Immunology Chapter 12
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This "immediate hyper sensitivity is caused by generation of IgE that binds to Fc receptors on mast cells. Contact with allergen causes release of histamine and other inflammatory mediators. This is the "common" allergy.
This is caused by small molecules that attach to "self" proteins altering their structure and imparting "foreignness" that leads to IgG production and cell destruction through complement and antibody-induced phagocytosis.
"Immune complex disease" caused by generation of antibodies to relatively small soluble proteins. Aggregates (complexes) of allergen and antibodies deposit in various tissues, activating complement and causing local tissue damage.
"delayed type hypersensitivity" that is also caused by small molecules or proteins covalently attaching to and altering "self" proteins, however rather than being mediated by antibody, DTH reactions are dependent upon Th cells and occasionally CTL.
The prerequisite for developing Type I hypersensitivity is the development of an ____ response against the allergen.
Mast cells as well as basophils and eosinophils express ___ that specifically binds IgE essentially irreversibly.
1. Unlike most Fc receptors, FcεRI can bind antibody ___ to the antibody binding its specific target.
2. How does this affect these cells?
2. They give the cells a "borrowed" antigen specific receptor which to sense a specific antigen.
True or false, a Mast Cell may be coated with IgG of multiple specificities.
False: It is coated with IgE
Do allergic reactions happen upon first exposure?
No, a sensitization phase is needed
1. During an allergic reaction, some proteins leach out of mucous membranes and are taken up by what?
2. They are then presented to which interacts with what?
2. Th2 cells that interact with B cells
For the allergic response, Th2 cells interact with B cells to drive class switching to ___ that in turn binds to __ cells via FcεR1.
Upon exposure to pollen, mast cells may sense the presence of an allergen that becomes attached to FcεR1-bound IgE and causes what?
These express the FcεR1 Fc receptor that is composed of one alpha, one beta, and two gamma chains.
When an allergen binds to a mast cell, what happens?
It becomes activated
Unlike B cells, there is no proliferation and acquisition of effector function phase after contact of antigen through surface antibody. What does the mast cell initiate instead?
the immediate release of products stored in pre-formed granules
For mast cells, antibody (IgE) binds to this receptor prior to contact with antigen.
True or false: Not only can mast cells secrete preformed products, but can also make other products that are secreted hours later.
This is one of the most important mast cell products for inducing symptoms of type I hyper sensitivity and is found ready-made in mast cell granules.
Histamine is a decarboxylated form of the amino acids histadine. It can be sensed by cells through specialized ___ receptors.
1. Histamine released by mast cells may interact with H1 receptors on ____ as well as ___.
2. What does this trigger?
1. Vascular Endothelial Cells; Smooth Muscle
2. Increases in vascular permeability and smooth muscle contraction. Causes epithelial cells lining respiratory passages to produce more mucous.
1. This is a condition where by the body produces an excessive number of eosinophils.
2. What can this cause?
2. Damage to endocardium as well as nerve damage
These are mast cell products with properties similar to histamines and newly synthesized after activation.
What do Eicosanoids consist of?
Leukotrienes and prostaglandins
These are over 100 times more potent that histamine.
These lipid compounds are synthesized from cis-arachidonic acid and are released hours after mast cell actvation.
Eosinophils are present in connective tissues underlying respiratory, gastrointestinal and urogenital epithelium.
They are involved in which type of hypersensitivity?
These cytokines enhance eosinophil output by the bone marrow so they are only available in large numbers when needed.
True or false: Eosinophils do not express FcεRI unless activated by local inflammatory products secreted by other cells so they won't swing into action unless something is already going on.
These contain granular products similar but not identical to Mast cells.
They are fairly rare cells (<1% WBC) that are actually developmentally related to eosinophils.
Basophils are involved with which type of hypersensitivity?
What cytokines drive production in both Basophils and eosinophils?
IL-3, IL-5 and GM-CSF
1. Basophils are probably critical cells for initiating ___ responses.
2. They are unsurpassed in ability to produce __ and __ at the begining of an immune response.
2. IL-4; IL-13
1. Basophils may act locally or they may travel instead to __ __ organs.
2. What does this most effectively influence?
1. Secondary Lymphoid
2. Th2 polarization
What do the IL-4 and the IL-13 produced by the basophil do with regards to switching which subclasses?
