Micro B-2 Bacterial Surface Structures And The Host Response

Front 1

What is the effect if the site of infection is the skin?
Mucosal?
Bloodstream (direct)?

Back 1

- Local proliferation: ascended or descended infection to neighboring site and (invasion of subcutaneous or submucosal levels: lymphatics -> systemic infection)
- Local proliferation: ascended or descended infection to neighboring site and (invasion of subcutaneous or submucosal levels: lymphatics -> systemic infection)
- Systemic infection

Front 2

MOA of interactions between bacteria and host defenses?

Back 2

- Initial colonization -> bacterial adherence or invasion can induce pro-inflammatory cytokine secretion by epithelial cells -> resident phagocytes of monocyte/macrophage lineage -> death of pathogen OR release of cytokines to enhance inflammatory response

Front 3

MOA of inflammation in response to bacterial infection?

Back 3

- Macrophage-derived IL-1 and TNF alpha -> fever AND increased tissue fluid flow from blood to lymphatic circulation -> Brings phagocytes, complement and existing antibodies

Front 4

During inflammation, what do PMNs do?

Back 4

- PMN's are marginated along the dilated venule wall -> Diapedesis (squeezing through basement membrane into extravascular space)

Front 5

During inflammation, what does vasodilation followed by exudation result in?

Back 5

- outpouring of fluid, cells, and fibrin (into alveolar spaces)

Front 6

What results from fibrin mesh and PMNs in the fluid in inflammatory focus?

Back 6

- fluid collection -> produces the swelling ("tumor“) aspect of acute inflammation

Front 7

What are the classic manifestations of inflammation?

Back 7

- swelling (tumor)
- vasodilation of surface vessles
- erythema (rubor)
- heat (calor) from increased skin temperature
- pain (dolor) from increase pressure and tissue damage
- loss of function because of reflex nerve inhibition or pain caused by movement.
- Purulent exudates – most dramatic in infections with pyogenic bacteria (staphylococci, streptococci, Neisseria)

Front 8

What types of cells are present in bacterial infections?

Back 8

- PMNs, macrophages, plasma cells and lymphoctes

Front 9

What is O2-independent killing mediated by?

Back 9

- enzymes within granules and antimicrobial peptides

Front 10

What is O2-dependent killing mediated by?

Back 10

- reactive oxygen species generated by the respiratory burst (does not affect anaerobic inf)

Front 11

What must bacteria be coated by for efficient uptake by PMNs or macrophages?

Back 11

- Must be coated by serum opsonins (IgG or C3b)

Front 12

What is the main function in generationf C3b by the alternative pathway?
Which type of bacteria will this occur?

Back 12

- to opsonize bacteria for uptake EARLY in infection; also feeds the classical pathway to cause lysis
- Clearance of both gram pos and neg bacteria

Front 13

What is function of classical pathway in bacteria?
What tpe of bacteria will bacteriolysis by clasical pathway occur?

Back 13

- Culminates in the generation of the membrane attack complex (MAC) with C5-9 components -> bacteriolysis
- gram-negative bacteria

Front 14

Early in infection, how is phagocytic uptake prevented as an effective bacterial defense against phagocytic killing?
Later in infection, how is phagocytic uptake prevented as an effective bacterial defense against phagocytic killing?

Back 14

- complement opsonins are important in uptake unless pre-existing antibody is present.
- opsonizing antibody can mediate uptake.

Front 15

What is the effective way to kill gram positive organisms?
What is the effective way to kill gram neg organisms?

Back 15

- opsono-phagocytosis but NOT killed by complement-mediated bacteriolysis
- killed by opsonophagocytosis and bacteriolysis.

Front 16

What is necessary in complemented-mediated bacteriolysis?

Back 16

- specific antibody

Front 17

What does bacterial capsule protect from?
What diseases do encapsulated bacteria most often cause?

Back 17

– usually inhibit deposition of C3b -> evade host complement
- meningitis, pneumonia, systemic infections via dissemination through the bloodstream or lymphatics

Front 18

What do M protein of Streptococcus pyogenes do?
Effect?

Back 18

- Act as anti-phagocytic ptns: receptor-specific binding of negative regulators of the complement cascade
- strep throat, skin infections

Front 19

What do porin proteins of Neisseria gonorrhoeae do?

Back 19

- Act as antiphagocytic ptns: receptor-specific binding of negative regulators of the complement cascade

Front 20

What do factor H-binding protein (fHBP) - a lipoprotein in Neisseria meningitidis do?
Effect?

Back 20

- Act as antiphagocytic ptns by down-regulating the alternative pathway
- meningitis, septicemia

Front 21

What do Osp proteins of Borrelia burgdoreferi do?
Effect?

Back 21

- Act as antiphagocytic ptns: receptor-specific binding of negative regulators of the complement cascade
- Lyme Disease

Front 22

Later in infection, what empowers the activation of the classical pathway?
Result?

Back 22

- the development of specific antibody
- Opsonophagocytic uptake via Fc receptor (cannot be blocked by capsules, unlike C3b-opsonization) AND Bactericidal activity, often with capsule as the target antigen.

Front 23

How can bacteria thwart a specific immune response to surface components?

Back 23

- Immunological differences in surface structures among strains within a species (lack of cross-protection)
- Molecular mimicry
- IgA proteases: inactivate specific Ab
- Antigenic variation of surface structures w/in same bacterium
- Binding of neg regulators of classical pathway (and/or alternative pathway)

Front 24

What are biofilms produced by?
Function?
What does biofilm detachment of bacteria lead to?

Back 24

- extracellular carbohydrates
- defense against host immune response and antibiotics
- sepsis

Front 25

How does host response to gram-negative bacteria harm the host?

Back 25

-toxic shock due to LPS: IL-1 and TNF from macrophages -> fever -> hypotension, decreased PMN and platelet counts, hemorrhage, DIC (at large amounts)

Front 26

Result of systemic exposure to endotoxin of gram neg bacteria?

Back 26

- Systemic release of TNF-alpha from macrophages in liver and spleen affects venules in all tissue simultaneously -> systemic edema -> dec BV, hypoptnemia, neutropenia followed by neutrophilia -> dec BV causes collapse of vessels -> DIC -> organ failure and death