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210 Cards in this Set
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- Back
- 3rd side (hint)
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What is the first line of defense provided by innate immunity?
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Epithelial barriers, specialized cells (intraepithelial lymphocytes), and natural antibiotics present in epithelia.
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Abbas pp 4
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What is the second line of defense provied by innate immunity?
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Phagocytes, NK cells, and complement.
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Abbas pp 4
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What alternative function do innate immunity components do?
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Innate immune responses enhance adaptive immune responses against the infectious agents.
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Abbas pp 4
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Why is adaptive immunity useful when we have perfectly good innate immunity?
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Microbes that are pathogenic for humans have evolved to resist innate immunity.
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Abbas pp 4
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Where do lymphocytes generally encounter antigen?
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Peripheral lymphoid organs
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Abbas pp 4 & 12
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What do secreted antibodies do?
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They neutralize and eliminate microbes and microbial toxins.
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Abbas pp 4
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Why do we need cell-mediated immunity?
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Antibodies do not have access to microbes that live and divide inside infected cells.
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Abbas pp 4
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What is the difference between helper and cytotoxic T cells?
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Helper T cells activate phagocytes to destroy microbes that have been ingested by the phagocytes into phagocytic vesicles. Cytotoxic T cells kill any type of host cells that are harboring infectious.
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Abbas pp 4
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What molecule class of antigens can B and T cells recognize?
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Most T cells recognize only microbial protein antigens, whereas antibodies are able to recognize many different types of microbial molecules, including proteins, carbohydrates, and lipids.
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Abbas pp 4
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Why do we care about passive immunity?
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An excellent example of passive immunity is seen in newborns, who are protected against infections by acquiring antibodies from their mothers through the placenta and milk.
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Abbas pp 5
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What 2 things are special about adaptive immunity?
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1) fine specificity 2) memory
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Abbas pp 6
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What is the clonal selection hypothesis?
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Clones of lymphocytes specific for different antigens arise before encounter with these antigens, each antigen selects a preexisting clone of specific lymphocytes and stimulates the proliferation and differentiation of that clone.
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Abbas pp 7
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What is clonal expanision?
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When lymphocytes are activated by antigens, they undergo proliferation, generating many thousands of clonal progeny cells, all with the same antigen specificity.
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Abbas pp 8
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What are the 5 phases of adaptive immune response?
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1) antigen recognition 2) activation of lymphocytes 3) elimination of antigen 4) decline 5) memory
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Abbas pp 8-9
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During which phase of the adaptive immune response does clonal expansion occur?
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Clonal expansion occurs during the activation phase.
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Abbas pp 9
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What else do you call elimination in adaptive immune response?
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This phase of antigen elimination is called the effector phase.
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Abbas pp 9
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What kind of cell death is present in the decline phase of the adaptive immune response?
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Apoptosis
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Abbas pp 9
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In what context do T cells recognize antigen?
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T cells only recognize peptide fragments of protein antigens that are bound to MHC molecules on the surface of APC cells.
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Abbas pp 10
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What are the two functions of CD4+ (helper) T cells?
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help B lymphocytes to produce antibodies and help phagocytes to destroy ingested microbes
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Abbas pp 10-11
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What do CD8+ (cytotoxic) T cells do?
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They lyse cells harboring intracellular microbes.
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Abbas pp 11
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Where do B cells arise and mature?
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All lymphocytes arise from stem cells in the bone marrow. B lymphocytes mature in the bone marrow.
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Abbas pp 11
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Where do T cells arise and mature?
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All lymphocytes arise from stem cells in the bone marrow. T lymphocytes mature in the thymus.
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Abbas pp 11
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Where do lymphocytes mature? (general)
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generative lymphoid organs
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Abbas pp 12
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How do CD4+ T cells "help"?
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They produce cytokines that activate B cells and macrophages.
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Abbas pp 12
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What are the effector cells of B lymphocytes lineage?
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Plasma cells
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Abbas pp 12
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Do memory cells produce antibodies?
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Memory cells are functionally silent.
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Abbas pp 14
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What is a non-innate mechanism of epithelial defense?
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Specialized cells (dendritic cells) located in the epithelium capture antigens and transport them to peripheral lymphoid organs.
