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66 Cards in this Set
- Front
- Back
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T/F epithelial barriers, phagocytes, complement and NK cells are ALL included in the Innate Immunity Responses to Pathogens
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T
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When is innate immunity most effective?
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During the first few hours (12 hours) then adaptive immunity kicks in
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What cells are included in the innate immune response?
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Eosinophils
Neutrophils Macrophages Dendritic Cells Natural Killer (NK) cells |
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Name the innate immunity cell:
Minor cell type comprises 1-5% of total leukocytes in human blood They are a type of granulocyte, and play a prominent role in responses to parasitic infections (also involved in allergic reactions and asthma). |
Eosinophils
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How do eosinophils induce their function?
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by degranulating and releasing:
- eosinophil cationic protein - major basic protein - eosinophil peroxidase - reactive oxygen and reactive nitrogen intermediates. |
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T/F Dendritic cells are considered phagocytes?
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true, they engulf microbes, degrade them and are primarily responsible for phagocytosing and presenting peptide antigens to lymphocytes.
Thus they are generally referred to as professional APCs |
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T/F Dendritic cells are less predominant than neutrophils, monocytes, macrophages.
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true
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*What is the primary function of the dendritic cell?
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to stimulate the adaptive immune response - the bridge btwn them.
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Natural Killer Cells - what percentage of leukocytes is NK cells?
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5-15%
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What is the primary job of NK cells?
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to produce cytokines **(specifically IFNinterferon-gamma - that activates macrophages) for macrophages early in infection and to kill virally infected - int this case host cells - (or some tumor) cells.
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T/F NK cells are lymphocytes.
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true, but, they are not MHC restricted so they are part of the innate immune response
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What cytokine does NK produce to activate macrophages?
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interferon gamma (IFN - gamma)
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What leukocytes are the most prolific in the immune system?
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neutrophils and macrophages
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Neutrophils (PMN) comprise over ____% of circulating ______.
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95% of granulocytes
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What cell has a multi-lobed nucleus?
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neutrophil
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What within infection sites are neutrophils attracted to?
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sites of infection by multiple signals including bacterial products.
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What is the primary job of neutrophil?
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to kill microbes - granulocytes that also kill fungi/mycoses
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Neutrophils phagocytose and what is within them (cytoplasm) to kill the microbes?
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Lysosomes (azurophillic primary granules) contain acid-hydrolases, myeloperoxidase and muramidase. Ingest bacteria are contained within vacuoles termed phagosomes.
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T/F neutrophils are similar to monocytes/macrophages.
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true
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What is a Macrophage called when it is in the blood?
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MONOcyte
Macrophages are in the tissue |
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What cell has a mononuclear horse-shaped nucleus?
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Monocytes and macrophages
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What are the 2 major functions of monocytes/macrophages?
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Professional Pahgocytes - to engulf particulate antigens and degrade microbes
APC - act as APC to take up, process, and present antigenic peptides to T cells (like dendritic cells) - activate adaptive response. |
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How do all these leukocytes know that the body is infected?
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general term - PRR - pattern recognition receptors
TLR - toll like receptors Can recognize: LPS, Murein, specific sugars on surface of microbes, proteins/lipids that have been damaged or unique to microbes |
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Once the leukocyte has been activated by a receptor what does it do?
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induced to phagocytose whatever it came into contact with.
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*T/F innate immune cells recognize body is infected by pathogen assoc. molecular patterns.
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True, ex: LPS, Murein, sugars, protein/lipids...
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Once the microbe is engulfed, what happens?
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Phagosome and lysosome (with enzymes) fuse = phagolysosome
- killing of microbes by lysosomal enzymes in phagolysosomes (possibly with ROS and NO) |
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What is the 3rd impt. function of Monocytes/Macrophages?
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Production of Cytokines and Chemokines - to let the rest of the immune system know what's going on.
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Is it a Cytokine or Chemokine?
Proteins prodcued by many different cell types that mediate inflammatory and immune reactions. ________ are principal mediators of communication between cells of the immune response. |
CYTOKINE
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Cytokine or Chemokine?
A large family of structurally homologous, low molecular weight _______ that stimulate leukocytes movement and regulate the migration of leukocytes form the blood to the tissues. |
Chemokines; subset of cytokines, work over longer distance
- chemoattracant - recruit additional cells to site of infection |
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T/F there are A LOT of chemokines.
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true
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There are ~30 cytokines, which ones do we need to know?
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TNF
IL-1 IL-12 Type I Interferon - IFN alpha, beta, and gamma |
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What are the previous mentioned cytokines impt for?
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Most impt. in the initial phases of the immune response.let body know that it IS infected and induce immune response at right time and in right place.
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TNFalpha and IL-1 are present when?
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At the initial time of infection
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What cytokine induces inflammation at the site of infection?
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TNF alpha and IL-1
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IL-12 is produced by macrophages..like all the others...and ultimately results in increased activation of what leukocyte?
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macrophages
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Does IL-12 induce activation of macrophages directly or indirectly; explain...
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initially uses NK to produce IFN gamma -> macrophage activation
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Why is IFN gamma is so impt that even the adaptive immune response days later will still be producing IFN gamma
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keeps macrophages active.
