Midterm 1 Flashcards
1
Q
What do microbe-host interactions facilitate?
A
Help us digest our food
Produce vitamins essential for life
Educate our immune system to keep ‘bad’ microbes out and protect us against environmental insult
2
Q
What is The Germ Theory of Infectious Disease
A
The theory that certain diseases are caused by the invasion of the body by microorganisms. The French chemist and microbiologist Louis Pasteur, the English surgeon Joseph Lister, and the German physician Robert Koch are given much of the credit for development and acceptance of the theory.
3
Q
What are Koch’s postulates?
A
- The microorganism must be found in abundance in all organisms suffering from the disease but should not be found in healthy organisms.
- The microorganism must be isolated from a diseased organism and grown in pure culture.
- The cultured microorganism should cause disease when introduced into a healthy organism.
- The microorganism must be reisolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent.
4
Q
An example of natural disasters and bacterial pathogens
A
Haitian cholera epidemics following the earthquakes in 2010 (~700,000 sick, nearly 9,000 dead)
5
Q
An example of hospital infections and bacterial pathogens
A
Spread of antibiotic-resistant ‘superbugs’ like Methicillin-Resistant Staphylococcus aureus (MRSA)
Secondary infections as complications in COVID-19
6
Q
An example of tainted food and bacterial pathogens
A
Listeria outbreak here in Alberta with meat processing
Multidrug resistant Salmonella in Foster Farms brand chicken (December 2013)
7
Q
How much of the population has been infected with M. tuburculosis?
A
1/3
8
Q
Leading causes of death globally
A
- Lower respiratory infections
- Neonatal conditions
- Diarrhoeal diseases
9
Q
Leading causes of death in high income countries
A
- Lower respiratory infections
10
Q
Leading causes of death in low-income countries
A
- Neonatal conditions
- Lower respiratory infections
- Diarrhoeal diseases
- Tuberculosis
11
Q
What does the death globally by age curve look like?
A
Bimodal
High under 5 years, significant drop, then increases steadily to 80-84 (maximum), then sharp drop after
12
Q
What is a pathogen?
A
An organism that can cause disease (damage the host)
13
Q
T/F all pathogens are oppurtunistic?
A
F
14
Q
Why don’t all interactions cause illness?
A
Because they can be effected by: microbe, host and enviornmental conditions
15
Q
What is pathogenicity?
A
Refers to the ability of an organism to cause disease (damage the host)
16
Q
What is virulence?
A
Refers to the degree of pathology caused by the organism
17
Q
What is infectivity?
A
Pathogen’s capacity for horizontal transmission and how frequently it spreads among hosts
18
Q
What are the common measures to define virulence?
A
50% infectious dose (ID50) and mortality (%).
19
Q
What is ID50?
A
Dose of bacteria at which 50% of the hosts (i.e. animals) are infected.
20
Q
What is Mortality (or case fatality)?
A
Percentage of the infected hosts that die
21
Q
What must bacteria maintain?
A
A resevoir
22
Q
What are some major issues associated with bacteria maintaing a resevoir?
A
Availability of essential nutrients
Lack of adherence sites or niches similar to host
Exposure to noxious chemicals/predators
Exposure to sunlight and extreme weather
23
Q
What are some survival strategies employed by bacteria when maintaining a resevoir?
A
Endo-sporulation (Gram positive)
Desiccation resistance (Gram negative)
Metabolic versatility
Dormancy
Genome plasticity
Colonize another host
Motility and chemotaxis
Alter membrane properties
Xenobiotic efflux (removing things from cells)
Biofilm formation
24
Q
What are Koch’s molecular postulates?
A
Proof that a gene product is an essential virulence factor
The pathogenic trait should be associated with the pathogenic members of the genus, species or strains.
Inactivation of the gene associated with the pathogenic trait should result in a measurable loss of pathogenicity or virulence.
Reversion or allelic replacement (complementation) of the mutated gene should restore pathogenicity.
25
How do we evaluate virulence factors?