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Abbas pp 14
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Who addresses the messenger APCs?
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Antigen-bearing dendritic cells display portions of the antigens for recognition by T lymphocytes.
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Abbas pp 14
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What is special about professional APCs?
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Professional APCs display antigens to T cells AND provide second signals.
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Abbas pp 14
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How do non-lymphocyte effector leukocytes work in innate and adaptive immunity?
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In innate immunity, macrophages and some granulocytes directly recognize microbes and eliminate them. In adaptive immunity, the products of B and T lymphocytes call in other leukocytes and activate the leukocytes to kill microbes.
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Abbas pp 14
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What are the peripheral lymphoid organs?
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Lymph nodes, spleen, and mucosal and cutaneous immune systems.
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Abbas pp 15
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What are 2 ways for antien to get to a lymph node?
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Carried in lymph, carried by dendritic cells in lymph.
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Abbas pp 15
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How does the spleen work/ how does it get/concentrate/destroy its antigen?
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Blood entering the spleen flows through a network of channels (sinusoids). Blood-borne antigens are trapped and concentrated by dendritic cells and macrophages in the spleen. The spleen contains abundant phagocytes, which ingest and destroy microbes in the blood.
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Abbas pp 15
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Give 2 examples of mucosal lymphoid tissues.
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Pharyngeal tonsils and Peyer's patches of the intestine.
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Abbas pp 15
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What does presence of a germinal center in a follicle signify?
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If B cells in a follicle have recently responded to an antigen, this follicle may contain a central region called a germinal center.
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Abbas pp 15
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Where do T cells reside in the spleen?
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In the spleen, T lymphocytes are concentrated in periarteriolar lymphoid sheaths surrounding small arterioles.
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Abbas pp 15
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Where do B cells and T cells reside in lymph nodes?
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B cells are concentrated in discrete structures called follicles located around the periphery, or cortex, of each node. T lymphocytes are concentrated outside, but adjacent to, the follicles, in the paracortex.
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Abbas pp 15
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Why do naive B cells localize to follicles?
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FDCs secrete a potein that belongs to a class of cytokines called chemokines, for which naive B cells express a receptor.
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Abbas pp 15
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What is the acronym for T cell residence in the spleen?
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PALS (periarteriolar lymphoid sheath)
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Abbas pp 17
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How can B & T cells "leave home" once activated?
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When the lymphocytes are activated by microbial antigens, they gradually reduce their expression of the chemokine receptors and are no longer constrained anatomically.
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Abbas pp 17
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Why do T and B cells NEED to "leave home"? (2 reasons)
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B cells and T cells migrate toward each ohter and meet at the edge of follicles, where helper T cells interact with and help B cells to differentiate into antibody-producing cells.
Activated lymphocytes end up in the circulation and can go to distant sites of infection. |
Abbas pp 17
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Where do naive T cells enter the lymph node?
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Specialized postcapillary venules called high endothelial venules (HEV)
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Abbas pp 18
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What do T cells express which allows them to bind to carbohydrate ligands of HEV cells?
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L-selectin, a surface receptor
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Abbas pp 18
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Do memory T cells exist?
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Yes, they appear to consist of cells that recirculate through lymph nodes.
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Abbas pp 19
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What molecular patterns can phagocytes recognize? (4)
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Bacterial LPS. Terminal mannose residues on glycoproteins. Double-stranded RNA. Unmethylated CpG nucleotides.
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Abbas pp 22
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What are the "antigen receptors" present in innate immunity?
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Pattern recognition receptors.
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Abbass pp 22
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How do host cells protect themselves against complement?
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Activation of complement proteins is blocked by regulatory molecules that are present on the host cells but are not present on microbes.
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Abbas pp 22
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Why don't microbes mutate the molecular patterns recongnized by innate immunity.
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Some can, but components of innate immunity have evolved to recognize structures of microbes that are often essential for the survival and infectivity of these microbes.
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Abbas pp 22
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How many microbial patterns can be recognized by receptors of innate immunity?
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Less than a thousand.
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Abbas pp 23
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How does adaptive and innate immunity differ in their distribution of receptors?
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Innate immunity: Nonclonal: identical receptors on all cells of the same lineage. Adaptive immunity: Clonal: clones of lymphocytes with distinct specificities express different receptors.
