Microbial Pathogenesis

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flora

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microorganisms which routinely colonize appropriate surfaces without causing disease

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pathogen

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organism able to cause disease

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virulence

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degree of pathogenicity

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virulence factors

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specific genes coding for pathogenic traits in bacteria

*also has to do with invasiveness and/or toxicity; can't be inactive (bacteria); different than virus

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virus

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needs host involvement;
inserts its DNA for host cells to replicate

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virulence mechanisms

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1. resistance to antibiotics
2. production of substances harmful to the host
3. evasion of the immune system
4. induction of harmful immune response
5. adherence to or invasion of host cell

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adherence to host cells

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-virulence mechansism
1. avoids 'flushing' mechanism
2. extracellular bacteria use receptor mediated attachment - with pili/fimbriae adhesins
3. viruses and intracellular bacteria use specific receptors as well before entering cell
4. ectoparasites mechanically attach and take nutrients

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Invasion of host cells (evasion of immune response)

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-virulence mechanism
1. bacteria penetrates or is taken up by cell
this provides:
-nutrients (bact) access to cell machinery (viruses)
-protection from immune system

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Production of substances released

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-virulence of mechanism
1. degradative enzymes
2. classic toxins
-exotoxins
-endotoxins
-Siderophores

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virulence in bacteria

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invasiveness and toxigenicity

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virulence in viruses

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the degree and nature of host cell involvement

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host immune response

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another virulence factor; adds to degree of virulence of a pathogen based on host

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exotoxins

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1.secreted INTO the environment
2. protein based; highly antigenic (means can make a vaccine via antibodies) (gram +)
3. several modes of action
4. made by gram +/-
5. very specific in there targets
6. plasmid/phage encoded -we can't notice them
7. A + B subunit mechanism

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degradative enzymes

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-used to breakdown things for food
-breaks down immune system to protect themselves

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examples of degradative enzymes
hemolysins
leukocidins
kinases
hyaluronidases
coagulase

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hemolysins - rbc
leukocidins - wbc
elastases -connective tissue
kinases - atp (phosphate groups)
hyaluronidases - joint capsules
coagulase - causes clotting -stapph aureus

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A + B subunit mechanism

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B breaks pathway for A to enter

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Exotoxin modes of action

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1. damage directly
2. disrupt cell communication
3. interference with internal cell processes

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Endotoxins

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1. LPS in outer membrane gram -
2. released with cell damage/death
3. low antigenicity/specificity
4. triggers multitude of host immune responses

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LPS three part composition

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core polysaccharide (highly conserved) + specific polysaccharide (responsible for serological diversity) + Lipid A

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LPS triggers a multitude of immune responses:

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1. induces cytokines (TNF and IL 1)
2. activates complement
3. triggers clotting mechanism
-induces fever; drops blood pressure

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affects blood pressure (decreases)

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LPS from endotoxins

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Amount of LPS important because

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low levels stimulates immune system response
2. too high levels causes problems

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Too much LPS secretion

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1. endotoxic shock develops
2. DIC (disseminated intravascular coagulation) - blood disorder; platelets adhere to endothelium and thus can't clot

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sideophores

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organisms have the ability to take a scare nutrient that we both end up fighting;
-iron binding compunds excreted by pathogens under stress
-host takes up iron to kill pathogen

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Avoidance/deactivation of Host immune response

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1. Inhibition
2. Induction/suppression of host cell apotosis
3. Intracellular replication
4. Antigenic manipulation

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Bacteria inhibition of Immune response

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1. opsonization by host antibodies
2. host wbc chemotaxis
3. phagocytosis by host wbc
4. phagocytic destruction of wbc
5. Host cell signal transduction

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Bacteria/viral induction/suppression of IR

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-stops apoptosis
-induces apoptosis of other cells

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antigenic manipulation

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1. antigenic mimicry
2. antigenic masking
3. antigenic alteration

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antigenic mimicry

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bacteria coat themselves with host antigens, pretending to be self-antigens

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antigenic masking

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bacteria binds Fb portions on antibodies, blocking them

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antigenic alteration

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bacteria shift their appearance, confusing immune system; IS never knows exactly what to destroy

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Host immune responses to pathogen causing disease processes

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1. endotoxic shock
2. cross-reacting antibodies
3. Superantigens
4. inflamation
5. immune complexes

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endotoxic shock

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we get sicker from our immune response more than organism;

ie hospital - misapplication of disease

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Cross-reacting antibodies

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antibodies to a microorg that would hurt another part of the body;

ie antiboidies against strep throat hurt the heart

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Superantigens

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tiny subset of T cells are activated and gives overwhelming immune response.

ie. strep and staph

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Inflammation

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tries to kill bugs, but you end up with fever