Mechanism of Disease - Introduction to microbial pathogenesis Flashcards

1
Q

Why do we care to understand how the body fights pathogens?

A

If you know how pathogens are causing disease you can fight them.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is a pathogen? Microbe? Pathogenicity?

A

Pathogen: Disease-producing agent

Microbe: Microscopic pathogen

Pathogenicity: Ability of pathogens (microbes) to cause disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is virulence? Virulence factors?

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is pathogenesis?

In simple terms?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the 7 steps in microbial disease?

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the ports of entry into the body? How do microbes try to get through each port?

A
  • 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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the hosts defenses of the GI tract?

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the hosts defenses within the respiratory tract?

A
  • 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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Why can viruses under 3 microns still get caught by the nasal cavity?

A

This is becasue viruses are not traveling alone so they are a glob of viruses larger than 3 microns.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the hosts defenses of the urogenital system?

A
  • pH
  • Mucosal integrity ( stratified squamous epithelium)
  • Mechanical force: Urine discharge
  • Local & regional (LN) dendritic cells & MQ
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the hosts defenses of skin, eye and ear?

A
  • Epidermal/mucosal integrity( junctions ect)
  • pH, dryness
  • Secretions: Tears, sebum, etc.
  • Normal microflora
  • Dendritic cells (Langerhans
    cells) & MQ
  • Local & regional (LN)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How do microbes contact target cell tissues? What are their objectives? Where does it look for molecules/ receptors?

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What can be target cells of microbes?

A

Target cells can be:

  • Epithelial cells (A)
  • Immune cells (LQ, MQ, dendritic cells) (B)
  • Primary or secondary targets ¡ Neuronal nerve endings (C)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What do microbes target in epithelial target cells? What are examples of virus that target the different domains?

A

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 well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How do microbes break through mucus?

A
  • 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.***

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is neuroaminidase?

A

Produced by bacteria to reduse the viscosity of bronchial mucus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the morphological diagnosis of this lesion, What is the name of the disease? Cause? What is its virulence factor?

A

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 well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How does a microbe colonize and amplify within the target cell?

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the possible outcomes of microbes colonizing and amplifying within the target cell?

A

Possible outcomes:
- Cell death (necrosis)

  • Directed cellular disfunction
  • Structural injury
  • Persistent or latent infection
  • Cell proliferation
  • Malignant transformation
  • *Inflammation (may occur along with many outcomes)
20
Q

What are the methods of microbes colonizing and amplifying in the target cell?

A
  • Direct invasion*
  • Transcytosis (1,3,7)
  • Intercellular junctions (2)
  • Phagocytosis (4,5,6) ( Dendritic cells , LQ & MQ), Transcytosis
  • Axonal invasion (7)
21
Q

What is transcytosis?

A

Transcytosis = movement of molecules within endosome from apex to base. Endocytosis (in), exocytosis (out). Common in epi- & endothelium.

22
Q

What is an example of direct invasion? What kind of bacteria is it? Is it gram positive or negative? Where does replication take place? What effect does it have on these cells? And what is the consequence?

A
  • Brachyspira hyodysenteriae
  • Gram Negative
  • Replication occurs in the Goblet cells within Mucigen droplets
  • Stimulates increased mucus production
  • LOS lyses epithelium in cecum & colon ( this causes necrosis of epithelium)
23
Q

What would be the morphological diagnosis of the lesion? Name of disease? Method of colonization/ amplification?

A
  • Direct invasion

Morphological diagnosis: Necrotizing/ hemorrhagic, Typhlocolitis, segmental( tubular organ) acute, severe,

Name of disease: Swine dysentary

Bacteria: Brachyspira hyodysenteriae

Causes false membranes with dead mucosa.

24
Q

W?hat is an example of transcytosis colonization/ amplification? What are the possible routes?

A
  • Transcytosis1

Example: PCV-2 (porcine circovirus 2), DNA virus, Disease: PMWS (postweaning multisystemic wasting syndrome)

  1. ) Via M cells : Mucus free (Over Peyer’s patches)
  2. ) Infects MQ & LQ in Lamina propria & submucosa
  3. ) Replicates in LQ (not MQ) Actively replicating cells
  4. ) ‘Leukocyte trafficking’ = systemic spread
25
Q

What is an example of colonization and amplification via intracellular junctions?

A
  • Dendritic cell 4 (Intercellular junctions 2 )
  • Capripoxvirus (DNA virus)
26
Q

What is occuring in this image? What is the morphological diagnosis?

A
  • Capripoxvirus (DNA virus)

Morphological diagnosis: Dermatitis, Serous, Multifocal, Subacute, mild

27
Q

What is an example of phagocytosis as a means to colonize/ amplify in the target cell?

A

Trojan horse

  • Leukocyte trafficking to regional LN
  • Systemic spread via lymphatics & blood vessels
28
Q

What is the morphological diagnosis of the tissue in the image? It is colonized by bacteria via the respiratory system, what is it colonizing in?

A

This is:

  • Rhodococcus equi - Gram positive

Morphological diagnosis: pneumonia, granulomatous, focally extensive, moderate, chronic

29
Q

What is an example of axonal invasion to colonize/ amplify within the target cell? What is another example that tries to target axons?