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Abbas pp 23
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What are the 3 components of innate immunity?
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Epithela, cells in circulation and tissues, several plasma proteins.
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Abbas pp 24
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What specific T cell recognizes somthing other than peptide antigen?
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Intraepithelial lymphocytes, including (gammadelta) T cells, often recognize microbial lipids and other structures shared by microbes of the same type.
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Abbas pp 24
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What's special about B-1 cells? Where do they reside? What antibody isotype do they produce? What do these antibodies recognize?
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Limited diversity of their antigen receptors. Found mostly in peritoneal cavity. IgM antibodies. Many are specific for carbohydrates in the cell walls of many bacteria.
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Abbas pp 25
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What lab values for PMNs do you expect to see normally? In an infected individual?
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4,000 to 10,000 per mm^3. 20,000 per mm^3
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Abbas pp 25
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What do PMNs and monocytes do?
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These blood cells are recruited to sites of infection, where they recognize and ingest microbes for intracellular killing.
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Abbas pp 25
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What is the first cell type that responds to bacterial/fungal infection?
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Neutrophils
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Abbas pp 25
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Which phagocytes are first to arrive? Which last longer?
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PMNs, macrophages.
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Abbas pp 25
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What is the difference between resident macrophages and macrophages that are differentiated from monocytes in blood?
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There is none.
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Abbas pp 25
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Who produces and What do TNF and IL-1 do?
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Resident macrophages produce these cytokines that stimulate the endothelial cells to rapidly express two adhesion molecules called E-selectin and P-selectin.
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Abbas pp 25
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Who produces chemokines at site of infection?
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Tissue macrophages that encountered microbe and the endotheilal cells responding to TNF and IL-1.
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Abbas pp 25
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What do chemokines do and how do TNF and IL-1 potentiate this effect?
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Chemokines stimulate a rapid increase in the affinity of the leukocyte integrins for their ligands on the endothelium. Concurrently, TNF and IL-1 act on the endothelium to stimulate expression of ligands for integrins.
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Abbas pp 26
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What is the sequence of events resulting in migration of leukocytes to extravascular site of infection?
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1)Selectin-mediated rolling 2)Integrin-mediated firm adhesion 3)chemokine-mediated motility
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Abbas pp 26
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How do leukocyte adhesion deficiencies manifest clinically?
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Increased susceptibility to infections.
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Abbas pp 26
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What class of pattern recognition receptors is responsible for binding to LPS, flagellin, and unmethylated CpG?
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Toll-like receptors.
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Abbas pp 27
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What transcription factor is activated by TLR signal cascade?
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NF-kappaB
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Abbas pp 27
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How does IFN-gamma work?
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IFN-gamma is a powerful activator of the microbicidal function of phagocytes.
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Abbas pp 27
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How do phagocytes interact with antibodies and complement and what is this called?
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Phagocytes express receptors for productions of complement activation and for antibodies, which coat microbes/opsonize microbes.
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Abbas pp 27-28
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What 3 enzyme classes are responsible for the killing of microbes in phagolysosomes?
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phagocyte oxidase, inducible nitric oxide synthase, lysosomal proteases.
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Abbas pp 28
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How can inflammation cause injury to host tissue?
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In strong reactions, phagocytic enzymes may be liberated into the extracellular space and may injure host tissues.
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Abbas pp 28
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What deficiency causes chronic granulomatous disease?
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Inherited deficiency of the phagocyte oxidase enzyme.
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Abbas pp 29
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What are 4 functions of macrophages?
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1) Killing phagocytosed microbes 2) Produce cytokines that are important mediators of host defense 3) secrete growth factors and enzymes that serve to remodel injured tissue 4) stimulate and respond to T cells.
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Abbas pp 30
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How do NK cells recognize normal vs. altered host cells?
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NK cells express receptors for molecules on host cells, and some activate and some inhibit NK cells. Altered host cells don't have the molecules that inhibit NK cells.
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Abbas pp 31
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How are normal host cells protected from NK cells?
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When the inhibitory receptors of NK cells encounter self MHC molecules, the NK cells are shut off.
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Abbas pp 31
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How do NK cells directly kill infected cells?