Compare the ability of wild type and mutant bacteria to survive in a host and cause disease
1. Dilute bacteria to known concentration
2. Infect host (assess success of initial inoculation)
3. Allow animals to get sick (wild type, takes days)
4. Harvest organs and assess bacterial growth and pathology
26
Five common steps in bacterial infection
1. Entry into the host body for colonization
* Migration to a niche
* Often requires attachment
2. Evasion of host defenses (innate and adaptive)
3. Obtain nutrients, multiply to significant numbers and spread
4. Damage the host and produce disease
* Direct damage due toxins of the bacteria
* Collateral damage due to immune responses
5. Transmission from infected to susceptible host
27
Entry into the human body occurs via:
Wounds and burns
Insect bites
Ingestion of tainted food
The eye
Inhalation
Genitourinary tract
28
What do bacteria use to enter the host?
Flagella
29
What is motility often directed by?
The ability to sense chemical (chemotaxis), light (phototaxis), oxygen (aerotaxis) or magnetic fields (magnetotaxis)
30
Entry into the host: Motility and Taxis
Example: E. coli UTIs
Urine is nutrient-rich
E. coli can gain access to bladder
Bladder periodically cleansed by urination
Combination of motility and chemotaxis
31
What is mucin and what are some features of it?
Acts as lubricant but also traps bacteria
Prevents microbes from accessing/binding to first layer of cells
Is expelled by goblet cells
Is non-uniform (patchy)
32
What is the lamina propria
The thin layer of loose connective tissue underneath the epithelial cells
33
What are some strategies for adhesion?
Flagella
Pili
Fimbriae
Afimbrial adhesins
34
What do hosts usually have to protect against bacterial pathogens?
Antimicrobial peptides
35
How do some human defensins work?
By disrupting bacterial cytoplasmic membranes
36
What is a key feature of defensins?
They have a +ve charge that is critical for their function.
37
Overcoming host antibacterial peptides can be accomplished by?
Secreting peptidases
Synthesizing capsular polysaccharide layers
(works by limiting diffusion)
Lipopolysaccharide binding (Gram-negatives)
38
Sites of infection are often nutrient rich, however, some specific nutrients such as ___ are limited and restrict growth
Fe
39
B. burgdorferi does not use iron, instead uses?
Mn
40
What are the solutions for limited iron availability for pathogenic bacteria?
Don’t use Fe
Acquire sequestered Fe.
41
What is one pathway in which bacteria can aquire sequestered iron?
Siderophores
42
What are siderophores?
Low molecular weight compounds that chelate Fe with high affinity
43
Many bacterial pathogens possess a variety of -------- to produce toxins and other virulence factors
Secretory systems
44
What are essential for pathogenicity?
Toxins and virulence factors
45
What are toxins (or effectors)
Virulence factors either secreted into the extracellular milieu or translocated into the host cytosol to damage the host and make it susceptible.
46
Toxins may categorized as follows:
Non-proteinaceous (“endotoxin”)
* Lipopolysaccharides
```
```Proteinaceous (“exotoxin”)
* A-B toxins
* Proteolytic toxins
* Pore forming toxins
* Other toxins
47
After causing damage through secretion of toxins and effectors the immune system responds by creating what?
Pus
48
What is pus?
DNA, proteins dead immune cells and other host cells
49
What are spreading factors?
Proteins like DNases and proteases that act as “meat tenderizers,” which facilitate spread into neighbouring tissues
50
What are some common mechanisms of transmission?
Inhalation: Coughing/sneezing, spores in air
Contaminated water: Fecal material
Vectors: insects
51
What does immunity function to do?
Keep most bacteria at bay or relegate them to controlled areas
52
What are the two main branches of mammalian immunity?
Innate immune system
Adaptiuve immune system
53
Describe some key features of the innante immune system
Defenses against infection ready for immediate activation prior to attack by a pathogen
No learning or memory
Not specific to a pathogen
Includes physical, chemical and cellular barriers
Begins to develop at conception, fully developed at birth
54
Examples of innate immune system
Barriers to infection (skin, microbiota, mucosal membranes)
Components of cell-mediated immunity
Complement
Chemokines and cytokines
55
What is the epithelia (or epithelial layers)
Cells that cover all of the external and internal surfaces of the body that are exposed to the environment.
A key initial defense system
56
Internal surface areas (called mucosal epithelia) are comprised of -------- epithelial layer.
