Biology 207 Exam #4 Flashcards
1
Q
Symbiosis
A
Close, prolonged physical or metabolic interactions between two or more populations
2
Q
The Human Microbiome
A
The indigenous microbial communities of the human body
*exist on all external and internal surfaces of the body
Significant positive effects of this symbiotic relationship
*useful metabolites, digestion, colonization resistance, immune responses
3
Q
Microbial Load vs. Body Site
A
Human to microbial cells ~ 1:1
Microbial cells are not even distributed at body sites, not typically associated with disease, often present in vastly diverse communities
4
Q
The Human Microbiome is dominated by four phyla of bacteria
A
Bacteroidetes & Firmicutes > Actinobacteria & Proteobacteria
5
Q
The Human Microbiome Cont.
A
Each body site is colonized predominantly by only certain bacterial species
The composition and diversity of the human microbiome is strongly determined by habitat
6
Q
The Human Microbiome Cont.
A
Carriage of microbial taxa varies between sites and between individuals while metabolic pathways for each site remain stable within a healthy population
7
Q
Genomics and the Human Microbiome
A
The humane intestinal microbiome contains at leas 100 times as many different genes as our own genome
*significantly enriched for metabolism of exogenous substrates
Numerous examples of genetic susceptibilities in animals manifesting only in the presence of a microbiome or specific microbiome composition
8
Q
Pregnancy and Human Microbiome
A
Acquisition of the microbiome in early life by vertical transmission and factors modifying mother-to-child microbial transmission
Birth mode, diet shape microbiome composition during early life
9
Q
Microbiome of the Skin
A
The skin surface varies greatly in chemical composition and moisture content
Three micro-environments: dry skin, moist skin, sebaceous skin
10
Q
Microbiome of the Skin Cont.
A
Each micro-environment shows a unique microbiota
*composition influenced by environmental factors and host factors
11
Q
Aerodigestive Tract
A
A tube that permits the external environment passage through the body
*epithelial cell lining that is covered with mucus, except the lowest part of the airways
12
Q
Bacterial Abundance
A
Increases as you move through the GI tract, with different sections providing distinct habitats for microbial growth
13
Q
Mucosal Layer
A
Prohibits microorganisms from engaging directly with the epithelial surface in healthy individuals
Enterocyte = epithelial cell
14
Q
Epithelium
A
The single layer lining the aero-digestive tract and is made up predominantly of epithelial cells, with lesser numbers of secretory cells and a small number of a variety of other cells
15
Q
Epithelium
A
The single layer lining the aero-digestive tract and is made up predominantly of epithelial cells, with lesser numbers of secretory cells and a small number of a variety of other cells
16
Q
Mucins
A
Proteins that are the major components of the extracellular mucus layer that protects and lubricates the epithelium
High-molecular-mass glycoconjugates with oligosaccharide chains in O-glycosidic linkages to a protein backbone
*form a mesh layer that absorbs water/forms gels
17
Q
Intestinal Mucus
A
Protected by mucus, forms a single, easily removable mucus layer, and in the colon forms a double layer, with the inner mucus layer firmly attached to the epithelium
Major building blocks giving mucus its properties are large glycoproteins called mucins
18
Q
Intestinal Mucus Cont.
A
In the small intestine, the mucus layer is penetrable, but the bacteria are kept away from the epithelium by antibacterial mediators
In the large intestine, the inner mucus layer is impenetrable to bacteria whereas the outer mucus layer is expanded and serves as the habitat for the bacteria
19
Q
Gut Microbiome
A
Architecture of the gut microbiome is largely determined by diet and physiochemical conditions in the gut
*pH gets higher when going from stomach to colon
*as pH increases, so does load of bacteria
Acidity of stomach and duodenum prevent many organisms from colonizing these regions
20
Q
Gut Microbiome Cont.
A
Mucosal layer prohibits microorganisms from engaging directly with the epithelial surface in healthy individuals
*mucosal layer = mucus + host defense molecules
In individuals with IBS, etc, disruption of the mucosal barrier allows bacteria to engage with the epithelium
21
Q
Colonization Resistance
A
How the gut microbiome prevents the invasion of new pathogenic species
*loss of colonization resistance by antibiotics can lead to intestinal infection, etc.
22
Q
Fecal Microbiota Transplant (FMT)
A
A procedure in which feces is collected from a tested donor, mixed with a saline, strained and placed in a patient
23
Q
The Healthy Lung is not conducive to…
A
Microbial colonization by mucosal anaerobes, Gram + bacteria and others
24
Q
Heathy Lungs
A
Aerobic, cilia, lower surface temperatures in trachea and bronchi
Surfactant in alveoli, surfactant proteins and anti-microbial peptides, very little mucin in alveoli, home of the only phagocytes to actively patrol an external surface
25
Healthy Lungs Cont.
