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157 Cards in this Set
- Front
- Back
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Advancements that led to modern immunology |
Microscale filters, microscopes, and new assays to detect immune molecules and immune cell functions |
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Explain the difference between infection and disease |
In infection, pathogens have overcome initial innate defenses and have started to multiply. Disease is when the host begins to manifest symptoms of infection. |
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What are the two possible causes of disease? |
The pathogen or the immune response to the pathogen. |
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How does skin defend against pathogens? |
Dead skin is inhospitable to viruses and sheds to prevent the over colonization of bacteria and fungi. |
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What do defensins do? |
They form pores in the bacterial membrane. |
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What do cathelicidins do? |
They bind to LPS and destroy the microbial cell wall. |
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What do sebaceous glands do? |
They produce sebum, a waxy oil that contains antimicrobial fatty acids that trap microbes. |
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How do sweat glands protect against pathogens? |
They produce lactic acid to lower pH and lysozymes to cleave peptidoglycan linkages. |
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What are the three main mucosal surfaces of the body? |
Respiratory, gastrointestinal, and urogenital |
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Name 5 ways the mucosal system fights against infection. |
1) Mucus traps microbes 2) lysozymes and lactoferrin sequester iron from microbes 3) lactoperoxidases generate superoxide anions 4) panetg cells secrete defensins 5) cilia propel mucous down into digestive system |
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5 principles of immunology |
1) Discrimination 2) diversity 3) specificity 4) Rapidity 5) memory |
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What are the two main functions of the innate immune system and how are they different from the main function of the adaptive immune system? |
Provide immediate antimicrobial effect and inform the adaptive immune system. The innate is not pathogen specific. |
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What do innate immune cells recognize? |
Pathogen associated molecular patterns (PAMPs) |
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What are the four cardinal features of the immune response and what are their Latin roots? |
Pain, swelling, redness and heat (dolor, tumor, rubor and calor) |
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What are the two main characteristics of hematopoietic stem cells? |
Self-renewal and differentiation into progenitor cells |
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Common myeloid progenitor |
Erythrocytes, platelets and myeloblasts |
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Common lymphoid progenitors become... |
Natural killer cells and lymphocytes |
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What is the composition of cells in blood? |
Erythrocytes - 90%, Platelets - 9%, and white blood cells - <1% |
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What is the most common white blood cell in a healthy individual? |
Neutraphil - 60% |
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What does Haemaroxylin stain and what color does it stain? |
It stains nuclei and granules dark purple |
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What does eosin stain and what color does it stain? |
It stains proteins non-specifically to stain cytoplasm bright pink. |
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What are the three polymorph nuclear leukocytes? |
Neutrophils, eosinophils, and basophils (mast cells) |
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What are the PMN'S responsible for? |
Recognition and elimination of extracellular pathogens |
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What do the PMN cells look like after a H&E stain? |
Neutrophils - dark nucleus with light pink cytoplasm, eosinophils - bright pink cytoplasm, basophils - purple granulated cytoplasm. |
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What are the three types of receptors found on PMN? |
Scavanger, complement, and FC receptors |
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What do scavanger receptors recognize and why does this allow them to not recognize self? |
They recognize common polysaccharide or lipid structures on microbes not found in mammalian cells. |
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What do complement receptors bind? |
Complement proteins that have coated opsonized microbes. |
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What does Fc receptors bind? |
They bind antibodies to microbes to use as surrogate receptors. Can bind to microbe or cell first. |
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What is the most abundant WBC? |
Neutrophils |
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What are the three functions of a neutraphil? |
1) phagocytosis 2) produces anti-microbial products 3) form extracellular traps (NETs) |
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What are the steps of phagocytosis? |
1) engulfment and degradation of large foreign bodies by the cell to form phagosomes. 2) the phagosomes fuse with lysosomes to become phagolysosomes 3) the microbes are then enzymatically and chemically degraded and released intra and extracellularly. |
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What cells perform phagocytosis? |
Neutrophils, eosinophils, basophils and macrophages |
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What is pinocytosis? |
Engulfment of soluble debris via the formation of invaginations in the cell membrane that become vesicles. They may fuse with lysosomes. |
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What cells perform pinocytosis? |
Dendritic cells and macrophages |
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What is the process of neutrophil extracellular trapping of pathogens? |
1) When microbial structures are recognized, chromatin decondenses and the nuclear membrane dissolves. 2) Intracellular proteins fuse with the chromatin and is released from the cell. 3) This net ensnares the microorganism and kills it. |
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What 2 products do eosinophils produce and what are their functions? |
Cathepsins - proteases activated by a low pH, histamine - increases capillary permeability |
