The pathogenises of infectious disease Flashcards
General principles about pathogens
They can replicated in two ways
- Within hosts
- Between hosts
They are transferred in two ways
- Vertical transmission
- horizontal transmission
Key steps in pathogen infection
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.
Entry mechanisms
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.
Types of transmission
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.
Examples of pathogen transmission
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
Early stages: Attatchment and invasion of an epithelial surface
- 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
Host defence mechanisms
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.
Innate vs adaptive overview
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.
Phagocytes and antiphagocyte strategies
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
overview: Inflamatry response
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
Later stages: spread of infection
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
Avoiding the immune response
- 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.
What effect host susceptibilty and pathogen virulence?
- 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.
Stages of host recovery
- 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,
Failure of host recovery
- 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).