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59 Cards in this Set
- Front
- Back
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What are interleukins and where do they come from? Originally, where did people say they came from?
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Interleukins are chemokines and come from keratinocytes.
Originally thought to come from leukocytes. |
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What are chemokines?
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Proteins that recruit cells
A gradient of chemokines is established and cells move based on that gradient. This how cells get into the dermis and epidermis to get rid invading organisms. |
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What are interferons?
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Inhibit viral infections.
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What happens to the expression of edhesion molecules when their is a skin infection?
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Adhesion molecules are upregulated to let leukocytes come into the skin so they can eliminate infection.
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Describe the general immune response of the skin to an infection.
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1. Keratinocytes get stressed through signals from infection, etc.
2. Keratinocytes secrete cytokines. 3. Langerhan cells pick up the stress signals (the cytokine) 4. Langerhan cells then leave the skin and enter the lumphatic system to find the right T cells so that the T-cells can see the invading pathogen. 5. Correct T-cell then leaves the lymph node and enters circulatory system 6. T cell climb back into skin to get rid of infection. 7. Some T-cells become memory cells so that the next time that infection comes, the T cells will sense the inflammatory signals provided by keratinocytes and get recruited immediately into site of infection |
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Epidermis as a pro-inflammatory organ: What are the 3 phases that occur in epidermis when an infection occurs?
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1. initiation
2. Amplification 3. Resolution |
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Epidermis as pro-inflammatory organ: Describe the initiation and amplication phases?
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Purpose of this phase is to allow more cells (leukocytes) to come into the infected area.
1. The first wave of cytokins released (proinflammatory) feed back on those keratinocytes to get them to release a second wave of factors. 2. Proinflammatory cytokines act on capillary endothelial cells, making them leakier. 3. Caps become leaky and allo fluid and leukocytes to come into the dermal area. 4. Leukocytes will migrate in the epidermis via a chemokine. 5. Keratinocytes also expression aghesion molecules for leukocytes and upregulation of adhesion molecules allow leukocytes to crawl up between desmosomes to get rid of infection |
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Epidermis as pro-inflammatory organ: Describe the resolution phase.
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Once leukocytes have killed the infectious agent, you must down-regulate the immune response. Keratinocytes secrete IL-10, a cytokine that pits the immune system to "sleep"
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Give an example of an adhesion molecule and what occurs to its expression when stress is sensed.
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ICAM-1
It is expressed in the skin that has just received an EARLY (leukocytes not there yet) signal. ICAM expression is up-regulated |
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Hyperative immune system causes disease collectively known as __________.
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Contact dermititis.
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40% of all occupational disease are ________________.
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Skin diseases
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What is atopic dermatitis?
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Immediate hypersensitivity reaction. Mediated by a special antibody called IgE, which is an Ab that has seen an allergen. Dermis is filled with mast cells that sit next to vessels. Mast cells have FC receptors that are specific for IgE. IgE binds to mast cells which causes the immediate release of histamine, causing itching and edema.
Occurs within seconds to minutes |
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What is irritant contact dermatitis?
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Deals with a caustic agent irritation (over washing hands or spilling substance on skin). Yields an inflammatory response
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What is Allergic dermatitis?
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not mediated by Ab, but by T-cells. Not a quick response but a delayed response.
Exposed to antigen for a long time prior to reaction. Reaction is delayed because it takes time for T-cells to come into the area. |
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What are the two phases of Allergic contact dermatitis?
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1. induction phase
2. elicitation phase |
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What is the induction phase of allergic contact dermatitis?
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Deals with binding of allergen (haptens)
Proteins get modified by haptens and ultimately get taken up by langerhan cells. Langerhan cells leave the skin to active T cells in the lymph node. |
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What is the elicitation phase of allergic contact dermatitis?
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Depends on dose of exposure, make take a long time before T-cells in curculatory system so that the next time u get exposed to allergen the T-cells are in big numbers to develop an inflammatory response.
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Is there inflammation in the induction phase of allergic contact dermatitis?