A
  • Axonal invasion7

example: BHV-5 (bovine herpesvirus 5)
- DNA virus

  • Bovine meningoencephalitis
  • Oropharyngeal, nasal & conjunctival endings of
    sensory neurons
  • Retrograde axonal transport to CNS

RABIES

30
Q

What is the morphological diagnosis of the image ?

A

morphological Dx: dermatitis multifocal subacute (since it is not acute or chronic) severe ( for this single hair follicle) (folliculosis)

Name of disease: dermatophytosis?

31
Q

What is used for systemic spread?

A

Local spread to neighboring cells is, Often used to gain sufficient numbers to initiate systemic spread.

32
Q

What are the ways systemic spread can occur?

A
  • Passively: In plasma or lymph, Free microbes
  • Actively : Leukocyte trafficking, Within LQ, MQ or dendritic cells, Cell-associated microbes, Lyse transport leukocyte to exit & infect intended target cell
  • Alternative: In the cytoplasm of nervous cells (neurons), Retrograde transport , Safe from immune system
33
Q

Why would microbes want to be within a cell?

A

Avoids immune detection.

34
Q

What is an example of a pathogen that spreads systemically passively? What are predisposing factors? Cause ? Method?

A

Aspergillus

Passive: In plasma or lymph, free microbes

  • Fungi, multiple species (hyphae)

Predisposing factors: Grain overload +/- antibiotic in feed ( it will cause bacterial imbalance and can allow fungi to proliferate and invade. )

Method:

  1. ) pH drops (acidic)
  2. ) Acid burns of rumen and/or omasum
  3. ) Mucosal barrier breached
  4. ) Fungi in deep tissues & blood stream
  5. ) Systemic spread
35
Q

What is the morphological diagnosis of this image? What about the etiological diagnosis?

A

morphologic diagnosis: chronic (caseous exudate) granulomatous (due to exudate present) multifocal severe (or moderate just not mild) hepatitis

Etiologic Dx: fungal hepatitis

36
Q

What is an example of a pathogen that spreads systemically actively? What is the method it colonizes? What is the steps to invasion/ proliferation?

A

Sarcocystis neurona (protozoan)

Possums shed this protozoa via the feces

Method of colonization: Leukocyte trafficking

Steps:

Comes out in feces -> gets ingested usually contaminated hay by horses -> penetrates intestinal mucosa -> invades epithelial cells of mucosa/ replicates within these cells -> rupture endothelial cells -> phagocytized by macrophages -> macrophages somehow get to the brain -> ( carried through capillaries into the brain matter ( unsure) -> macrophages die in capillaries of the brain or near brain and sarcocystis will then replicate in the vascular epithelial cells and cause the same issue as they do in the intestinal mucosa.

37
Q

What is the consequences of sarcocystis neurona invading the CNS epithelial tissue?

A

Vascular damage:
- Inflammation

  • Neuronal & neuropil necrosis
38
Q

What is the morphological and etiological diagnosis of the image below?

A

Morphological diagnosis: myelitis (spinal cord) hemorraghic ( necrotizing since hemorrhage is likely causing necrosis) multifocal or multifocal to coalescing ( if your looking at the whole brain and spinal cord it would be focal or focally extensive. acute ( horse cannot survive long with this so it must be acute)
Etiological diagnosis: Protozoal myelitis

39
Q

What are enveloped viruses? Are they more or less environmentally resistant?

A
  • enveloped virus is less resistant
    • they grab part of cell membrane, which helps them avoid the immune system, but when out in environment they are alot less resistant.
40
Q

In this histological slide of a patient with rabies? What is being indicated with the yellow arrow?

A
  • Yellow arrow: Neurons ( pink thing is virus within the neuron)
  • inclusion body- negri bodies ( rabies inclusion bodies)
41
Q

What is the path of Rabies virus to the brain?

A

Replicates a little at site of entry but wants to travel to the ganglia and then will go inside of the brain, kills neurons and then will go to salivary glands

42
Q

What is the etiological diagnosis of this image? Morphological diagnosis?

A

• multifocal, enchephalitis, lymphocytic, subacute ( has plasma cells, acute also not wrong, but since lymphocytes/ plasma cells subacute is most correct) ( non suppurative , also lymphoplasmacytic possible modifier also ok to just say mononuclear)

Etiological Dx: Viral encephalitis

43
Q

How do pathogens colonize distant cells?

A
  • Direct invasion
  • Transcytosis
  • Phagocytosis

This leads to infection/ replication

44
Q

Why wouldnt microbes traveling to colonize distant cells be stopped by lysozomes?

A

Microbes may (virulence factors):

  • Block lysosome-phagosome fusion
  • Block lysosomal enzymes
  • Escape to cytosol
45
Q

What are the possible outcomes for cells that microbes are trying to colonize (distant)?

A

Possible outcomes:
- Cell death (necrosis)

  • Directed cellular disfunction
  • Structural injury
  • Persistent or latent infection
  • Cell proliferation
  • Malignant transformation
  • *Inflammation (may occur along with many outcomes)