Immunity to Pathogens

Question 1

for a successful invasion of the host, the pathogen must overcome both the…

Answer 1

innate and adaptive immune responses

Question 2

Innate immunity to viral infections is largely though the induction of?

Answer 2

Type I interferons (IFN-α and IFN-β)

Question 3

How are IFN-α and IFN-β induced?

Answer 3

via Toll-like receptors (TLRs) that detect viral dsRNA in infected cells

Question 4

what 3 things are induced by IFN-α/β receptor signaling?

Answer 4

1. Mx proteins
2. Rnase L
3. Protein kinase R

Question 5

What do Mx proteins do?

Answer 5

inhibit virus transcription and assembly

Question 6

What does Rnase L do?

Answer 6

degrades viral mRNA

Question 7

What does protein kinase R do?

Answer 7

blocks protein translation

Question 8

What happens when IFN-α and IFN-β bind to the appropriate receptor on NK cells?

Answer 8

induces lytic activity

Question 9

What further enhances the lytic activity of the NK cells in response to IFN-α and IFN-β ?

Answer 9

IL-12 produced by innate immune cells such as dendritic cells

Question 10

What 4 methods does antibody use to contain the spread of viruses?

Answer 10

1. block viral attachment to host cells
2. preventing fusion of viral envelope with host cell membrane
3. agglutination and opsonization
4. activation of classical complement pathway

Question 11

What occurs after antibody activates the classical complement pathway in terms of viral killing?

Answer 11

opsonization of viral particles by C3b and lysis of enveloped virus by the membrane attack complex

Question 12

Cell-mediated immunity is responsible for eliminating viruses once…

Answer 12

cells have already become infected

Question 13

What 4 things are involved in cell mediated viral clearance

Answer 13

1. IFN-γ secreted by CD4+ Th1 cells and CD8+ CTL has direct antiviral activity
2. CTLs target and kill virus infected cells
3. NK cells are directly lytic for infected cells and also kill by ADCC
4. Macrophages are activated by IFN-γ and kill by ADCC

Question 14

What are 6 ways in which viruses can evade the immune response (briefly)

Answer 14

1. evade action of IFN-α and IFN-β
2. inhibit viral antigen presentation (3 ways)
3. Constant alteration of viral antigens
4. Modulation by capping and shedding
5. Interfering with complement function
6. Suppression of Antiviral immune responses (3 ways)

Question 15

How do viruses evade IFN-α and IFN-β action?

Answer 15

by blocking or inhibiting the action of dsRNA-dependent protein kinase R

Question 16

what are the three ways in which viruses inhibit viral antigen presentation?

Answer 16

1. down regulating class I MHC
2. Inhibiting TAP transporter
3. Down regulating class II MHC expression on APCs

Question 17

what are the two ways in which viruses can alter their antigens?

Answer 17

1. genetic drift through point mutations in the genome

2. genetic shift through exchange of genetic material with viral reservoirs in other hosts

Question 18

What are two examples of ways in which viruses can interfere with complement function ?

Answer 18

1. production of a C3 binding protein that increase decay of C3 convertase
   - inhibits alternative pathway
2. C4b binding protein that inhibits classical pathway

Question 19

What are three ways in which viruses can suppression immune responses

Answer 19

1. activating Treg cells
2. Altering the Th1/Th2 balance
3. destroying essential lymphoid tissues

Question 20

through what two means to bacteria invade the body?

Answer 20

Mucosal surfaces or breaks in the skin

Question 21

What 4 things are requires to establish a bacterial infection?

Answer 21

1. attachment to host cells
2. Proliferation
3. invasion of tissue
4. damage to host cells (sometimes due to toxins)

Question 22

Low level infections can be controlled by..

Answer 22

the innate response - primarily phagocytosis by neutrophils

Question 23

Immunity to extracellular bacteria is achieved largely through..

Answer 23

production of antibody by plasma cells in regional lymph nodes and submucosa

Question 24

What are the 4 roles of antibody in terms of extracellular bacterial infection?

