Infections

Question 1

List the 4 categories of disease-causing pathogens.

Answer 1

• extracellular (bacteria, parasites, fungi)
• intracellular (bacteria, parasites)
• viruses
• parasitic worms

Question 2

What are the primary barriers to infection?

Answer 2

• physical: skin, mucosal surfaces

- chemical

Question 3

Describe the skin as a barrier to infection.

Answer 3

• keratinocyte layers
• dry
• acidic

Question 4

Describe the mucosal surfaces a barrier to infection.

Answer 4

• mucus
• ciliated epithelium
• secretory IgA

Question 5

Describe chemical barriers to infection.

Answer 5

• skin is dry and acidic. pathogens that can withstand acidic conditions are more likely to infect after direct tissue damage
• lysozymes are secreted in tears and saliva. antibacterial; degrades peptidoglycan layer of both gram positive and gram negative bacteria
• antimicrobial peptides are secreted by epithelial cells and phagocytes create pores in pathogen membranes

Question 6

List antimicrobial peptides (AMPs) secreted by epithelium and phagocytes.

Answer 6

• defensin and cathelicidins: anti-bacterial, viral, and fungal
• histatins: anti-fungal

Question 7

Define PAMPs.

Answer 7

Pathogen-Associated Molecular Pattern

• conserved surface peptide or epitope
• recognized by resident immune cells
• alerts immune system of the type of pathogen and location of invasion

Question 8

Define TLRs.

Answer 8

Toll-Like Receptors

• primitive, highly conserved PAMP recognition receptors
• stimulates intracellular signaling
• increases cytokine production and immune cell recruitment

Question 9

List TLRs responsible for recognizing bacteria.

Answer 9

• TLR2 (both - lipoproteins)
• TLR4 (only gram negative - LPS)
• TLR5 (both - flagellin)

Question 10

List TLRs responsible for recognizing viruses.

Answer 10

• TLR3
• TLR7
• TLR8

Question 11

List TLRs responsible for recognizing both bacteria and viruses.

Answer 11

• TLR9

Question 12

Define NOD-like receptors.

Answer 12

• intracellular

- cytosolic PAMP receptors

Question 13

Define NOD1.

Answer 13

• recognizes gram NEGative
• peptidoglycan breakdown products
• ex: salmonella

Question 14

Define NOD2.

Answer 14

• recognizes BOTH gram negative and gram positive
• recognizes myco. TB (fungal)
• found enriched in gut cells

Question 15

Describe the relationship between Crohn’s Disease and NOD2.

Answer 15

• some people with Crohn’s have a NOD2 mutation
• if you have a NOD2 mutation…can’t effectively recognize bacterial and fungal PAMPs
• causes dysbiosis and disease symptoms

Question 16

Define glucan receptors.

Answer 16

• recognizes B-glucans on FUNGAL cell walls

Question 17

Define scavenger receptors.

Answer 17

• recognizes BACTERIAL cell wall components

Question 18

What does PAMP receptor activation lead to?

Answer 18

• inflammatory cytokines
• recruit immune cells
• activates T cells (initiate adaptive immunity)
• promote bactericidal killing by activating AMPs and ROS production
• phagocytosis and respiratory burst

Question 19

List PAMP receptors.

Answer 19

• TLRs (BACTERIAL, VIRAL, FUNGAL)
• NOD (some BACTERIAL, myco. TB)
• glucan (FUNGAL)
• scavenger (BACTERIAL)

Question 20

Pair up complement-mediated actions with the pathogens they affect.

Answer 20

• MACs - only gram NEGATIVE; (gram positive and fungi are resistant due to their cell wall composition)
• Opsonization by C3/C3R - broad acting; BACTERIAL

Question 21

Complement deficiencies render patients significantly more susceptible to…?

Answer 21

• bacterial infection

- esp. Neisseria meningidits and pneumococci

Question 22

Define respiratory burst.

Answer 22

• after C3R PAMP receptor activation, macrophages and neutrophils are activated to kill the pathogen
• phagosome with pathogen fuses with lysosome containing ROS to damage microorganism

Question 23

Define chronic granulomatous disease.

