Please enable JavaScript.
Coggle requires JavaScript to display documents.
Microbial Pathogenesis I - Coggle Diagram
Microbial Pathogenesis I
Important Definitions
(will be clarified on the exams)
Disease
- Damage caused by presence of microorganisms or their products
Colonization
- Presence of microorganisms without diesease at that point (this applies to surfaces only, ie. blood cannot be colonized)
Infection
- Always means a disease when referring to a patient (if there are no symptoms, it's a colonization; if there are symptoms, it's an infection)
Carrier State
- Colonized with a pathogen
Pathogen
- an organism that has the potential to cause disease
Overt vs. Opportunistic pathogens
Overt Pathogens
have a higher probability of causing disease in an otherwise healthy host
Opportunistic pathogens
have a lower probability and usually require a debilitated or compromised host
Normal Flora
- Organisms frequently found on or within the body of healthy persons (can cause disease under the right conditions)
Colonized sites
: alimentary/intestinal tract, upper respiratory tract, distal genitourinary tract, skin
Normally Sterile sites
: blood, CSF, interstitial fluid and spaces, lymph
These prime the immune system and help to exclude pathogens while also producing nutrients
The presence of bacteria doesn't always mean disease is ongoing or that antibiotics need to be prescribed
Microbiota
- microorganisms in or on our body (not always benign and can change and affect losts of aspects of biology)
Functions and stages of pathogenesis/disease
Encounter
Exogenous
- Disease started soon after encounter (no stable relationship)
Endogenous
- Stable relationship broken down
Entry
Where in or on the body did we initially contact the bacteria?|
Mucosal membranes are basically "open" to the outside (skin isn't really a great entry point)
Stabbing (direct inoculation)
If we can interfere with their adherence to the surfaces, we can modify entry (generally based on ligand-receptor interactions)
Virulence factors are pili, fimbriae, fibrillae
Spread (+/-)
Movement from surface through tissues and body (invasion)
Cellular invasion
happens easily with professional phagocytes (macrophages, PMNs)
Bacterial mediated endocytosis to get into non-phagocytes (done by phagocytosis, not lysis lest cell explode)
Some gram negative bacteria have
type III secreted proteins
which are injected into the host cell
Some bacteria escape the phagosome into the cytoplasm
Not all bacteria spread to cause disease
Multiplication
Incubation Period
- Time it takes for the inoculum to result in clinical damage
Acquisition of Fe from transferring by
siderophores
is an example of a factor that affects multiplication and virulence
Inoculum
- the original colony of a pathogen?
Evasion of host defenses
Consider whee the ogransms are and which defenses they will encounter
Complement
- found beyond the mucosal surface
Opsonizes -
C3b
Lysis of gram negative bacteria -
Membrane Attack Complex (MAC)
Inflammation -
C3a, C5a
There are mechanisms for evading complement
Don't bind or activate complement (passive)
Inhibit activation and amplification of Complement (bind factor H to reduce complement - active)"
Activation of complement away from the membrane, not where it's needed (passive)
Degrade complement proteins by secreting proteases (active)
Phagocytes need to be evaded (found beyond the mucosal surface)
Extracellular pathogens
Inhibit recruitment of phagocytes (inhibiting complement/cytokines)
Kill the phagocytes
Prevent phagocytosis
Prevent opsonization
Prevent binding to receptors
Intracellular pathogens
Inhibit phagolysosome fusion
Escape from phagolysosome into cytoplasm
Inhibit oxidative burst
Resist antimicrobial functions
Antibodies
Antigenic mimicry
- microbial surface components look like host
Antigenic cloaking
- binds host proteins to bacterial surface to look like host
Antigenic variation
- change antigenic composition in real time
Antigenic variety
- numerous serological types
Antibody degradation
Cell mediated immunity
Alter host response from cell mediated response to antibody response
Damage
Cytotoxicity
- kills host cell
Necrosis vs. Apoptosis
From outside - toxins
From inside - intracellular growth
Apoptosis -
type III secreted proteins
Pharmacology/Physiology
- alters host cell function (usually uses toxins)
Host immune/inflammatory response - host causes damage to itself in response
Nonspecific - inflammatin, abscess
Specific immune response
Antibodies
Cell mediated
Toxins
Endotoxins
- LPS from gram-negatives only (TLR4)
Damage caused by host through macrophages producing cytokines (TNF, IL-1, IL-6)
Generally are carbohydrates
Exotoxins
- Most have A-B structural motif
Genrally are proteins
A is the active portion, B is the binding portion
Mechanisms
Lytic
- lyse host cells
Cytotoxic
- kills cells by altering functions (is cytolethal)
Pharmacological
- alter host cell function (not cytolethal)
Extracellular enzymes
Superantigens
Stimulate T cell responses in antigen-independent manner
Binding of Vbeta to T cell receptor resulting in cytokine cascade
Type III Secreted Proteins
Injected into host cell
Outcome
a. Transmission to new host (+/-)
b. Recovery or not