1
Q
disease
A
any condition in which the normal structure or function of the body is damaged or impaired
2
Q
pathogen
A
a disease causing microrganism
3
Q
Steps of immune response
A
- recognition phase
- activation phase - fighting invader
- effector phase - destroying invader
4
Q
nonspecific (innate) immune response
A
first line of defense - lacks immunological memory
5
Q
specific (adaptive) response
A
resistance to a particular foreign agent
has memory
6
Q
- recognizing pathogens
A
- specialised receptors in cells recognize foreign pathogens
- these are known as PRRs (pattern recognition receptors) - lots of diversity in animals
7
Q
TLRs (toll-like receptors)
A
- found in both vertebrates & invertebrates
- dif TLRs recognize dif PAMPs - mammals have at least 10 TLRs
- sensing of PAMPs by cells of the immune system (through their PRRs) sets off the NEXT stage of the immune response
8
Q
DAMPs
A
- TLRs recognize DAMPs: damage-associated molecular patterns
- signals of damage to an endogenous cell by a pathogen
- can include: membrane damage; molecules released by stress, dead, or dying cells; signals of tissue damage
9
Q
PAMPs
A
- TLRs recognize MAPS : microbial-associated molecular patterns
- carbohydrates, polypeptides, & nucleic acid molecules expressed by viruses, bacteria, & parasites
10
Q
Having PRRs inside the cell helps. . .
A
guard against pathogens that can breach the cell membrane undetected
11
Q
- Activation of the immune response
A
PAMP sensing PRRs leads to:
1. secretion of defensins or other antimicrobial peptides
2. production of pro-inflammatory cytokines
3. activation of the complement system
4. phagocytosis
ALL ARE NON-SPECIFIC & PART OF THE INNATE IMMUNE RESPONSE
- targeted responses to specific threats by the adaptive immune response (takes days or weeks)
12
Q
Secretion of defensins
A
- type of antimicrobial peptide is an ancient form of defense
- are positive
- defensins disrupt the structural integrity of pathogen membranes & some viral envelopes
13
Q
Phagocytosis
A
once pathogens have been disrupted or identified, they must be removed from the cell
- the process in which a cell encloses large particles in a phagocytic vacuole (phagosome) & engulfs them
14
Q
2 consequences of phagocytosis
A
- activation of a pro-inflammatory response to recruit additional immune cells to sire of injury / threat
- activation of adaptive immune system by antigen presentation to T and B cells
15
Q
What links the innate & adaptive immune response?
A
antigen presentation by phagocytes
16
Q
the dendritic cell is a component of?
A
the innate system
17
Q
the T cell is a component of ?
A
the adaptive system
18
Q
Outline the process that occurs after microbes enter a break in skin
A
- microbes enter through break in skin & are phagocytosed by dendritic cells
- activated dendritic cell carries microbial peptides to local lymph node
- activated dendritic cell activates specific T cells to respond to microbial peptides bound to MHC proteins on dendritic cell surface
- activated T cells migrate to site of infection via the blood
19
Q
Where do B and T cell mature/
A
B cells mature in bone marrow
T cells mature in thymus
20
Q
antigen
A
a molecule that can induce an adaptive immune response or that can bind to an antibody or T cell receptor
21
Q
What happens after T cell gets activated?
A
- it will proliferate
- differentiates into cytotoxic T cells + helper T cells
- cytotoxic T cells will move to site of infection & directly kill parasites or virus-infected cells by secretion of cytotoxic molecules
- helper T cells don’t actually kill pathogens
- instead, they release cytokines that recruit other cells to the site of injury
22
Q
What happens after you activate a B cell?
A
it starts making antibodies which bind tightly to their target pathogen, inactivating it or marking it for destruction by phagocytosis or complement-induced lysis
- proliferates & differentiates into EFFECTOR B cells
23
Q
So whats the difference between t and b cells?
A
T cells KILL the pathogen
B cells BIND to the pathogens, secrete antibodies, and allow them to be digested by phagocytes
24
Q
So what’s the difference between t and b cells?
A
T cells KILL the pathogen
B cells BIND to the pathogens, secrete antibodies, and allow them to be digested by phagocytes
25
Why does the adaptive immune response require so much time to be effective?
1. the right T & B cells need to recognize the pathogen
2. T and B cells needs to expand / proliferate
3. T & B cells need to neutralize the threat
26
How do B cells provide long-lasting memory of infection?
- after encountering their specific target antigen, some B cells will become long-lived memory B cells
- secondary exposure to this target will result in a faster, more intense immune response
27
What causes the diversity of T & B receptors & antibodies?
