Week 2 Lecture - Host and Parasite

Question 1

Characteristics of a Host:

Answer 1

• Macroorganism, usually multicellular
• Phylogenetically a higher level
• Eukaryote normally, but could be prokaryote

Question 2

Characteristics of a Parasite:

Answer 2

• Living on/in the host -> damage -> possibly disease
• Obtains necessities of life from the host
• No sharp distinction between normal and pathogenic, but parasitism has a unilateral benefit

Question 3

Types of parasites, broadly:

Answer 3

• Non-living: unique proteins (prions), nucleic acids (viroid)
• Non-living/living?: virus
• Prokaryotes: bacteria
• Eukaryotes: microscopic fungi, protozoa, helmiths (worms which may be non-microscopic)

Question 4

What is commensalism?

What is mutualism?

Answer 4

Commensalism is a relationship between a microorganism and host that is altogether neutral (no damage to each other)

Mutualism is a relationship that is beneficial for both the microorganism and the host

Question 5

What is the ratio of host cells : microbe cell number?

Answer 5

1 host cell : 10 microbe cells

Question 6

What percent of the human genome are human endogenous retroviruses (HERVs) accountable for?

Answer 6

HERV’s have contributed ~ 8% of the human genome without any serious problems and even encoding for some vital functions (i.e. the placenta development is encoded by viral-origin DNA)

Question 7

Which microorganisms are considered a normal part of the microbe flora? Which are NOT normal?

Answer 7

• Normal: bacteria, microscopic fungi
• Not normal: viruses, protozoa, helminths

Question 8

What are some benefits to microorganisms for commensalism/mutualism?

And benefits for the host?

Answer 8

• Microorganism Benefits: shelter and food, colonisation on the tissues. Rarely, they will enter the tissue and cause disease
• Host Benefits: prevent colonization of harmful microbes, often producing antimicrobial compounds (e.g. lactic acid in the vagina). Also GI bacteria process/degrade food components, producing Vitamin K and B12

Question 9

How many species of parasitic/pathogenic microorganisms are there?

Answer 9

>1400

Question 10

What are 4 ways that parasites can damage humans?

(the answers are kind of stupid but directly from the slide)

Answer 10

• Entry/penetration form surface into tissues (invasivity)
• Passively enter through wounds (damaged tissue integrity)
• Actively via enzymes
• Multiplication/replication in tissue -> pathogenic effects

Question 11

What is the difference between obligate, facultative, and opportunistic parasites?

Answer 11

• Obligate: always pathogenic, never found in normal flora
• Facultative: conditionally, based on risk factors, a parasite may be either part of the normal flora or pathogenic. they don’t need a host to live, so may also be free living organisms and not parasitic
• Opportunistic: members of the environment normally, not pathogenic at all for healthy people, but take advantage in disorders - especially immunosuppression

Question 12

What are 3 risk factors for facultative pathogen infection?

Answer 12

• Physical/mental stress
• Acute diseases, wounds, burns
• Chronic debilitating conditions (like diabetes, alcoholism, nutritional defects, leukemia + immunosuppression, etc.)

Question 13

What are some examples of infection that have iatrogenic origins?

Answer 13

These are caused by medical diagnosis and/or therapy

• Antibiotics and other drugs can cause changes in normal flora
• Surgery, especially oral surgery
• Prosthetics, catheters

Question 14

What is a nosocomial infection?

Answer 14

An infection that results from time in a hospital or other health care facility. Infection could come from anyone, including patients, staff, or visitors

Question 15

What are 4 viruses that replicate in immune cells, causing immunodeficiency?

Answer 15

• HHV-6 (human herpes virus)
• HHV-7
• HIV
• EBV (Epstein-Barr Virus aka HHV-4, infects B cells, causes mono)

Question 16

What is the difference between pathogenicity and virulence?

Answer 16

• Pathogenicity: ability of the whole population of a given microbe species to elicit disease in their hosts
  
  • simpler def’n: “ability to cause disease”
  • pathogenicity is determined by virulence factors
• Virulence: ability to elicit a disease by a smaller population of the species.
  
  • simpler def’n: “degree of damage caused by a pathogen”

Question 17

What are the 4 Koch Postulates?

Answer 17

Criteria to identify the causative agent of a particular disease

1. Microorganism/pathogen must be present in all cases of the disease
2. Pathogen can be isolated from the disease host and grown in pure culture
3. Pathogen from the pure culture must cause the disease when inoculated into a healthy, susceptible laboratory animal
4. Pathogen must be reisolated from the new host and shown to be the same as the originally inoculated pathogen

Question 18

What might increase or decrease virulence? What is it called when virulence is lost?