One
57
What is nutritional immunity
Host proteins (ex. lactoferrin, transferrin, ferritin, etc.) that sequester vital nutrients like iron
58
What is the mucociliary escalator
A major barrier against infection in which cilia are continually beating and push microorganisms out of the body
59
What is the mucociliary escalator composed of?
Mucus-producing goblet cells and ciliated epithelium
60
What does the mucociliary escalator cover?
Most of the bronchi, bronchioles and nose
61
Resident, commensal microbiota help protect against infection by
Filling a niche and outcompeting potential pathogens and sometimes producing bactericidal compounds
62
What are some examples of antimicrobials produced by host microbiota?
Colicins
Lugdunin
Bte1 and Bte2
63
What are colicins?
Proteins produced by E. coli that kill other E. coli strains (narrow spectrum)
64
What is lugdunin?
An antibiotic produced by S. lugdenensis, a colonizer of the nose, which prevents colonization by S. aureus
65
What is Bte1 and Bte2?
Bacteroidetes fragilis T6SS effectors that mediate competition with other microbiota in the mammalian gut
66
What are the categories of innate immune cells?
Phagocytes
Natural Killer Cells
Mast Cells
67
Differences between innate immune cells
1. Localization
DCs are fixed in defined locations
PMNs and monocytes migrate through bloodstream
2. Cell Census
More PMNs than monocytes
PMNs short-lived compared to monocytes
3. Cell Differentiation
Monocytes differentiate to macrophages and DCs upon entering tissue
PMNs activated by bacteria to enter tissue but no differentiation
68
Where do neutrophiles target?
Infection sites
69
Neutophil cell communication
Activates immune cells and allows them to respond to invasion in a cooperative fashion
Signaling pathways activate neutrophils to undergo extravasation/transmigration
Involves cytokines (chemical messengers)
Surface receptors allow immune cells to respond
Cells use chemotaxis (complement, bacterial molecules, cytokines) to home in on infection
Adhesion molecules allow cells to snare passing phagocytes needed in tissue
70
What are the two routes for transmigration into tissue:
paracellular (between endothelial cells)
transcellular (through endothelial cells)
71
What guides neutrophils to sites of transmigration
Chemokines
72
Process of neutrophil recuitment
Different adhesion molecules are produced in the vasculature of different tissues, which bind to specific receptors expressed on the surface of the neutrophils.
Chemokines bind to receptors on neutrophils and induce conformational changes in integrins.
Conformational changes in integrins allow neutrophils to adhere to vasculature.
Neutrophils actively choose sites for transmigration.
73
What are oponins?
Antibodies or other substances (like complement) that bind to foreign microorganisms making them more susceptible to phagocytosis.
74
What are opsonins recognized by?
Opsonins are recognized by receptors on the surface of neutrophils.
Antibodies -> FcR
C3b (complement) -> C3bR
75
What does opsonization facilitate?
Opsonization facilitates molecular recognition of a microbe by a neutrophil.
76
Describe and diagram neutophil phagocytosis
Ingestion
Killing
- Fusion of phagosome and lysosome
- Phagolysosome: release of lysozyme, proteases, defensins; production of peroxide, superoxide, hyperchlorous acid, nitric oxide; degradation of bacteria
- Release of bacterial fragments
77
The neutrophil oxidative burst
A critical antimicrobial mechanism, involves the catalytic conversion of dimolecular oxygen into superoxide anion by the NADPH oxidase complex.
Neutrophils produce a mix of toxic compounds in the phagolysosome: hypochlorous acid (by myeloperoxidase, or “MPO”), superoxide anion (via NADPH oxidase), singlet oxygen, hydrogen peroxide and hydroxyl radicals; reactive nitrogen species originate from nitric oxide synthase (“NOS”), which produces nitric oxide.
78
Innate immunity first line of defence
Skin is a physical barrier
Cilliated cells and mucus in respiratory tract
Commensal microbiota
79
Innate immunity second line of defence
Innate immune cells
Phagocytic cells (like neutrophils) and phagocytosis
Antimicrobial substances
80
What are the two parts of adaptive immunity?
