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MICB 402 > Introduction > Flashcards

Introduction Flashcards

1
Q

what is the purpose of our immune system (5)

A
  • prevent invasion by pathogens/parasites
  • kill pathogens/parasites/microorganisms
  • kill infected cells and cancer cells
  • detect and remove dying cells
  • repair injured tissues
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2
Q

what are essential functions to our immune system to not compromise our own bodies (2)

A
  • must be able to discriminate between self and not-self; discriminate between dangerous from innocuous such as pathogens, microbes, cancerous cells vs. commensal microbes, normal cells, food, pollen, etc
  • should function quickly and then re-establish homeostasis
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3
Q

what occurs if our immune system malfunction

A
  • disease
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4
Q

what are examples of the diseases that result from immune system malfunction (4)

A
  • autoimmunity or inflammatory disease
  • allergies and asthma
  • obesity
  • cancer
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5
Q

what is the most common cause of premature death in human history

A
  • infectious disease
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6
Q

what makes COVID-19 fatal for humans (3)

A
  • acute respiratory distress syndrome (ARDS) becomes a major issue in critically ill patients
  • injury to the lungs from viral infection and unchecked inflammation results in rapid and progressive shortness of breath
  • respiratory failure
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7
Q

what percentage of deaths were due to infectious disease in min-19th century England

A
  • 60%
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8
Q

what can explain variance in the deaths from infectious diseases in different places (3)

A
  • hygiene
  • vaccines
  • antibiotics
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9
Q

which organisms have defences against pathogens

A
  • multicellular organisms
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10
Q

what are jawed vertebrates’ three layers of defence (3)

A
  • physiological and anatomical barriers (epithelia, mucus, stomach acid, peptides, commensals)
  • innate immune responses
  • adaptive immune responses (T and B cells)
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11
Q

what is the epithelia structure and main general function (2)

A
  • composed of cells packed tightly together
  • provides a physical barrier between internal and external environments
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12
Q

what does the epithelia comprise

A
  • comprise skin and linings of body’s tubular structures (gastrointestinal tract, respiratory tract, urogenital tract)
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13
Q

mucosal epithelial cells (2)

A
  • secrete mucous, a thick and viscous fluid
  • mucous coats microorganisms and prevents their attachment to the epithelia
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14
Q

what do epithelial cells express (2)

A
  • toll-like receptors that can detect and respond to infection from pathogens secreting cytokines and anti-microbial peptides
  • results in induction of inflammation
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15
Q

how are the adaptive and innate immune systems connected (2)

A
  • they are interdependent
  • in the first week of infection, the innate immune responses limit the infection and activate the adaptive immune responses
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16
Q

what is the adaptive immune response comprised of (2)

A
  • T cell and B cell-mediated responses
  • random and highly diverse repertoire of T and B cell receptors, followed by clonal selection and expansion
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17
Q

what are the characteristics of the adaptive immune response (2)

A
  • highly specific
  • generates immunological memory (basis of vaccines)
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18
Q

what is the main limitation of adaptive immunity

A
  • clones need to expand and differentiate before participating in host defence (clonal selection takes times)
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19
Q

what are disadvantages of the adaptive immune system and examples (2)

A
  • inappropriate responses
  • allergies, autoimmunity
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20
Q

innate immune system

A
  • universal and evolutionarily conserved mechanism of host defence
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21
Q

what is the innate immune system comprised of (3)

A
  • surface pattern recognition receptors (PRR) that identify dangerous microbes, membrane bound attachment receptors, and “opsonic receptors” on macrophages and dendritic cells
  • secreted PRR’s and complement
  • intracellular PRRs to detect pathogens within cells
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22
Q

innate immune system

A
  • universal and evolutionarily conserved mechanism of host defence
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23
Q

what are the key features of the innate immune system (3)

A
  • controls the infection by limiting spread during the first few days; this is sometimes sufficient to protect against infection
  • provides protection against a wide variety of pathogens (non-specific)
  • controls the type of adaptive immune response that will develop by “sensing” the nature (what and where) of the infectious agent
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24
Q

what are the main functions of the innate immune system (6)

A
  • opsonization
  • activation of complement cascades
  • coagulation cascades
  • phagocytosis
  • activation of pro-inflammatory cytokines/chemokines
  • induction of apoptosis
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25
Q

where are cells in the immune system produced (2)