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Activation triggers the discharge of proteins contained in the NK cells' cytoplasmic granules toward the infected cells. Some proteins alter permiability of membranes and some molecules activate enzymes that induce apoptosis.
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Abbas pp 32
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How do NK and macrophage cells cooperate?
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Macrophages ingest microbes and produce IL-12, IL-12 activates NK cells to secrete IFN-gamma, and IFN-gamma activates the macrophages to kill the ingested microbes.
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Abbas pp 32
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Describe evolutionary struggle between immune system of host and virus.
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Host uses CTLs to recognize MHC-displayed viral antigens, viruses shut off MHC expression, and NK cells have evolved to respond to the absence of MHC molecules.
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Abbas pp 32
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Which complement pathways are part of innate immunity?
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Alternative and lectin pathways
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Abbas pp 32 and 34
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Which complement pathway is part of adaptive immunity and is it humoral or cell-mediated?
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Classical pathway, humoral
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Abbas pp 34
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Lectin pathway activates proteins of which pathway: classical or alternative?
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Classical.
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Abbas pp 34
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What is the central component of complement?
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C3
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Abbas pp 34
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How does C3-->C3b work?
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The major proteolytic fragment of C3, called C3b, becomes covalently attached to microbes and is able to activate downstream complement proteins on the microbial surface.
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Abbas pp 34
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Describe 3 functions of complement in host defense.
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1) C3b opsonization of microbes 2) Breakdown products are chemoattractants for PMNs and monoytes and promote inflammation 3) formation of polymeric protein complex that inserts into the microbial cell membrane, disturbing the permeability barrier.
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Abbas pp 34
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What are the principal sources of cytokines in innate immunity?
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Macrophages
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Abbas pp 34
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What are the principal sources of cytokines in cell-mediated immunity?
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helper T cells
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Abbas pp 34
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What are the principal cell sources of tumor necrosis factor (TNF)?
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Macrophages, T cells
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Abbas pp 35
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Wha are the biologic effects of TNF on endothelial cells?
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Activation: inflammation, coagulation
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Abbas pp 35
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Which complement pathways are part of innate immunity?
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Alternative and lectin pathways
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Abbas pp 32 and 34
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Which pathway is part of adaptive immunity and is it humoral or cell-mediated?
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Classical pathway, humoral
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Abbas pp 34
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Lectin pathway activates proteins of which pathway: classical or alternative?
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Classical.
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Abbas pp 34
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What is the central component of complement?
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C3
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Abbas pp 34
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How does C3-->C3b work?
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The major proteolytic fragment of C3, called C3b, becomes covalently attached to microbes and is able to activate downstream complement proteins on the microbial surface.
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Abbas pp 34
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Describe 3 functions of complement in host defense.
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1) C3b opsonization of microbes 2) Breakdown products are chemoattractants for PMNs and monoytes and promote inflammation 3) formation of polymeric protein complex that inserts into the microbial cell membrane, disturbing the permeability barrier.
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Abbas pp 34
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What are the principal sources of cytokines in innate immunity?
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Macrophages
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Abbas pp 34
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What are the principal sources of cytokines in cell-mediated immunity?
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helper T cells
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Abbas pp 34
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What are the principal cell sources of tumor necrosis factor (TNF)?
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Macrophages, T cells
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Abbas pp 35
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Wha are the biologic effects of TNF on endothelial cells?
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Activation: inflammation, coagulation
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Abbas pp 35
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What is the biologic effect of TNF on PMNs?
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activation
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Abbas pp 35
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What is the biologic effect of TNF on the hypothalamus?
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fever
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Abbas pp 35
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What is the biologic effect of TNF on the liver?
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synthesis of acute phase proteins
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Abbas pp 35
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What is the biologic effect of TNF on muscle and fat?
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catabolism (cachexia)
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Abbas pp 35
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What is the biologic effect of TNF on many different cell types?
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Apoptosis
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Abbas pp 35
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What cells are activated by TNF?
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Endothelial cells and neutrophils
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Abbas pp 35
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What are the principal cell sources of interleukin (IL-1)?
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Macrophages, endothelial cells, some epithelial cells.
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Abbas pp 35
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What biologic effect does IL-1 have on endothelial cells?
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Activation: inflammation, coagulation
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Abbas pp 35
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What biologic effect does IL-1have on the hypothalamus?
