Bacterial Pathogenesis and Host Defenses

Question 1

What is a pathogen?

Answer 1

bacteria capable of causing disease

Question 2

What is virulence?

Answer 2

quantitative measure of pathogenicities measured by the number of bacteria required to cause disease

Question 3

What is LD50?

Answer 3

number of bacteria necessary to kill half the host

Question 4

What is ID50?

Answer 4

number of bacteria necessary to cause infection in half the hosts

Question 5

What are virulence factors?

Answer 5

properties of a bacteria which assist in causing disease ex: pili, capsules, toxins, etc.

Question 6

What are the stages of bacterial pathogenesis?

Answer 6

1. Transmission from an external source into the body
2. Evasion of initial host defenses
3. Attachment to mucous membranes
4. Colonization at attachment site
5. Sometimes spread and reattachment
6. Disease symptoms caused by toxins or tissue invasion followed by inflammation
7. Non specific and specific immune host responses
8. Progression or resolution of the disease

Question 7

What are the mechanisms of bacterial disease?

Answer 7

TIT
1. Tissue invasion followed by inflammation

2. Toxins (exotoxins and endotoxins)
3. Immunopathogenesis eg. Rheumatic fever

Question 8

How does transmission occur between humans?

Answer 8

DNTT

1. Direct contact cg infections mono
2. Non-direct contact eg. fecal-oral
3. Transplacental
4. Transferred blood products or contaminated needles

Question 9

How does transmission occur non-human to human?

Answer 9

SWAI

1. Contaminated soils eg. Tetanus
2. Contaminated water eg. Legionnaires’ disease
3. Direct from animals eg. Cat Scratch fever
4. Insect vectors eg. Lyme disease

Question 10

What are the portals of entry?

Answer 10

RiGGS!
Respiratory tract- largest mechanism

GI tract- second

Skin

Genital tract

Question 11

What are bacterial structures that effect virulence?

Answer 11

Structures that allow bacteria to attack!

1. Pili eg. N. gonorrhea to urinary tract epithelium
2. Capsules eg. Strep. pneumonia
3. Glycocalyx eg. Strep. viridans in heart valves
4. Endotoxin eg. Gram negative bacteria
5. Biofilms eg. Pseudomonas in cystic fibrosis patients
6. Bacterial Secretion Systems eg. T3SS in Salmonella typhimurium

Question 12

What are secreted enzymes that effect virulence?

Answer 12

LICC

1. Collagenase & hyaluronidase eg. Strep. pyogenes cellulitis
2. Coagulase eg. Helps coat Staph. aureus with fibrin to help PROTECT from phagocytosis
3. Immunoglobulin A protease eg. Degrades IgA allowing Strep. Pneumonia to adhere to mucous membranes
4. Leukocidins Destroy neutrophilic leukocytes and macrophages eg. Staphylococci and group A Streptococci

Question 13

What are other bacterial factors that effect virulence?

Answer 13

1. M protein - antiphagocytic protein produced by Strep. pyogenes found on surface of bacteria, helps bacteria to survive
2. Protein A - binds to IgG and prevents activation of complement (complement necessary to lyse bact)
3. Invasins - bacterial molecules which promote bacterial entry or contact with host cells - eg. Heliobacter pylori
4. Outer membrane proteins - produced by Yersinia species to inhibit phagocytosis and cytokine production (cell signaling)
5. Pathogenicity Islands (PAIs) – code for groups of virulence factors particularly in Gram negatives (get rid of PAI, bacteria loses ability to cause disease)

Question 14

What are endotoxins?

Answer 14

1. Lipid A component of Gram negative bacteria
2. Encoded in chromosome, plasmid or phage
3. Become toxoids (inactivated) when treated with formaldehyde, and/or heat and used for protective vaccines
4. A-B subunit structure (A portion has toxic activity and B portion is involved in binding to cells)
5. Only weakly antigenic; no toxoids made

Question 15

What are exotoxins? What are the biological effects of exotoxins?

Answer 15

Secreted by gram pos and gram neg bacteria, may be genetically encoded chromosome, plasmid or phage

1. Alter cellular components
2. Act as super-antigens and cause inapproprite release of cytokines
3. Inhibit protein synthesis
4. Increase synthesis of cAMP
5. Alter nerve impulse transmissions

Question 16

What are the biological effects of endotoxins?

Answer 16

1. Induce the release of endogenous pyogenes
2. Increase vascular permeability
3. Imitate complement and blood coagulation cascades
4. Cause fever, hypotension, disseminated intracellular coagulation and shock

Question 17

What are the components of innate immunity?

