Host Immune Responses to Bacterial Infections

Question 1

What are the 4 factors that determine the outcome of a bacterial infection?

Answer 1

1) The resistance of the host.
2) The virulence of the organism.
3) The presence of damaged tissue.
4) The location of the organism in the body.

Question 2

Name the two cell wall antigens of bacteria and what kind of bacteria they are found in.

Answer 2

1) Peptidoglycan + techoic acid; Gram(+) bacteria.

2) Lipopolysaccharide (LPS; T-independent antigen); Gram(-) bacteria.

Question 3

How does LPS function as an antigen?

Answer 3

1) LPS directly activates B cells to produce IgM antibodies.
2) LPS is also a potent activator of macrophages.
3) It is a somatic (O) antigen (specific sugars).

Question 4

What is capsular antigen? What does it do?

Answer 4

Capsular antigen (also called K antigen) functions a lot like LPS: the polysaccharide-rich capsules of bacteria directly activate B cells to produce IgM anticapsular antibodies.

Question 5

Fimbria antigen will stimulate the release of antifimbria antibodies…

What does antifimbria antibodies do?

Answer 5

Antifimbria antibodies prevent bacterial attachment to mucosal surfaces.

Question 6

What is another name for flagellar antigen? What is the function of flagella-antibodies? How effective are flagella antibodies?

Answer 6

Flagellar antigen is also called H antigen.

Antibodies against flagella can immobilize motile bacteria.

Flagellar antibodies are NOT significant in reducing bacterial pathogenesis.

Question 7

Which bacteria produce exotoxins? What are exotoxins responsible for? Give 2 examples.

Answer 7

BOTH gram-positive and gram-negative bacteria MAY secrete proteinaceous exotoxin, which is responsible for the diseases caused by the organisms that do produce exotoxin.

2 examples are: tetanospasmin (clostridium tetani) and botulinal toxin (clostridium botulinum).

Question 8

What are toxoids? What do they induce in the host?

Answer 8

Toxoids are substances derived from exotoxins and are highly immunogenic.

They induce the formation of antitoxins in the host.

Question 9

What are the extracellular sites of infection (bacterial growth)?

Answer 9

1) Interstitial spaces, blood and lymph.

2) Epithelial surfaces.

Question 10

What are the intracellular sites of infection (bacterial growth)?

Answer 10

1) Cytoplasmic.

2) Vesicular.

Question 11

T or F?

Extracellular bacteria have the capacity to survive for long periods of time in phagocytic cells, therefore, they can cause tissue damage while their both outside and inside phagocytes and other cells.

Answer 11

FALSE.

Extracellular bacteria DO NOT have the capacity to durvive for long periods in phagocytic cells, therefore, they only cause damage while they are outside phagocytes and other cells.

Question 12

How do extracellular bacteria cause disease?

Answer 12

1) By producing toxins (exotoxins, endotoxins).

2) By inducing inflammation which results in tissue damage at the site of infection.

Question 13

Name the 2 components of innate immunity to extracellular bacteria.

Answer 13

1) Phagocytic cells.

2) Complement activation on bacterial surfaces.

Question 14

Name one of the phagocytic cells involved in the innate immunity to extracellular bacteria; how does it eliminate the bacteria?

Answer 14

Neutrophils; and by phagocytosis!

duh

Question 15

What extracellular bacteria are susceptible to the innate immunity’s complement-mediated lysis?

Answer 15

Gram-negative bacteria.

Question 16

T or F?

Opsonization is a component of the innate immunity’s response to extracellular bacteria.

Answer 16

TRUE.

Question 17

Which cytokines are responsible for local mast cell degranulation and the release of vasoactive mediators (like histamine) that mediate vasodilation and extravasation of leukocytes into tissues in the innate immunity’s response to extracellular bacteria?

Answer 17

C5a, C4a, and C3a.

Question 18

What is a chemotactic cytokine involved in the inflammatory response of the innate immunity’s response to extracellular bacteria?

Answer 18

C5a.

Question 19

What are the 3 results of complement activation in the innate immunity’s response to extracellular bacteria?

Answer 19

1) lysis of microbes.
2) Phagocytosis of microbes opsonize with complement fragments.
3) Inflammation.

Question 20

What are the 4 components of the adaptive immunity’s response to extracellular bacteria?

Answer 20

1) Neutralization of bacterial toxins.
2) Opsonization (IgG) and Fcy receptor-mediated phagocytosis.
3) Complement activation via the classical pathway (IgG, IgM).
4) Prevention of bacterial adherence to muosal surfaces.

Question 21

T or F?

Facultative intracellular bacteria can survive, and in some instances, multiply in phagocytic cells (mainly macrophages).

Answer 21

TRUE.

Question 22

T or F?

Within the macrophage, intracellular bacteria are protected from extracellular host defense mechanisms.

Answer 22

TRUE.

Question 23

What does the presence of antibodies that are produced during intracellular bacterial infections indicate?

Answer 23

Antibodies produced during intracellular bacterial infections merely indicate exposure to antigen but does NOT denote protective immunity.

