The pathogenises of infectious disease Flashcards

1
Q

General principles about pathogens

A

They can replicated in two ways
- Within hosts
- Between hosts

They are transferred in two ways
- Vertical transmission
- horizontal transmission

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2
Q

Key steps in pathogen infection

A

1) Infection: Attatchment and entry
- They must evade protective boundaries

2) Invasion: spread (local or systematic)
- they must counter local defenses

3) Microbe proliferation: multiplication (growth)
- They must gain resources from the host

4) Immune evasion: countering host defences
- Evade/ neutralise host defences

5) Onward transmission: Exit the host
- They leave the body in an infectious form

6) Pathology/ disease: host damage
- THis is not always required for pathogen proliferation but often occures.

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3
Q

Entry mechanisms

A

Entry mechanisms tend to involve eyes (not skin) or the alimentary canal (mouth to anus) which has the respiratory and urinary tracts extending off -> designed to interact with the environment

Two groups:
- Routes leaving antimicrobial defence intact.
o Biting arthropods
o Skin wound/ animal bite
o Microbial attachment/ penetration mechanisms

  • Routes that involve impairing the antimicrobial defences.
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4
Q

Types of transmission

A

Airborne:
- Aerosol: travel > 1 metre, float in the air, inhaled
- Droplets: travel <1, fall to the ground, cannot be inhailed

Faecal- oral:
- The germs that cause illness are found in the feces of an infected person, and are spread to another person.
- Germs often transferred to food and injested.

Infection by insect bite:
- Insects are the vectors and tranfer the pathogen
- Advantages
o Pathogens makes the most of a pair of wings and a biting devise
o They may be able to grow within the vector
- Disadvantages
o They must be able to withstand a vector and a host immune response.

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5
Q

Examples of pathogen transmission

A

Aerosol transmission:
- M.tuberculosis causing pulmonary and Milary tuberculosis and some localised infection
- Bordetella pertussis causing whooping cough

sexual/ contact transmission:
- Neisseria gonorrhoeae causing Gonorrhea
- Chlamydia causing Uretheritis/ conjunctivitis
- HIV causing Acquired immume deficiency syndrome (AIDS)

Faecal oral tranmission:
- Polio virus causing asymtompatic and polio myelitis

Biting insects:
- Plasmodium falciparum causing malaria

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6
Q

Early stages: Attatchment and invasion of an epithelial surface

A
  • First, the pathogen must penetrate the mucous layer.
  • Further penetration into the host (invasion) requires either:
    o Moving between cells (junction);
    o Moving through cells (surviving phagocytosis).
  • After crossing the basement membrane, the pathogen grows either intracellularly or extracellularly, which requires cellular invasion.
  • At all stages, the pathogen must survive immune attack.

Different pathogens have different targets-> Our cells have lots of receptors and molecules on their surface, therefor there are many molecules which pathogens can exploit to gain entry.

Example: HIV
- Target: CD4 T cells
- Microbial ligand: Viral envelope gpl20 proteins
- receptor: CD4 protein

Example: M.tuberculosis
- Target: Macrophage
- Microbial ligand: absorbed C3b
- Receptor: CR3

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7
Q

Host defence mechanisms

A

Host defence mechanisms

1) Creating a hostile environment
o Environment, e.g. pH (in the stomach) and temperature

o Nutrients, e.g. sequestering iron;
—> Most of the iron is complexed with molecules, so pathogens must have a mechanism to remove the iron.

o defence peptides.

2) Identification of the pathogen,
o molecular discrimination of self from non-self.

3) Killing of pathogen,
o cellular mechanisms for clearing pathogens.

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8
Q

Innate vs adaptive overview

A

Generic (Innate)
* Identification of non-self molecules.
* Innate immunity
* Pathogen Associated Molecular Patterns (PAMPS).
* Limited number of cells required:
o All receptors on all phagocytes;
o The phagocytes are always on
o fast;
o ‘cheap’ in terms of resources.

Specific (Adaptive)
* In vertebrates, specific identification.
* Adaptive immunity.
* Antibodies and T-cell receptors (TCRS) with modifiable receptors.
* Very, very, large number of cells required:
o One receptor per lymphocyte;
o Needs to be primed;
o slow;
o Highly resource intensive.

