Exam 1 SA

Question 1

Give two examples of secreted bacterium proteins that act as virulence factors, but are not exotoxins

Answer 1

hyaluronidase and phospholipase

Question 2

Bacterial exotoxins are divided into two categories based on the effect that theyhave on host cells. What are the names given to these categories?

Answer 2

cytolytic and cytotonic

Question 3

Identify the similarities and differences between the exotoxins produced by V.cholerae O1 and C. diphtheriae, respectively. Consider the structure of the toxins, their mode of action, and the consequences for affected host cells.

Answer 3

Toxin structure: both have A and B protein subunits (B subunits bind to host cell; A subunits enter cell). Cholera toxin (CT) in 1A:5B family; diphtheria toxin (DT) in 1A:1B family.
Mode of action: CT activates adenylate cyclase; DT inhibits protein translation.
Consequence for affected cell: CT causes hypersecretion of water and electrolytes (cytotonic); DT causes cell death (cytolytic).

Question 4

Specifically, what kind of T cells are involved in a DTH reaction?

Answer 4

TH1 T cells

Question 5

Give a named example of a cytokine that is produced by the responding T cells, and identify its major function.

Answer 5

Tumor necrosis factor alpha - pro-inflammatory cytokine.

Question 6

How are antigens processed for presentation to T cells during a DTH reaction? In what form, and on what type of cell, are the antigens presented to the responding T cells?

Answer 6

Pathogen proteins are endocytosed, or pathogen cells are phagocytosed, by macrophages.
Proteases then digest pathogen proteins into peptides, which are processed via the exogenous pathway of antigen presentation.
The peptides are loaded onto MHC II, and presented on the surface of the macrophage to responding TH1 cells.

Question 7

How does the capsule prevent phagocytosis of the bacteria during the immunesystem’s early induced response?

Answer 7

There are no pattern recognition receptors on phagocytes for polysaccharide capsule (i.e. capsule is not a PAMP).

Question 8

What effector component(s) unique to the adaptive immune response is/are required to defeat this virulence factor?

Answer 8

Antibodies (IgM and IgG/IgA) that can bind specifically to the polysaccharide capsule

Question 9

Describe two mechanisms by which the effector component(s) identified in (b) allow encapsulated S. pneumoniae organisms to be recognized by phagocytes during an adaptive immune response.

Answer 9

(1) IgM binds capsule. Complement fixed by bound IgM. Complement acts as opsonin [phagocytes have cell surface receptors for complement].
(2) IgG/IgA binds capsule. IgG/IgA acts directly as an opsonin [phagocytes have cell surface receptors for constant regions (CH) of IgG and IgA].

Question 10

What is the usual portal of entry for influenza virus in humans?

Answer 10

Respiratory tract

Question 11

What effector components of the adaptive immune response would be involved
in combating an influenza virus infection?

Answer 11

IgA (antibody) and CTL’s specific for influenza virus antigens

Question 12

Briefly outline the steps in the host–pathogen interaction that takes place during influenza A virus infection of humans.

Answer 12

(1) entry into the host [respiratory tract, via droplets].
(2) adherence to host cells [of the respiratory epithelium].
(3) penetration into host cells.
(4) intracellular growth/reproduction, leading to formation of new virus particles.
(5) cell and tissue damage (caused directly by virus, and enhanced by immune response).
(6) shedding of virus/spread to surrounding cells (inhibited by immune response)

Question 13

Among patients who are undergoing the same antibiotic therapy, why are only some at risk for developing antibiotic-associated gastrointestinal disease?

Answer 13

Colonizing C. diff that survives antibiotics that kill most Gin organisms

Question 14

Given two strains of C. difficile, one of which can only colonize people, while the other can cause gastrointestinal disease, what specific virulence factor would
you expect to be present in the latter but absent from the former?

Answer 14

Exotoxins are required to cause GI disease

Question 15

Briefly outline the events that take place in the affected patients, beginning with the initiation of antibiotic therapy, which culminate in gastrointestinal disease caused by C. difficile.

Answer 15

1) Colonizing C. diff survives antibiotics that kill many normal GI organisms
2) Death of normal flora leaves uncolonized mucosal surface available to be occupied by growth of C. diff.
3) As numbers of C. diff increase, so does concentration of their exotoxin, which can exceed threshold necessary for overt disease to be caused

Question 16

How does a macrophage detect the presence of Gram-negative bacteria?

Answer 16

It has cell surface receptors that bind to lipopolysaccharide (LPS, “endotoxin”) from the outer membrane of Gram-negative bacteria.

