Comparative Immunobiology of Host-Pathogen Interactions

Question 1

Why can’t you fully activate the immune system?

Answer 1

1. energy
2. highly susceptible to secondary infection (from depleted stores)

Question 2

What is the driver for evolution of invading microbes? i.e. what characterisitcs do microbes “want” to successfully invade a host?

Answer 2

• evasion strategies that overcome immune defense mechanisms
• increase potential for survival
• speed

Question 3

What are a couple of ways in which pathogens can take advantage of immune mechanisms?

Answer 3

1. antigenic variation
2. expression of immune suppressor genes

Question 4

What is the ultimate goal for animal hosts when dealing with infection?

Answer 4

avoiding death

Question 5

Name and describe three pathogens and their primary way to overcome host defenses

Answer 5

1. Plasmodium falciparum: causes rosette formation with uninfected eythrocytes creating a pseudo-shell of protection
2. Tyrpanosoma brucei: releases its surface Ags into solution to act as decoy proteins
3. Listeria: hijacks the calthrin-dependednt endocytic machinery to invade mammalian cells - uses non-phagocytic R to enter phagocytes

Question 6

What is the result of the biological arms race in the context of hosts and pathogens?

Answer 6

develop new traits and behaviours

Question 7

why do pathogens have an advantage compared to hosts to evolve new traits?

Answer 7

1. quicker proliferation
2. exhange genes

Question 8

Describe how Leishmania major evades the immune system

Answer 8

1. creates inflammatory response to draw in monocytes that will differentiate into MFs
2. uses non-phagocytic R to enter MF (backdoor)
3. Reinforcements such as Tcells, IFN-g, and ROIs make the MF angry and elicit it to apoptose; however, Leishmania inhibits apoptosis

Question 9

Name 7 challenges for zoonotic pathogens that arise from using different hosts

Answer 9

1. changes in physical barriers may restrict entry
2. different host physiology (e.g. temperature, oxygen access)
3. antimicrobial defenses may be quite different: repertoire vs potency
4. inter-host proximity
5. environmental conditions
6. intracellular pathogens: entry into HC
7. extracellular pathogens: particular relevance of Ab responses

Question 10

What are three modes in which evolution provides a mechanism for organisms to change?

Answer 10

1. improve on the existing model (e.g. apoptosis)
2. adapt to outside pressures (e.g. Abs and specificity)
3. respond to changes in internal requirements (e.g. vascularization)

Question 11

Describe the two plant antimicrobial defenses

Answer 11

1. PAMP-triggered immunity (PTI): conserved microbial elictors (elicit entry into cells) called PAMPs are recognized by PRRs on the external face
2. Effector-triggered immunity (ETI): recognition by intracellular Rs of pathogen virulence molecules called effectors

Question 12

How do microbes evade plant PTI responses?

Answer 12

1. hide/shed PAMPs
2. downregulate the PRRs
3. disable PRR signaling

Question 13

Why is it important that the innate IS is localized and ready to go?

Answer 13

defends you early to prevent spread of pathogen

Question 14

What is the function of NETs?

Answer 14

trap and expose pathogen to antimicrobial factors + concentrate the factors

Question 15

Why does the innate responses come down shortly after the adaptive response appears?

Answer 15

prevent damage

Question 16

What are two important dimensions that play critical roles in the repertoire of immune antimicrobial emchanisms exhibited across animal species today? Briefly describe each one

Answer 16

1. phylogeny: evolutionary distance
2. ontogeny: development from embryo –> fetus –> adult (age)

Question 17

Give an example of how novel functional features often result from evolution of individual components

Answer 17

Complement pathway: mammals have multiple complement pathways – alternative, lectin, classical (Ab mediated). However, the classical pathway only evolved once the adaptive system (which produces Abs) evolved/only present in animals with an adaptive immune system

Question 18

What is the advantage of having three different compelement pathways?

Answer 18

redundancy - variety of ways to be activated + if pathogen inhibits one pathway, you still have the others

Question 19

Why do some studies work in mice but not people?

Answer 19

1. age of mouse (ontogeny)
2. evolutionary distance (phylogeny)
3. stress
4. exposure to pathogen
5. type of pathogen

Question 20

What is functional pleiotropy?

Answer 20

tool doing multiple things –> investing less energy + more cohesive response (e.g. during neutrophil recuirtment: activate neutrophils, tell them where to go; increase endothelial permeability etc)

Question 21

What is a big negative for the conservation of immune defenses?

Answer 21

many pathogens can jump from species to species –> zoonotic disease