Mechanism of Disease - Introduction to microbial pathogenesis Flashcards
Why do we care to understand how the body fights pathogens?
If you know how pathogens are causing disease you can fight them.
What is a pathogen? Microbe? Pathogenicity?
Pathogen: Disease-producing agent
Microbe: Microscopic pathogen
Pathogenicity: Ability of pathogens (microbes) to cause disease
What is virulence? Virulence factors?
Virulence: Combination of factors that increase the efficiency of a microbe (or Virulence: pathogen) to invade, spread, replicate, evade the immune system, cause disease and spread to a new host
Virulence factors: Gene-determined molecules that enable a pathogen to cause Virulence disease (invade, replicate, avoid destructions from the immune factors system, proliferate & spread to another host). May be integral (part of the microbe) or synthesized (usually by the host cell)
What is pathogenesis?
In simple terms?
PATHOGENESIS: the sequence of events and mechanisms that underlie a disease process. I.e. the way a disease or lesion develops.
Simple terms: Story of the disease
What are the 7 steps in microbial disease?
1.) Access body through a port of entry
2.) Contact target cell (tissue/organ)
3.) Colonize & amplify in target cell (tissue/organ)
Spread locally, neighboring cells (tissues/organs)
4.) Spread systemically (blood, lymph, PNS)
5.) Colonize LN and/or distant tissues
6.) Injure or kill [distant] target cells (tissues/organs)
What are the ports of entry into the body? How do microbes try to get through each port?
- Alimentary canal (GI tract)via Ingestion
Respiratory system via Inhalation
Urogenital system via Ascension
Integumentary system, eye and ear via Direct contact, Breach of skin, or membranes (penetration)
What are the hosts defenses of the GI tract?
- Mucous produced by goblet cells
- IgA
- Enzymes & other secretions (i.e. gastric acid, pancreatic enzymes)
- GALT (gut-associated lymphoid tissue) / Peyer’s patches
- Local & regional (LN) dendritic cells & MQ
- Normal flora
What are the hosts defenses within the respiratory tract?
- Turbulence
- Nasal cavity: >1µm (best 3-5 um)
- Bronchi/bronchioles: 2nd catchment area
- Local & regional (LN) dendritic cells & MQ.
- Tonsils
Lower respiratory tract
- Mucus + gel
- Mucociliary apparatus
- IgA
- BALT (bronchial- associated lymphoid tissue)
Local & regional (LN) dendritic cells & MQ: Alveolar MQ
Why can viruses under 3 microns still get caught by the nasal cavity?
This is becasue viruses are not traveling alone so they are a glob of viruses larger than 3 microns.
What are the hosts defenses of the urogenital system?
- pH
- Mucosal integrity ( stratified squamous epithelium)
- Mechanical force: Urine discharge
- Local & regional (LN) dendritic cells & MQ
What are the hosts defenses of skin, eye and ear?
- Epidermal/mucosal integrity( junctions ect)
- pH, dryness
- Secretions: Tears, sebum, etc.
- Normal microflora
- Dendritic cells (Langerhans
cells) & MQ - Local & regional (LN)
How do microbes contact target cell tissues? What are their objectives? Where does it look for molecules/ receptors?
- Microbes start breaching the barrier at the port of entry (mucosa, epidermis, alveoli, etc.)
- Objective: Invade & injure target cell (tissue) Microbes tend to target specific cell types/populations
Microbe looks for receptors/molecules in:
- Mucus (secretion) associated with target cell
- ECM surrounding target cell
- Membrane of target cell: Molecules involved in cell structure and/or metabolism
What can be target cells of microbes?
Target cells can be:
- Epithelial cells (A)
- Immune cells (LQ, MQ, dendritic cells) (B)
- Primary or secondary targets ¡ Neuronal nerve endings (C)
What do microbes target in epithelial target cells? What are examples of virus that target the different domains?
Cell polarity results in different expression of membrane receptors in these domains:
- Apical domain: E.g. influenza virus (airway epithelium)
- Basolateral domain: E.g. parvovirus (small intestine)
How do microbes break through mucus?
- If target cells (GI and respiratory tracts) are protected by mucus, microbes need to break through mucus.
- Microbial [mostly bacterial] mechanisms when encounting mucus:
- Motility (motile bacteria, e.g. spirochetes)
- Enzyme digestion of mucus: Often part of the microbe’s use of mucus as source of energy
- Target mucus-free cells, e.g. M cells, Goblet cells.
**ALL of these are virulence factors as they increase the ability of microbes to reach, and colonize, target cells.***
What is neuroaminidase?
Produced by bacteria to reduse the viscosity of bronchial mucus
What is the morphological diagnosis of this lesion, What is the name of the disease? Cause? What is its virulence factor?
Virulence factor: Enzyme digestion of mucus
Morphological Diagnosis: Pneumonia, Focally extensive, Acute, Fiberous/ fiberonecretizing
Name of disease: Shipping fever
Cause: Stress related, cold, ect
BacteriaL Mannheimia haemolytica is a normal bacteria found in ruminants, but is oppertunistic so the immunosuppression from travel allows bacteria to proliferate and overgrow.
How does a microbe colonize and amplify within the target cell?
- Microbe is bound to target cell or adjacent
ECM/secretion - Microbe replicates in cell or adjacent ECM/mucus
- If in cell, microbe can take control of some of the cells
metabolic systems