02- Microbio of patogenic factors

Question 1

Pathogenic factors

Answer 1

process by which microorganisms cause infection

Question 2

The Microbe

Answer 2

● Few are pathogenic
● Many benefit the host
○ Some can provide resources for us → vitamin K

Question 3

t/f: Host factors greatly influence the relationship between microbe and host

Answer 3

true

Question 4

t/f: Our normal flora is only as healthy as we are

Answer 4

true; ● As our health diminishes with age and nutrition → decline in quality of normal flora

Question 5

Commensalism

Answer 5

One organism benefits from the relationship
ex. Saprophytic mycobacteria of the ear and external genitals
○ Live on secretions and sloughed-off cells
○ Cause no benefit or harm to the host

Question 6

Mutualism

Answer 6

● Both organisms benefit from the relationship
● We measurably are better with microorganism present
○ We can quantify this

Question 7

Parasitism

Answer 7

● One organism benefits from the relationship at the expense of the other
● Host is harmed
● This is an infectious process

Question 8

Two types of flora are

Answer 8

Resident microbiota & Transient microbiota

Question 9

Resident microbiota

Answer 9

• permanently colonize the host
  ○ Acquire this normal flora after birth
  ○ Through every exposure on the earth

Question 10

Transient microbiota

Answer 10

temporarily colonize the host
○ Commensal or mutualistic relationship
○ Not part of our normal flora
○ Acquired due to changes in our environment

Question 11

Difference between flora of the gut and flora of respiratory

Answer 11

●	Normal flora of gut is different from that of resp tract, skin, urogenital, etc
●	The environment in each are completely different
Skin
○       Dry 
○	Exposure to sun
○	Different textures/frictions
Respiratory tract
○	Wet
○	Moist
○	Dark

Question 12

Distribution and composition of normal flora determined by the following factors:

Answer 12

• nutrients
• physical and chemical factors
• mechanical factors
• other host factors such as age, nutritional status, disability, stress, personal hygeine, lifestyle, geography, occupation

Question 13

Normal Flora

Answer 13

Normal conditions → normal flora colonizes the host without causing disease
● In many circumstances the normal flora benefits host
○ Preventing growth of pathogenic microbes
○ Make it more difficult for us to be infected b/c they colonize the sites
● Process commonly referred to as Microbial Antagonism

Question 14

t/f: the flora is better at getting nutrients than pathogens

Answer 14

true

Question 15

Microbial Antagonism

Answer 15

● Normal flora is fit → more resilient against infections

● Makes us stronger than if we did not have normal flora

Question 16

Microbial Antagonism example

Answer 16

● E. coli produce bacteriocins
○ Protect the turf
● These proteins inhibit growth of closely related species of bacteria
○ Such as Salmonella and Shigella
○ These can cause serious GI infections or gastroenteritis
○ Bacteriocins kill theses species
● E.coli present → we need to be exposed to a lot of salmonella and shigella to actually get sick

Question 17

Balance btw normal flora and pathogenic microbe is altered:

Answer 17

● Microbial antagonism fails
● Immune system cannot eradicate the microorganism
● Disease can result

Question 18

Disruption of this balance may be induced by a number of factors, including:

Answer 18

● Age
● Antibiotic use
● Changes in hygiene
● Nutritional status

Question 19

Normal flora changed vs unchanged

Answer 19

Normal flora unchanged → C. diff does not cause disease

Normal flora changed → C. diff grows, reproduces, and causes disease

Question 20

Opportunistic infections occur when:

Answer 20

1. Microbes from the host normal flora move from their normal habitat → causing disease
2. The host’s immune system is weakened/compromised
3. Changes occur in the composition of the host normal flora

Question 21

Most pathogenic microorganisms cause disease via the process outlined below:

Answer 21

●	Contact/Exposure
●	Adherence
●	Evasion of Host Defenses and Penetration
●	Damage of Host Cells
●	Transmission

Question 22

Contact/Exposure: Portals of entry

Answer 22

1. Mucous membranes → represent a significant portal of entry
2. Skin
3. Direct deposition beneath mucous membranes or skin

Question 23

Adherence

Answer 23

● Pathogen attaches itself to host tissues at portal of entry
● Adhesins on cell surface molecules located on the pathogen
○ Binding specifically to surface “receptors” located on the cells of host tissues
● Adhesins are host specific and tissue specific

Question 24

Adherence

Answer 24

● Has to be a match btw host and microorganism receptor in order for adhesion to occur
● No adherence = no infection
● Mismatch = no harm = no infection