Answer 24

1. Prevent attachment + colonization
2. Neutralize bacterial exotoxins or endotoxins
3. Opsonize for phagocytosis
4. Activate classical complement pathway

Question 25

What are the 4 results of activating complement for fighting extracellular bacteria infection?

Answer 25

1. lysis of gram negative bacteria by MAC 2. production of C3b opsonin 3. production of anaphylatoxins - cause mast cells to degranulate 4. chemotactic factors produced to attract neutrophils and macrophages

Question 26

Briefly, what are the 6 ways in which extracellular bacteria can evade the immune system?

Answer 26

1. Production of cell surface appendages 2. Secretion of proteases that cleave secretory IgA 3. Changes in amino acid sequence of key cell surface structures 4. Expression of surface structures like capsules 5. Toxin production 6. Interfering with complement system

Question 27

How do surface appendages help bacteria avoid the immune response?

Answer 27

enhance ability to attach to mucosal epithelium

Question 28

How do proteases help bacteria avoid the immune response?

Answer 28

reduce half life of secretory IgA and prevent IgA mediated agglutination of bacteria

Question 29

How does changing the amino acid sequence of surface structures help bacteria avoid the immune response?

Answer 29

allows them to evade the IgA response

Question 30

How do surface structures like capsules help bacteria avoid the immune response?

Answer 30

inhibit phagocytosis

Question 31

How does toxin production help bacteria avoid the immune response?

Answer 31

interfere with phagocytosis by killing leukocytes

Question 32

what are 4 ways in which extracellular bacteria interfere with the complement system

Answer 32

1. Capsules fail to stabilize C3 convertase - inhibits alternative pathway 2. Resistance to MAC with capsules 3. Secrete decoy proteins that deviate from the normal complement activation site 4. acceleration of complement breakdown by secreted enzymes

Question 33

What are the 3 ways in which intracellular bacteria colonize phagocytic cells?

Answer 33

1. inhibiting lysozome fusion 2. Resisting oxidative/lysosomal attack 3. Escaping the phagosome following phagocytosis

Question 34

What form of cell mediated immunity protects against intracellular bacterial infections?

Answer 34

A DTH response

Question 35

Th1 cells release __ that activates macrophages and increases phagocytic ability/activity

Answer 35

IFN-y

Question 36

What else do Th1 cells activate? what does this achieve?

Answer 36

CTLs kill infected macrophages, releasing bacteria, which are then phagocytosed and killed by activated uninfected macrophages

Question 37

What is formed in response to persistent bacterial infection/cell mediated response?

Answer 37

granuloma and extensive tissue necrosis due to accumulation of lysosomal enzymes

Question 38

What parasite has cell surface antigens that go though various maturational stages?

Answer 38

Plasmodium sp

Question 39

What parasite has a large repertoire of genes coding for variable surface glycoprotein that can be expressed sequentially?

Answer 39

Trypanosoma

Question 40

How is protection to helminths achieved?

Answer 40

both humoral and cell-mediated immunity

Question 41

What special adaptations do Schistosoma have that help them avoid the immune response?

Answer 41

1. decreased expression of antigens 2. antigen masking with host ABO 3. Induces strong Th2 response which downregulates Th1 required for clearance

Question 42

What do worm antigens in the gut cause?

Answer 42

IgE-sensitized mast cells in the lining of the gut to degranulate

Question 43

What does mast cell degranulation in the gut cause?

Answer 43

Increased vascular permeability and the secretion of eosinophil chemotactic factor that allows worm-specific IgG and eosinophils to reach worm

Question 44

What do eosinophils do when they reach the worm?

Answer 44

Bind to IgG coated worm and release granule contents including major basic protein (MBP)

Question 45

What causes the worm to be expelled?

Answer 45

Smooth muscle contraction stimulated by histamine

Question 46

What else is important in maintaining acute inflammatory responses to helminths?

Answer 46

Activation of tissue mast cells by anaphylatoxins (C3a and C5a) generated by complement breakdown