The lung is a low microbial biomass site
26
Monosaccharides
The most basic units of carbohydrates and cannot be hydrolyzed to simpler compounds
*glucose, fructose, galactose
27
Polysaccharides
Polymeric carbohydrate molecules composed of long chains of monosaccharide units bound together by glycosidic linkages
Range in structure from linear to highly branched, often quite heterogenous, may be soluble or insoluble
*starch and cellulose are polysaccharides composed of a or b glucose monomers
28
What makes all polysaccharides different?
The types and rations of different monosaccharides in the polysaccharide
The chemical linkages that join all the monosaccharides
29
Dietary Fiber
The edible parts of plants or analogous carbohydrates that are resistant to digestion and absorption in the human small intestine, with complete or partial fermentation in the large intestine
Includes polysacc, oligosacc, lignin, plant substances
*carbohydrate polymers with >10 monomeric units are not hydrolyzed by the endogenous enzymes in the small intestines of humans
30
Digestion Cont.
Only short glycan substrates can penetrate bacterial cell walls -> as consequence, the digestion of dietary polysacc
requires export of sugar-cleaning enzymes into the intestinal lumen
31
Digestion Cont.
A secretion signal is needed on the gene sequence to target the enzyme to outside the bacterial cell
Among all genes encoding hydrolases with predicted signal peptides, 72% belong to Bacteroidetes members
32
Digestion Cont.
Through the action of bacterial polysaccharide digestive enzymes, significants amounts of free monosaccharides can be liberated in the GI tract
These monosaccharides can be used as metabolic precursors by bacteria in the colon (anaerobic)
*either anaerobic respiration or fermentation
33
Carboxylic Acids
The general formula of a carboxylic acid is R-COOH, with R referring to the rest of the molecule
34
Colon
Firmicutes are the primary source of fermentation by-products in the intestine (colon)
35
Colon
Firmicutes are the primary source of fermentation by-products in the intestine (colon)
36
The Microbiome, Fermentation and Fiber Metabolism
Increased epithelium health/function
Decrease inflammation
37
Acquisition of function in GI tract bacteria by horizontal gene transfer
Agar degradation locus what discovered
Homologs were found in the gut bacterium that was isolated from Japanese individuals who consume seaweed
Frequent in Japanese population, absent from other data
38
Fermentation in Food
Fermentation historically important method of food preservation
*acid produced inhibits growth of many spoilage organisms and food-borne pathogens
*bacteriocins and some secondary metabolite can also inhibit the growth of other microbes
39
Other important preservation methods
Salting, drying, addition of various herbs or spices, canning
40
Lactic Acid Fermentations
By lactic acid and acetic acid producing bacteria
*tastes due to in part of the production of lactic and/or acetic acid, as well as other molecules produced by fermentation and/or secondary metabolism
41
Fermented milk products
Milk is sterile in cow's udder
*rapidly becomes contaminated during milking and handling (lactic acid bacteria reside on cow's udder)
Aesthetic features of milk change due to production of acid, proteases, exo-polysaccharides and flavor compounds (secondary metabolites)
*causes milk proteins to coagulate or curdle, sours flavor, thickens the liquid
42
Fermented milk products Cont.
Production of fermented milk products no longer rely on naturally occurring lactic acid bacteria
*starter cultures are added to milk
43
Starter Cultures
A preparation of living microorganisms, which are deliberately used to assist the beginning of fermentation, producing specific changes in the chemical composition and sensorial properties of the substrate
*carefully selected to produce desirable flavors/textures
*must be carefully maintained and protected against contamination by other microbes
44
Cheese Production
Made from a wide variety of animals
*classification is based on percentage of water content
Cottage cheese easiest cheese to make
*pasteurized milk inoculated with starter culture -> culture causes milk proteins to coagulate -> heated and cut into small pieces to facilitate drainage of liquid
45
Cheese Production Cont.
Most all cheeses undergo further microbial processing termed ripening or curing
Enzyme "rennin", a protease is added to fermenting milk to hasten protein coagulation
46
Cheese Production Cont.
Curds salted after whey is separated and pressed, ripened to encourage changes in texture and flavor
*can take weeks to years
Long ripening produces more acidic cheese
*certain organisms produce certain characteristics
47
Yogurt
Milk is inoculated with starter culture -> incubated 40-45 for several hours
*controlled incubation ensures proper levels of acid production, proteolytic activity and flavor compound generation
48
Probiotics
Most common: Lactobacillus, Bifidobacterium, Bacillus coagulans, Saccharomyces boulardii
49
Variation in Probiotic Activity
Not all strains and species of probiotic microbes will have the same activity in all aspects of probiosis
50
Pickling
Originated as way to preserve vegetables
*uses naturally occurring lactic acid bacteria residing on vegetables (unlike using starter culture)
Vast majority today are used with vinegar
51
Alcoholic fermentation by yeast
Some yeasts ferment sugars to produce ethanol and carbon dioxide
*yeasts are used to make variety of alcoholic beverages as well as vinegar and bread
52
Bread
Rises due to carbon dioxide produced through fermentation of sugars by baker's yeast
Characteristic flavor of sourdough bread due to addition of lactic acid bacteria to the bread making mixture
53
What factors influence the growth of microorganisms in food?
