03/18/19

INFECTION AND HOST RESISTANCE

 Virulence factors - “structures”

*Virulence - measure/degree of pathogenecity
- some are more virulent than others.
Ex. Diarrhea - *10 shigella cells to cause shigellosis
*100-1000 salmonella cells to cause salmonellosis
*Pathogenecity - ability to cause an illness

VIRULENCE FACTORS
- are phenotypic characteristics that enable microbes to cause disease (virulent)

1. Attachment
2. Obligate Intracellular Pathogens
3. Facultative Intracellular Pathogens
4. Capsules
5. Flagella
6. Exoenzymes
7. Toxins
8. Escaping Immune Response

1. ATTACHMENT
- pathogens need to attach to cell surface to cause disease.
- specific pathogens need to attach to specific cell surface molecules to cause disease.

RECEPTOR/INTEGRIN
- certain molecule on the surface of a host cell that a
particular pathogen is able to recognize and attach to.
- present on host cell
Ex. Respiratory virus can not cause GI contraction.
- most are glycoprotein molecules
ADHESIN/LIGAND
- certain molecule on the surface of a pathogen that is
able to recognize and bind to a particular receptor.
- present on pathogen
- enable pathogens to attach to host cells.

MICROBES:

 Streptococcus pyogenes
Adhesin/Ligand: Protein F
Receptor/Integrin: Fibronectin receptor (found in many host cells)

 Human immunodeficiency virus

Adhesin/Ligand: gp120
Receptor/Integrin: CD4 receptor (found in T-helper cells)

 Bacterial Fimbriae (Pili)

- long, thin, hairlike, flexible projections
- enable bacteria to attach to surfaces
- enable bacteria to form along (colonization factor)
Ex. * Fimbriated strains of Neisseria Gonorrhoeae
- attaches to inner walls of urethra and cause urethritis
* Fimbriated strains of Escherichia Coli
- able to anchor themselves to the inner walls of the bladder and cause cytitis
* Fimbriae of group A beta hemolytic streptococci has a protein.
* M. protein can (1) attach bacterium to pharyngeal cells and (2) protect the bacterium
 from phagocytosis (antiphagocytic function)

2. OBLIGATE INTRACELLULAR PATHOGENS

- Rickettsia and Chlamydia
- Ehrlichia spp. and Anaplasma phagocytophilum (intraleukocytic pathogens)
- Plasmodium spp. (intraleukocytic pathogens)

3. FACULTATIVE INTRACELLULAR PATHOGENS

- can live inside and outside the cell.
- Mycobacterium tuberculosis
- Toxoplasma gondii
- Brucella abortus
- Francisella tularensis
- Legionella pneumophila
- Listeria monocytogenes
- Salmonella spp.
- Yersinia pestis

4. CAPSULES
- cannot be phagocytized
- serves as an antiphagocytic function
- protect bacteria from being phagocytized by phagocytic WBC: Klebsiella pneumoniae,
Haemophilus influenzae and Neisseria meningitidis, Streptococcus pneumoniae

5. FLAGELLA
- enable flagellated (motile) bacteria to invade aqueous areas of the body that non flagellated (non
motile) bacteria are unable to reach.
- enable bacteria to avoid phagocytosis

6. EXOENZYMES
- major mechanisms by which pathogens cause disease
- designed to destroy/digest

a) Necrotizing enzymes
- cell decay/ death
b) Coagulase
- enzyme that forms blood clot
c) Kinases
- destroys blood clot
d) Hyaluronidase
- “cement-like”
- intercellular gene
- keep the cells together
e) Collagenase
- collagen
- collagen + protein + abscorbic acid = keeps collagen
f) Hemolysins
- “lysin” (destruction)
- “hemo” (RBC)
- destroys RBC
- harvest nutrients: iron and protein
g) Lecithinase
- lecithin - phospholipids
- cell membrane and organelles are protected by phospholipids
A. NECROTIZING ENZYMES
- destroys tissues
Microbe: Streptococcus pyogenes
Exoenzyme: Proteases
Condition: Necrotizing fasciitis

Microbe: Clostridium spp.

Exoenzyme: Proteases and lipases
Condition: Gas gangrene (Myonecrosis)

B. COAGULASE
- binds to prothrombin forming staphylothrombin
Ex. A lot that surrounds staphylococcus

C. KINASE
- a.k.a fibrinolysins
Fibrin - made of platelets (“meshwork”)
- attachment sites or clot formation
- targets fibrins
- are enzymes that lyse (dissolve) clots.

WHY?
To enable pathogens to escape from clots.
Ex. *Streptococci = Streptokinase
* Staphylococci = Staphylokinase

*Thrombosis - excessive clot formation.

D. HYALURONIDASE
- “spreading factor”
- enables pathogens to spread through connective tissue by breaking down hyaluronic acid.
* Hyaluronic acid is a cell “cement”.
Ex. Staphylococcus, Streptococcus and Clostridium

E. COLLAGENASE
- composed of proteins
- enables the pathogens to invade tissues
* Collagen - the supportive protein found in tendons, cartilage and bones
Ex. Gas gangrene & clostridium perfringens has both collagenase and hyaluronidase

F. HEMOLYSINS
- destroys erythrocytes (RBC)
- iron from destroyed RBC is utilized by the pathogen

*In the lab:

- Hemolytic reactions are tested on blood agar:
> Alpha-hemolytic
- green zone surrounding the colony (partial hemolysis)
> Beta hemolytic
- clear zone around the colonies (complete hemolysis)
> Gamma hemolytic
- no reaction at all

G. LECITHINASE
 - destroys cell membrane
- enables pathogen to rapidly destroy extensive areas of tissue, especially muscle tissue
- Lecithin is a collection of phospholipids
Ex. Clostridium perfringens

7. TOXINS
- Endotoxins and Exotoxins

 Endotoxin - integral part of bacterial Gram-negative cell wall

- cause Septicemia ( a very serious disease consisting of chills, fever, prostration)
- present in Gram-negative (LPS) (Lipid A)
- cause septic shock
*Lipid A- causes massive dilation
 Exotoxin - produced inside the cell then released.
- secreted by pathogens
- often named after their target organs: neurotoxins, enterotoxins, cytotoxins, exfoliative
toxin, erythrogenic toxin, and diptheria toxin.

 EXUDATES - the most potents is neurotoxin (affects CNS); produced by C. tetani, (Tetanospasmin,
C. botulinum (botulinal toxin))
*Tetanospasmin lead to spastic paralysis
*Botulinal toxins lead to flaccid paralysis

 Enterotoxin - affect GIT causing diarrhea and sometimes vomiting

Ex. Bacillus Cereus, Clostridium difficile, C. perfringens, Salmonella spp., Vibrio Cholerae,
some S. aureus, some E. coli