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9
Q

Phagocytes and antiphagocyte strategies

A

Phagocytes have receptors which recognise non-self cells and engulf them

Antiphagocyte strategies:
- Kill phagocyte
- Resist being killed
- Inhibit phagocytosis
- Block phagocytosis

Exmple: Staphylococci
- Type of interferance: Kill phagocyte, inhibit phagocytosis, resist killing, block phagocytosis
- Important factors: Leucocidin, SpA binding AbFc, Chips, Capsules.

Example: Mycobacteria
- Type of interferance: resist killing/ digestion
- Important factor: Cell wall

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10
Q

overview: Inflamatry response

A

Infection leads to the inflamatry response
- Cells detect invader
- Signalling to recruit more immune cells
- Response: heat, swelling puss

The immune response must be tightly regulated as it can cause damage if too extreme
- pathogens are able to manipulate the infalmatry response to harm host
- Example: Tuberculosis and coughing

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11
Q

Later stages: spread of infection

A

Pathogens can spread:

1) Locally to the site of infection
2) Systemically via:
- Lymphatic system (system can be manipulated-> e.g. TB)
- Blood strem
- Cerebrospinal fluid
- Nervous system

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12
Q

Avoiding the immune response

A
  • Avoid,
    o Grow in ‘immune privileged’ sites
    o e.g. intracellularly or in neural tissue (neural tissues are not easily recycled and changed).
  • Evade,
    o Express surface components that are not or poorly immunogenic so the immune response does not recognise the pathogen.
    o e.g. capsules (similar to host cells) or express few surface components.
  • Attack,
    o Expression of factors that,
     attack immune cells, e.g. AB-toxins,
     Supress immune function.
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13
Q

What effect host susceptibilty and pathogen virulence?

A
  • Genetic constitution,
    > gene presence and polymorphism (in host and pathogen)
  • Physiological status,
    > including nutrition, gene expression.
    > Example: If you are run down, you are more vulnerable to infection.
  • Environmental stress, -> e.g. neurological conditions.
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14
Q

Stages of host recovery

A
  • Elimination of pathogen
  • Down-regulation of immune responses,
  • Repair of tissue and or organ damage
    o Which may be complete, partial ,or not achieved, depending on the severity of the damage and the tissues involved.
  • Induction of immunity,
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15
Q

Failure of host recovery

A
  • Host death may be important or essential for pathogen transmission, (e.g. spore-forming pathogens)
    o Clostridium tetani causing tetanus -> body must decay to release spores
  • Host death may be harmful to host transmission,
    o Expecially for vector born diseases.
  • Chronic infection may be important for pathogen persistence:
    o Mycobacterium tuberculosis;
    o HIV;
    o Plasmodium falciparum (causing Malaria).
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16
Q

Overview

A

Key steps:

Transmission between hosts
- Aireborne
- Faecal-oral
- Insect bites
- Sexual tranmission

Entry into host
- Mainly through the alimentary canal and eyes

Attatchent and invastion of epithelial cells

Host defence mechanisms
- Hostile environment
- Identification of pathogen
- Killing pathogen (Phagocytes)

Antiphagocytic mechanisms by the pathogen

Spread of infection
- Locally
- Systematically

Immune response
- Adaptive
- Innate (inflamatry response)

Evasion of the immune response
- Avoid
- Evade
- Attack

How do pathogens damage the host?

Host recovery
- Elimination of pathogen
- Down regulation of immune response
- Repair of tissue or organ damage
- Induction of immunity

Failure of host recovery
- Host death may be part of pathogen transmission
- Host deat may be inimical to host transmission
- Chemical infection may be important for pathogen persistance.

17
Q

How to pathogens damage the host?

A

Damage may be necesary or a by-product

1) Direct damage: damage and death of cells becuase of pathogen growth (e.g. Polio-> Incidental death of neural cells due to viral replication)

2) Exo-toxins: Specific death or inactivation of host cell function (e.g. Tetanus -> Bacteria kills the host by paralyses, promoting replication and spread)

3) Inflammation: Over stimulation of innate immune response cuasing cell, tissue and organ damage

4) Immunopathology: Specific immune response damaging host cells, tissues or organs (Rheumatic fever -> Incidental action of antibodies reacting with heart muscle or valves)

5) Diarrhoea: Loss of fluid throught the intestine (Cholera -> Diahrea due to cholera toxin promotes microbial spread)