Answer 18

• Increasing virulence: mutations, GMO, bioterrorism
• Decreasing virulence: mutations, attenuation
• Microorganism loses virulence -> avirulent

Question 19

How can virulence be measured?

Answer 19

• Measured by number of germs
• How many microbe(s) defined among standard circumstances induces pathological conditions = dose
  
  • ID₅₀ = infective dose inducing disease in 50% of hosts
  • DL₅₀ = lethal dose causing death in 50% of hosts
    
    • can also be measured as DL₉₀, DL₁₀₀ etc
  • TCID₅₀ = tissue culture infecting dose - damaging 50% of cultures

Question 20

What would be considered a small number of germs that -> disease and are thus highly virulent?

And as a large number of germs/low virulence?

Answer 20

• Small # of germs that are highly virulent: 1-10²
• Large number of germs that have low virulence: >10⁵

Question 21

How would a bacterial endotoxin work to be poisonous to a host and what is a major example of one?

Answer 21

Because bacteria replicate and die quickly, their endotoxins are released into the host during bacterial infections.

Major example is LPS (liposaccharide) in Gram negative bacteria

Question 22

What are some non-toxic virulence roles of the bacteria capsule?

Answer 22

1. Protection - including the anti-phagocytic activity involving masking/hiding antigens
2. Adhesion to host cells
3. Antigen variations in one species - helping evade the immune system

Question 23

What are 4 “non-toxic” (according to slide but they sound pretty toxic to me) extracellular enzymes secreted by bacteria that have an antiphagocytic effect?

(again might be a bit more than we need to know)

Answer 23

• Leukocidines - pore-forming chemicals that kill leukocytes, helping the bacteria evade the immune system
• Coagulase - reacts with prothrombin to make an active form that converts fibrinogen to fibrin. Apparently fibrin helps certain types of bacteria evade phagocytosis
• Hemolysins - by definition they lyse red blood cells, but some can also lyse WBC’s
• Proteases (pretty broad)

Question 24

What are some virulence factors in which bacteria use enzymes to facilitate invasion?

Answer 24

• Solubilizing cells and tissues of the host
• Streptokinase (fibrinolysin)
• Collagenase
• Hyaluronidase

Question 25

What are two ways that bacterial exotoxins can damage the host **cell surface**?

Answer 25

* **Membrane damage** / pore formation * **Superantigens**: APC MHCII + TCR binding -\> cytokine production -\> toxic shock * staphylococcus aureus: toxic shock syndrome toxin, TSST

Question 26

What are 4 ways that bacterial exotoxins can damage a cell with **intracellular** mechanisms?

Answer 26

* **A + B toxin** (two protein component complexes - A: "*a*ctive," toxic effect; B: *b*inding to cell surface) * **Inhibition of protein synthesis** (diptheria) * **Overproduction of mediators, neurotransmitters** (acetylcholine release -\> tetanus) * **Hypersecretion** (cholera toxin causes severe electrolyte loss/diarrhea)

Question 27

What can be beneficial about the bacterial endotoxin LPS?

Answer 27

A small amount of it is an **immunostimulant**, essential for strong innate immunity.

Question 28

What is the structure of LPS?

Answer 28

Have to know it, sajnos

Question 29

What is a "**reservoir**" in terms of sources of infection

Answer 29

Animals or humans or other vehicles that permanently carry pathogenic microbes

Question 30

How might someone get an infection from an "endogenous" source?

Answer 30

From the normal flora, or by activation of latent/persistent microbes

Question 31

What the fuck does "vertical spread" mean in terms of transmission of infection?

Answer 31

Spreading to the next generation, as in through the placenta

Question 32

What is incubation time?

Answer 32

Symptomless period between the moment of infection and the onset of symptoms/disease outbreak May take a few hours to months, years, even decades

Question 33

What is the difference between bacterial colonization and dissemination?

Answer 33

* **Colonization** is irreversible, occurs at/near the site of entry. Microbes multiple and cause local infections * **Dissemination** is the spreading of the bacteria into the body, causing a generalized infection.

Question 34

What are the symptoms of **Systemic Inflammatory Response System** (SIRS)?

Answer 34

* generalized weakness, malaise, warm skin, rash * high (\>38°C) or low (\<36°C) body temperature * tachycardia (\>90/min) * tachypnea (\>20/min) * WBC count increase (10-12x10 9 /L)

Question 35

What are some consequences of sepsis?

Answer 35

* Systemic Inflammatory Response Syndrome * Aggravation: organ hypoperfusion * Septic shock: hypotension * Resistance to medications * Death (multiorgan dysfunction syndrome, MODS)

Question 36

What might be the results of symptomless infections in childhood? (labeled as very important on the slide)

Answer 36

* Lifelong immunity (i.e. toxoplasma) * Cross immunity (HSV-1/HSV-2)

Question 37

What is a **latent** infection?

