigen called allergens.
Genes are involved in these reactions
In individuals that have a predisposition to having allergies they have this abnormal response to an allergen. The individual becomes sensitized as part of their primary immune response. If they see that allergen again they have a secondary immune response that gives rise to all of the features associated with the allergic reaction.
Activation of adaptive immune system
In response to a pathogen ——– cells ———– a microbe in a process called ————. The ——– cell changes different ——– molecules on its surface and becomes ———. They then ———- to areas of the body where there are ———. In addition to ——- the cells start to express more —- molecules on their surface to present a ——– from the degraded bacteria on their surface. They then come into contact with —– – cells (not activated) which have —– receptors on their surface. If these ——- receptors are activated they will ——- and drive the ——- immune system by activating different —- cells
This process is the same for when an allergen is presented instead of a pathogen
In response to a pathogen dendritic cells phagocytose a microbe in a process called macropinocytosis. The dendritic cell changes different adhesion molecules on its surface and becomes premigratory. They then migrate to areas of the body where there are lymphocytes (e.g. lymph node). In addition to migration the cells start to express more MHC (major histocompatibility complex) molecules on their surface to present a peptide from the degraded bacteria on their surface. They then come into contact with naive T cells (not activated) which have antigen receptors on their surface. If these antigen receptors are activated they will proliferate and drive the adaptive immune system by activating different T cells
Name the immune cell described below:
Multilobed nuclei
First responders to infection so have receptors on their surface that recognise microbes. When they detect the microbes they are activated. They can degranulate and release contents that kill microbes
Most abundant but short lived.
Phagocytosis
Neutrophils
Name the immune cell described below:
Called granulocytes together
Smaller
Contribute to the secondary immune response
Degranulation
Basophils and eosinophils
Name the immune cell described below:
In the circulation for a day
Phagocytosis and cytokine production
Differentiate into macrophages when they have migrated to the peripheral tissues
Monocytes
Name the immune cell described below:
Innate immune cells
Contribute to secondary immune response and hypersensitivity reactions
Produce cytokines (pro cytokines during acute inflammatory response)
Are plastic = can change their phenotype depending on their environment (e.g. pro inflammatory or anti inflammatory)
Antigen presenting cells (APC)
Macrophages
Name the immune cell described below:
B cell that makes antibodies
In type 1 hypersensitivity reaction they produce iGE antibody
Plasma cell
Name the immune cell described below:
Innate immune cell
Recognise autoantibodies (antibodies against their own self antigens)
Cover the surface of tissues during autoimmune disease
Target cells for destruction by releasing granules
Natural killer cells
Name the immune cell described below:
Primary and secondary response
Long lived
Degranulation and cytokine production
Mast cells
Name the immune cell described below:
Antigen presenting cells
Phagocytosis
Cytokine production
Bridge between innate and adaptive immune response
Dendritic cells
Name the immune cell described below:
Drive adaptive immune response
B and T cells
——— are the primary immune system ——- of type —, — and —- ——— reactions. They have —- heavy chains and — light chains, —– antigen binding sites and —– effector function controlling region.
They are split into —- domains;
—— —— domain referred to as —– regions. They have a highly ——– amino acid sequence which equips the —— with limitless ability to recognise different ——.
——— region referred to as the —- region. The —– —– sequence doesn’t change. this region engages with the —- system. This region can activate ———- as a response of binding to the microbe. There are —- receptors on the —– immune cells which can recognise this region and activate the immune cells.
Antibodies are the primary immune system mediators of type 1, 2 and 3 hypersensitivity reactions. They have 2 heavy chains and 2 light chains, 2 antigen binding sites and 1 effector function controlling region.
They are split into 2 domains;
Antigen binding domain referred to as Fab regions. They have a highly variable amino acid sequence which equips the antibodies with limitless ability to recognise different allergens.
constant region referred to as the Fc region. The amino acid sequence doesn’t change. this region engages with the immune system. This region can activate complement as a response of binding to the microbe. There are Fc receptors on the innnate immune cells which can recognise this region and activate the immune cells.
Heavy chain isotypes - differences in Fc regions
There are – different types of heavy chain isotypes.
Different isotypes of antibodies have different —– and are located in different —– compartments
Type 1 hypersensitivity reaction involves —–.
Type 2 and 3 hypersensitivity reactions involve —– and —-.
The —– receptors on the — cells are specific for each class of antibody.
The Fc —– receptor recognises IgE and the Fc —- receptor recognises IgG.
This means that the —- region engages with different parts of the —– system and drives different —– responses. Therefore you activate different parts of the —– system to eliminate the —– making it a better response.