A
  • in the bone marrow through hematopoiesis
  • cells are constantly replenished as needed
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26
Q

how does the immune system responses change over time and why (2)

A
  • the immune responses to infections decrease with time
  • as we grow older, there are fewer hematopoiesis sites, decreasing our ability to replenish new immune cells
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27
Q

innate immune system cells: neutrophils
- key characteristics (4)

A
  • short lived
  • abundant in the bloodstream
  • abundantly produced each day
  • key soldier for innate immunity; they are essential to living
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28
Q

innate immune system cells: neutrophils
- activation (2)

A
  • not activated in the blood; when activated, they migrate to the tissues and survive for 1-2 days
  • highly motile and attracted to sites of infection by cytokines produced by epithelial cells and resident macrophages, and complement C5a
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29
Q

innate immune system cells: neutrophils
- strategies for killing pathogens (3)

A
  • phagocytic dependent
  • phagocytic independent
  • NETs
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30
Q

innate immune system cells: neutrophils
- phagocytic dependent killing of pathogens

A
  • phagocytosis of antibody-opsonized pathogens and killing of ingested bacteria by production of reactive oxygen and nitrogen species
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31
Q

innate immune system cells: neutrophils
- phagocytic independent killing of pathogens

A
  • degranulation: various digestive proteins are released in 3 types of granules to kill pathogens
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32
Q

innate immune system cells: neutrophils
- NETs (2)

A
  • release of neutrophil extracellular traps which contain fibres of chromatin and serine proteases
  • trap and limit the spread of pathogens
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33
Q

innate immune system cells: monocytes
- categories (2)
- differences (2)

A
  • inflammatory (classical and conventional)
  • patrolling (non-conventional)
  • differ in chemokine receptors, cytokine production, antigen uptake and presentation
  • can be differentiated by expression of CD14 and CD16 markers in humans
34
Q

innate immune system cells: monocytes
- inflammatory monocytes

A
  • differentiate into macrophages or dendritic cells depending on cytokine environment
34
Q

innate immune system cells: monocytes
- patrolling monocytes (4)

A
  • crawl along blood vessels looking for injury to the endothelium
  • do not differentiate into macrophages
  • armed with PRRs
  • have a role in Alzheimer’s, long-COVID, and another diseases
35
Q

innate immune system cells: macrophages
- general characteristics (3)

A
  • relatively long-lived cells, but limited self-renewal potential
  • some derived from monocytes (gut), but other populate tissue during embryogenesis and can self-renew (brain, liver)
  • arrive at sites of infection after neutrophils
36
Q

innate immune system cells: macrophages
- receptors (4)

A
  • full of receptors that differ depending on location in the body
  • various chemokine receptors for substances released by damaged cells, histamine from resident mast cells and basophils, and cytokines/chemokines released by resident macrophages and dendritic cells
  • various phagocytic receptors, mannose receptors, Fc receptors, complement receptors
  • various signalling receptors
37
Q

innate immune system cells: macrophages
- methods of killing pathogens (2)

A
  • highly phagocytic; can ingest 100+ pathogens before dying of their own digesting compounds
  • ingest pathogens into phagosomes which fuse with lysosomes where pathogens are killed because of the production of several reactive oxygen and nitrogen species
38
Q

innate immune system cells: macrophages
- invasion by pathogen

A
  • some bacteria can evade macrophage defences and grow within cells
39
Q

innate immune system cells: macrophages
- types (3)

A
  • M1 macrophages produce inflammatory cytokines
  • M2 macrophages produce chemokines and enzymes arginase which may be important for tissue repair
  • Mreg macrophages produce significant amount of IL-10
40
Q

innate immune system cells: dendritic cells
- general characteristics (3)

A
  • present in small numbers
  • many different subsets
  • similar lifespan to macrophages
41
Q

innate immune system cells: dendritic cells
- activation (2)

A
  • immature cells in tissues that act as guarders of infection
  • once activated, they mature and migrate to lymph nodes to interact with T cells, innate lymphoid cells (ILCs like NK cells), and B cells
42
Q

innate immune system cells: dendritic cells
- characteristics of immature cells (6)