Question 25

Bacterial Structures

Answer 25

Fimbriae/Pili, flagella

Question 26

Adherence proteins

Answer 26

M protein, Opa protein, etc…

Question 27

Glycocalyx

Answer 27

Capsule, slime layer

Question 28

t/f: Has to be a match btw host and microorganism receptor in order for adhesion to occur

Answer 28

true ● No adherence = no infection ● Mismatch = no harm = no infection

Question 29

adhesins

Answer 29

● Microorganisms must produce | ● Adhesins will bind to the receptors that are aligned with host cells

Question 30

1. Bacterial structures

Answer 30

● Adhesins are present on the fimbriae and flagella of many pathogenic bacteria ● Fimbriae help bacteria hold onto the host cell

Question 31

2. Adherence Proteins

Answer 31

● M proteins produced by Streptococcus pyogenes (GAS) ○ M protein allow it to bind to cell surface ● Appear as hair-like projections from the cell surface ● Mediates attachment of bacteria to epithelial cells of the host ● Many subtypes ○ Some more strongly associated with specific diseases than others ● More wide variety of adhesins → more type of tissues and organs it affects

Question 32

3. Glycocalyx

Answer 32

Well organized and firmly attached to cell wall → “capsule” | Unorganized and only loosely attached to the cell wall → “slime layer”

Question 33

3. Glycocalyx: Unorganized and only loosely attached to the cell wall → “slime layer”

Answer 33

● Facilitates formation of biofilms ● Not restricted to organism that is producing it ○ Can also protect other organisms

Question 34

3. Glycocalyx | Well organized and firmly attached to cell wall → “capsule”

Answer 34

● K1 capsule associated with some strains of Neisseria meningitidis type b ○ Leading cause of gram negative bacterial meningitis ● This adhesin binds to epithelial cells of the ventricles and vascular endothelium of the brain ○ Without adhesin → decreased opportunity to cause meningitis ● Causing meningitis

Question 35

Biofilms

Answer 35

● Colony of bacteria that adheres to surfaces (living and nonliving) ○ Organic → host tissues ○ Fomites → hard surfaces, inorganic material (those inside the host too)

Question 36

where are biofilms embedded?

Answer 36

in an extracellular slime layer

Question 37

biofilms surfaces include

Answer 37

``` ○ Teeth ○ Medical catheters ○ Heart valves ○ Hip replacement components ○ Contact lenses ○ Industrial food equipment ```

Question 38

t/f: biofilms are Highly resistant to disinfectants and antibiotics

Answer 38

true ○ This is why we are careful with hip, heart valve, or knee replacement ○ Put on antibiotic to prophylactically → protect against infection ○ Bacteria is able to enter the bloodstream and land on replaced knee, hip, or heart ○ Often pre-treat individuals that underwent implantation surgery

Question 39

t/f; biofilms May involve multiple bacterial species and consist of many layers

Answer 39

t/f: true ○ Bacteria producing slime layer + other bacteria

Question 40

t/f: biofilms do not shelter microorgansims from host denfences

Answer 40

false; ○ This is why they can be resistant to antibiotics

Question 41

t/f: there are many treatments able to penetrate the slime layer

Answer 41

false: very few antibiotics

Question 42

Enzymatic bacteriophages

Answer 42

● Uses bacterial cells to replicate ○ Does not like human host but LOVES bacteria ● Viruses that have capacity to produce enzymes that destroy slime layer ○ Use bacteria to replicate ○ Rupture bacteria when they want to get out of organism

Question 43

Evasion of Host Defences

Answer 43

● Exposed to microorganism | ● Microorganism is able to bind to host cell tissues

Question 44

Cannot evade host defenses → aborted infections

Answer 44

● Immune cells clear us from microbes before we become symptomatic ● Infection has not occurred

Question 45

Capsule

Answer 45

facilitates microorganisms ability to evade host cell defenses ● Impairs phagocytosis ● Prevent phagocytic cell from adhering to the microbe ● Increasing virulence of the pathogen ● With time → host will produce antibodies against the capsule

Question 46

Cell wall

Answer 46

``` ● M proteins increase virulence ● Helping bacteria resist phagocytosis ○ WBC e.g. Streptococcus pyogenes ● Mycolic acid present in the cell wall of Mycobacterium tuberculosis increases virulence ○ Inhibits phagocytosis ○ Resists digestion by phagocytosis ○ Cannot be gram stained ○ Has to be acid fast stain ```