Humoral (antibodies)
Cell-mediated
81
T/F adaptive immunity matures throughout life and develops highly specific responses to individual pathogens
T
82
What is the hallmark of adaptive immunity
Memory – Previous exposures to a pathogen lead to an enhanced immune response upon re-exposure
83
What is an antigen?
Substances that react with either antibodies or T lymphocyte antigen receptors (T-cell receptors, “TCRs”).
A wide range of molecules can act as antigens, including proteins, lipoproteins, many polysaccharides, some nucleic acids and certain techoic acids
84
What is an immunogen?
An antigens that elicits an immune response
85
What are antibodies or immunoglobulins
Proteins produced by plasma cells that bind to specific regions of antigens (called epitopes) via a variable antigen-binding site.
86
What is the epitope?
The part of an antigen that is recognized by the immune system (including antibodies, TCRs and B-cell receptors).
87
Antigens are presented in the context of the
Major histocompatibility complex (MHC).
88
MHC class I is found on
All nucleated cells and platelets.
89
MHC class II is found on
professional antigen presenting cells (ex. B-cells, DCs, macrophages, neutrophils, etc.)
90
What is an essential process for T-cell function.
Antigen presentation
91
Antigens that are generated endogenously (i.e. within the cell) are:
Digested by the proteasome
Loaded onto MHCI in the endoplasmic reticulum by the TAP (transporter associate with antigen processing)
Exported to the cell surface (through the Golgi and in a secretory vesicle).
92
T-cells become activated when
The TCR binds to the corresponding MHC molecule
93
In the case of the cytotoxic T-cell, the CD8 co-receptor binds to
β2-microglobulin of MHC I
94
The cytotoxic T-cell response
In the case of the cytotoxic T-cell, the CD8 co-receptor binds to β2-microglobulin of MHC I.
Release of granule content into cells
Cell death by apoptosis
95
What do MHC class II molecules bind to?
Peptides that are derived from proteins degraded in the endocytic pathway
96
Antigen presentation on MHC II involves:
Digestion of the phagocytosed foreign antigen through the endocytic pathway
Processing of MHC II through the endoplasmic reticulum and export through the Golgi apparatus to another cellular compartment termed the MHC class II compartment (MIIC). MHC II is stabilised by an invariant chain (Ii).
Digestion in the MIIC leaves a piece of the Ii in the MHC II molecular antigen binding groove. This is called the class II-associated Ii peptide (CLIP) (this is indicated by the red “protein” in the diagram above).
There is a chaperone mediated exchange of CLIP for an antigen processed through the endocytic pathway in the phagolysosome.
The antigen-loaded MHC II molecule is then exported and presented on the surface of the cell.
97
What is the example role of Tfh
Class switching (long-term humoral immunity)
98
What is the example role of Th2
Antibody production by B-cells
99
What is the example role of Th1
Macrophage activation
100
What is the example role of Th17
Neutrophil activation
101
What is the example role of iTreg
Immune tolerance
Lymphocyte homeostasis
102
What do TH1 cells activate
Macrophages
103
The CD4 co-receptor recognizes and binds to
The β1 and β2 subunits of MHCII.
104
What do TH2 cells activate
B-cells
105
What does Tfh mediate
Class-switching
106
What is class-switching (or affinity maturation)
Long-term humoral immunity is associated with immunoglobulin isotype switching (Tfh).
107
Five major classes of antibodies:
gA, IgG, IgM, IgD and IgE that vary in oligomermic state.
108
IgM antibodies
1st antibody that is produced
Pentamer
109
IgG antibodies
Major circulating antibody
Found in extracellular fluid, blood, lymph
Can cross the placenta
110
IgA antibodies
Found in body secretions (ex. saliva, tears, breast milk, colostrum, gastrointestinal secretions and mucous)
Present in secretions as a dimer
111
- Binding of antibodies to antigens inactivates antigens by:
o Neutralization (blocks viral binding sites; coats bacteria and/or opsonization)
o Agglutination of antigen-bearing particles, such as microbes
o Precipitation of soluble antigens
o Complement fixation (activation of complement)
112
The functions of antibodies are to
enhance phagocytosis or to cause cell lysis