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fever
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Abbas pp 35
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What biologic effect does IL-1 have on the liver?
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synthesis of acute phate proteins
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Abbas pp 35
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What cytokines act on the hypothalamus to induce fever?
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TNF, IL-1
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Abbas pp 35
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What cytokines activate endothelial cells?
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TNF, IL-1
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Abbas pp 35
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What cytokines act on the liver to induce synthesis of acute phase proteins?
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TNF, IL-1, IL-6
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Abbas pp 35
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What are the pricipal cell targets and biologic effects of chemokines?
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Leukocytes: chemotaxis, activation
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Abbas pp 35
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What are the principal cell sources of chemokines?
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Macrophages, endothelial cells, T lymphocytes, fibroblasts, platelets.
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Abbas pp 35
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What are the principal cell sources of Interferon-gamma?
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NK cells, T lymphocytes.
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Abbas pp 35
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What does IFN-gamma activate?
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Macrophages
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Abbas pp 35
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What 3 findings characterize septic shock?
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Low blood pressure (shock), disseminated intravascular coagulation (DIC), and metabolic disturbances (acidosis).
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Abbas pp 36
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What cytokine is responsible for septic shock?
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Very high levels of TNF.
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Abbas pp 36
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What kind of interferon is used in viral hepatitis treatment?
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A type I interforon called IFN-alpha.
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Abbas pp 36
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Name 4 plasma proteins of innate immunity other than complement.
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Plasma mannose-binding lectin (MBL). Surfactant proteins protect airways from infection. C-reactive protein (CRP) opsonize microbes.
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Abbas pp 36
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What is an acute phase response to infection?
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Increase in levels of many plasma proteins of innate immunity rapidly after infection.
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Abbas pp 36
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What components of innate immunity combat extracellular bacteria and fungi?
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Phagocytes, complement system, acute phase proteins.
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Abbas pp 36
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What components of innate immunity combat intracellular bacteria and viruses?
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Phagocytes, NK cells.
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Abbas pp 36
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How do Listeria and mycobacteria evade phagocytosis?
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Listeria monocytogenes produces a protein that enables it to escape from phagocytic vesicles. The cell walls of mycobacteria contain a lipid that inhibits fusion of vesicles containing ingested bacteria with lysosomes.
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Abbas pp 36
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What 2 things do dendritic cells and macrophages do to activate T cells?
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Express surface molecules called costimulators. Secrete cytokine IL-12.
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Abbas pp 37
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How can complement activation be a second signal?
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The combination of antigen recognition and C3d recognition initiates te process of B cell differentiation into antibody-secreting cells.
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Abbas pp 37
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Why is it appropriate that macrophages and complement activate cell-mediated and humoral immunity, respectively?
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Intracellular and phagocytose microbes need to be eliminated by cell-mediated immunity, the adaptive response mediated by T lymphocyes. Microbes that are ingest by or live in macrophages induce costimulators and IL-12 that stimulate T cell responses. In contrast, blood-borne microbes need to be combated by antibodies, which are produced by B lymphocytes during humoral immune responses. Blood-borne microbes activate the plasma complement system, which in turn stiulates B cell activation and antibody production.
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Abbas pp 38
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How can 1 pathogen activate both humoral and cell mediated branches of adaptive immunity?
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If virus is free in the blood, the immune system needs to produce antibodies that bind the virus and prevent them from infecting host cells. (humoral) After virus has infected host cells, activate cytolytic T lymphocytes to kill the infected cells. (cell-mediated)
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Abbas pp 42
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What is MHC?
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A genetic locus whose principal products function as the peptide display molecules of the immune system.
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Abbas pp 42
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What is MHC restriction?
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In every individual, different clones of T cells can see peptides only when these peptides are displayed by that individual's MHC molecules.
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Abbas pp 42
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What 2 moieties do TCRs have to recognize?
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TCR recognizes some residues of peptide antigen and also recognizes residues of MHC molecule that is displaying that peptide.
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Abbas pp 42
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At what 2 times do T lymphocytes need to see antigen presented by APCs?
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Naive T lymphocytes need to see antigens presented by "professional" APCs to initiate immune responses against protein antigen. Differentiated effector T cells again need to see antigens presented by various APCs, to activate the effector functions of the T cells in humoral and cell-mediated immune responses.