Question 47

Coagulase →

Answer 47

facilitates coagulation ● Coagulate fibrinogen in the blood to form fibrin ● Fibrin clot protects bacteria from phagocytosis ○ It will be protected within the hosts fibrin, platelets, etc ○ The body will think its one of its own ● Isolates the microbe from other defenses of the host ● Produced by some Staphylococci spp. ○ Round shaped ○ Gram positive → all staph are ○ Coagulase positive → More viral

Question 48

Coagulase positive →

Answer 48

More viral

Question 49

all staph are

Answer 49

○ Gram positive

Question 50

Kinase

Answer 50

● Degrades fibrin ● Digest clots formed by the body ● Isolate the wound and clots created by the bacteria as protection from phagocytosis

Question 51

Streptokinase produced by Streptococcus pyogenes

Answer 51

● Produce kinase to bust open clots ○ Helpful if they are living in clot ○ Helpful if they want to penetrate deeper into tissues ● Can digest and degrade healthy clots → increases fitness of microorganism ○ Get deeper into tissues

Question 52

Staphylokinase produced by Staphylococcus aureus

Answer 52

● Produce kinase to bust open clots | ● Can digest and degrade healthy clots → increases fitness of microorganism

Question 53

Facultative intracellular bacteria are able to survive inside immune cells via the following mechanisms:

Answer 53

Neisserias: ● They don’t have to live in host cell to survive but if they can they will ● They can inhibit the effects of lysosome on their membrane 1. Escaping phagosomes before fusing with host cell lysosomes 2. Preventing phagosomes-lysosome fusion 3. Reducing effectiveness of toxic compounds within lysosome 4. Producing cell walls resistant to lysosomal proteases

Question 54

Penetration of Host Tissues

Answer 54

● Our tissues are sterile ● The deeper into tissue you go → fewer immune cells ● Less oxygen → advantageous to certain bacteria ● Goal is to get deeper

Question 55

Hyaluronidase

Answer 55

● Degrades hyaluronic acid ● Hyaluronic acid → polysaccharide that holds host cells together ○ Allows neighbouring epithelial cells to stick together ● Allows bacteria to penetrate deeper into host tissues ● Bacteria is sheltered from outermost surface of the skin

Question 56

Collagenase

Answer 56

● Degrades collagen fibers at the base of superficial tissues ○ Collagen acts as basement membrane for epithelial cells to adhere to ● Allows bacteria to move deeper into the host ● More oxygen poor and fewer immune cells the deeper you go

Question 57

Some bacteria enter host cells that are NOT phagocytic

Answer 57

● Make cells welcome them ● Produce invasins ● Allow bacteria to invade NON phagocytic cells ○ The epithelial cells of the intestines

Question 58

Penetration of tissues; advantages

Answer 58

● Abundance of nutrients ● Protected from immune system ● Partially protected from antibiotics

Question 59

Damage to Host Cells

Answer 59

If a pathogen is successful in evading the host immune response → host cell damage and disease results ● They want us to have symptoms ○ Vomit, cough, sneeze ○ They want to move onto and transmit to someone else ● May damage us to gain nutrients ○ They want our iron to grow and reproduce

Question 60

Host cell damage can occur via the following mechanisms:

Answer 60

1. Appropriating host nutrients 2. Causing direct damage to tissues surrounding site of invasion 3. Producing toxins 4. Inducing hypersensitivity reactions (allergy)

Question 61

1. Appropriating host nutrients

Answer 61

● Iron is required for the growth of most pathogenic bacteria ● Iron is tightly bound to iron-transport proteins in humans ○ Hemoglobin ○ Tightly controlled in human body ● Low availability of iron produces a microbial iron deficiency

Question 62

Bacteria employ several strategies to obtain iron from host:

Answer 62

Siderophores Direct binding to host iron-binding proteins Producing toxins

Question 63

1. Appropriating host nutrients: Siderophores

Answer 63

● Bind to iron more tightly than host iron-transport proteins ○ Have higher affinity to iron ● Iron-siderophore complex taken up by siderophore receptors on bacteria ● Bacteria has iron to grow and reproduce

Question 64

1. Appropriating host nutrients: Direct binding to host iron-binding proteins

Answer 64

● Bacteria-iron complex | ● Takes iron up itself

Question 65

1. Appropriating host nutrients: Producing toxins

Answer 65

● Toxins cause damage directly to host cells ● Bacterial toxins kill host cells ● Release iron stores from host ● Pathogen acquires iron via receptor binding