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What is an eosinophils main function? |
To degranualate which causes damage to microbial membranes and death. |
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What do eosinophils release during degranualation? |
Products that damage membranes, increase vascular permiability, and chemotaxis, the process of recruiting additional immune cells. |
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What is the lowest frequency granulocyte in the body? |
Basophil/mast cell |
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What sets apart mast cells from other granualocytes? |
Use mainly IgE Fc receptors to display antibodies on cell surface for recognition. Mainly responsible for allergies. |
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What is the main product of basophils? |
Histamine |
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What is the difference between monocytes and macrophages? |
Monocytes are found circulating in the blood and macrophages derive from them and are found in tissue. |
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How are macrophages stained using a H&E stain? |
Pink cytoplasm and single purple nuclei |
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The three main receptors for monocytes and macrophages |
Fc antibody, scavanger, and complement. They recognize opsonized material. |
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How do macrophages regulate inflammation and induce an adaptive immune response? |
They produce cytokines |
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How are dendritic cells stained with H&E stain? |
Pink cytoplasm and purple round nucleus |
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Are DC's Pino or phago? |
Pino |
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Are DC'S myeloid or lymphoid? |
Both |
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What are three specialized functions of DCs? |
T-cells development, antigen depots for t and b cells, tailoring immune responses to different types of pathogens |
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What are the presentation pathways for antigens of intra and extracellular microbes |
MHC1 to CD8 Cytotoxic t-cells and MHC 2 to CD4 helper t-cells |
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Name two other cell types that can present antigens to lymphocytes |
Macrophages and lymphocytes |
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What do NK cells look like in an H&E stain? |
Pink cytoplasm with purple granules and a round purple nucleus |
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What are the innate properties of NK cells? cells? cells? |
They can recognize and kill infected cells via degranulation. |
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What are the adaptive properties of the NK cells? |
Proliferate in response to microbes, express a limited amount of diversity version of adaptive immune receptors. |
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What two processes must lymphocytes undergo in order to have effector function? |
Proliferation and differentiation |
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Describe a receptor on a lymphocyte |
They are semi-unique, semi-random antigen receptors that undergo somatic rearrangement. |
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Describe the type of antigen that B-cells recognize. |
They recognize antigens in their native conformation. |
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What happens after T-cells are activated by dendritic cells? |
Proliferate extensively and differentiate into effector cells producing Cytotoxic molecules to kill infected cells or cytokines to further stimulate adaptive immune response. |
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Name of 3 mechanisms CD8 T-cells use to kill infected cells. |
Express porforin (to permeable membranes), cell surface receptors (to activate apoptosis pathways), and cytokines (to induce apoptosis). |
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What is the main purpose of CD4 T-cells? |
Produce cytokines that direct the immune response. |
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Why are CD4 cells master regulators? |
Ensures that the type of immune response is appropriate for the type of infection. |
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What are the secondary immune organs |
Lymph nodes, spleen, mucosal lymphoid tissues |
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How do lymphocytes leave the lymph nodes if they do encounter their antigen? |
High endothelial venule |
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What are the structural details that allow lymphatic capillaries to allow fluids and cells to enter? |
They have an open maple leaf like structure that allows fluids and cells to easily enter. This does not require any specific molecular interaction. |
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Where do blood borne pathogens initiate immune responses? |
The spleen |
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Where do mucosal pathogens initiate an immune response? |
Peyer's patches/mesenteric lymph node |
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Where are the HEVs located in lymph nodes relative to arteries, capillary beds and veins? |
They are specialized structures after the capillary bed. |
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How do APCS bring antigen into the lymph node? |
They enter the affarent lymphatic and encounter t and b cells in the cortex. |
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Name two ways that lymphocytes enter the lymph nodes. |
Lymphatics and HEV |
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From which vessel do mature B cells exit the bone marrow? |
Central sinus vein |
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Name 5 immune cells that mature in the bone marrow. |
Granulocytes, b-cells, monocytes, dendritic and NK cells |
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Why is it not important for innate cells to undergo negative selection? |
Because PAMPs are not molecules produced by healthy human tissue. |
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What mechanism allows DC'S, monos and MCS to exit cells? |
Diapedesis |
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What anatomical structure do T cells travel through in order to enter the thymus? |
HEV |
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What two types of selection must t cells pass in order for them to mature? |
Positive selection to select useful cells and negative selection to select self reactive cells (Central Tolerance). |