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Abbas pp 42-43
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What are Langerhans cells?
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In the skin, the epidermal dendritic cells are called Langerhans cells.
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Abbas pp 43
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To which peripheral lymphoid organ do antigens from epithelium and connective tissue go?
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Lymph node
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Abbas pp 43
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To which peripheral lymphoid organ do blood-borne antigens go?
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Spleen
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Abbas pp 43
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Other than receptor mediated endocytosis, how might dendritic cells capture microbes?
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Some soluble microbial antigens may enter dendritic cells by pinocytosis.
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Abbas pp 44
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What happens when a microbe binds to Toll-like receptors on dendritic cells, resident macrophages, and epithelial cells?
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Production of inflammatory cytokines such as TNF and IL-1.
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Abbas pp 44
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When dendritic cells are activated, what happens?
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Activated dendritic cells lose their adhesiveness for epithelia and begin to express surface receptors that are specific for chemoattracting cytokines (chemokines) produced in the T cell zones of lymph nodes. During migration, dendritic cells mature from cells designed to capture antigens into APCs capable of stimulating T lymphocytes. i.e. increased sythesis and stable expression of MHC molecules and costimulators.
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Abbas pp 44
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How efficient is T cell response to microbial antigens?
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A T cell response to microbial antigen begins in the lymph node draining that site within 12 to 18 hours.
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Abbas pp 46
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What are the most potent APCs for activating naive lymphocytes?
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Dendritic cells are the most potent APCs for activating naive T lymphocytes.
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Abbas pp 46
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What type of APC is abundant in all tissues?
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Macrophage
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Abbas pp 46
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How are B cells similar to other APCs?
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B lympocytes ingest protein antigens and display them to helper T cells in context of MHC.
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Abbas pp 46
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What kind of cells do CTLs "read"?
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All nucleated cells
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Abbas pp 46
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How does cross-presentation allow CD8+ cells to mature and recognize viral peptides on non-professional APCs?
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Professional APCs ingest non-professional APCs and display the antigen peptide to prime naive T cells so they can read the antigen on non-professional APCs.
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Abbas pp 46-47
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What are human MHC proteins called?
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HLA (human leukocyte antigen)
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Abbas pp 47
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Which aspect of Class I and II MHC molecules resemble each other: subunit structure or overall structure?
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Overall structure
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Abbas pp 48
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Where are the polymorphic residues located in class I MHC molecules?
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Alpha 1 and Alpha 2 domains of the Alpha chain.
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Abbas pp 48
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What coreceptor is bound by the alpha 3 domain of MHC1?
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CD8
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Abbas pp 48
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Where are the polymorphic molecules located in Class II MHC molecules?
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Alpha 1 and Beta 1 domains.
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Abbas pp 48
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What coreceptor is bound by the beta 2 domain of MHC2?
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CD4
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Abbas pp 48
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Which MHC molecule can accomodate bigger peptides?
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MHC 2
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Abbas pp 48
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How many class I molecules can a cell express?
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Any cell can express 6 different class I molecules.
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Abbas pp 48
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How many class II molecules can a cell express?
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up to 10 to 20 different class II molecules may be expressed.
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Abbas pp 48
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How do we get diversity in MHC?
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MHC molecules are encoded by inherited DNA sequences and variations are not induced by gene recombination.
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Abbas pp 48
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Which APCs express Class I MHC
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All nucleated cells express Class I MHC
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Abbas pp 48
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Which APCs express Class II MHC?
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Professional APCs (dendritic cells), macrophages and B lymphocytes.
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Abbas pp 48
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What is the significance of co-dominant MHC expression?
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Increases number of different MHC molecules that can present peptides to T cells.
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Abbas pp 50
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What is the significance of polymorphic MHC genes.
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Ensures that different individuals are able to present and respond to different microbial peptides.
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Abbas pp 50
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How can MHC bind related but unique peptides?
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Only one or two residues in a peptide have to fit into an MHC molecule's cleft. Thus MHC molecules are said to have a "broad" specificity for peptide boinding.
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Abbas pp 51
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Why is it important that, once bound, a peptide stays bound to MHC for a long time (up to days)?