IgE to IgG4 subclasses
Basophils express __ ligand which allows then to interact with CD40 expressing B cells.
1. What do 40% of the Caucasian population have a genetic predisposition to produce higher levels of what?
2. What is this called?
This type of hypersensitivity reaction has an early display and late phase independent of affected tissue.
1. The second phase of hypersensitivity I (6-8 hours later) results in a phase of swelling tissue. This is due to what?
2. What is the first immediate reaction due to?
1. Mast cell release of histamine
2. Synthesis of prostaglandins and leukotrienes
1. Normally, type I reactions are localized. What is a body wide type I reaction known as?
2. What happens during this?
1. Systemic anaphylaxis
2. Widespread activation of Mast cells leading to disseminated permeability of vasculature and constriction of smooth muscle.
Loss of blood volume causes a huge drop in blood pressure, shock, and organ failure.
1. People with known allergies often carry this to prevent shock. What does the syringe contain?
2. What does this do?
2. Stimulates re-formation of tight junctions in vascular permeability induced by histamine. This limits swelling and reduces airway constriction
What is the drug that prevents mast cell degranulation?
What can one do in order to desensitize themselves from an allergy?
Immunize oneself with allergen to induce IgG responses rather that amplifying IgE response. Therefore, mast cell is never triggered and type I no longer manifests.
1. This type of hypersensitivity is mediated by antibody IgM and IgG and induced by drugs that react with proteins on the surface of cells.
2. What is the target in this sensitivity?
3. What does this reaction result in?
1. Type II
2. RBCs or platelets
3. Hemolytic anemia or thrombocytopenia
1. This drug can induce type II response that forms a covalent bond with a serine residue on the enzyme transpeptidase.
2. What does this normally prevent in bacteria?
2. prevents cell wall formation
1. For type II reaction, RBCs can be tagged by ___.
2. How can the formed antibody destroy RBCs>?
1. complement 3b
2. By complement-mediated lysis or by tagging them for Fc-mediated phagocytosis by macrophages
Various people have different surface glycolipids on their blood cells.
1. What is known as the type A blood?
2. What is known as type B blood?
Genes for blood antigens are __ expressed
They can express, A, B, O , or AB antibody
This type of hypersensitivity reaction is known as Immune Complex Disease or Serum Sickness.
1. What is this mediated by?
2. What is the response mounted against?
1. IgG plus complement , but complememnt-activated mast cells may supply histamine that enhances inflammation.
2. soluble proteins, can cause deposits in various organs
What triggers type III hypersensitivity?
Large amounts of injected antibody
At first, in the type III hypersensitivity response, the small immune complexes don't fix complement and are rapidly cleared from circulation. What happens in the late immune response?
Medium sized complexes appear and do not fix complement and are not quickly cleared. Once they connect and grow, they fix complement but are deposited in small blood vessels.
Type III can be demonstrated via what reaction?
Arthus reaction, can form vessel ruptures called erythema
What Type III responses are not artificially induced?
Chronic viral hepatitis or bacterial endocarditis
1. This type of hypersensitivity is known as delayed type hypersensitivity or contact sensitivity. Symptoms appear 2-3 days after exposure.
2. What is this mediated by?
1. Type IV
2. Th cells (usually Th1) caused by agents of pathogens, to toxins, metals, and proteins found in food
1. This plant can trigger type IV response.
2. What does it contain that causes this?
1. Poison Ivy
2. Pentadecacatechol which reacts with covalent bonds rendering them foreign.
What does Pentadecacatechol do for type IV reactions?
DCs process this in context of class II MHC to CD4 T cells. It also modifies intracellular proteins and are presented to CTL upon re-exposure to PDC.
Th1-polarized T cells activate macrophages which produce pro-inflammatory factors while CTL can directly attack cells modified by CTL leading to destruction of cells. Causing, red, raised weeping lesions.
1. What is the genetic component associated with celiacs disease for type IV response?
2. What response occurs?
1. HLA-DQ phenotypes
2. Th1 cells respond to glutin peptides in context of HLA DQ2 and DQ8
Glutamine is acted upon by the enzyme transglutaminase and converted to glutamate. Glutamate is negatively charged and causes APC-processed peptide to interact with peptide binding groove of HLA-DQ and get presented to T cells.
1. What test for type IV response is used for tuberculosis?
2. What protein derivative from Mycobacterium tuberculosis reacts with this?
1. Mantoux test
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