Question 17

What two kinds of signaling molecules does the macrophage secrete after it
detects the bacteria?

Answer 17

cytokines and chemokines

Question 18

Explain what happens during the local inflammatory response that follows.
Indicate which cellular and molecular features of the response account for the redness, swelling, heat, and pain that are characteristic of inflammation.

Answer 18

(1) Pro-inflammatory cytokines cause activation of endothelial cells in local capillaries (leading to vasodilation and increased vascular permeability).
(2) Vasodilation (dilating of capillaries) causes local redness and heat.
(3) Increased vascular permeability allows extravasation of effector cells (monocytes, neutrophils) from the blood into the tissues specifically at the site of infection.
(4) Increased vascular permeability also causes swelling (by increased fluid leakage from blood into the tissues), and (indirectly) leads to pain (pressure on nerves from swelling; inflammatory mediators produced by extravasating effector cells).

Question 19

What adaptive immune system component would be important for controlling the viremia?

Answer 19

Antibody (IgG and IgA)

Question 20

How are naïve CD8+ T-cells activated?

Answer 20

Dendritic cells present peptide antigens on MHC I to naïve CD8+ T-cell, and co-stimulate it with cytokines.

Question 21

After activation, CD8+ T-cells proliferate and differentiate into CTLs. Briefly outline how virus-specific CTLs recognize and destroy virus-infected host cells

Answer 21

Specific viral antigen presented to CTL on MHC I by virus-infected cell (recognition).
Directed release of granules (containing perforin and granzyme B) onto target host cell plasma membrane. Perforin creates pores in target cell membrane through which granzyme B (a protease) enters the cell.
Granzyme B triggers apoptosis (programmed cell death, “suicide”) of target cell.

Question 22

How are these bacteria recognized by phagocytes as things that should be engulfed?

Answer 22

Specific pattern-recognition receptors on phagocyte (i) bind directly to pathogen-associated molecular pattern (PAMP) on bacterium, or (ii) bind to opsonins that coat the bacterium.

Question 23

What are two humoral component(s) of the innate immune system that can directly enhance the process of phagocytosis by individual cells?

Answer 23

Complement large fragments, acute phase proteins

Question 24

Briefly outline the events that take place after engulfment of a bacterium, and which culminate in its death inside the phagocyte. In your description, indicate when during this sequence of events each of the major classes of specific mechanisms used by phagocytes to kill bacteria is brought to bear.

Answer 24

(1) phagosome containing bacterium is acidified (acid brought to bear on bacterium).
(2) phagosome fuses with lysosome to form the phagolysosome (pre-formed antibacterial enzymes, competitors, and peptides from inside the lysosome now come into contact with bacterium).
(3) respiratory burst activated by formation of phagolysosome (toxic oxygen and nitrogen species are made from scratch within the phagolysosome which encloses the bacterium).

Question 25

What is the main cell type in the body which expresses CD4 on its surface?

Answer 25

CD4+ T cells

Question 26

Why is the decline in the number of CD4+ cells in the body only gradual during the clinically latent stage of HIV infection?

Answer 26

The body makes new CD4+ T-cells almost as quickly as they are killed by HIV infection

Question 27

Explain the normal functions of CD4+ cells during an adaptive immune response, and indicate how the loss of these cells can explain the immunodeficiency characteristic of acquired immune deficiency syndrome (AIDS).

Answer 27

1) Naive CD4+ T cells (TH0), when activated by dendritic cells, differentiates into either TH1 or TH2 cells
2) Most TH1 cells recognize their antigen presented by and activate macrophages
3) All TH2 cells and a few TH1 cells recognize their antigen presented on by B cells and activate B cells to proliferate and differentiate into plasma cells that produce antibody

Question 28

On what cell types are the two kinds of lymphocyte antigen receptor found?

Answer 28

B cells [B-cell receptor] and T cells [T-cell receptor].

Question 29

Under what conditions are foreign peptides recognized by each kind of antigen receptor?

Answer 29

B-cell receptors can recognize soluble peptides. T-cell receptors can recognize only peptides that are bound to MHC molecules.

Question 30

Explain briefly how diversity is generated in the protein sequences of mature lymphocyte antigen receptors.

Answer 30

Antigen receptor (AgR) genes are composed of protein-coding DNA cassettes (V, J, C for light chains; V, J, D, C for heavy chains). Each cassette is present in multiple copies, all of which differ slightly in sequence.
Pseudo-random DNA recombination occurs during development of each individual lymphocyte.
Randomly-chosen copies of each type of cassette (V, J, and C) are joined together to encode the AgR light chain, and the AgR heavy chain (V, J, D, and C).