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Through what anatomical structure do T cells leave the thymus? |
HEV |
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How do cancer cells and pathogens travel throughout the body? |
By the lymphatics |
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Describe two ways that DCs can become activated. |
They can sense PAMPs directly or be signaled from other innate cells. |
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Once activated, what are the 3 actions of the DCs? |
Stop pinocytosis, upregulate MHC proteins, and migrate to lymph nodes. |
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What cell type presents antigen to t cells and where does this occur? |
DC'S and lymph nodes |
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What is the main way antigens are brought to the lymph nodes? |
Macrophages |
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What is the problem if only b cells recognize the antigen. |
There is only a short lived antibody response. |
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How do T and b cells enter the spleen? |
Splenic artery |
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How is the white pulp organized |
In cocentric sheaths around arterioles in t and b zones. |
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How do naive and effector cells leave the spleen? |
The splenic vein |
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How do mucosal lymphoid tissues differ from normal lymph nodes in terms of their general outcome following antigen recognition? |
They are more focused on self tolerance. |
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Relative to our own cells, how many bacteria exists in or outside of the human body? |
10^2 |
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How does the innate immune system recognize all different microbes? |
Evolutionarily conserved structures are recognized. |
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What three factors contribute to microbial structures the innate immune system recognizes on microbes? |
Difficult to mutate and survive, similar in many related microbial species, not present on host cell. |
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What are the 4 general steps to an infection/immune response? |
1) microbe infection 2) innate response 3) signal to adaptive 4) adaptive response |
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Describe the two benefits of the PAMP/PRR recognition system for innate immune cells. |
Maintains self/non-self discrimination and allows responses to be tailored to specific microbes |
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What types of PAMPs are unique to yeast/bacteria, viruses? |
Yeast/bacteria - unique lipid/carbohydrates not found on host cells, viruses - unique nucleic acids |
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TLR |
Recognizes many components of microbes both extracellularly and endosomal. |
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RIG |
Nucleic acids of viruses intracellularly |
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NLR |
Intracellular imbalances due to infection |
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Lectin |
Recognizes fungal polysaccharides extracellularly. |
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Scavanger receptors |
Extracellular Lipoprotein and polysaccharides from bacteria |
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Where do scavanger receptors express? |
Extracellularly and in endosomes |
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How do scavanger receptors know whether to make an anti-inflammatory response (during no infection) and inflammatory response (during infection)? response (during infection)? response (during infection)? |
Other receptors that recognize self or non self are paired with scavanger receptors. |
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What do lectins recognize? |
Scavanger - polysaccharides attached to proteins, broken down and recycled. Self - sends signals between cells, microbe -polysaccharides on bacteria cause cross linking and activation of innate pathways |
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What is the main outcome of lectin-microbe recognition? |
Phagocytosis/internalization |
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Are TLRs hetero or homodimers? homodimers? homodimers? |
Both |
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describe the shape and location of TLRs on cells. |
They are Cresent shaped and found in cell membranes. |
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TLR 1,2,4,7,8,9, 11, 12 |
Extracellular intact structures on bacteria, fungi, ligands |
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TLR 3,7,8,9,13 |
Intracellular nucleic acids |
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How many TLR'S do humans and mice have? |
10 TLRs and 12 TLRs |
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Are TLRs only involved with immunity? |
No, they are also involves with cell differentiation and reproduction. |
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Cellular consequences of TLR signals |
1) stop pinocytosis/phagocytosis 2) increase expression of antigen expression and costimulatory proteins 3) migrate to draining lymph nodes 4) produce cytokines |
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What do most TLRS signal through? |
My88 |
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What do TLR 3 signal through? |
TRIF |
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What do TLR 4 signal through? |
My88 and TRIF |
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Why are TLRS able to elicit different responses even though they go through similar signaling pathways? |
Differing TLRs and cell types |
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Why are mice rarely deficient in microbial infection if they missing one type of TLR? |
TLR redundancy |
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What kind of infections are mice deficient in MyD88 susceptible to? |
Bacterial |
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What type of infection are mice deficient in TRIF susceptible to? |
Some viral (herpes virus) |
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Tumor Necrosis Factor (TNF) |
General inflammation, cell recruitment, cell death |
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Interleukin 12 (IL-12) |
Immune responses to extracellular pathogens, inflammation, initiation of adaptive response |
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Type 1 Interferons (IFN-I) |
Immune responses of intracellular pathogens poise cells for infections, initiation of adaptive response |
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Interleukin 6 (IL-6) |
