Pathogenesis

Question 1

What is pathogenesis?

Answer 1

Mechanism of disease production

Question 2

What is pathogenicity?

Answer 2

The ability of an organism to inflict damage on the host

Question 3

What is virulence?

Answer 3

The relative ability of a pathogenic organism to cause disease

Question 4

What are virulence factors?

Answer 4

Genes, molecules, or structures that contribute to virulence

Question 5

What are commensals?

Answer 5

Organisms that live in harmony with us

Question 6

What are saprophytes?

Answer 6

Organisms that live in the environment

Question 7

What are pathogens?

Answer 7

Organisms that cause disease

Question 8

What are opportunist pathogens?

Answer 8

Organisms that behave as pathogens when given the right “opportunity” in a “compromised host”- may be commensals or saprophytes

Question 9

What are primary pathogens?

Answer 9

Can cause disease in healthy subjects

Question 10

What does the innate immune system involve?

Answer 10

Anatomical barriers, flushing mechanisms (motility), chemical, microbial colonisation resistance

Question 11

What are the physical skin barriers?

Answer 11

Skin/ mucous membranes/ respiratory tract/ intestinal tract/ genitourinary tract

Question 12

What cells are involved in the innate immune system?

Answer 12

Epithelial/ leukocytes (neutrophils, monocytes)

Question 13

What are Toll-like receptors?

Answer 13

Recognise PAMPs

Question 14

What are PAMPs?

Answer 14

Pathogen Associated Molecular Patterns

Question 15

How is fever caused?

Answer 15

Microorganisms/ infected cells/ foreign molecules= macrophage and T cell response= Endogenous pyrogen (proteins produced by leukocytes, hypothalamus thermostat) (IL1, TNF)= neural response= fever

Question 16

When do microorganisms cause disease?

Answer 16

Host defences fail to control organisms or organisms overcome host defences

Question 17

What defence failures commonly lead to infections?

Answer 17

• Anatomical barriers= wounds
• Flushing mechanisms (motility)= damaged respiratory cilia (smoking), catheter in bladder
• Chemical= decreased acidity in the stomach (H2 blockers), proton pump inhibitors
• Microbial colonisation resistance- antibiotic use

Question 18

How are host defences overcome?

Answer 18

Attach, penetrate and spread within the host, survive and multiply, cause damage o trigger a reaction, exit host

Question 19

What are the sites of attachment and entry?

Answer 19

Skin

Mucosal surfaces= conjunctiva, respiratory tract, gut, urogenital tract

Question 20

How is the skin infected?

Answer 20

• Skin impervious to most microorganisms
• Infection needs injury or insect vectors
• Direct contact= hookworm and schistosome larvae/ infection of hair follicle/ dermatophytes and wart viruses

Question 21

How are mucosal surfaces infected?

Answer 21

• Thinner epithelia because of functions
• Common factors (motility, IgA)
• Site-specific factors (chemical-= toxic molecules and iron restriction, sites for attachment)

Question 22

How does pathogens attach?

Answer 22

• Non-specific (dextran on teeth) r lock and key (host and microbe molecules)
• Influenza= neuraminic acids (sialic acids)
• Rhinovirus/ common cold= ICAM1 (Intercellular Adhesion Molecule 1)
• Uropathogenic E Coli= P fimbriae (attachment pilus= threads/projections) and P antigen

Question 23

How do pathogens spread within the host?

Answer 23

Blood= most common- bacteraemia/viraemia suggests invasiveness of the organism/virus
ECF and lymph- lymphangitis
Nerve cells- HSV, VZV, Rabies
Body spaces- CSF, pleura, peritoneum

Question 24

How do pathogens survive and multiply?

Answer 24

Resisting complement and phagocytes
Extracellular survival= capsules, antiphagocytic mechanisms
Intracellular survival= in phagocytes or other cells

Question 25

What are the mechanisms of injury?

Answer 25

Direct= cell damage by viruses, bacterial exotoxins
Indirect= bacterial endotoxins, immunopathology (reaction causing disease), systematic effects (fever)

Question 26

What are bacterial exotoxins?

Answer 26

Bacterial protein toxins excreted by the organism with variety of specific actions

Question 27

What are bacterial endotoxins?

Answer 27

Lipopolysaccharide (LPS) constitutive component of Gram-negative bacteria

Question 28

What are the differences between exotoxins and endotoxins?

Answer 28

Ex= lysis, pore formation, inhibited protein synthesis, hyperactivation of cell, blocks inhibition of synapse, blocks transmission at synapse
Endo= activates endothelial cells, mast cells, platelets, clotting, complement, PMNs, macrophages/ many intermediary mechanisms including TNF and Interleukin release/ Fever, Distributive Shock, Disseminated intravascular coagulation (DIC), hypoglycaemia

Question 29

What are the routes of transmission?

Answer 29

Respiratory or salivary/ faecal-oral/ contact/ sexually/ vector= arthropods, tick

Question 30

What is persistence?

Answer 30

Shedding= EBV, Tapeworms
Latent infection= Herpes simplex virus, Varicella zozter virus, Mycobacterium tuberculosis
Slow infection following acute inflammation= HIV-AIDS, HTLV1-Leukaemia
Slow infection no acute phase= Creutzfeldt-Jacob disease

Question 31

What are the outcomes of encounter between host and microorganism?

Answer 31

• Acute illness followed by immunity
• Asymptomatic or sub-clinical
• Colonisation
• Chronic illness
• Latency and potential for later illness

Question 32

Examples of virulence factors

Answer 32

Adhesions, enzymes, capsules, antiphagocytic factors, toxins

Question 33

Examples of host factors determining outcome

Answer 33

• Genetic factors= HbS and malaria/ MHC Class 2 and leprosy/ secretor status and recurrent UTI
• Age (very young or old)
• Other conditions= diabetes mellitus, immunocompromise