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The slow off-rate ensures that once an MHC molecule has acquired a peptide, it will display the peptide long enough to maximize the chance that a particular T cell will find the peptide it can recognize and initiate a response.
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Abbas pp 51
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When do MHC molecules bind to peptide antigens?
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MHC molecules acquire their peptide cargo during their biosynthesis and assembly inside cells.
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Abbas pp 51
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From where in the cell do Class I MHC acquire peptide?
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cytoplasmic proteins
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Abbas pp 53
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From where in the cell do Class II MHC acquire peptide?
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intracellular vesicles
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Abbas pp 53
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Why are the available MHC molecules not constantly occupied by self peptides and unable to present foreign antigens?
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new MHC molecules are constantly being synthesized, ready to accept peptides, and they are adept at capturing any peptides that are present in cells, and T cells are adept at recognizing peptides.
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Abbas pp 53
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Why do we not develop immune responses to self antigens?
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T cells specific for self antigens are either killed or inactivated.
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Abbas pp 53
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Do you find empty MHC molecules on the cell surface?
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No
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Abbas pp 53
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Which cells process peptides from endocytic vesicles?
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Professional APCs
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Abbas pp 53
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Which cells process peptides from the cytosol?
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All nucleated cells
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Abbas pp 53
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Where are class II MHC molecules?
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APCs constantly synthesize class II MHC molecules in the ER.
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Abbas pp 54
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What occupies the cleft of MHC II prior to fusion with endosomes?
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CLIP (class II invariant chain peptide)
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Abbas pp 54
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What removes CLIP from class II in the endosome?
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DM
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Abbas pp 54
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What are immunodominant epitopes?
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Peptides from the intact antigen that can bind the MHC molecules present in the individual.
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Abbas pp 54-55
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How do cells ensure production of peptides that will fit MHC Class I?
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Some classes of proteasomes efficiently cleave cytosolic proteins into peptides with the size and sequence properties typical of class I MHC-binding peptides.
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Abbas pp 58
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How do cytosolic peptides come together with MHC class I?
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TAP (transporter associated with antigen processing) picks up peptides from the cytoplasm and actively pumps the peptides across the ER membrane into the interior of the ER.
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Abbas pp 58
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How might viruses try to evade CD8+ T cell recognition via altering MHC class I?
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1) Removing newly synthesized MHC molecules from the ER
2) Inhibiting the transcription of MHC genes 3) Blocking peptide transport by the TAP transporter. |
Abbas pp 58
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What counterbalances viruses' evasive maneuver of reducing MHC class I expression on the cell surface?
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NK cells of innate immune system to recognize and kill virally infected cells that have lost class I MHC class I expression.
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Abbas pp 58
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How do helper T cells "help"? (2 ways)
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1) Help B lymphocytes to produce antibodies
2) Help phagocytes to ingest and destroy microbes |
Abbas pp 58
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How can an APC provide both signals I and II to T cells?
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Signal I: antigen recognition by TCR
Signal II: Costimulators and cytokines |
Abbas pp 60
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Why does the book focus on antigen capture and presentation to T cells?
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The antigen receptors of B cells and the antibodies that are secreted usally recognize antigens in the native conformation, without any requirement for antigen processing or display by a specialized system.
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Abbas pp 60
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What 2 functions do cellular receptors serve?
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1) They detect external stimuli
2) They trigger responses of the cells on which the receptors are expressed |
Abbas pp 63
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What kinds of chemical structures do antibodies recognize?
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Proteins lipids, carbohydrates, nucleic acids, simple small chemical groups
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Abbas pp 64
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What chemical structures do TCRs recognize?
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Peptides in the context of MHC (exception: gamma-delta T cells)
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Abbas pp 64
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What is the difference between CDR and hypervariable region?
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Trick question: There is none.
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Abbas pp 64
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What part of the antibody is responsible for signal transduction?
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Trick question: Antigen receptors are noncovalently attached to other invariant molecules whose function is to deliver the activation signals.
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Abbas pp 64
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What is cross-linking?
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When adjacent antigen receptors of lymphocytes bind to two or more antigen molecules, the receptors are pulled together into an aggregate.