Answer 37

One where the pathogen remains symptomless in the body until it is activated upon intrinsic/extrinsic factors

Question 38

What is a **persistent** infection?

Answer 38

The pathogen is activated regularly, sometimes symptomless but can still infect others

Question 39

When is a person a **carrier** of infection?

Answer 39

When they can spread it continuously w/o having symptoms

Question 40

What is the reason to take antibiotics even after your symptoms have disappeared?

Answer 40

Because the *times of microbial and clinical recovery are different*

Question 41

What are some unspecific ways that the body inhibits attachment, entry, and facilitates removal of microbes?

Answer 41

* skin integrity * cilia movement in respiratory tract * pH variable on skin (from sebum), in the vagina and stomach, etc. * Enzymes: tears have lysozymes, mouth and GI tract have other antimicrobial enzymes * Osmolality in urine * Accelerated peristaltic movement, vomiting

Question 42

What are some **Cell Surface Receptors** on phagocytotic cells?

Answer 42

C type lectin Toll-Like Receptor (TLR) 1,2,4,5,6

Question 43

What are some **Endosomal Receptors** on phagocytotic cells?

Answer 43

C-type Lectin Toll-Like Receptor (TLR) 3,7,8,9

Question 44

What two types of molecules do the non-specific immune system phagocytes detect?

Answer 44

* **PAMPs**: pathogen-associated molecular pattern. i.e. LPS, gram pos bacterial cell wall peptidoglycan, lipoteichoic acid, flagellin, N-formylmethionin, hypomethylated CpG-DNA, ss/dsDNA, ss/dsRNA * **DAMPs**: damage associated molecular pattern. Intracellular components of lysed cells. May be nuclear polypeptides, mitochondrial DNA, ROS, matrix proteins, heat shock proteins

Question 45

What are 5 aspects in the cascade of events in the activation of innate immunity?

Answer 45

1. ​**Activation of Interferon Regulatory Factors (IRF)** - produce interferons, activate IFN-stimulated genes in immune and adjacent cells 2. Formation of **intracellular inflammasomes** and stress granules 3. **Protein Kinase R (PKR) activation** -\> RNAaseL activation -\> degradation of foreign RNA 4. **Caspase activation** -\> apoptosis of infected cells 5. **Release of pro-inflammatory mediators** like IL-1,-2,-8 and TNF alpha, etc

Question 46

How do bacteria induce the complement system with part of their cell wall?

Answer 46

With **mannose binding lectin** (MBL) -\> MASP1/MASp2 protease activation -\> C4/C2 split -\> C3 convertase -\> production of C3a and C3b fragments

Question 47

What is the C3b fragment responsible for?

Answer 47

Opsonization, help phagocytes eat bacteria

Question 48

What type of antibodies are produced early in **primary infection?**

Answer 48

**IgM** - rapid but transient effect

Question 49

When are **IgG** antibodies produced?

Answer 49

Later in the course of primary infections ("seroconversion"), then rapidly and in high level during secondary infections.

Question 50

Which antibody is on the surface of mucous membranes, responsible for mucosal immunity (MALT, GALT)

Answer 50

**IgA** Inhibits binding of microbes to mucosal cell receptors Forms a dimer

Question 51

What are some ways that tuberculosis evades the immune system?

Answer 51

* Damages macrophages * Inhibitions activation of IFN-gamma * Inhibits fusion between phagosome-lysosome

Question 52

What do shigella, listeria, and rickettsia do to evade the immune system?

Answer 52

Damage the lysosomal membrane

Question 53

What do salmonella and coxiella do to evade the immune system?

Answer 53

Inhibit lysozomal enzymes

Question 54

What do neisseria and enteric bacteria do to evade the immune system?

Answer 54

Inhibit activation of the complement system ("serum resistance") - inhibit opsonization

Question 55

What does Neisseria meningitidis B do to evade the immune system?

Answer 55

self antigen mimicry (?)

Question 56

What type of cells destroy virus-infected cells?

Answer 56

* NK cells activated by IL-12 * Cytotoxic T cells * Other phagocytes based on MHC-II antigen presentation

Question 57

What are some ways that viruses evade the immune system?

Answer 57

* Replicating in immune cells (like HIV, HHV) * Persistence * Cell-to-cell spreading, avoiding antibodies * Antigen variations (how the cold and flu virus always changes) * Inhibition of MHC synthesis (adenoviruses) * Interleukin mimicry (EBV) * Complement fragment neutralization (HSV-1 - C3b)

Question 58

There's a lot of other crap in here that's better covered in immunology so I'm not putting it here. Take a look at the lecture slides though.

Answer 58

Stop this now, no more cards