Conditions naturally present in food -> "intrinsic" factors
Environmental conditions -> "extrinsic" factors
Combine to determine which microbes grow in particular foods and at what rate
54
Intrinsic Factors
Water availability, pH, nutrients, biological barriers, antimicrobial chemicals
Microbes multiply most rapidly in moist, nutritionally rich, pH neutral foods
55
Water Availability
Foods vary dramatically in terms of water availability
*milk have higher water content -> supports microbes
*bread has low water content -> defined pops. can grow
Water activity (aw) used to designate amount of water available in foods
*most bacteria require above 0.90 aw
*most fungi require above 0.80 aw
56
pH
Important in determining which organisms can survive and thrive on specific foods
*many microorganisms inhibited by acid conditions
Lactic acid bacteria not inhibited by low pH
*used in fermentation of milk products, can cause spoilage of unpasteurized milk
Yeast and other fungi are able to survive a low pH
*most acid foods spoil from fungal contamination as opposed to bacteria
57
Nutrients
Nutrients present in food determine organisms that can grow in foods
58
Biological Barriers
Rinds, shells and other outer coverings help protect foods from microbial invasion
*microorganisms will eventually breakdown coverings and cause spoilage
59
Antimicrobial Chemicals
Some foods and spices naturally contain antimicrobial chemicals that inhibit growth of organisms responsible for spoilage
60
Extrinsic Factors
Extent of microbial growth largely dependent on storage of food
*microbes multiply rapidly in warm, oxygen-rich environments (also in low oxygen anaerobic con.)
Include storage temperature, oxygen levels, humidity
61
Storage Temperature
Affects the rate of microbial growth
*below freezing water availability is significantly decreased
*at low temperature, growth is very slow or non-existent
62
Atmosphere
Presence of absence of oxygen affects type of microbial population
*moisture promotes the growth of spoilage microorganisms
63
Preservation methods include:
Canning, pasteurization, cooking, refrigeration, freezing, drying/reducing water availability
64
Cooking
Can destroy non-spore forming organisms, alters characteristics of food
*if heat is uneven, some organisms may survive in undercooked portion of food
65
Refrigeration
Preserves food by slowing growth rate of spoilage organisms
*many organisms unable to multiply in low temperatures
66
Freezing
Stops microbial growth (water unavailable due to ice formation)
*portion of organisms remaining can grow when food is thawed
67
Drying/reducing water availability
Inhibits microbial growth by decreasing available moisture
*molds may grow eventually
68
Irradiation
Damages microbial DNA
69
Filtering
Will not remove viruses
0.2 micron (microbial cell filtering) vs. cheesecloth (particulate filtering)
70
Heating
Efficacy depends on temperature and time at that temperature
Boiling may not kill endospores
71
Pasteurization
Process of heating a liquid to below the boiling point to destroy microorganisms
72
Heating/Boiling Milk
Has been recognized since the early 1800s
*was used to reduce milk-borne illness
Increased milk production and distribution led to outbreaks of milk-borne diseases
73
Heating/Boiling Milk Cont.
Common milk-borne illnesses included typhoid fever, undulent fever, scarlet fever, etc
Tuberculosis can also be transmitted via un-pasteurized milk
74
Heating/Boiling Milk Cont.
1918, drinking unpasteurized milk could transmit the bacterium that caused brucellosis from domestic farm animals to humans
In combination with improved management practiced on dairy farms, milk-borne illnesses were virtually eliminated with commercial implementation of pasteurization
75
Heating/Boiling Milk Cont.
At very high temperatures, micelles of the milk protein casein irreversibly aggregate and impart a cooked flavor to the milk
Pasteurization reduced the pathogenic bacteria in milk without changing flavor
*includes high temper, short-time pasteurization
*HTST: 161 for 15 secs
76
Types of Pasteurization
Ultra-pasteurization holds the milk at a temp of 140 C fro two seconds (refrigerated, extended storage)
Ultra-heat-treating processing holds the milk at a temp of 140 C (sterilized, not pasteurized)
*lets people store milk for months without refrigeration
77
What else is pasteurized?
Any juice sold on the shelf at room temperature has been sterilized, not pasteurized (usually by UHT)
*all truly pasteurized need to be refrigerated
78
What else is pasteurized?
Any juice sold on the shelf at room temperature has been sterilized, not pasteurized (usually by UHT)
*all truly pasteurized need to be refrigerated
79
Sterilization
Refers to any process that eliminates, removes, kills or deactivates all forms of life and other biological agents present in a specified region
80
Does boiling a liquid sterilize it?