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Abbas pp 66
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Why are antibodies considered "effector molecules of humoral immunity"
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They function to neutralize and eliminate microbes and toxins.
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Abbas pp 66
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If you find IG domain in an uncharacterized protein, what might you guess about its function?
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Most of the proteins possessing Ig domain are involved in sensing signals from the environment and from other cells.
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Abbas pp 66
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Which CDR is most variable?
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CDR3
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Abbas pp 66
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What constitutes the Fab of an antibody?
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The whole light chain and the V and first C domain of the heavy chain
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Abbas pp 66
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What constitues the Fc of an antibody?
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The heavy chain not present in Fab
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Abbas pp 66
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Where is the hinge region of an antibody?
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Between the Fab and Fc regions of most antibody molecules.
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Abbas pp 66
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What are the names of the 2 light chains?
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Kappa and Lambda
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Abbas pp 68
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What purpose do hinge regions of antibodies serve?
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Hinge regions enable the molecule to move, enabling them to simultaneously bind antigen epitopes that are separated from one another by varying distances.
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Abbas pp 68
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What isotypes are epxressed in naive B cells?
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Membrane-bound IgM and IgD.
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Abbas pp 68
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What are linear determinants?
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epitopes recognized based on sequence
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Abbas pp 68
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What are conformational determinants?
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epitopes recognized based on shape
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Abbas pp 68
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What are neodeterminants?
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epitopes that are hidden within antigen molecules and are exposed as a result of a physicochemical change.
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Abbas pp 68
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What is the difference between affinity and avidity?
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Affinity is the strength with which one antigen-binding surface of an antibody binds to one epitope of an antigen. Avidity is the total strength of binding resulting from 2-10 antigen-antibody bonds.
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Abbas pp 68
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How does one make monoclonal antibodies?
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Fuse B cells with myeloma cells and grow hybridomas which secrte antibody of desired specificity.
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Abbas pp 70
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Why can't you use mouse monoclonal antibodies repeatedly in humans?
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Humans see the mous Ig as foreign and make an immune response to the injected antibodies.
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Abbas pp 70
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Is there a difference in the general properties of CDRs between TCR and antibodies?
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Nah
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Abbas pp 70
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How many residues must TCR recognize of the MHC peptide?
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As few as 1 to 3 residues.
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Abbas pp 71
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What subpopulation of T cells can recognize glycolipid antigen?
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NK-T cells
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Abbas pp 71
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Which molecules are responsible for signaling in TCR complex?
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The CD3 and (squiglly greek letter) chain transmit some of the signals that are initiated when the TCR recognizes antigen.
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Abbas pp 71
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What do coreceptors CD4 and CD8 bind to?
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They recognize nonpolymorphic portions of MHC molecules.
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Abbas pp 72
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What does IL-7 do?
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Interleukin-7, which is produced by stromal cells in the bone marrow and thymus, stimulates proliferation of B and T lymphocyte progenitors before they express antigen receptors.
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Abbas pp 73
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What is positive selection?
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Immature T cells are selected to recognize self MHC molecules.
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Abbas pp 73-74
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What is negative selection?
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Immature B and T lymphocytes are selected against high-affinity recognition of self antigens present in the bone marrow and thymus, respectively.
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Abbas pp 74
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What step signifies the commitment of a lymphocyte to B cell lineage?
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Recombination of one Ig Vh gene segment with one D and one J segment.
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Abbas pp 75
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What 3 kinds of enzymes are involved in VDJ recominase?
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Recombinase, exonuclease, ligase
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Abbas pp 75
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What contributes to combinatorial diversity?
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Limited by the number of available V, D, and J gene segments.
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Abbas pp 75
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What 3 mechanisms contribute to junctional diversity?
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1) exonucleases may remove nucleotides from V, D, and J gene segments at the time of recombination
2) an enzyme called terminal deoxyribonucleotidyl transferase (TdT) takes nucleotides that are not parts of germline genes and adds these nucleotides randomly to the sites of V(D)J recombinations forming to so-called N regions. 3) Overhanging DNA sequences may be generated during an intermediate stage of recombination that are then filled filled in by "P-nucleotides" |
Abbas pp 75
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Why is CDR3 so variable?
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The site of V(D)J recombination encodes the amino acids of CDR3.
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Abbas pp 75
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