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NO
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What are haptens? How can they act as antigens?
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Small lipid soluble molecules that must be covalently bound to endogenous proteins to generate an immune response.
Sometimes these biotransformed haptens will become reactive and bind to proteins in the skin. Some haptens absorb UV-light, become reactive species, and bind to proteins. These adducted proteins (protein + hapten) or proteins bound to metals like Ni, have a different conformation and act as the antigen. Dendritic cells will pick up these antigens and present pieces of the protein with the hapten on it to T cells |
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Are haptens immunogenic?
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No
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How are haptens bound to proteins?
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Done through biotransformation via enzymes found in skin that normally detoxify haptens.
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If haptens become reactive, what happens during the immune response?
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Haptens percolate in and bind to proteins in the skin. Langerhan cells pick the adducted proteins up. There is no inflammation associated with this first phase so you never know that this is happening.
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What is the INTERESTING function of langerhan cells?
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Langerhan cells might have to tolerate the immune system so that the immune system does not attack modified proteins on the skin
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What are major histocompatability antigens (MHC) or human leukocyte antigens (HLA)?
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Langerhan cells pick up adducted proteins and process them into little pieces and present them onto special transplantation antigens -- MHC and HLA
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How many MHC classes are there?
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2 classes
Type 1 and Type 2 |
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Describe Class 1 MHC.
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They are found on ALL cells and are not specific to antigen specific cells.
It is an important flag that tells the immune system that "Im infected" |
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Describe the events that occur when the immune system realizes you are infected due to the display of MHC.
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A T cell (CD8t) that has been educatedx will come by and recognize the infected cell and kill it.
CD8t cell will turn into the cytotoxic T lymphocytes and will go back into the skin and kill off pathogens. In the deased state, the CD8t cells come in and kill of the hapten modified cells, which causes a large inflammatory response. |
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What is considered a diseased state? Why is it called this?
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In the deased state, the CD8t cells come in and kill of the hapten modified cells, which causes a large inflammatory response.
Called the diseased state because you will not die if your cells are modified with hapten, but the CD8t cells kills the hapten modified cells anyway. CD8t cell comes under and inflammatory stimulus and they receive the chemokine/cytokine signal from the keratinocytes. Leave proinflammatory molecules and cause the capillaries to become leaky. Cytotoxic lymphocytes enter epidermis via adhesion molecules. CTLs start killing off keratinocytes. This is characteristic of the diseased state. |
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Describe Class II MHCs?
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These are not found on every cell. They are only present on antigen presenting cells.
Antigens are loaded in a special cleft on the MHC. The cleft picks up the peptides and presents them to T cell receptors in the lymph node. Langerhan cells look for the right T cells. With the righ co-stimulatory molecules (MHC + peptide piece), it will activate a T cell and the T cell will then develop based on the signals of the dendritic cell into either an effector cell or a down regulatory cell. |
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What is an effector cell?
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Cytotoxic cell
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What is a down-regulator cell?
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Cells important for shutting off responses.
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Blistering disease can be due to what two factors?
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1. genetics
2. development of autoimmunity |
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What is epidermolysis bullose simplex?
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Genetic
mutations in hemidesmosomal proteins. Defective protein components found intracellularly in the basal cells. Develop blisted that cleaves at the basal cell layer. |
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What is Junctional Epidermolysis bullosa?
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Genetic
Mutation against hemidesmosomes - mainly targets type 17 The blister that develops keeps the basal cell layer intact, and will pull away from the basement membrane. (Epidermis and dermis separate) |
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What is Dystrophic epidermolysis bullosa?
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Genetic
Targets collagen type 7 in basement membrane. Type 7 anchors the BM to the dermis. Blistering due to abrasion and eventually get fusion of the dermal-dermal areas because you dont have the outer epidermis to protect it. The epidermis compensates by producing a large stratuc corneum layer and it tries to mitten the hands so that you have less surface area. |
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What is Bullous Pemphigoid?
