Principles of Infection Flashcards
Recall the types of host-microbe interactions
- Commensalism- normal flora
- Mutualism?
- Parasitism
Summarise some opportunistic infections associated with HIV
Oral candidiasis
- Herpes zooster
- Pneumocytosis carnii
- Cytomegalovirus
How can be commensals be pathogen sometimes?
- At another site
- Due to immunosuppression
- By-passing defences
Give examples of commensals that turn into pathogens in different sites
Staphylococcus aureus in the nose (commensal)
• Staphylococcus aureus in a post-operative wound infection (pathogen)
Escherichia coli in GI tract (commensal)
• Escherichia coli in urinary tract causing UTI (pathogen)
Staphylococcus epidermidis on skin (commensal)
• Staphylococcus epidermidis bloodstream infection following infection of an intravenous line (pathogen)
Recall sterile body sites- no commensal organism
- Lower respiratory tract
- Blood
- Bone, joint and subcutaneous connective tissue
- Female upper genital tract
- Urinary tract (not distal urethra)
- CNS including CSF and eye
- Other viscera e.g. liver, spleen, pancreas
What is a pathogen?
a microbe that can initiate infection, often with only small numbers, via natural routes, despite natural barriers and immune defences
Name a strict pathogen that will always cause disease
Bacillus anthracis (anthrax)
What are virulent microbes?
• Highly pathogenic microbes
What is virulence dependent on?
- Virulence – degree to which it causes disease
- virulent strains
- gene content alters phenotype
- host susceptibility
What is pathogenic potential?
potential to cause pathological disease
According to germ theory what does a microorganism have to do?
- Be present in every case of the infection
- Be cultured from cases in vitro
- Reproduce disease in an animal
- Be isolated from the infected animal
Describe the balance between pathogenic mechanisms and defensive mechanisms
Pathogenic mechanisms: adhesion, capsule, toxins
Defensive: neutral barriers, defensive cells, complement, immune response
Defences of tissue and blood
• usually involves tissue damage and controlled by feedback mechanisms
Natural non-specific barriers:
- physical conditions (dry, acidic), sloughing, microflora, lysozyme,
- toxic lipids, lactoferrin, lactoperoxidases, tight junctions, bile, mucin,
- cilliated epithelia, bile, cryptdins, phagocytes, intraepithelial lymphocytes
Natural adaptive barriers:
MALT( mucosa-associated lymphoid tissue), SALT(skin), GALT(gut), associated lymphoid tissue, secretory IgA
Types of infection
- Local surface infection; wound
- Invasive penetrate barriers – local spread
- Systemic via blood to other sites
- Effects at different site from colonisation - toxinsspecific disease, endotoxins SEPSIS
Recall local and systemic symptoms
Local symptoms (inflammation)
• Redness, swelling, warmth, pain
• Pus – pyogenic infection
Systemic symptoms
• Fever, rigors, chills, tachycardia(heart rhythm disorder), tachypnoea(rapid breathing)
Acute inflammation pathogen examples:
• Acute inflammatory response e.g. infection with Streptococcus pyogenes or Staphylococcus aureus
• Toxin mediated e.g. diphtheria (Corynebacterium diphtheriae)
tetanus (Clostridium tetani)
What is chronic infection?
- Slower onset or post-acute
- But may still have major local and systemic symptoms
- Chronic inflammatory response
- Results when host does not succumb immediately to infection, but cannot clear infection e.g. TB (Mycobacterium tuberculosis), Chronic osteomyelitis (Staphylococcus aureus)
What is asymptomatic infection?
- Infection with a pathogenic microbe (not a commensal or part of the normal flora)
- Inflammatory response is mild or none at all
- Damage to the host is mild or not at all
Example: No symptoms present e.g. Chlamydia trachomatis
(urethral infection in men, cervical infection in women)
50% males are asymptomatic
80% females are asymptomatic
e.g. herpesvirus shedding post-acute infection
What is reactivation of latent infection?
The virus never goes away it’s always in the body
- When you get older, the virus may be reactivated and this causes shingles or herpes Zoster
Stages of infection
- Acquisition from spread – 9Fs
- Colonisation – adherence
- Penetration and Spread – local or general
- Immune evasion
- Tissue damage
- Shedding and transmission
- Resolution
- Not all microbes need all stages
F-List:
- Fingers
- Fresh Air
- Fomites – (objects or materials which are likely to carry infection)
- Fluids (blood etc.)
- Faeces
- Flies
- Food
- Foetus
- Fornication
Examples of mucosal contact:
- genital tract – gonorrhea, chlamydia, HIV, HepB, syphilis
- Saliva – Herpes, CMV, EBV
- Skin – Staphylococci, VZV, HPV,
• fungal infections
Describe adherence of pathogens
• Surface adhesion structures of bacteria and viruses
• Host mucosal surfaces
• Specific receptors on host cells
e.g. Influenza A virus – hemagglutinin and sialy-oligosaccharides
• HIV and CD4 + CXCR5 surface proteins of CD4 cells– specific cell entry
How does Neisseria gonorrhoeae allow bacterium to adhere to blood group?
Fimbriae of Neisseria gonorrhoeae allow the bacterium to adhere to the P blood group antigen of uroepithelial cells
What are the virulence factors?
- Promote Colonisation and adhesion To establish infection e.g. adhesins
- Promote Tissue Damage Growth and transmission e.g. toxins, tissue degrading enzymes
What is whopping cough?
a toxin mediated disease Bordetella pertussis
• Invasive adenylate cyclase lethal toxin (dermonecrotic toxin) - superantigen tracheal cytotoxin pertussis toxin adheres to ciliated epithelial cells, PTx
What is the net effect of whopping cough pathogen?
• Net effect - permits multiplication at mucosal surface prevents localised immune activation and attack promotes survival and transmission
Give examples of intracellular pathogens
Mycobacterium tuberculosis Listeria Salmonella hidden from serum killing, complement, antibodies
Describe some evasion mechanisms of pathogens
Antigenic variation (e.g. N gonorrhoeae)
- Capsules can stop contact with phagocyte
o S. pneumoniae or B anthracis
- Inhibit phagolysosome formation
o M tuberculosis, Listeria monocytogenes
- Immunosuppress host
o Some bacterial toxins; some viruses block antigen presentation – Herpes
How do pathogens cause tissue damage?
DIRECT: cytolysis of infected cells
INDIRECT VIA NATURAL IMMUNE RESPONSE:• Over-activity of immune defences
– Endotoxin – all Gram-negative bacteria SEPSIS
INDIRECT VIA ADAPTIVE RESPONSE: IL-4, IgE, cytotoxicity
Describe TB pathology
• Cell-mediated delayed type hypersensitivity response (Type IV)
TB granuloma spherical collection of lymphocytes, macrophages and epithelioid cells with a small area of central caseation necrosis and tissue becomes destroyed
What is shedding of infection
o In order to perpetuate, microbe must find a new host
o Host damage not always linked to transmission
o Humans ‘dead-end’ host in some pathogen evolution
o Some symptoms facilitate transmission
How do microbes cause host damage?
Direct damage by microbes or toxins o Systematically ▪ Exotoxins – C diphtheriae C tetani o Locally ▪ Enzymes; Staph aureus ▪ Toxins; Clostridium perfringens, V cholera
- Caused by host’s immune response
o Immunopathology