Depends on what was the liquid was to start with and how long you boil the liquid
81
Food Spoilage
Encompasses any undesirable physical change in food
*generally not harmful
Considered unsafe because high numbers of spoilage organisms indicate that conditions have favored microbial growth, which may include potential food-borne pathogens
82
Food Spoilage Cont.
Range of bacteria important in food spoilage
*psychrophilic organisms can multiply in refrigerator
Endospore forming organisms can survive cooking and in some cases canning processes (Clostridium, Bacillus)
Range of fungi spoil foods
*fungi grow in readily acidic and low-moisture environments
83
Food-borne Illness
Results from a failure in proper use of preserving, preparation or cooking techniques to avoid growth of microbial pathogens
Intoxication and Infection
84
Intoxication
Disease that results from ingestion of foods containing preformed microbial toxins
*microorganism that produce toxins do not have to infect the host
4-12 hrs for time of onset
85
Infection
Results from the ingestion of pathogen-contaminated food followed by growth of pathogen in the host
24-48 hrs from time of onset
86
Risk Factors for Foodborne Illness
Type of microbe or toxin ingested
Inoculum size
Inadequate stomach acidity
Reduction or change in normal microbiota of host
Susceptible populations include
87
How do you tell if there has been an outbreak of a food-borne illness?
Cluster cases by symptoms
Isolate pathogen from cases
Identify common food to all cases
Isolate pathogen from suspected food
Re-trace distribution of suspected food
Isolate pathogen from suspected food at common distribution point
88
Food Intoxication
Illness resulting from consumption of an exotoxin produced by organisms growing in food product
*toxin is responsible, not organism
89
Heat Stable Enterotoxins
Produced by strains of Staphylococcus aureus
Stable upon heating at 100C for 30 min
Protected from hydrolysis by duodenal/jejunal enzymes
Elicit net secretion of ions and water (rapid onset of diarrhea, no fever)
90
S. aureus Food Poisoning
Generally a human carrier
*common skin and nasal commensal microbe
Inoculated into food during preparation
*food left at room temperature allows organisms to grow and produce toxin
Toxin is heat stable and not inactivated by cooking!
91
Canning
An extremely effective method of food preservation
Heat processing at high temps for fixed time -> destroys microbes -> inactivates endogenous spoilage enzymes -> oxygen driven out -> vacuum is formed upon cooling that prevents recontamination
92
Canning Cont.
Designed to destroy endospores
*improper canning can promote germination of endospores (when temp is not high enough, etc.)
93
Botulism
Paralytic disease caused by ingestion of a neurotoxin
*produced by Clostridium botulinum, gram + spore forming anaerobic rod
Growth of organism or production of toxin may not result in change in taste or appearance of food
94
Botulism Cont.
Disease characteristics (adults, 12-14 hrs after ingestion)
*nausea, fatigue, visual impairment, etc.
Disease characteristics (infants, days-weeks)
*constipation, facial expression, weakness, etc.
Widely found in soil, dust, honey
*mainly impact infants
95
Bacillus Cereus
Gram positive spore forming rod (fac. anaerobe)
Widely disseminated in nature
Can cause diarrheal disease (found in grains)
96
Food-borne Infection
Requires consumption of living organisms
*invasion of the large intestine mucosal surface by the infection
Symptoms do not appear for a least one day after ingestion
*major symptom is diarrhea
97
Food-borne Infection Cont.
Thorough cooking of food immediately before consumption will kill microbes responsible for infection
*prevents infection
98
Salmonella and Campylobacter
Commonly associated with poultry products
*inadequate cooking can result in food-borne infection
Cross-contamination can result in transfer of pathogens to other foods
99
Salmonellosis
Symptoms: Gastroenteritis and Food Poisoning
*nausea, vomiting, abdominal pain, fever, etc.
Generally short lived and range from mild-moderate
*vary depending of virulence of strain and # of infecting organisms
100
Salmonellosis Cont.
Causative Agent: Salmonella (motile, gram -, enterobac.)
101
Campylobacter jejuni
Most common cause of bacterial diarrhea in the world
*inadequately cooked poultry, untreated water, unpasteurized milk, exposure to animals with diarrhea
Self-limiting, antibiotics not needed, causes fever, nausea, cramps, etc
*low infectious dose, replicates in the small intestine
102
Campylobacter jejuni Cont.
Curved s-shaped gram - rods
*motile with a singular polar flagellum at one or both ends, micro-aerophile, grows best 42C
Toxins: adenyl cyclase activating cholera toxin-like enterotoxin, cytotoxin
103
Pathogenic E. coli
Can cause food poisoning (intoxication) or food-borne infection
*depends on strain of E. coli, depends on pathogenic mechanisms encoded in the accessory genome of that strain
104
Listeriosis
Listeria monocytogenes is the cause
*may lead to bacteremia and meningitis
Found in soil and water
*psychrotolerant - grows at refrigeration temperatures
Listeria is killed by cooking and pasteurization
*transmitted to people by food
105
Listeria mococytogenes
Tolerates high salt concentration
*can survive a pH range of 4.4-96
Primary food-borne sources: unpasteurized milk, deli meats, etc.