Answer 17

MC (MARY CARLSON my mama will protect you…all the time)
1. Macrophages: Phagocytize and digest bacteria

2. Complement: Assist host immune cells and antibody in lysis of bacteria and virus-infected cells

Question 18

What are the components of acquired immunity?

Answer 18

1. Antibodies-
   a. Cytolytic,
   b. Neutralizing (antibody that reacts with viral attachment protein, covers up attachment protein so no longer can infect)
   c. Opsonins (created for anything that is foreign)
2. Cytotoxic T Cells- Kill antibody-coated bacteria and virus-infected cells (viral antigens on surface, antibodies react with them, T cells see that and kill cel)

**Aquired–only occur after you have stimulus from one of foreign parasites you’ve experienced

Question 19

What is passive immunity?

Answer 19

Administration of preformed antigen-specific antibodies to help protect from disease

ex. Human rabies immune globulin–preformed human rabies antibodies that you give to someone you thing has rabies, then they don’t have to generate antibodies themselves

Question 20

What is active immunity?

Answer 20

Administration of specific antigens to stimulate an individual to develop immunity to help protect from a disease

ex. Influenza vaccine–give person virus that is less likely to produce disease, body generates immune response, so when virus comes in it is neutralized/limited

**some diseases have passive and active, some just have passive

Question 21

What are the differences between live and killed viruses?

Answer 21

1. Live are better because they go through natural progression of virus replication in humans
2. Killed are injected into blood, so you get less of immune response

Question 22

What are the three bacterial strategies to deal with phagocytic cells?

Answer 22

1. Avoiding contact with phagocytes
2. Inhibition of engulfment
3. Survival within the phagocyte

Question 23

How does the bacteria avoid contact with the phagocyte?

Answer 23

1. The bacteria can reside in a niche not patrolled by phagocytes.
2. The bacteria can suppress inflammation and/or chemotaxis.
3. The bacterium can coat itself with host proteins (more later).

Question 24

How do bacteria inhibit engulfment by phagocytes?

Answer 24

1. Many bacterial capsules are anti-phagocytic.
2. Some surface polysaccharides (such as those that aid in biofilm structure) are anti-phagocytic.
3. Some bacteria produce specific anti-phagocytic products.
4. Capsules can inhibit phagocytosis AND complement activation

Question 25

How do bacteria survive within phagocytes?

Answer 25

Intracellular survival is mediated by bacteria in three basic ways: Escape the phagosome Shigella, Lysteria Adapt to the phagosome Coxiella, Leishmania Modify the phagosomal compartment Salmonella, Legionella, Mycobacteria, etc.

Question 26

What are the other methods of avoidance by bacteria?

Answer 26

LPS O-antigen Blocks MAC access - keeps at “arm’s length.” Complement component peptidases Destroy complement components. This inactivates the components AND stops complement activation.

Question 27

What is antigenic variation?

Answer 27

Use to avoid acquired immune response 1. Some bacteria spontaneously change the profile of the surface proteins that they express. 2. Antibodies are formed in response to specific antigens on the bacteria. 3. Because of a delay in the immune response (antibody formation), the bacteria can stay one step ahead by producing variants of itself. Ex. Trypanosome Variant-Specific Glycoprotein (VSG) cassettes.

Question 28

What is immunological disguise?

Answer 28

Use to avoid acquired immune response 1. Bacteria coat themselves with host proteins 2. Disguised by “self” proteins – camouflage! 3.Examples: E.g. proteins produced by some bacteria bind Antibodies – BACKWARDS! E.g. The Treponema pallidum parasite coats itself with host fibronectin. E.g. S. aureus produces coagulase and clumping factor. This leads to the deposition of host fibrin on the bacterial surface.

Question 29

**How does staphylococcus avoid immune response?

Answer 29

1. Synthesizes protein A 2. Bacteria looks normal to immune system, disguises itself by having normal cellular proteins bind to it, so that immune system doesn't see it, then it's not killed

Question 30

What are the important aspects of pseudamonas?

Answer 30

1. Gram - 2. Involved in CF pts 3. Forms biofilm (mixture of bacteria over areas of body)--can occur in place where joints have been replaced 4. Mechanisms of antibiotic resistance

Question 31

What is quorum sensing? (Salmonella and pseudamonas)

Answer 31

1. Bacteria go in and don't sythesize all of their virulence factors so they won't look to foreign to the body 2. Synthesize autoinducers 3. Bacteria multiplies--when conc of those molecules increase, bind to surface of cell, and set off rxn to make a HUGE amt of virulence factors, enough to sur 4. Occurs in biofilms, made up of individual bacteria and things it secretes