There are 5 different types of heavy chain isotypes.
Different isotypes of antibodies have different functions and are located in different tissue compartments
Type 1 hypersensitivity reaction involves IgE.
Type 2 and 3 hypersensitivity reactions involve IgG and IgM.
The Fc receptors on the immune cells are specific for each class of antibody.
The Fc epsilon receptor recognises IgE and the Fc gamma receptor recognises IgG.
This means that the Fc region engages with different parts of the immune system and drives different immune responses. Therefore you activate different parts of the immune system to eliminate the allergen making it a better response.
Fc receptors
Decorate the surface of —– immune cells and enable the immune system to recognise when the —– is bound to an —–. It can then —— different parts of the immune system depending on the —– bound.
Decorate the surface of innate immune cells and enable the immune system to recognise when the antibody is bound to an antigen. It can then activate different parts of the immune system depending on the antibody bound.
Sensitization stage of Type 1 HS (early phase)
- —– breached tissue barrier
- ——– cells phagocytose the ——. The ——- cell changes different ——- molecules on its surface and becomes ———.
- They then —— to the ——— ——–.
- In addition to ——– the cells start to express more —– molecules on their surface to present a ———- from the degraded ——— on their surface. They then come into contact with —– – cells (not activated) which have — receptors on their surface. If these — receptors are activated they will differentiate into —- effector cells by the actions of —–. The —- effector cells help activate —– cells. Both the —- and — cells leave the — —-.
- The cells travel to where the allegen —– the body
- The —- cells produce cytokines, —–, —– and —– that instruct the —— cells to produce —–.
- —– can bind directly to the —- or to Fc —- receptors on —- cells. —— cells are ——– for the effector stage.
- Excess —– is taken up by the lymphatics
- —– encounters —- cell in the blood and binds to Fc ——- receptors to sensitise them
- —- encounters —- cells in other tissues and binds to Fc —- receptors to sensitise them.
- Allergen breached tissue barrier
- Dendritic cells phagocytose the allergen. The dendritic cell changes different adhesion molecules on its surface and becomes premigratory.
- They then migrate to the lymph nodes.
- In addition to migration the cells start to express more MHC molecules on their surface to present a peptide from the degraded allergen on their surface. They then come into contact with naive T cells (not activated) which have Fc receptors on their surface. If these Fc receptors are activated they will differentiate into Th2 effector cells by the actions of IL-4. The Th2 effector cells help activate B cells. Both the Th2 and B cells leave the lymph nodes.
- The cells travel to where the allegen entered the body
- The Th2 cells produce cytokines, IL-4, IL-5 and IL-13 that instruct the plasma cells to produce IgE.
- IgE can bind directly to the allergen or to Fc epsilon receptors on mast cells. Mast cells are sensitized for the effector stage.
- Excess IgE is taken up by the lymphatics
- IgE encounters basophil cells in the blood and binds to Fc epsilon receptors to sensitise them
- IgE encounters mast cells in other tissues and binds to Fc epsilon receptors to sensitise them.
Effector stage of type 1 HS - early phase
- Allergen enters tissue where the sensitised —- cells are present.
- Allergen binds —- molecules attached to the —- cells via Fc —- receptors.
3/4. —- cells —– and secrete ——-.
- Breakdown of —- cells releases —— mediators.
- Tissue specific symptoms of —– response
- The — cells can also produce —– which can act on the —— that is close by and change the expression of —– molecules on the surface.
- Allergen enters tissue where the sensitised mast cells are present.
- Allergen binds IgE molecules attached to the mast cells via Fc epsilon receptors.
3/4. Mast cells degranulate and secrete cytokines
- Breakdown of mast cells releases inflammatory mediators.
- Tissue specific symptoms of allergic response
- The mast cells can also produce cytokines which can act on the vasculature that is close by and change the expression of adhesion molecules on the surface.
Effector stage of type 1 HS - early phase
- Allergen enters tissue where the sensitised —- cells are present.
- Allergen binds —- molecules attached to the —- cells via Fc —- receptors.
3/4. —- cells —– and secrete ——-.
- Breakdown of —- cells releases —— mediators.
- Tissue specific symptoms of —– response
- The — cells can also produce —– which can act on the —— that is close by and change the expression of —– molecules on the surface.
- Allergen enters tissue where the sensitised mast cells are present.
- Allergen binds IgE molecules attached to the mast cells via Fc epsilon receptors.
3/4. Mast cells degranulate and secrete cytokines
- Breakdown of mast cells releases inflammatory mediators.