A
  • high antigen capture
  • low co-stimulatory molecule expression
  • low MHC class I and II expressions
  • negligible inflammatory cytokine expression
  • poor activation of T cells susceptible to NK killing
  • role in maintaining tolerance
43
Q

innate immune system cells: dendritic cells
- characteristics of mature cells (6)

A
  • low antigen capture
  • high co-stimulatory molecule expression
  • high MHC class I and II expression
  • high inflammatory cytokine expression
  • migrate to lymphoid organs
  • potent T cell and NK cell activation
44
Q

innate immune system cells: innate lymphoid cells (ILCs)
- general characteristics (2)

A
  • cells that belong to the lymphoid lineage, but don’t express antigen specific receptors like BCRs and TCR of B cells and T cells
  • do not undergo clonal selection or expansion when stimulated
45
Q

innate immune system cells: ILCs
- counterparts (2)

A
  • NK cells though as innate counterparts of CD8 cytotoxic T cells and often grouped with ILC1 type cells
  • ILC1s, ILC2s, and ILC3s may be innate counterparts of T helper cell 1, T helper cell 2, and T helper cell 17 subsets
46
Q

innate immune system cells: ILCs
- activation (2)

A
  • response to signals from infected or injured tissue
  • migrate from site of production to infected or injured tissue and complete maturation into one of the ILC subsets
47
Q

innate immune system cells: ILCs
- functions (2)

A
  • secrete various cytokines that induce innate responses and regulate DC activity/maturation
  • ILC-derived cytokines help drive CD4 T cell subset differentiation
48
Q

innate immune system cells: NK cells
- functions (4)

A
  • kill tumours and virally infected cells by inducing apoptosis
  • modulate T cell development
  • major source of important innate immune cytokines (IFN gamma)
  • can kill cells with antibody bound to surface
49
Q

innate immune system cells: NK cells
- activation (3)

A
  • activated by dendritic cells
  • receptors for MHC I molecules and stress induced ligands act as inhibitory and activating receptors; complex balance of signalling determines if NK cell will be activated to kill or not
  • IL-12 is a potent NK cell activator
50
Q

NKG2D

A
  • NKG2D on NK cells binds to the NKG2D ligand on tumour cells to induce cytotoxicity ad IFN-gamma production
51
Q

SH2 domains

A

bind tyrosine-phosphorylated sequences in specific protein targets

52
Q

innate immune system cells: NK cells
- methods of killing target cells (2)

A
  • direct release of cytotocic granules using perforin and granzyme
  • receptor-mediated apoptosis via expression of Fas ligan or TRAIL
53
Q

innate immune system cells: eosinophils
- general characterIstics (2)

A
  • phagocytic cells, but less efficient than neutrophils
  • important in immune responses to parasites
54
Q

innate immune system cells: eosinophils
- method of killing (2)

A
  • binding of IgG-opsonized parasite to Fc receptors on eosinophils triggers degranulation
  • eosinophil peroxidase and cationic proteins of granule are deposited onto parasite surface to kill it
55
Q

innate immune system cells: basophils (4)

A
  • least abundant granulocyte
  • involved in immune response to parasites as they express IgE receptors and IL-4
  • associated with vide variety of inflammatory conditions as they contain histamine
  • strong association with allergies
56
Q

innate immune system cells: mast cells
- types (2)

A
  • mucosal mast cells
  • connective tissue mast cells
57
Q

innate immune system cells: mast cells
- mucosal mast cells

A
  • stimulate non-inflammatory responses against gut microbiota and IgE-mediated responses against intestinal parasites
58
Q

innate immune system cells: mast cells
- connective tissue mast cells (2)

A
  • release granules of pro-inflammatory mediators when activated and proteases that break down extracellular matrix
  • synthesize and secrete chemokines, cytokines, prostaglandins, and leukotrienes
59
Q

T cell activation (4)

A
  • requires 3 signals
  • signal 1: TCR/MHC-peptide interaction
  • signal 2: co-stimulation
  • signal 3: specific cytokines or combinations of cytokines from variety of accessory cells
60
Q

what are the effector CD4 T cell types (5)

A
  • Th1 cells
  • Th17 cells
  • Th2 cells
  • Tfh cells (follicular helper)
  • T regulatory cells
61
Q

what does the appropriate activation of DCs allow for

A
  • appropriate organization of other adaptive and innate immune system cells
62
Q

what causes inflammation

A
  • physical or chemical insults or invasion by microorganisms
63
Q

types of inflammation (2)