General effects acts on hypothalamus to increase body temperature. |
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Where can RIG I like receptors be found? |
Cytoplasm |
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What do all identified RLR bind? |
Nucleic acids from viruses |
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How many known RLRs do viruses have? |
8 |
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Which protein do all RLR signal through? |
IPS - 1, an adaptor protein on mitochondria |
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What is the main cytokine produced in response to RLR recognition and what is the purpose of this cytokine? |
Type 1 Interferons (IFN-I) which make cells non-permissive for virus growth, cause dendritic cells to migrate towards draining lymph nodes |
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How does IFN poise cells during the pre-infection state? |
1) it senses the infected cell by recognition of the DSRNA bound to RIG-I and transcription OS IFN-I that is secreted by cell 2) it poises the neighbor cell by IFN-I binding to receptor increasing the expression of protein kinase (PKR) and (OAS). 3) phosphorylation and inactivation of eIF-2alpha to shut down protein synthesis |
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How does IFN cause cells to respond to post-infection? PKR and 2'5'-OAS |
Stops translation and stops transcription |
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What do NLR's recognize? |
Host and microbial ligands, intracellular ions |
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What are the functions of NLRs? |
Induce apoptosis, inflammatory cytokines, or cellular differentiation |
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Dana Philpott |
Showed NOD1 and NOD2 proteins recognize bacterial peptidoglycans |
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Gabriel Nunez |
NALP3 recognizes peptidoglycans |
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What three events happen as a result of NLR recognition? |
1) oligomerization of NLR 2)recruitment of adapter proteins 3) activation of Caspase-1 |
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What is the function of Caspase-1 in relation to NLR function? |
Converts all pro-cytokines into active versions that are secreted from cell |
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What 2 cytokines are produced in response to NLR recognition? |
IL-1 beta and IL-18 which cause inflammation |
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TLR poise NLR signaling |
TLR signals increase pro-IL-1 BETA and pro-IL -18 so NLR signals result in Caspase-1 conversion of those cytokines |
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NLR poise TLR signaling |
Secreted IL-1 BETA binds to receptor further increasing expression of MyD88 and IRAK4 |
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What are the 2 main purposes of the complement immune system? |
Detection and destruction of microbes and initiation of the adaptive immune system |
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Hans Buchner |
Observed serum could kill bacteria even if animal was not immunized. |
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Jules Bordet |
Discovered a heat sensitive component of serum that could lyse bacteria. The lysis "complemented" the immunity granted by antibodies. |
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What is the structure of the C3 protein? |
An alpha/beta heterodimer linked by a disulfide bond. |
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What are the resulting products when the thioester group on the C3 protein are attacked by R-O-H? |
Ca fragment and c3b attachment to protein |
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What happens when the thioester is attacked by water? |
An unstable c3b and inactivation of ic3b. |
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How does the C3 become hydrolyzed into C3b in the spontaneous pathway? |
Thioester group is attacked |
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Name 4 characteristics of natural antibodies? |
Low affinity, poly reactive, spontaneously produced, and develop in fetal liver |
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What is the most useful function of natural antibodies? |
Recognize microbes for downstream activation of classical complement cascade |
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What is the final result of all the complement cascades? |
Membrane attack |
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What are two mechanisms the membrane attack complex (MAC) can kill cells? |
Hypotonic lysis and loss of membrane potential |
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Describe the order of the potency of the anaphalotoxins? |
C5a>C3a>>>C4a>C2b |
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What is the main function of complement in coordination with the innate immune system? |
They activate macrophages and granulocytes and aid in transport of antigen to lymph nodes |
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What are the two main complement receptors? |
CR1 and CR2 |
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What does CR1 primarily recognize and which cell type primarily expresses it? |
Binds primarily to C3b on macrophages |
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Which complement molecule promotes phagocytosis of CR1-bound complexes? |
C5a |
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What are the three main functions of the complement system and primary molecules involved in each? |
1) aid in killing microbes (MAC and phagocytosis), 2) transport of antigens to lymph nodes (iC3b,CR2) 3) initiate inflammation (anaphylotoxins) |
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What are the 3 main mechanisms of complement cascade activation? |
Spontaneous C3 hydrolysis, MBL binding, C1q binding |
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What is the primary function of NK cells? |
NK cells service host cells for changes |
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During infection, what leads to the loss of inhibitory receptors on host cells resulting in NK cell mediated cell killing? |
Pathogens use of host ribosomes |
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What are the two pathways NK cells use to kill infected/damaged host cells? |
1) perforin-Granzyme B-BID-Caspase 9-Caspase 3 2) TNFR-FADD-CASPASE 8-Caspase 3 |
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What are the end results of both the perforin/granzyme pathway and the Death receptor pathway in terms of how cells are killed? |
Caspase 3 activation, DNA fragmentation, membrane blebbing |