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How does inflammation begin in relation to cytokines?
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TNFalpha can cause epithelial cells to 'ball up" and become smaller, which leads to and
inc. blood supply = increased permeability, inc. delivery of proteins and leukocytes inc. permeability -> inc. tissue entry of proteins and leukocytes |
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An increase in migration leads to..
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inc. entry of leukocytes into tissue
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an increase in tissue activation leads to...
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interaction between leukocytes, endothelial cells, extracellular matrix components, cytokines, chemokines, hormones and antigen/pathogen
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The blood with leukocytes is flowing quickly past the infection site, so how is it going to get through the epithelial cells and to the infection site?
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the cytokines, produced by the macrophages are present on the surface of the epithelial cells and as the leukocytes roll by, they have a weak interaction and it slows them down and then have a stronger interaction leading to them squeezing between epithelial cells and arriving at the site of infection.
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How does the endothelial get the leukocyte to slow down and 'roll'? what cytokines are involved?
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chemokines produced by macrophages induce the epithelial cell to express: selectin (which attracts selectin ligand on surface of leukocyte).
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After the leukocytes as has a weak binding with selectin, what occurs next?
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now that it slows down it can have the opportunity to have a higher binding with it's integrin and the chemokine/receptor on the endothelial cell (shift from low to high affinity) and are clustered
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What happens once it has reached the high affinity binding state?
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the expression of integrin ligands on the endothelium are increased (as a result of TNF alpha and IL-1
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T/F After the endothelial cells have expressed more integrin ligand are they stable?
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YES they are stably adhered
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once stably adhered, where do the leukocytes go?
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they tranmigrate through the endothelium - chemokines act on the cell to draw the cell toward the site of infection.
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Some components of the innate immune response are common to all pathogens (no matter if site is sterile, or there is a microbe there): such as?
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Phagocytosis (or degranulation) to kill microbes (and to present antigen)
Cytokine production to induce inflammation and reactive endothelium |
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So, if there is a generic innate immune response for all pathogens, what about whether it is intracellular or extracellular pathogen? Does it change according to that?
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Yes, especially to viruses
Why? Because some PRR are on the surface of the cell and some are within the cell (on endosomal membrane) - which respond to microbes that have already been phagocytosed. |
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T/F The toll-like receptors regardless of whether they are on the surface of the cell or in the cytoplasm share a common signaling cascade.
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true, all of them recruit adapter proteins, activate protein kinases, and activate transcription factors.
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Because they have the same signaling cascade does it matter whether it is bacterial or viral pathogen?
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no, the TLR will always result in production of transcription factors that produce inflammatory cytokines.
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How is it that intracellular TLR are so helpful in combating viral infections.
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they are better at activating IRF3 and IRF7 which activate IFNalpha/beta = helps combat viral infections.
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What are the 2 diff. categories Interferon?
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Alpha and beta
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How many subtypes to IFN alpha vs. beta come in?
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alpha - 13
beta - 1 |
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What is interferon alpha primary produced by?
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monocyte and macrophages
- and dendritic |
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What is interferon beta produced by?
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virtually any cell infected with a virus - even endothelial cell
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What is the most potent stimulus for IFNs ?
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viral nucleic acids - as detected by pattern recognition receptors (PRR)
ex: dsRNA, ssRNA, unmethylated CpG DNA |
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So, once these intracellular TLR's are activated how does it stop Viruses from replicating?
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enzymes that interfere with transcription of viral RNA or DNA and viral replication
shares message with neighboring cells so it is difficult to spread. |
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What is 2',5' oligoadenylate synthetase and RNase?
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is produced (induced) by IFN and promotes viral RNA degradation
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What is dsRNA-activated serine/threonine protein kinase (PKR)?
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is produced (induced) by IFN and blocks viral transcriptional and translational events.
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Type 1 IFN is really the only good way to prevent spread and kill virus without killing host cell...but to completely ERADICATE the disease...what must occur?
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The immune system has no way of killing an intracellular pathogen without killing the infected host cell. Therefore, the immune system simply kills host cells infected with intracellular pathogens.
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How does the immune system kills it's own infected cells to eradicate the disease? What leukocytes are involved?
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Cytotoxic T Cells (of adaptive immune system) - kill the cell or help it undergo apoptosis - prevents viral replication and viral spread, but is damaging to the tissue and overall is best
NK cells (innate immune system) - also kills virally infected cells - also produce IFN gamma for macrophages |
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T/F In general, the innate immune system is very effective at reducing pathogen load early during an infectin.
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True
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What is the innate immune system NO really great at?
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to completely eradicatethe pathogens from the body. Moreover, the innate immune system has no way to prevent future infections.
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What is necessary to completely eradicate pathogens and to establish immunological memory to the pathogen?
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adaptive immune system.
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*What is the principle cell that links the innate immune response to the adaptive immune response (macrophanges can do this too)
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Dendritic Cells
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How do Dendritic Cells activate the adaptive immune response?
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Using processed microbes to present (APC) to antigen specific T-cells
Dendritic Cells are: - Cytokine producers Phagocytic Cells (but more specialized toward antigen presentation) |
