W12 Principles of infection Flashcards
Infections and Host-Microbe interactions
Symbiosis → commensalism + mutualism + parasitism
Commensalism → normal flora
Parasitism → pathogen
Colonisation → asymptomatic (no symptoms) carriage → infection
Parasite
harmless/beneficial in healthy people (immunocompromised)
Conditional (from commensal to opportunist) (and from pathogen
Full pathogen (initiates infection via natural route, despite immune defences)
Saprophyte
- free living organism
- host-dependent
AIDS defining infections
Pneumocystis carinii Cryptococcus Toxoplasma Herpes simplex infections Cryptosporidia Histoplasma
Opportunistic infections associated
with the declining CD4 cell counts in HIV infection
Bacterial skin infections
Oral candidiasis
Multidermal
Herpes zooster
Oral hairy leucoplakia
(EBV reactivation)
Tuberculosis
Cytomegalovirus
Disseminated mycobacteriosis
Commensals can sometimes be pathogens
In healthy individuals, the commensal microbes (normal flora) will do no harm
Colonisation (not infection)
BUT
If the host’s defenses are weakened (immunocompromised) infection may occur;
This is called opportunistic infection
Pathogen short definition
A microbe that causes disease
Commensals and Pathogens
Infection implies - harm is done to the host i.e. causes disease
Usually the host will manifest an inflammatory response to a pathogen, but not to a coloniser (commensal) at a normally non-sterile site
Staphylococcus aureus (commensal v pathogen)
Staphylococcus aureus in the nose (commensal)
Staphylococcus aureus in a post-operative wound infection (pathogen)
Escherichia coli (commensal v pathogen)
Escherichia coli in GI tract (commensal)
Escherichia coli in urinary tract causing UTI (pathogen)
Staphylococcus epidermidis (commensal v pathogen)
Staphylococcus epidermidis on skin (commensal)
Staphylococcus epidermidis bloodstream infection following infection of an intravenous line (pathogen)
Commensals can sometimes be pathogens - basic reasons
At another site
Due to immunosuppression
By-passing defences
Normally Sterile Body Sites
Sites without a normal flora are sterile
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
Pathogen
A pathogen is a microbe that can initiate infection, often with only small numbers, via natural routes, despite natural barriers and immune defences
Some organisms are strict pathogens
Some organisms are strict pathogens
i. e. will always cause disease e. g. Bacillus anthracis (anthrax)
Some are conditional pathogens
Virulent
Highly pathogenic microbes are said to be virulent
Virulence
degree to which it causes disease
- virulent strains - gene content alters phenotype - host suceptibility
Koch’s Postulates
Robert Koch 1843 – 1910
1st to show a specific organism as cause of a disease – anthrax
Then for tuberculosis (Mycobacterium tuberculosis) and cholera (Vibrio cholerae)
“GERM THEORY”
A microorganism has to: (Koch’s Postulates)
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
Koch’s Postulates changes
We now know not all organisms can be cultured e.g. M.leprae; Treponema pallidum; some viruses
Can detect their DNA or RNA genomes by PCR
Not universally applicable to all diseases
e.g. cancers associated with viruses (HepB; EBV)
Balance between the microbe and the host
Properties of the microbe (Pathogenic mechanisms): Adhesins Toxins Capsule Etc.
Properties of the host Defensive mechanisms: Natural barriers Defensive cells Complement Immune response
Leads to Genome evolution
Natural Barriers
Skin Lungs Gut GU tract Eyes
non-specific:
physical conditions (dry, acidic), sloughing, microflora, lysozyme, toxic lipids, lactoferrin, lactoperoxidases, tight junctions, bile, mucin, cilliated epithelia, bile, cryptdins, phagocytes, intraepithelial lymphocytes
adaptive:
MALT, SALT, GALT, associated lymphoid tissue, secretory IgA
Defences of tissue and blood
usually involves tissue damage and controlled by feedback mechanisms
non-specific:
transferrin, complement, acute phase proteins (released by liver)
phagocytes- monocytes and macrophages, PMN’s –neutrophils
macrophage activation
adaptive:
antibodies
T cells
Local
surface infection; wound
Invasive
penetrate barriers - spread
Systemic
via blood to other sites
Effects at different site from colonisation
toxins
endotoxins
Immunopathology
- inflammation causes tissue damage
- cross reactive antigens e.g. Streptococci and rheumatic heart disease
- granuloma e.g. Tuberculosis
Local symptoms (inflammation)
Redness, swelling, warmth, pain
Pus – pyogenic infection
Systemic symptoms
Fever, rigors, chills, tachycardia, tachypnoea
Inflammation
Response to tissue injury -
functions to bring serum molecules and cells to site of infection
Changes caused by inflammation
increase in blood supply
increase in capillary permeability
Migration of cells from blood to tissue
(Polymorphs, macrophages)
Ordered Process – regulated
vasodilation, oedema, complement activation, mast cell degranulation, PMNs recruitment, clotting
Pyogenic Infection
Pus cell
(neutrophil)
Streptococci
Acute Infection
Rapid onset
Major local and systemic symptoms
Acute inflammatory response
e.g. infection with Streptococcus pyogenes or Staphylococcus aureus
Toxin mediated
e.g. diphtheria (Corynebacterium diphtheriae)
tetanus (Clostridium tetani)
Chronic Infection
Slower onset or post-acute
But may still have major local and systemic symptoms
Chronic inflammatory response
Results when host doses not succumb immediately to infection, but cannot clear infection
Asymptomatic Infection
Infection with a pathogenic microbe (not a commensal or part of the normal flora)
Inflammatory response in mild or none at all
Damage to the host is mild or not at all
No symptoms present
Asymptomatic Infection examples
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
Chronic Infection examples
e.g. TB (Mycobacterium tuberculosis) Chronic osteomyelitis (Staphylococcus aureus)
Virulence Factors
Promote
Colonisation and adhesion
To establish infection
e.g. adhesins
Promote
Tissue Damage
Growth and transmission?
