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
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
3
Q
what occurs if our immune system malfunction
A
- disease
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
5
Q
what is the most common cause of premature death in human history
A
- infectious disease
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
7
Q
what percentage of deaths were due to infectious disease in min-19th century England
A
- 60%
8
Q
what can explain variance in the deaths from infectious diseases in different places (3)
A
- hygiene
- vaccines
- antibiotics
9
Q
which organisms have defences against pathogens
A
- multicellular organisms
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)
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
12
Q
what does the epithelia comprise
A
- comprise skin and linings of body’s tubular structures (gastrointestinal tract, respiratory tract, urogenital tract)
13
Q
mucosal epithelial cells (2)
A
- secrete mucous, a thick and viscous fluid
- mucous coats microorganisms and prevents their attachment to the epithelia
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
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
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
17
Q
what are the characteristics of the adaptive immune response (2)
A
- highly specific
- generates immunological memory (basis of vaccines)
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)
19
Q
what are disadvantages of the adaptive immune system and examples (2)
A
- inappropriate responses
- allergies, autoimmunity
20
Q
innate immune system
A
- universal and evolutionarily conserved mechanism of host defence
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
22
Q
innate immune system
A
- universal and evolutionarily conserved mechanism of host defence
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
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
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