V(D)J recombination
- the genome of each B & T cell undergoes random rearrangement of a set of regions known as V, D, & J, all of which are part of the genes coding for antibodies
- dif V,D,J combinations = dif antigen binding sites = dif antigens recognized
28
Animals have. . . (as part of defense system)
- basal innate immunity
- innate complement system (aids activities of both adaptive & innate systems by marking pathogens)
- adaptive immune response (antibodies & specialized cells)
29
Plants have. . . (as part of defense system)
- no circulating antibodies or cells
- structural barriers: cuticle, cell wall
- basal innate immunity = pathogen triggered immunity (PTI)
- mediated by the equivalent of a PRR
- effector triggered immunity (ETI); often "gene for gene" interaction
- mediated by dif receptors
- adaptive systemic signals emanating from infection sites (systemic acquired resistance)
- toxic molecules, programmed cell death
30
Bacterial adaptive defences: the CRISPR system
- infection from phage or similar is recorded in CRISPR array & expressed in subsequent infection
- 2 components: CRIPSR array + Cas protein
- Cas protein (degrade pathogens)
- CRIPSR used to retain memory of previous infection
3 steps: adaptation, expression, interference
31
What causes diseases?
- single pathogen (could be)
- imbalance in microbial communities
- any lineage besides archaea
32
Viruses
- infectious agent
- not cellular
- cannot reproduce by itself
- needs a host cell to make copies of itself
- comprised of a genome (DNA or RNA), capsid (protein) & sometimes a membrane (lipid)
- no ribosomes, organelles, energy metabolism
- small (nano - rather than micrometre)
- most are plant pathogens
33
Why are viruses hard to treat?
because they use the host's cellular machinery for replication - you have to stop the host from making DNA
34
bacteria
- lack a membrane-bound organelles, nucleus, & cytoskeleton
- dif cell walls (peptidoglycan in bacteria)
- gram stain is used as a broad way to differentiate bw bacteria based on cell wall structure
- penicillin targets peptidoglycan
- dif rRNA sequences (so dif ribosomes)
35
Parasitic protists
- eukaryotes
- cause many diseases, like malaria, toxoplasmosis
- limited treatment options because they are eukaryotes, just like us
36
Fungi
- one of the most common diseases in people (e.g. dandruff)
- a number of species are also able to kill people
- invasive fungal infections kill more people than TB or malaria
- 150 people die an hour from fungal diseases
37
How do pathogens, overall, cause damage to the host?
- colonise a host
- grow within the host
- evade host immune system & defense
- damage the host
- leave the host
38
What do viruses lack?
- metabolic processes
- ribosomes
39
what is the optimal outcome for a microbe?
- reproduction & survival
40
types of host-microbe interactions
- MUTUALISM - both microbe + host benefit
- COMMENSALISM - microbe benefits but offers no benefit OR harm
- PARASITISM: microbe benefits to the detriment of the host, as is often the case for pathogens
41
primary vs asymptomatic vs opportunistic
primary pathogens - cause overt, immediate disease
asymptomatic cases - may affect single person for years with no clear symptoms
opportunistic pathogens - cause disease only if immune system is weakened
42
the damage response framework
- microbes can cause disease with either TOO LOW OR TOO HIGH of immune response
- e.g. toxic shock syndrome caused due to production of way too many toxins & activated T cell
- overactive immune responses can cause disease in absence of a pathogen, e.g. allergies & autoimmune diseases
43
virulence
severity of harmfulness of a disease or poison
can or cannot be easier to transmit (if im dying in bed cause of some disease then it's unlikely i'll see many people so transmission chances r low)
44
Red queen hypothesis
- host & pathogen are constantly trying to outsmart each other
- one thrives at the expense of the other
pathogens cause disease + decrease a host's ability to reproduce so HOST INTERESTED IN defending against pathogens
pathogens INTERESTED IN INFECTING host - e.g. easier access to nutrients
these 2 are incompatible - endless conflict; leads to both host + viral evolution
45
how can resistance move bw some bacteria easily?
- bacteria may have specific genes to break down antibiotics, often carried on small pieces of DNA (plasmids)
- these plasmids or fragments can move bw species
exposure to fungicides in agriculture means the fungus is drug resistant when it enters a human
resistance has emerged to all known fungicides
46
why do some vaccines fail?
- there is variation bw microbe strains
- or. . . some modify their appearance quickly
- they target immune cells specifically (e.g. HIV kills memory B cells so it can't actually destroy HIV)
- few antigens are available that induce a protective response
- or, people's immune systems vary
47
most important criterion for antimicrobial chemicals
- must inhibit or kill microbe but NOT host
- usually work by inhibiting an ASPECT of microbe's biology that is unique & not found in humans
48
Discuss some of the ways new antimicrobial compounds can be discovered.
discovery through:
1. massive chemical screens
2. luck & then hard work
3. screening microbes (& plants) for active agents
4. traditional medicine for clues
49
cancer
a large group of diseases with different properties & prognoses, but 2 unifying commonalities:
1. all cancers are caused by unchecked cell proliferation
2. have the ability to invade other tissues
50
what is a tumour?
a tumour is simply a mass of cells - not all are cancerous
benign tumours dont have ability to invade other tissues
some blood cancers are liquid
51
hereditary vs nonhereditary cancers
hereditary retinoblastoma --> inherited mutant Rb gene; occasional cell inactivates its only good Rb gene copy; excessive cell proliferation leading to retinoblastoma
also possible that it isnt hereditary & genes on both chromosomes mutate
52
vast majority of cancers are. . .