e.g. toxins
M protein of Streptococcus pyogenes
M protein of Streptococcus pyogenes
acts as adhesin and
structural component of cell wall
Electron micrograph
1 micron dia
M-protein fibrills
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
Spread of Infection
DIRECT CONTACT
INDIRECT CONTACT
AIRBORNE
BLOOD PRODUCTS
HUMAN SOURCES
Go to toilet Bugs on fingers, toilet seat, etc Direct spread to others Contamination of food Contamination of drinking water by sewage Contamination of vegetables by sewage Breathing air – flu, TB,
Adherence
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
Neisseria gonorrhoeae
Fimbriae of Neisseria gonorrhoeae allow the bacterium to adhere to P blood group antigen of uroepithelial cells
Adhesins in bacterial CW
Adhesin receptor on host CM
Whooping Cough: a toxin mediated disease
Bordetella pertussis Invasive adenylate cyclase lethal toxin (dermonecrotic toxin) - superantigen tracheal cytotoxin pertussis toxin, PTx
Whooping Cough: a toxin mediated disease - NET EFFECT?
permits multiplication at mucosal surface
prevents localised immune activation and attack
promotes survival and transmission
Multiplication
This occurs after internalisation of the microbe
Multiplication results in a focus of infection
Counter non-specific & specific defences
Gastric pH
e.g. gut infections - Salmonella spp
“colonisation resistance” of normal flora
Continuing adherence prevents physical removal by micturition, peristalsis
IgA proteases in Neisseria gonorrhoeae
avoids mucosal immune defence
Local surface infection only
Vibrio cholera
Some strains of N. gonorrhoeae
Local Invasion
Shigella, some Staph aureus
Deeper Invasion
Through blood, lymph, (nerves)
S. typhi, N. meningitidis, Staph aureus
Multipliation may be critical for transmission
Respiratory, faeco-oral or sexual contact
Evasion of host defences
Each step in specific and nonspecific immunity
– multiple specific mechanisms
Antigenic variation (e.g. N. gonorrhoeae)
Capsules can stop contact with phagocyte
S. pneumoniae or B. anthracis
Inhibit phagolysosome formation
M. tuberculosis, Listeria monocytogenes
Immunosuppress host
some bacterial toxins;
some viruses block antigen presentation - Herpes
Intracellular pathogens:-
e.g. Mycobacterium tuberculosis
Listeria
Salmonella
hidden from serum killing, complement, antibodies
Direct damage by microbe or toxins
Direct damage by microbe or toxins
Systemically:
Exotoxins – C. diphtheriae C. tetani
Locally;
Enzymes; Staph aureus
Toxins; Clostridium perfringens, V. cholera
Caused by host’s immune response
immunopathology
Over-activity of immune defences
Endotoxin – all Gram-negative bacteria leading to SEPSIS
types of “hypersensitivity”
e.g. Type 4 – granuloma in TB
Cross-reaction of antibodies (damage by immune defences)
Cross-reaction of antibodies against streptococcal antigens with host antigens
myocardium, synovium, brain
Streptococcus pyogenes in Rheumatic Fever
Tuberculosis: cellular 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
Shedding of infection
In order to perpetuate, microbe must find a new host
Host damage not always linked to transmission
Humans ‘dead-end’ host in some pathogen evolution
Some symptoms facilitate transmission
Mucosal contact
genital tract – gonorrhea, chlamydia, HIV, HepB, syphilis
Saliva – Herpes, CMV, EBV
Skin – Staphylococci, VZV, HPV,
fungal infections