Answer 23

• defective NADPH oxidase
• cannot carry out respiratory burst
• cannot kill pathogens
• susceptible to recurrent fungal and catalase postive bacteria

Question 24

What are the 2 innate anti-viral effectors?

Answer 24

• interferon type 1

- NK cells

Question 25

Describe the role of Type 1 interferons in anti-viral immunity.

Answer 25

- release of Type 1 IFN is stimulated by anti-viral TLRs (3, 7, 8) - IFNa and IFNb are secreted from the infected cell and stimulate transcription of IFN-Stimulated Genes (ISGs) in neighboring cells - prevent viral synthesis and spread

Question 26

What is the difference between Type 1 and Type 2 IFN?

Answer 26

- Type 1 (a, b) = antiviral | - Type 2 (g) = antiviral and antibacterial

Question 27

Describe the role of NK cells in anti-viral immunity.

Answer 27

- recruited to site of infection - stimulated by IFN - occurs before stimulation of T cells and adaptive immunity

Question 28

Describe the role of antibody-mediated opsonization in infection clearing.

Answer 28

- works for EXTRAcellular BACTERIA and FUNGI - antibody binds to surface markers => allows for phagocytosis by macrophages - S. aureus can evade this with Protein A

Question 29

Describe the role of antibody-mediated neutralization in infection clearing.

Answer 29

- specific to BACTERIA (NOT virus) - antibody binds to bacterial toxins and clears them - ex: cholera in the gut

Question 30

Describe the role of antibody-mediated complement activation in infection clearing.

Answer 30

- recall: only gram negative bacteria are susceptible to MACs

Question 31

Describe the role of T cells in infection clearing.

Answer 31

- only for INTRAcellular bacteria | - Th1 mediated

Question 32

Describe the mechanism by which virally infected cells are cleared.

Answer 32

- CD8 T cell mediated | - NK cells (IFN)

Question 33

How are parasitic infections controlled?

Answer 33

- complement - IgE (antibody-dependent cellular cytotoxicity) ==> bound to eosinophils; eosinophil-mediated killing

Question 34

Describe the immune response against: influenza virus.

Answer 34

- recognition by TLR3, 7, 8, 9 - activates Type 1 IFN and NK cells - extracellular pathogen - T-cell: CD8 mediated killing - resistant to antibody-mediated neutralization

Question 35

Describe the immune response against: candida albicans (extracellular fungi).

Answer 35

- recognition by glucan receptor - affected by AMPs (defensin, cathelicidins, histatins) - resistant to MACs - affected by antibody-mediated opsonization

Question 36

Describe the immune response against: staphylococcus aureus (gram positive, extracellular, bacterial)

Answer 36

- recognition by TLR2, 5, 9, scavenger - affected by AMPs: defensins, cathelicidins - resistant to MACs - affected by chemical barrier lysozymes - affected by antibody-mediated opsonization and neutralization

Question 37

Describe the immune response against; neisseria meningiditis (gram negative, extracellular, bacterial).

Answer 37

- recognition by TLR2, 4, 5, 9, scavenger - affected by AMPs: defensins, cathelicidins - affected by MACs, opsonization, complement - affected by chemical barrier lysozymes

Question 38

Describe the immune response against: Vibrio cholera (gram negative, extracellular, bacteria, toxin).

Answer 38

- recognition by TLR2, 4, 5, 9, scavenger - affected by AMPs: defensins, cathelicidins - affected by chemical barrier lysozymes - affected by antibody-mediated neutralization - affected by MACs, opsonization, complement

Question 39

Describe the immune response against: mycobacterium tuberculosis (intracellular, bacteria).

Answer 39

- recognition by NOD2 - affected by AMPs: defensins, cathelicidins - affected by chemical barrier lysozymes - Th1 mediated response - resistant to antibody-mediated processes

Question 40

Describe the immune response against: schistosoma mansoni (parasite).

Answer 40

- complement | - IgE and eosinophil mediated killing