Chapter 15: Microbial Mechanisms of Pathogenicity

pathogenicity

ability of pathogen to cause dz in host

virulence

enhanced ability of pathogen to cause infection

virulence factor

characteristic or trait of pathogen that makes it harmful/dangerous (ex. capsules, toxins, antigenic variation → Ag change appearance/composition ex. virus spikes)

mechanisms of pathogenicity

different ways a pathogen can cause an infectious disease

mechanisms of pathogenicity

1. # of invading microbes

2. portals of entry

3. adherence

4. penetration of host defenses

5. evasion of host defenses

6. damage to host cells

7. portals of exit

portals of entry

1. mucous membrane @ respiratory, GI, genito-urinary tracts

2. (broken) skin

3. parenteral route

   1. non-oral (bypass GI tract)

   2. pathogens deposited into bloodstream

   3. “injection” into blood vessel (ex. needles/insect bites)

number of invading microbes

• if # pathogens ↑ → overwhelm host defenses → infection → dz!

• some bacteria produce toxins → cause death of host (lethality of toxin)

ID₅₀ (Infectious Dose 50)

# pathogens required to make 50% of population sick

• measures virulence of microbe

• low ID₅₀ → ↑ infectiousness/virulent (very dangerous)

• high ID₅₀ = ↓ infectiousness/virulent

• indicator for portal of entry to cause dz

LD₅₀ (Lethal Dose 50)

amount (concentration) of toxin required to kill 50% of population

• measures potency of toxin

• ↓ LD50 = ↑ toxin lethality

• ↑ LD50 = ↓ toxin lethality

adherence (adhesion)

ability of pathogen to attach to host tissues/cells

bacterial adhesins (ligands)

substances on pathogen that bind to receptors on host cell (may act as VF)

• vs. antigenic determinant → binds to Ab

types of adhesins (5)

1. capsules

2. fimbriae

3. *M proteins

4. *Opa proteins

5. hooks (anchors)

*in bact. C.W.

coagulase

(penetration factors / bacterial enzymes)

helps form blood clot → stops blood flow → host defenses cannot reach bacterium; bact. can also surround themselves in a clot

kinase

(penetration factors / bacterial enzymes)

breaks down blood clot surrounding bacterium → free to spread

hyaluronidase

(penetration factors / bacterial enzymes)

breaks down hyaluronic acid in connective tissue

collagenase

(penetration factors / bacterial enzymes)

breaks down collagen in CT

IgA protease

(penetration factors / bacterial enzymes)

destroys IgA antibodies

survival inside phagocytes

(evasion of host defenses)

• pathogen escapes from phagosome before lysosomal fusion

• prevention of fusion of lysosome w/ phagosome

• resist lysosomal enzymes (ex. mycolic acid)

antigenic variation

(evasion of host defenses)

pathogens change their surface antigens (antigenic determinants) via genetic mutations/recombination

• a key virulence factor in VIRUSES (w/spikes)

• ex. influenza virus, HIV

toxin

(=Ag) poisonous substance acting as Ag produced by pathogens (ex. toxigenic bact.)

• may produce fever, cardiovascular problems, diarrhea, shock (sudden ↓ BP)

• many cases toxin creates symptoms

• key virulence factor in bacteria

• exotoxins (3): made of proteins → strong immune response

• endotoxins: made of lipids → weak immune response

toxingenicity

ability of pathogen to produce a toxin

toxemia

presence of toxin in bloodstream

toxoid

chemically modified toxin → no longer toxic (harmless - ex. vaccination)

• stimulates immune response w/o harming host

antitoxin

antibody/Ig against a toxin (NOT against bact!)

• injected into host (artificial passive immunity)

toxin production

• may involve bacterial plasmids that carry genes for toxins

  • as a result of lysogeny involving phage (bacterial virus) conversion

  or

  • as a result of DNA transfer involving a conjugation pilus

lysogeny (toxin production)

1. bact. virus/phage contains DNA (gene) for toxin

2. attach to non-toxigenic bact.

3. (phage conversion) DNA incorporates w/ non-toxigenic bact. plasmid (DNA)

4. prophage created via lysogenic cycle

5. nontoxigenic → toxigenic bact.

DNA transfer (toxin production)

transfer of toxin DNA genes from donor cell (toxigenic cell) to recipient cell (non-toxigenic cell) via conjugation pilus

immunogen

act as an antigen (stimulates immune system)

• ex. toxin

• stimulates immune system to produce Ab’s

strong immunogen (toxin)

• (strong immune response) good stimulator of immune response → Ab’s made → no fever*

• ex. protein toxins

*exception: Type I exotoxin (super Ag) produce fever

weak immunogen (toxin)

• (weak immune response) poor stimulator of immune response → no Ab’s made → fever

• ex. lipid & polysaccharide toxins

exotoxins (7)

• bacterial source: secreted by mostly gram-positive (some gram-negative)

• location: metabolic byproduct of live bacterium (secreted + released)

• comp: PROTEIN (strong immune response)

• toxicity: high (↓ LD₅₀)

• fever: NO

• neutralized by antitoxin (Ab): YES (b/c strong immune response)

• LD₅₀: small (very dangerous)

summary: mostly gram positive, protein, no fever

endotoxins (7)

• bacterial source: secreted by gram-negative

• location: LPS of C.W. outer membrane

• comp: LIPID

• toxicity: low (↑ LD₅₀)

• fever: YES

• neutralized by antitoxin (Ab): NO (b/c poor immune response)

• LD₅₀: large (not so dangerous)

summary: gram negative, lipid, fever

type I exotoxoms

• name: superantigens

• characteristics: Ag’s that cause very strong immune response

• MOA: super Ag → proliferation of T cells → release cytokines → FEVER, nausea, vomiting, shock

type II exotoxins

• name: membrane-disrupting (MD) toxins

• characteristics: cause lysis of host cells by disrupting cell membranes

• MOA: MD toxins form channels in C.M. OR disrupt phospholipid part of C.M.

type III exotoxins

• name: A-B toxins

• characteristics: consist of 2 parts (A/B), most common type of exotoxins

• MOA: A-B toxins inhibit protein synthesis in host cells

endotoxins & pyrogenic response

endotoxin from dying gram neg. bact. C.W. → LPS → lipid toxin

1. macrophage ingests gram-negative bacterium

2. bacterium degraded in a vacuole, releasing endotoxins (LPS) → macrophage produce cytokines

3. cytokines (from macrophage) released in blood stream → hypothalamus (temp. control center of brain)

4. hypothalamus reset body’s thermostat to a higher temp → fever

fungal toxins

• contaminate food supply

• provoke an allergic response

• carcinogenic (cancer-causing)

  • ex. Aflatoxin

parasitic protozoa

(k. protista)

• large # protozoa feed on host tissue

  • cause damage to intestinal lining → diarrhea or dysentery (mucous blood diarrhea)

• avoid host defenses by:

  • growing in phagocytes

  • antigenic variation (VF)

parasitic helminths (worms)

(k. animalia)

• not very pathogenic

  • use host’s nutrients or tissues w/o killing host

• presence in GI tract in ↑ numbers interferes w/ host food absorption → fatigue/weight loss (d/t anemia)

portals of exit (5)

(leave same way they entered the body)

1. respiratory tract: coughing/sneezing

2. gastrointestinal tract: feces/saliva

3. genitourinary tract: urine/genital secretions

4. skin

5. blood: arthropods that bite, needles, or syringes