A
  • acute: typically short duration and an initial response to infectious agent
  • chronic: last months or year and could be due to the persistence of an infectious agent, aging and senescent cells, high fat diet, etc
64
Q

inflammatory response: resident mast cells

A
  • release histamine, prostaglandins, leukotrienes, pro-inflammatory cytokines, etc
65
Q

inflammatory response: resident macrophages/dendritic cells

A
  • secrete pro-inflammatory cytokines/chemokines, prostaglandins, ad leukotrienes upon pathogen recognition
66
Q

pro-inflammatory cytokines

A
  • TNF-alpha, IL-1, IL-6
67
Q

what do pro-inflammatory cytokines TNF-alpha, IL-1 and IL-6 do (2)

A
  • induce fever
  • induce production of acute phase proteins that function similar to antibodies by binding bacteria, opsonizing for phagocytosis, and activating complement
68
Q

what do pro-inflammatory cytokines TNF-alpha and IL-6 do

A
  • stimulate vascular endothelial cells and macrophages to secrete CSFs, which induce hematopoiesis in bone marrow
69
Q

what do pro-inflammatory cytokines TNF-alpha and IL-1 do (2)

A
  • act on vascular endothelial cells to increase blood vessel permeability and expression of cell adhesion molecules (CAM) and E-selectin
70
Q

pro-inflammatory chemokines (2)

A
  • activate G protein coupled receptors on leukocyte surface
  • cause integrins to change conformation, increasing affinity for CAMs on endothelial walls and enabling neutrophils to bind tightly to vessel wall
71
Q

PAMP (3)
- what does the acronym stand for
- definition
- what is it recognized by

A
  • pathogen-associated molecular pattern
  • not a host structure, but shared by large groups of pathogens and is essential for their survival (LPS, LTA, etc)
  • recognized by PRRs that are germ-line encoded (not associated with TCR and BCR random recombination of gene segments)
72
Q

toll-like receptors
- activation (2)

A
  • activated when binding of ligand to its leucine rich region induces formation of a dimer
  • generally functions as homo-dimers, but formation of hetero-dimers increase ligand diversity
73
Q

toll-like receptors
- structure (3)

A
  • extracellular domain: contains leucine-rich regions that interact with ligans
  • single pass transmembrane domain
  • cytoplasmic tail with Toll-IL-1 domain to interact with signalling protein
74
Q

toll-like receptors
- location (2)

A
  • some located in plasma membrane of cells and detect pathogens present in extracellular space
  • some located in endosome membranes and detect pathogens that entered cell by phagocytosis/endocytosis and are being degraded in phagosome/endosome
74
Q

toll-like receptors
- function (2)

A
  • binding of ligand to TLR can initiate signalling cascade that results in activation of transcription
  • activated TF can promote transcription of gees that encode pro-inflammatory cytokines, interferons, anti-microbial peptides or chemotactic factors depending on the TLR activated
75
Q

NF-kappa-beta (2)

A
  • family of transcription factors
  • sites located in many pro-inflammatory cytokine genes
76
Q

inactive NF-kB (2)

A
  • retained in cytoplasms by I-kB (I = inhibitor) through non-covalent interactions
  • I-kB has a cytoplasmic retention signal
77
Q

activation of NF-kB

A
  • activation of I-k kinases results in phosphorylation of I-kB subunit, causing it to dissociate from NF-kB and become degraded
  • NF-kB has a nuclear localization signal and is translocated to nucleus where it can promote transcription of genes with kB sites in their promoter
78
Q

RIG-I-like receptors (RLR) (3)

A
  • detect viral RNA in cytoplasm of cells during virus replication or gene expression
  • can recognize uncapped RNA or dsRNA
  • recognition results in signalling cascade that causes production of type I interferons
79
Q

cGAS-STING pathway
- function
- pathway steps (2)

A
  • detects dsDNA in cytoplasm of cell (viral or bacterial DNA)
  • cGAS catalyzes production of cyclic GAMP from GTP and ATP
  • cGAMP bind to STING, leading to activation of transcription factors that results in type I interferon production
80
Q

what do interferons do (2)

A
  • interfere with virus propagation inside infected cells
  • lead non-infected cells to start protective methods against pathogen

MICB 402 (11 decks)

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