SPORADIC (caused by somatic mutations so not passed on)
53
how does a tumor form (simply)?
normal cell has cell division & apoptosis occurring at constant rate (homeostasis)
INCREASED cell division, normal apoptosis --> tumour
normal cell division, DECREASED apoptosis --> tumour
54
disregulation of WHICH 4 main cellular mechanisms gives rise to cancer?
1. alterations in cell proliferation
2. alterations in DNA damage response
3. alterations in cell growth
4. alterations in cell survival
all these sustain the cancer phenotype
55
the karyotypes of late-stage cancers reveal. . .
extreme genetic instability, with widespread chromosomal gains, losses, & rearrangments (karyotype looks crazy)
56
2 major classes of genes are mutated in cancer genes
1. tumour suppressor genes
2. dominant oncogenes (oncogenes are mutated forms of NORMAL PROTO-ONCOGENES)
57
what might mutations cause
- over-expression of the gene product
- aberrant activity
- imitation of normal growth and death signals
58
what are proto-oncogenes?
a group of genes that cause normal cells to become cancerous when they are mutated
59
what does mutation in one copy of proto-oncogene lead to? (this is gain of function)
hyperactive oncogene; excessive cell survival, proliferation or both
proto-oncogenes become oncogenes in a DOMINANT MANNER (only 1 gene copy)
60
recessive mutation (loss of function)
mutation inactivates one copy of tumour suppressor gene - second mutation inactivate second gene copy
complete loss of tumour suppressor gene activity
excessive cell survival, proliferation or both
recessive
61
what are tumour suppressor genes?
- have roles in cell cycle control or the DNA damage response
- checkpoint genes such as cyclins, CDKs, etc. control the transition from 1 cell cycle phase to the next
62
what happens when a checkpoint fails?
- p53 is a G1 checkpoint sensor, always expressed in cells
- when it senses DNA damage, it stimulates production of p21
- e.g. X-ray damage DNA
- p21 binds to G1 CDKs, preventing their activation & stopping cycle progression
- if the damage is too severe to be repaired, the cell will undergo apoptosis
- CELLS DON'T PASS ON DAMAGED DNA
63
p53 is a recessive tumour suppressor
- p53 is a key sensor of DNA damage, mutated in roughly 50% of cancers
- loss of a single copy of p53 is not enough for a cell to lose its damage sensing properties
mutations to BOTH COPIES are need before loss of p53 function (so p53 won't bind to DNA and the damaged DNA will replicate)
64
how do proto-oncogenes have different functions from tumour suppressors?
- they stimulate cell growth
- inhibit cell death or terminal differentiation
genes in growth signaling pathways are often proto-oncogenes --> these pathways respond to external stimuli (growth factors) by setting off a cascade of signalling that leads to cell growth & division
65
what do mutations do to proto-oncogenes?
normally proto-oncogenes function only when a signal binds to receptor; but mutations cause the pathway to ALWAYS be active even without the growth factor signal / stimulus
66
or proto-oncogenes, a mutation in ANY STEP of the signalling pathway will. . .
have similar effects (e.g. lead to untimely cell division and proliferation)
some proto-oncogenes prevent cells from undergoing APOPTOSIS in the presence of pro-apoptotic signals (eg. sensing severe DNA damage by p53)
67
Peto's paradox
Large animals are:
1. made of many cells
2. long lived
so, if cancer risk depends on how big you are, and how long you live, elephants should get cancer much more often than mice
68
So why don't large animals get cancer as often?
most animals have 2 functional p53 alleles
- 2 dif research groups have shown that elephants have up to 20 copies of the p53 gene
- their cells are far more capable of tolerating DNA damage
69
devil facial tumour disease
- responsible for death of up to 80% of tasmanian devils in some sites
- sick animals develop multiple tumours all over the face that prevent them from feeding
- die from starvation or secondary infection
IT IS TRANSMISSIBLE
70
how is DFTD transmitted to other tasmanian devils?
analysis of karyotpes shows that DFTD is transmitted through the cancerous cells themselves; the JUMP from one animal to another, evading the immune system
71
Why do most cancers develop later in life?
developing cancer requires accumulating multiple mutations and this takes time
72
what can impact cancer risk?
environmental & behavioural forces (e.g. smoking, using refrigerators)
Biology 1
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