106
Listeriosis Cont.
Infection causes severe disease in vulnerable groups
*L. monocytogenes in an intracellular pathogen (uptake by phagocytes results in growth of the bacterium)
Mortality rate is high
*non-invasive: diarrhea, chills
*invasive: septicemia, meningitis
107
Other causes food-borne/waterborne illness
Vibrio cholerae
*gram -, toxin producing, safe water is critical to control
Amoebic dysentery
Traveler's diarrhea
Clostridium perfringens
Norovirus
108
Infection
The invasion of an organism's body tissues by a disease causing agents, the persistence of those agents and the reaction of host tissues to the infectious agents
109
Infectious Disease
The disease that results from infectious by a transmissible agent (from host to host, via intermediate, etc.)
*all infectious diseases are infections, not all infections are infectious diseases
110
Passive barrier to infection
Skin
Normal Microbiota
Mucus, phagocytes, peptides
Blood and lymph nodes
Rapid pH change
Flushing of urinary tract
Epithelial cells
111
Anti-Microbial Peptides
Small, typically positively charged, peptides with potent antimicrobial activities
*produced by many cells in the body, including neutrophils and cells of the mucosa
Many AMPS display a direct and rapid antimicrobial activity by causing disruption of the physical integrity of the microbial membrane and/or by translocating across the membrane into the cytoplasm of bacteria to act on intracellular targets
112
Host Response to Infection
Barrier Function -> Primary Innate Defenses -> Activated Innate Defenses -> Immune Defenses
113
Bone Marrow
Source of the white blood cells that are the major mediators of host defense
114
Mast Cells
Found throughout the body in all tissues
*are increased in the tissues of allergic individuals
115
Macrophages
Found throughout the body in all tissues and many are derived from monocytes that have left the blood
116
Neutrophils
Most abundant white blood cell in body
*predominant cell in pus
Granulocyte: polymorphonuclear leukocytes
Ambulance of the immune system: produced in high numbers quickly in bone marrow upon infection and travel to site of infection to exert anti-microbial activity
117
Phagocytosis
Carried out primarily by macrophages and neutrophils
Attachment of phagocyte to microbe can be mediated by specific receptor interactions or by charge interactions
118
Killing Ingested Microbes
Phagocytic cells use reactive oxygen radicals to kill ingested bacterial cells by oxidizing key cellular constituents of the ingested microbe
Respiratory burst is a series of catalyzed reactions in the phagolysosome that creates reactive oxygen metabolites
119
Killing Ingested Microbes Cont.
Occurs within the phagocytic vacuole of the phagocyte, which is not damaged by the toxic oxygen products
Degradative enzymes are also found in the phagolysosome
120
Neutrophils Cont.
Neutrophils also "throw" neutrophil extracellular traps around nearby pathogens
After interacting with bacteria, neutrophils can undergo an unusual form form of cell death
*spews a latticework of DNA impregnated with antimicrobial peptides into the immediate area that traps bacteria in this mesh
121
Innate Immunity
Multicellular organisms have evolved the ability to recognize microbes and to eliminate them without causing damage to self
The recognition system is a host receptor - microbial ligand interaction
122
Microbe-Associated Molecular Structures
Ex.
Lipopolysaccharides
Teichoic acids
Unmethylated CpG motif
dsRNA
Mannans
Flagellin
123
Pattern Recognition Receptors
Host-encoded receptors that bind MAMPs
Expressed on phagocytes and many cells in the body
Include a number of receptors: TLR, NLR, CLR. etc.
124
Pattern Recognition Receptors Cont.
Stimulation of PRRs activates transcription factors in a host cell to induce production of cytokines and other factors
125
Cytokine
Protein
Binds to a specific receptor
Intercellular signaling molecule
Can act locally or systemically
Can have multiple effects, depending on the target cell binding the cytokine
126
Intercellular Signals Induced by the MAMP-PRR Interactions
Signals that mediate inflammatory responses
Signals that control induction of leukocyte effector functions
Signals that function in activation of adaptive immunity
127
Acute Inflammation
Redness, warmth, pain, swelling and altered function
Inflammation is the process of leukocyte movement from the blood into a tissue and/or increased localized vasodilation
128
Bone Marrow Cont.
