MICB 402 > Introduction > Flashcards

Introduction Flashcards

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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
where are cells in the immune system produced (2)
- in the bone marrow through hematopoiesis - cells are constantly replenished as needed
26
how does the immune system responses change over time and why (2)
- 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
27
innate immune system cells: neutrophils - key characteristics (4)
- short lived - abundant in the bloodstream - abundantly produced each day - key soldier for innate immunity; they are essential to living
28
innate immune system cells: neutrophils - activation (2)
- 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
29
innate immune system cells: neutrophils - strategies for killing pathogens (3)
- phagocytic dependent - phagocytic independent - NETs
30
innate immune system cells: neutrophils - phagocytic dependent killing of pathogens
- phagocytosis of antibody-opsonized pathogens and killing of ingested bacteria by production of reactive oxygen and nitrogen species
31
innate immune system cells: neutrophils - phagocytic independent killing of pathogens
- degranulation: various digestive proteins are released in 3 types of granules to kill pathogens
32
innate immune system cells: neutrophils - NETs (2)
- release of neutrophil extracellular traps which contain fibres of chromatin and serine proteases - trap and limit the spread of pathogens
33
innate immune system cells: monocytes - categories (2) - differences (2)
- 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
innate immune system cells: monocytes - inflammatory monocytes
- differentiate into macrophages or dendritic cells depending on cytokine environment
34
innate immune system cells: monocytes - patrolling monocytes (4)
- 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
innate immune system cells: macrophages - general characteristics (3)
- 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
innate immune system cells: macrophages - receptors (4)
- 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
innate immune system cells: macrophages - methods of killing pathogens (2)
- 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
innate immune system cells: macrophages - invasion by pathogen
- some bacteria can evade macrophage defences and grow within cells
39
innate immune system cells: macrophages - types (3)
- 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
innate immune system cells: dendritic cells - general characteristics (3)
- present in small numbers - many different subsets - similar lifespan to macrophages
41
innate immune system cells: dendritic cells - activation (2)
- 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
innate immune system cells: dendritic cells - characteristics of immature cells (6)
- 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
innate immune system cells: dendritic cells - characteristics of mature cells (6)
- 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
innate immune system cells: innate lymphoid cells (ILCs) - general characteristics (2)
- 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
innate immune system cells: ILCs - counterparts (2)
- 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
innate immune system cells: ILCs - activation (2)
- 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
innate immune system cells: ILCs - functions (2)
- secrete various cytokines that induce innate responses and regulate DC activity/maturation - ILC-derived cytokines help drive CD4 T cell subset differentiation
48
innate immune system cells: NK cells - functions (4)
- 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
innate immune system cells: NK cells - activation (3)
- 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
NKG2D
- NKG2D on NK cells binds to the NKG2D ligand on tumour cells to induce cytotoxicity ad IFN-gamma production
51
SH2 domains
bind tyrosine-phosphorylated sequences in specific protein targets
52
innate immune system cells: NK cells - methods of killing target cells (2)
- direct release of cytotocic granules using perforin and granzyme - receptor-mediated apoptosis via expression of Fas ligan or TRAIL
53
innate immune system cells: eosinophils - general characterIstics (2)
- phagocytic cells, but less efficient than neutrophils - important in immune responses to parasites
54
innate immune system cells: eosinophils - method of killing (2)
- 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
innate immune system cells: basophils (4)
- 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
innate immune system cells: mast cells - types (2)
- mucosal mast cells - connective tissue mast cells
57
innate immune system cells: mast cells - mucosal mast cells
- stimulate non-inflammatory responses against gut microbiota and IgE-mediated responses against intestinal parasites
58
innate immune system cells: mast cells - connective tissue mast cells (2)
- release granules of pro-inflammatory mediators when activated and proteases that break down extracellular matrix - synthesize and secrete chemokines, cytokines, prostaglandins, and leukotrienes
59
T cell activation (4)
- 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
what are the effector CD4 T cell types (5)
- Th1 cells - Th17 cells - Th2 cells - Tfh cells (follicular helper) - T regulatory cells
61
what does the appropriate activation of DCs allow for
- appropriate organization of other adaptive and innate immune system cells
62
what causes inflammation
- physical or chemical insults or invasion by microorganisms
63
types of inflammation (2)
- 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
inflammatory response: resident mast cells
- release histamine, prostaglandins, leukotrienes, pro-inflammatory cytokines, etc
65
inflammatory response: resident macrophages/dendritic cells
- secrete pro-inflammatory cytokines/chemokines, prostaglandins, ad leukotrienes upon pathogen recognition
66
pro-inflammatory cytokines
- TNF-alpha, IL-1, IL-6
67
what do pro-inflammatory cytokines TNF-alpha, IL-1 and IL-6 do (2)
- induce fever - induce production of acute phase proteins that function similar to antibodies by binding bacteria, opsonizing for phagocytosis, and activating complement
68
what do pro-inflammatory cytokines TNF-alpha and IL-6 do
- stimulate vascular endothelial cells and macrophages to secrete CSFs, which induce hematopoiesis in bone marrow
69
what do pro-inflammatory cytokines TNF-alpha and IL-1 do (2)
- act on vascular endothelial cells to increase blood vessel permeability and expression of cell adhesion molecules (CAM) and E-selectin
70
pro-inflammatory chemokines (2)
- 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
PAMP (3) - what does the acronym stand for - definition - what is it recognized by
- 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
toll-like receptors - activation (2)
- 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
toll-like receptors - structure (3)
- 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
toll-like receptors - location (2)
- 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
toll-like receptors - function (2)
- 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
NF-kappa-beta (2)
- family of transcription factors - sites located in many pro-inflammatory cytokine genes
76
inactive NF-kB (2)
- retained in cytoplasms by I-kB (I = inhibitor) through non-covalent interactions - I-kB has a cytoplasmic retention signal
77
activation of NF-kB
- 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
RIG-I-like receptors (RLR) (3)
- 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
cGAS-STING pathway - function - pathway steps (2)
- 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
what do interferons do (2)
- interfere with virus propagation inside infected cells - lead non-infected cells to start protective methods against pathogen
MICB 402
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