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Autoimmune
Ab against collagen type 17. To diagnose, take pt's sera and react it against a normal skin section. Goal is to determine where the patient's sera is reacting Basal layer splitting the basement membrane from the dermis. |
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What is Pemphigus?
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Autoimmune
Ab to desmosomes found in upper layers, esp spinsoum Will see the basal cell layer is fine but the spinosum cell layer is a mess |
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What is Epidermolysis Bullosa Acquista?
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Autoimmune
you acquire it antibodies against type 7 collagen |
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Sunlight has _________ energy wavelengths.
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high
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The most mutagenic UV rayes are_______ and they are filtered by the ozone so they do not bombard us.
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UV-C
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What wavelengths are longer and can cause sunburns due to its energy?
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UV-B
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How do we protect ourselves?
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We protect ourselves by up-regulating the amount of melanin that is made. But UV-B rays are absorbed by DNA, causing adducts like thymine dimers that can cause mutations when the cell tries to repair DNA.
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How does UV-A damage the skin?
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UV-A penetrates skin more deeply and is not absorbed by DNA. It makes reactive oxygen species, which can indirectly adduct and damage DNA. UV-A also induces inflammatory responses that can promote skin cancer.
Higher degree of UV-A exposure correlates with melanoma development. |
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Why do UV-A and UV-B down regulate the immune system?
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Important to keep the immune system calmed down since skin is always getting damaged by UV. Dont want your immune system to keep comind and finding those proteins that got damaged.
The downside of the down-regulation is that you can have activation of viruses, some of which may be oncogenic. |
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Photosensitivity can be caused by different states. Describe how lupus patients are affected.
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Lupus patients are very photosensitive and start developing immune responses to damaged skin proteins.
Some patients have mutations in heme biosynthesis. They accumulate a precursos for hemoglobin (porphoryns) that absorb UV-A and make toxic free radicals. |
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How is tetracyclin affected by UV light?
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Tetracycline is aactivated by UB light and made into a reative species.
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(T/F) Lighter skinned people have less problems with photosensitivity because more light passes through the epidermis.
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Falso. Light skinned people have more problems since more light passes through the epidermis.
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How does UV act as an oncogenic agent?
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UV induced skin cancer can promote cancer by thymine dimers, suppress the immune system, and activate oncogenic viruses in the skin.
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How can polyaromatic hydrocarbons be considered carcinogenic? Where are they found?
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Polyaromatic hydrocarbons are found in coal/tar/second hand smoke. Enzymes in our skin will try to combat these pollutants.
The PAH are not carcinogenic themselves; however, they get biotransformed by the p450 enzymes that then make it carcinogenic. |
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How can heat/wounds contribute to cancer?
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Heat/wound repair are not involved in oncogenic agents themselves. They provide a lot of factors for growth and repair that may allow outgrowth of mutated cell. During this outgrowth, the cell can get other mutagenic events that will then cause more mutation and become a tumor.
Called progression |
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What are the 3 phases of skin carcinogenesis?
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1. Initiation
2. Promotion 3. Progression |
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What happens during the initiation phase of skin carcinogenesis?
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Mutation caused by something that is oncogenic
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What happens during the promotion phase of skin carcinogenesis?
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Promotion is caused by would healing responses/damage repair. This can allow the outgrowht of this initiated mutated cell. You can either get an immune response to these cells and get rid of them or you can get so many other mutations that occur during the outgrowth that you finally hit another oncogene.
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What happens during the progression phase of skin carcinogenesis?
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You have an outgrowth called a papilloma that is a tumor or multiple genes damaged. Or the outgrowth can be invasive and then it is called a carcinoma.
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What is p53 known as?
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tumor suppressor
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What is histyocytosis X?
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langerhan cell type tumors
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What is squamous cell carcinoma?
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found in the stratum spinosum
invasive and aggresive |
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What is basal cell carcinoma?
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derived from basal cell layer. It is the least invasiv despits its natural ability to continuously replicate
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What are melanomas?
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They are highly metastatic and deadly. The fact that melanocytes have migrated from the neural crest cells may explain why they are so metastatic
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