The bone marrow pumps out more leukocytes in response to inflammation
129
Pathogens have specific mechanisms to
Gain access to the body and attain a unique niche
Acquire necessary nutrients in vivo
Multiply and persist
Avoid, subvert or circumvent innate host defenses
Evade acquired specific immune responses
Cause tissue damage or disease
Exit and transmit infection to new hosts
Mechanisms of virulence are genetically encoded virulence genes and having these genes distinguishes pathogens from non-pathogens
130
Adherence in Infection
Pathogenic bacteria and viruses often adhere specifically to epithelial cells through interactions between molecules on the surfaces of the pathogen and the host cells
Can be facilitated by fimbriae, pili, flagella, capsule, other cell-surface adhesions
131
Biofilms and Infections
Biofilms play an important role in chronic infections by enabling persistent adherence and resistance to bacterial host defenses and antimicrobial agents
132
Pathogen Colonization
Pathogens may grow locally at the site of invasion or may spread throughout the body
The availability of appropriate nutrients is the most important parameter affecting pathogen growth
133
In vivo
Nutrients can be limiting
*iron is a growth-limiting nutrient
Host-derived transferrin, lactoferrin and lipocalin are very high affinity iron-binding molecules that function to sequester iron in the host to limit infection
Many pathogens produced iron-chelating compounds caused siderophores to counter iron sequestration
134
Avoiding host defenses
Capsules and biofilms help protect against phagocytosis
135
Pathogens can block phagocytosis
Some pathogens can stop phagocytosis by injecting phagocytes with effectors (T3SS)
Ex. Yersinia uses t3SS to inject host phagocytic cells with infectors -> precent actin polymerization, block phagocytosis
136
Some pathogens hide out inside host cells
Complement and antibodies act only within extracellular spaces
Some pathogens remain intracellular after being ingested
137
Pathogens and Phagocytosis Cont.
Some pathogens stop the phagolysosome from maturing
Some can escape the phagosome before it fuses with a lysosome
138
Virulence Factors
Promote pathogen infection and host cell damage
Enzymes that break down host tissue: proteases, nucleases, lipases
Toxins: exotoxins, endotoxins
Sometimes clustered together on pathogenicity islands
139
Endotoxins
Lipopolysaccharides found in the outer membrane of most gram-negative bacteria
*released as bacteria die
Serves as a MAMP which binds to certain PRRs on leukocytes
*causes cytokine release
140
Endotoxins Cont.
Repeating O-antigen side chain that faces out from the microbe and the membrane proximal core glycolipid and lipid A
141
Damage-Framework Hypothesis
Microbial pathogenesis is an outcome of an interactions between a host and a microorganism
The host-relevant outcome of the host-microorganism interaction is determined by the amount of damage to the host
Host damage can result from virulence factors and/or the host response to the presence of the microorganisms
142
Damage-Framework Hypothesis
Top weak of a host response can result in disease
*opportunistic infections
Too strong of a host response can result in disease
*sepsis, hypersensitivity, cytokine storm
143
Horizontal Transmission
Individual to individual
144
Vertical Transmission
Maternal to neonatal
Infectious agent may cross placenta from the mother to fetus
145
Direct Contact Transmission
Person to person spread of microorganisms through actual physical contact
146
Indirect Contact Transmission
Occurs when a susceptible person comes in contact with a contaminated object or contact with contaminated material
Fomite - an inanimate object or substance that is capable of transmitting infectious organisms from one to another
147
Ingestion
Food, water, "fingers"
Fecal-oral transmission
Infection is via the gastrointestinal tract
148
Giardiasis
Ingestion of water or food contaminated with cysts
*can survive for months with exposure to cold water
Spreads very easily
149
Human to Human Disease Transmission
Fecal-oral Spread
Respiratory or Salivary Spread
Venereal Spread
150
Routes of Transmission
From:
Oropharynx
Respiratory
Gastrointestinal
Urogenital tract
Skin
Milk
Blood
151
Inhalation
Infection is via the respiratory tract
Aerosol transmission
152
Droplet vs. Aerosol Transmission
Although droplets produced by an infectious individual through coughing or sneezing may convey infection at short distance, the number and viral load of aerosols produced through speaking and other expiratory activities are much higher than those of droplets
Aerosols are small enough to linger in air, accumulate in poorly ventilated spaces, and can be inhaled at both short and long ranges
153
Factors affecting airborne transmission
Movement of aerosols is more strongly influenced by airflow direction and pattern, type of ventilation and air filtration and disinfection
154
Routes of Acquisition
Dose of infectious inoculum is a critically important variable!