- Tissue specific symptoms of allergic response
- The mast cells can also produce cytokines which can act on the vasculature that is close by and change the expression of adhesion molecules on the surface.
Effector stage of type 1 HS - late phase reaction
- The change in ——– molecules on the vasculature surface can recruit ——.
2/3/4/. —– effector cells, activated — cells and —— produce —— that promote —— recruitment and activation.
- Cross linking of —– bound Fc receptors with —– results in the release of mediators from —– and —– that promote tissue damage.
- Recruited —- and —- also release mediators that can result in tissue damage.
- The change in adhesion molecules on the vasculature surface can recruit leukocytes.
2/3/4/. Th2 effector cells, activated mast cells and basophils produce cytokines that promote eosinophil recruitment and activation.
- Cross linking of Ig bound Fc receptors with allergens results in the release of mediators from basophils and eosinophils that promote tissue damage.
- Recruited macrophages and neutrophils also release mediators that can result in tissue damage.
Effector stage of type 1 HS - late phase reaction
- The change in ——– molecules on the vasculature surface can recruit ——.
2/3/4/. —– effector cells, activated — cells and —— produce —— that promote —— recruitment and activation.
- Cross linking of —– bound Fc receptors with —– results in the release of mediators from —– and —– that promote tissue damage.
- Recruited —- and —- also release mediators that can result in tissue damage.
- The change in adhesion molecules on the vasculature surface can recruit leukocytes.
2/3/4/. Th2 effector cells, activated mast cells and basophils produce cytokines that promote eosinophil recruitment and activation.
- Cross linking of Ig bound Fc receptors with allergens results in the release of mediators from basophils and eosinophils that promote tissue damage.
- Recruited macrophages and neutrophils also release mediators that can result in tissue damage.
what can happen if the late phase reaction of type 1 HS persists?
There is persistence of inflammatory mediators = chronic inflammation
What are the determinants favouring atopy (people who have allergic reactions)?
Genetic determinants (HLA genes, Th2 cytokine genes)
Environmental determinants
Triggering events
What are the determinants favouring atopy (people who have allergic reactions)?
Genetic determinants (HLA genes, Th2 cytokine genes)
Environmental determinants
Triggering events
What are the auto antibodies involved int HS type 2?
IgG and IgM
HS type 2 response
——— and ——- cells have Fc receptors that can recognise —–. This activates the cells which then activated ——–. This results in the production of —– which can decorate the cells that the autoantibody is attached to which eventually results in —— (pores). It can also result in the production of anaphylatoxins which can cause ——- immune cells to contribute to tissue destruction
The activated — cells can release granules, some of which can punch a whole in the target cell. The macrophages can phagocytose the cell
Macrophages and NK cells have Fc receptors that can recognise IgG. This activates the cells which then activated complement. This results in the production of C3b which can decorate the cells that the autoantibody is attached to which eventually results in MAC (pores). It can also result in the production of anaphylatoxins which can cause innate immune cells to contribute to tissue destruction
The activated NK cells can release granules, some of which can punch a whole in the target cell. The macrophages can phagocytose the cell
HS type 2 response
——— and ——- cells have Fc receptors that can recognise —–. This activates the cells which then activated ——–. This results in the production of —– which can decorate the cells that the autoantibody is attached to which eventually results in —— (pores). It can also result in the production of anaphylatoxins which can cause ——- immune cells to contribute to tissue destruction
The activated — cells can release granules, some of which can punch a whole in the target cell. The macrophages can phagocytose the cell
Macrophages and NK cells have Fc receptors that can recognise IgG. This activates the cells which then activated complement. This results in the production of C3b which can decorate the cells that the autoantibody is attached to which eventually results in MAC (pores). It can also result in the production of anaphylatoxins which can cause innate immune cells to contribute to tissue destruction
The activated NK cells can release granules, some of which can punch a whole in the target cell. The macrophages can phagocytose the cell
Determinants favouring atopy (people who have an allergic reaction)
Genetic - HLA genes - code MHC molecules, Th2 cytokine genes - IL-4, IL-5, IL-13
Environmental
Trigger events
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Therapy for Type I HS
Antihistamines - Bind histamine receptors on target organs
Lipoxygenase antagonists - Block production of leukotrienes from innate immune cell membranes
Bronchodilators - Block mast cell degranulation and promote smooth muscle relaxation
Corticosteroids- Inhibit cytokine production
Anti-IgE immunotherapy - Therapeutic mAbs that bind human IgE to reduce free IgE
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