Question 31

Define what is meant by “invasion” in this context.

Answer 31

spread of pathogen not restricted in location near Portal of entry. spreads into deeper tissue.

Question 32

For an opportunistic pathogen, such as Candida albicans, which lacks specific virulence factors for invasion, what kinds of extrinsic factor(s) (i.e. ones external
to the microbe) could allow invasive disease to be caused

Answer 32

Environment within the host could allow the growth of the pathogen. For example, Candida albicans is naturally found in the body. Invasive disease is caused by the overgrowth of this pathogen. If the population size of the resident organisms increases due to the death of other types of endogenous organisms, allows for the space for Candida albicans to grow and cause disease.

Question 33

After entry of an obligate-extracellular bacterial pathogen into a host, briefly
outline the sequence of all the events that lead up to invasion: (i) if the
bacterium secretes a cytolytic exotoxin

Answer 33

Once infected, the obligate bacteria can secrete a cytolytic exotoxin that can can kill the infected cell, allowing the pathogen to gain access to the underlying tissue

Question 34

After entry of an obligate-extracellular bacterial pathogen into a host, briefly outline the sequence of all the events that lead up to invasion: (ii) if the bacterium secretes the enzyme, hyaluronidase.

Answer 34

bacterium adhered to the mucosal epithelium. secrete hyaluronidase - degrades extracellular matrix between cells. once degraded, pathogens squeeze through, still producing hyaluronidase, until it reaches the tissue and the barrier has been breached.

Question 35

What is an antigen?

Answer 35

any molecule that can be recognized by a specific receptor on a B or T cell

Question 36

What is an epitope?

Answer 36

actual molecular structure that interacts with a single antibody molecule or B or T cell receptor

Question 37

Briefly outline the steps that occur between the initial binding of antigen to the B-cell receptor on a naïve B cell, and the accumulation of high levels of IgG in the serum. Describe activation of the B cell, as well as the subsequent events.

Answer 37

1) B cells bind to antigen, membrane bound receptor endocytosed, and the pathogen is destroyed
2) proteins processed and presented on B cell’s MHC II to activate the correct CD4+ T cells
3) T cells help activate the B cell, which becomes a plasma cell and secretes immunoglobulin as an antibody
4) Binding site improved by somatic hypermutation
5) effector/constant regions undergo isotype switching

Question 38

What is the usual portal of entry for Vibrio cholerae O1 in humans?

Answer 38

GI tract

Question 39

Not all serotypes of Vibrio cholerae can cause cholera. What specific kind of virulence factor would you expect to be common only to the cholera-causing
serotypes of this bacterium?

Answer 39

cholera toxin

Question 40

Briefly outline the steps in the host–pathogen interaction that takes place during infection of humans by Vibrio cholerae.

Answer 40

1) entry into host via ingestion into GI tract
2) adherence to host cells of GI epithelium
3) extracellular growth and shedding in feces
4) cholera toxin production
5) cell and tissue damage
6) Immune response, IgA neutralizes toxin

Question 41

What cytokine would you expect to be produced by the infected epithelial cells?

Answer 41

a/b interferon

Question 42

For HSV, what distinguishes a lytic infection from a latent infection?

Answer 42

lytic - HSV reproducing

latent - it’s not

Question 43

Explain how the adaptive immune response brings primary HSV infection under control, and indicate why this immune response is ineffective against the latently-infected nerve cells.

Answer 43

1) Adaptive immune response generates HSV-specific antibodies to CTLs
2) Antibody neutralizes and CTLs kill infected epithelial cells
3) Latent infected nerve cells cannot be recognized by CTLs
4) Because HSV does not reproduce in latently infected nerve cells, HSV peptides are not displayed on their MHC 1

Question 44

What general mechanism is used by R. rickettsii to avoid being killed after phagocytosis?

Answer 44

bacteria rupture the phagosome membrane and escape into the cytoplasm of the host cell

Question 45

Give an example of a specific virulence factor that is employed by R. rickettsii
during this process.

Answer 45

phospholipase

Question 46

Considering its location within the infected host cell, what kind of T-cell response would be required to clear R. rickettsii infections? How are antigens processed for presentation to T cells during R. rickettsii infection, and in what form are the antigens presented to the responding T cells?

Answer 46

CTLs.
RR proteins present in the cytoplasm of infected cell. peptides from bacterial proteins will be generated via endogenous pathway, loaded onto MHC 1, and trafficked to cell surface
Peptide antigens displayed by MHC 1 will be presented to responding CTLs