Route of transmission has to match up with the route of acquisition and the infectious agent's mechanism of infection for the disease to occur
155
Arthropod/Vertebrate to Human Disease Transmission
Vector
Vertebrate Reservoir
Vector-Vertebrate Reservoir
All can be controlled by controlling vectors or by controlling animal infection
156
Direct inoculation
Vector-mediated transmission
*insect bite
Animal or human bite
Needle stick, blood transfusion
157
Ro
Average number of people who will contract a transmissible infection from one person with the disease
If Ro > 1, number of people with the disease will rise
If Ro < 1, the number will decline
SARS CoV-2 Ro: 4-7
158
Infection versus Disease
Contact with an infectious agent does not guarantee that a person will actually contract the disease
159
Parabolic Curve of the Damage-Response Framework
The dose of the infectious agent slides the damage-response framework curve up or down
Each infectious agent has its own damage-response framework curve
160
Disease Outcome
The dose received of a pathogen, as well as the immune status of the host, makes a significant difference in the disease outcome
Thus, simply being exposed will not necessarily cause disease
161
Iceberg Concept of Infectious Diseases
Infection and disease after exposure is determined by route of transmission, length of exposure, dose of inoculum, route of acquisition, type of infectious agent and level of pre-existing immunity
162
Virus
Genetic element that cannot replicate independently without a living a host cells
*infect bacteria, archaea, eukaryotes
Virus particle (virion): extracellular form of a virus
*exists outside host and facilitates transmission
163
Virion
It consists of a nucleocapsid
*capsid (protein coat), nucleic acids
Two main categories:
*naked, enveloped
164
Enveloped Viruses
Have membrane surrounding nucleocapsid
*lipid bilayer with embedded proteins
Envelope makes initial contact with host cell
*much of the membrane is picked from host cell, most infect animal cells
165
Virus Cont.
Do not carry out their own metabolism
*some still need to carry enzymes with them to carry out certain function (lysozyme-like, cleavage, etc.)
RNA viruses ~ also need RNA replicases
Retroviruses ~ need reverse transcriptase
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Baltimore Scheme to classify viruses
Based on relationship of viral genome to its mRNA
***mRNA must be made in order to make protein so no matter what the viral genome looks like, mRNA somehow has to be made from it
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Positive strand RNA
The sequence of the genome and the mRNA are the same
*mRNA can be translated immediate after entering the cell
These viruses encode RNA replicase, which is an enzyme that replicates viral RNA
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Coronaviruses
Enveloped viruses
Single stranded, + sense RNA genome
Respiratory or fecal-oral transmission
Spike protein mediates ACE2-dependent cell entry
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Coronaviruses Cont.
Viral shedding peaks rapidly after SARS-CoV-2 challenge but qPCR remains positive for at least a week beyond detectable live virus
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Influenza Virus
Causes infection of the upper/lower respiratory tract
Enveloped
- sense, ssRNA
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Influenza A Viruses
Exists in many species
Different strains of Influenza A viruses infect different animals species like birds, humans and pigs (strains remain largely species-specific)
*pig as an intermediate host
Considered zoonotic pathogens because genetic reassortment in an intermediate host allows emergence of new hybrid strains
*type A flue virus is constantly changing its genome and is generally responsible for large flu epidemics
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Influenza B Viruses
Only found in humans
*causes a less severe reaction than type A flue virus
*more limited host-range
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Structure of Influenza Virus
The virions of influenza A and B viruses contain 8 different RNAs
*in influenza A, the 8 genomic RNA segments code for 11 proteins
Virus replicates in the cell nucleus, not cytoplasm, because the virus requires host machinery to cap the mRNAs
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Structure of Influenza Virus Cont.
Surface glycoproteins determine subtype
H -> binds sialic acid
N -> cleaves sialic acid
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Antigenic Drift
Small genetic changes in surface-exposed proteins that alter a few individual epitopes on an antigen
Occurs in all types of influenza
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Antigenic Shift
Large genetic change that allows the virus to evade host immunity, resulting in an epidemic/pandemic
Only occurs in influenza A
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Influenza-induced Tissue Destruction & Disease
Primary site of viral infection is the upper part of the lower airways and replication in these cells
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Influenza-induced Tissue Destruction & Disease Cont.
Innate followed by adaptive immune response to the virus is important for viral clearance, but can cause significant damage to lung tissue
Inflammation in the bronchial tree and Cytokine Storm during the inflammatory response causes symptoms of the flue
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Influenza-induced Tissue Destruction & Disease Cont.
The entire process leads to increased susceptibility to secondary bacterial infection due to unregulated inflammatory response in the lungs
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Vaccines
Manipulation of adaptive immune system in an antigen-specific manner to mimic infection by a specific pathogen
Results in stimulation of protective immunity against a pathogen without causing the disease of that pathogen
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Principle of Vaccination
To induce a "primed" state so that on first contact with the relevant infection, a rapid and effective secondary immune response will be mounted, leading to prevention of disease
*should contain some of the antigens of the microbe that the immune response is directed against
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Types of Modern Vaccines
Attenuated microbes - "live vaccine"
Killed micro-organisms
Subcellular microbial fragments or toxins
Micro-organism DNA
Micro-organism RNA
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mRNA Vaccines
Have been genetically modified to optimize physical stability and translatability, including reducing the induction of an interferon/anti-dsRNA response
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Antibody
Heterodimeric bivalent receptor specific for an antigen (Ag) ...can bind two identical Ag molecules
A protein complex, made up of four polypeptides, two heavy chains and two light chains joined by disulfide bonds
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Where do antibodies come from?
B lymphocytes secrete antibodies into the circulation and tissues of the body
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How do antibodies work?