Question 66

2. Direct damage to tissues surrounding site of invasion

Answer 66

● Obligate intracellular bacteria → have to be in host cell to live ○ Cannot get nutrients for themselves ○ E.g. chlamydia ○ Once nutrients diminished = need to get out → cell lysis ○ This manifests as signs and symptoms ● Intracellular bacteria/viruses metabolize + multiply in host cells ● Host cell typically ruptures to facilitate their release ● This destroys host cell ● Once released, pathogens spread to other tissues in great numbers

Question 67

3. Producing toxins

Answer 67

● Some pathogenic bacteria produce toxins ○ This directly affects normal activity in host cells ● Wide in variety ``` This alters normal metabolism of host cells: ● Inhibit protein synthesis ● Destroy blood cells and blood vessels ○ Toxin: hemolysin → RBC ● Disrupt nervous system function ○ Toxin: neurotoxins ● Directly affect and destroy whole cell ○ Cytotoxin ```

Question 68

Exotoxins

Answer 68

produced by bacteria that are gram positive and gram negative ● Directly damage host cell ○ Called a cytotoxin ● Actively synthesized by bacteria and released

Question 69

Endotoxins

Answer 69

only associated with gram negative bacteria ● Gram negative → lipid A polysaccharide ○ Intrinsic component of gram negative bacteria membrane ● Physically a part of gram negative outer membrane ● Occurs when cell is dividing ● Little bit of outer membrane tears off and little bit of endotoxin is released ● Also released when phagocyte engulfs gram negative bacteria and destroys it ○ Endotoxin will be released ● Prescribe antibiotic that destroys cell wall ○ Cause bacteria to lysis ○ Release endotoxin

Question 70

Exotoxins

Answer 70

● Produced inside some living pathogenic bacteria as a normal part of growth and metabolism ○ Intentions → cause damage to host tissues ● Secreted into the surrounding environment, or released during cell lysis ● Soluble in bodily fluids ○ Rapidly transported throughout host ○ Systemic infection ■ Dissolves so WELL into bodily fluids ○ Highly toxic in nature ○ Exposure can be fatal

Question 71

Diseases associated with exotoxin producing bacteria are caused by

Answer 71

the effect of the toxin on host cells, not the pathogen itself ● Ingestion/exposure to the toxin is sufficient to produce disease ● Not infection but the toxin that is causing the issue ● Consume toxin that the food made

Question 72

A - B Toxins

Answer 72

Consist of A & B polypeptides:

Question 73

Part A →

Answer 73

Active enzymatic component | ● This will change how the cell functions

Question 74

Part B →

Answer 74

→ Binding component ● This will bind to the host cell ● Toxin will enter the host cell

Question 75

Exotoxins: Membrane disrupting toxins

Answer 75

``` Induce cell lysis via: ● Formation of protein channels ○ Leukocidins → WBC ○ Hemolysins → RBC ● OR disruption of phospholipid layer of cell membrane ○ Phospholipase ○ Adverse effects for cell function ```

Question 76

Exotoxins: Superantigens

Answer 76

``` associated with shock and DIC Provoke an intense immune response ● Not processed inside macrophages ● They bind directly to MHC Class II proteins on macrophage surface ○ Directly activate T-cells ○ Does not need an intermediate to speak to T-cell ● Results in excessive production of: ○ IL-2 → drives septic shock ○ TNF → drives septic shock ○ Tissue factor → drives DIC ```

Question 77

Superantigen causes

Answer 77

``` ● Fever ● Nausea and vomiting ● Diarrhea ● Shock ● Sometimes death ```

Question 78

t/f: Portals of exit are generally the same as the portals of entry

Answer 78

``` true ● Respiratory tract ● Gastrointestinal tract ● Genitourinary tract ● Skin, conjunctiva, blood, etc… ```

Question 79

Endotoxins (Lipid A)

Answer 79

● Released when Gram negative bacteria are killed (or multiply through budding) ○ Cell wall lysis ○ Releasing endotoxin ● Gram positives are not associated with endotoxins ○ They do not have outer membrane ● All are pathogen associated molecular patterns ○ Stimulate macrophages to release high concentrations of IL–1 ○ We have aggressive reaction to lipid A ● All endotoxins produce the same signs and symptoms regardless of the pathogen ○ Common mechanism of action due to excessive IL-1 ○ Chills ○ Fever ○ Weakness ○ Generalized aches ● Increased production of TF ○ Activates extrinsic & intrinsic coagulation cascade ○ Associated with DIC ○ Obstructive clots in capillaries, inducing tissue death ● Shock and death of the host in severe cases