Question 24

Macrophages are stimulated to secrete IL-12 by which bacteria?

Answer 24

Intracellular bacteria.

Question 25

IL-12 is a potent activator of what cells?

Answer 25

NK cells.

Question 26

Once the macrophages secrete IL-12 to activate NK cells, these activated NK cells produce ___1___, which activates ___2___ and promotes the killing of intracellular bacteria.

Answer 26

1) IFN-y.

2) Macrophages!

Question 27

T or F?

Adaptive immunity to intracellular bacteria is principally humoral mediated.

Answer 27

FALSE.

Adaptive immunity to intracellular bacteria is principally CELL mediated.

Question 28

Which helper T cells respond to MHC class II-associated peptide antigens derived from bacteria in the endosome and IL-12 from the macrophage?

Answer 28

CD4+ helper T cells.

Question 29

T or F?

The activated CD4+ T cell expresses CD40L and secretes IFN-y, both of which activate macrophages; enhancing the killing of the microbes in the phagolysosomes.

Answer 29

TRUE.

Question 30

Which cells respond to the intracellular bacterially induced MHC 1-peptide complex to kill the infected macrophage?

Answer 30

CD8 + cytolytic T cells.

Question 31

What are bacterial superantigens? What do they bind to? What is the result of this binding?

Answer 31

Bacterial superantigens are soluble bacterial proteins, including various exotoxins, which bind simultaneously to all TCRs bearing certain SPECIFIC VB DOMAINS regardless of their antigenic specificity and to the a-chain of a class II MHC molecule on APCs without a need for intracellular processing.

Question 32

T or F?

Bacterial superantigens need to be intracellularly processed before they bind to the a-chain of a class II MHC molecule on APCs.

Answer 32

FALSE.

They do not need to be intracellularly processed to do this.

Question 33

Cross-linkage of a T cell receptor and class II MHC molecule by a superantigen provides an activating signal that induces what?

Answer 33

T cell activation and proliferation.

Question 34

T or F?

Since superantigens bind to outside of the TCR antigen-binding groove, any T cell expressing a particular VB domain will be activated by a particular superantigen.

Answer 34

TRUE.

Question 35

Name some microorganisms that have been shown to be associated with superantigens.

Answer 35

S. aureus, streptococci, mycoplasmas and some viruses (like rabies virus).

Question 36

Name the 8 major ways bacteria can evade host immune mechanisms.

Answer 36

1) Killing the phagocyte.
2) Inhibition of membrane attachment.
3) Inhibition of fusion of lysosomal granules and phagosome.
4) Resistance to killing/digestion in the phagolysosome.
5) Escape from the phagosome.
6) Evading sIgA response via protease secretions that cleave sIgA dimers.
7) Antigenic variation.
8) Gram-positive bacteria are resistant to complement-mediated lysis.

Question 37

How do some bacteria inhibit membrane attachment?

3 ways

Answer 37

1) By having a hydrophillic capsule, these bacteria protect themselves from phagocytosis; these capsules are rich in SIALIC ACIDS.
2) Pathogenic streptococci have M protein that alters cell surface membranes.
3) S. aureus has protein A, which binds to the Fc portion of IgG, thereby competing with Fc receptor on phagocytic cells… ALSO, pathogenic streptococci can secrete a coagulase enzyme that produces a fibrin coat around the organism, shielding it from phagocytic cells.

Question 38

How does virulent mycobacterium tuberculosis evade host immune mechanisms?

Answer 38

These produce sulfatides that inhibit the fusion of lysosomal granules and the phagosome.

Question 39

How are some bacteria resistant to killing and digestion in the phagolysosome?

Answer 39

Cell wall lipids render some resistant to lysosomal killing (ie, in C. pseudotuberculosis).

Question 40

What is listeriolysin O? What does it do?

Answer 40

This is an enzyme that mediates escape from the phagosome by lysing the phagosome. Listeria monocytogenes uses this.

Question 41

What cells of the innate immune system aid in protection from fungal infections?

Answer 41

Macrophages and neutrophils.

Question 42

How do neutrophils protect the host from fungal infections?

Answer 42

Neutrophils may phagocytose fungi for intracellular killing or release their lysosomal enzymes extracellularly and damage the fungus.

Question 43

Cationic proteins (defensins) play a crucial role in ______ (intracellular/extracellular?) killing.

Answer 43

Intracellular.

Question 44

What is the clinical consequence of an animal being neutropenic in regard to fungal infections?

Answer 44

Animals with neutropenia are extremely susceptible to opportunistic fungal infections.

Question 45

How are facultative intracellular fungal parasites that live in macrophages eliminated?

Answer 45

These are eliminated following activation of macrophages hy IFN-y secreted by NK cells and T cells, or, lysis of the macrophage by CD8+ CTLs.

(This is the same mechanism as the elimination of intracellular bacteria)

Question 46

What is the protective role of humoral immunity in fungal infections?

Answer 46

The premise is false; the role of humoral immunity in fungal infections has not been established.