Receptor-Ligand Interactions: the primary mechanism of the immune system
*receptor specificity: only one ligand binds a specific receptor
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Antigen
A molecule recognized by the antigen receptors of the adaptive immune system: antibodies and T cell receptors
*usually a protein
An allergen is an antigen derived from a non-infectious source, etc.
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Antigens & Epitopes
Epitope: the specific molecular structure on an antigen that is specifically bound by antigen receptors
Antigen receptors: Immunoglobulin, T cell receptor
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Genomic rearrangements to generate an antibody
A single B cell randomly selects which light chain gene locus to use and the other light chain locus is silenced for the life of that cells and all its subsequent clones
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How many possible novel Ag receptors can be made by B cells in the body?
Combinatorial diversity and Junctional diversity
*as a result of the potential number of DNA recombination possibilities
In the periphery, the DNA in that region of the B cell is subject to high levels of mutation, resulting in even more DNA sequence possibilities in the variable regions of immunoglobulin loci
Recombination of V, D, J regions produces unique antigen receptors
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B cell development cont.
Clonal selection & B cell differentiation is an antigen-dependent process that occurs in the periphery
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TcR rearrangement
Very similar to Ig rearrangement
T cell development occurs in the thymus and is similar (but very different) to B cell development in the bone marrow
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Antigen Binding: Immunglobulin vs. TcR
Antibody (Ig) binds directly to an Ag - binds epitope on the antigen
The T cell receptor (TcR) binds to only a fragment of an Ag, when it is held in place by an MHC molecule
*binds to Ag peptide plus MHC in a very specific way
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Major Histocompatibility Complex (MHC)
Whole Ag does not bind to an MHC molecule: a peptide fragment derived from the native Ag binds to an MHC molecules
Length of the antigen peptide bound in the MHC groove depends on the type of MHC molecule
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MHC I
Found on all nucleated cells in the body
MHC I presents Ag peptides derived from intracellular compartments after cleavage of Ag into peptides
Restricted recognition of both the APC and target cell for destruction by CD8+ T cells
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MHC II
Found on antigen-presenting cells at baseline at high levels and inducible to even higher levels in presence of inflammation & cytokines
MHC II presents Ag peptides derived from extracellular compartments after cleavage of the Ag into peptides
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CD8 T cell Activation
The CD8 molecule aids in stabilization of the TcR-peptide-MHCI interaction
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Why would a B cell undergo switching of the heavy chains that it produces?
The function, not the antigen binding, of antibody is due to its heavy chain. B cells will switch their heavy chains when they receive a special signal from a Th cell that also reacts to the same antigen
*the helper T cell helps determine the fate of what the immune system does when an antibody binds to its Ag
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CD4 T cell Activation
The CD4 molecule aids in stabilization of the TcR-peptide-MHCII interaction
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T Cell Activation - 2 step process
MHC ~ AgPeptide ~ TCR Binding
Co-stimulation of T Cells by Dendritic Cells
*cytokines & secondary receptor signaling
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Lymphatic System
Open-ended second circulatory system in the body and connects the tissue sites to the lymph nodes, spleen and circulatory blood system
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Where do APC-T cell and T cell-B interaction occur?
Spleen and Lymph nodes
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Th-B cell Interactions & Ab Isotype Switching
CD4 Th Cell Help for B Cell Proliferation and Memory Development
CD4 Th Cell Help for Isotype Switching
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Isotype Switching
Gene rearrangement of the constant region genes in the heavy-chain locus results in isotype switching
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Fc Receptor
Cell surface receptor that binds the Fc region of an antibody (does nit bind the Fab region)
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Antibody Isotype Switching
Isotype switching of an antibody produced by a B cell retains the same Ag binding specificity but changes the function of that Ab because the constant region of the heavy chain is switched out
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Immunity Against Intestinal Parasites
B cells
Th cells
IgE
Mast cells
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Allergic Responses
B cells
Th cells
IgE
Mast cells
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Symbiosis in the GI tract: Microbial Co-Existence without Tissue Damage
slgA is made in the intestine and one of its major functions is binding to the bacterial microbiota and preventing it from invading the mucus layer and adhering to the epithelium, without inducing inflammation
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Immune Responses
B cells, CD4 T cells and CD8 T cells can all undergo primary and secondary responses, depending on the Ag stimulus, due to clonal expansion and the development of memory cells
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Immune Responses
B cells, CD4 T cells and CD8 T cells can all undergo primary and secondary responses, depending on the Ag stimulus, due to clonal expansion and the development of memory cells
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Immune Memory after SARS CoV2 Infections
Consists of antibodies, memory B cells, memory CD8+ T cells and memory CD4+ T cells
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Microbial Metagenome vs. Human
Human genome only encodes 17 glycoside hydrolases (GH) that are involved in digestion
In contrast, the microbial metagenome in the gut encodes >9,000 glycoside hydrolases, polysaccharides lysases, glycosyltransferases and carbohydrate esterases
