Pathogenesis Flashcards
What is pathogenesis?
Mechanism of disease production
What is pathogenicity?
The ability of an organism to inflict damage on the host
What is virulence?
The relative ability of a pathogenic organism to cause disease
What are virulence factors?
Genes, molecules, or structures that contribute to virulence
What are commensals?
Organisms that live in harmony with us
What are saprophytes?
Organisms that live in the environment
What are pathogens?
Organisms that cause disease
What are opportunist pathogens?
Organisms that behave as pathogens when given the right “opportunity” in a “compromised host”- may be commensals or saprophytes
What are primary pathogens?
Can cause disease in healthy subjects
What does the innate immune system involve?
Anatomical barriers, flushing mechanisms (motility), chemical, microbial colonisation resistance
What are the physical skin barriers?
Skin/ mucous membranes/ respiratory tract/ intestinal tract/ genitourinary tract
What cells are involved in the innate immune system?
Epithelial/ leukocytes (neutrophils, monocytes)
What are Toll-like receptors?
Recognise PAMPs
What are PAMPs?
Pathogen Associated Molecular Patterns
How is fever caused?
Microorganisms/ infected cells/ foreign molecules= macrophage and T cell response= Endogenous pyrogen (proteins produced by leukocytes, hypothalamus thermostat) (IL1, TNF)= neural response= fever
When do microorganisms cause disease?
Host defences fail to control organisms or organisms overcome host defences
What defence failures commonly lead to infections?
- 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
How are host defences overcome?
Attach, penetrate and spread within the host, survive and multiply, cause damage o trigger a reaction, exit host
What are the sites of attachment and entry?
Skin
Mucosal surfaces= conjunctiva, respiratory tract, gut, urogenital tract
How is the skin infected?
- 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
How are mucosal surfaces infected?
- Thinner epithelia because of functions
- Common factors (motility, IgA)
- Site-specific factors (chemical-= toxic molecules and iron restriction, sites for attachment)
How does pathogens attach?
- 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
How do pathogens spread within the host?
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
How do pathogens survive and multiply?
Resisting complement and phagocytes
Extracellular survival= capsules, antiphagocytic mechanisms
Intracellular survival= in phagocytes or other cells
What are the mechanisms of injury?
Direct= cell damage by viruses, bacterial exotoxins Indirect= bacterial endotoxins, immunopathology (reaction causing disease), systematic effects (fever)
What are bacterial exotoxins?
Bacterial protein toxins excreted by the organism with variety of specific actions
What are bacterial endotoxins?
Lipopolysaccharide (LPS) constitutive component of Gram-negative bacteria
What are the differences between exotoxins and endotoxins?
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
What are the routes of transmission?
Respiratory or salivary/ faecal-oral/ contact/ sexually/ vector= arthropods, tick
What is persistence?
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
What are the outcomes of encounter between host and microorganism?
- Acute illness followed by immunity
- Asymptomatic or sub-clinical
- Colonisation
- Chronic illness
- Latency and potential for later illness
Examples of virulence factors
Adhesions, enzymes, capsules, antiphagocytic factors, toxins
Examples of host factors determining outcome
- 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
