Pathogens and the Host Flashcards
What are signs and symptoms of clinical infection?
inflammation
pain
pyrexia
tachycardia
rigors
increased white cell count
Increased C reactive protein (CRP)
What is a pathogen?
organism that can cause disease
What is a commensal?
A commensal is an organism which is part of normal flora e.g. E. coli in the gut, Staph aureus in the nose, axilla
How do we know if organism is a pathogen or commensal?
koch’s postulates:
organism must be found in all cases of the disease
able to be cultured outside the body for several generations
should reproduce the disease on inoculation
sterile vs non-sterile sites
knowledge of
normal flora for site
organism’s pathogenicity
clinical context
What is pathogenicity?
The capacity of a micro-organism to cause an infection
What are requirements for pathogenicity?
infectivity- ability to become established
virulence- ability to cause harmful effects once established
How is infectivity achieved?
Attachment
E. coli-
P-fimbriae
Receptor on uroepithelial cells
Acid resistance
Helicobacter pylori-
Urease
Makes ammonia from urea
How is virulence achieved?
Conferred by virulence factors
Genetically determined microbialcomponents-
Invasiveness
Toxin production
Evasion of immune system
specific to strains not species (staphaureus does not share same pathogenicity as other staphylococci)
How is invasiveness achieved in streptococcus pyogenes (Group A streptococci)?
connective tissue breakdown
-hyaluronidase
-collagenase
fibrinolysis
-streptokinase enzyme
Describe exotoxins?
released extracellularly by the micro-organism
Describe endotoxins?
structurally part of the gram negative cell wall
Describe enterotoxins?
exotoxins which act on the GI tract
Describe the exotoxin: Tetanus?
Clostridium tetani (obligate anaerobe)
Infection of dirty wounds
Toxin production:
Binds to nerve synapses
Inhibits release of inhibitory neurotransmitters
Death caused by respiratory paralysis
Treated by debridement, antibiotics and antitoxin
Describe the enterotoxin: Cholera?
Vibrio cholerae-
Colonises small intestine
Enterotoxin production:
Increases cAMP levels
Inhibits uptake of Na+ and Cl- ions
Stimulates secretion of Cl- and HCO3- ions
Passive (massive) outflow of H2O
Causes death by dehydration
Treated by rehydration
Describe super antigens?
Certain exotoxins of Strep pyogenes and Staph aureus
Able to stimulate division of T cells in the absence of specific antigen
Overwhelming cytokine production causes “toxic shock”
How is endotoxin structured?
Component of the Gram-negative bacterial cell wall:
Lipopolysaccharide-
Lipid A -THE NASTY PART
Oligosaccharide core
Specific polysaccharide chain
What is meaning of MRSA and MSSA staphylococcus aureus?
MRSA- methicillin resistant staph aureus
MSSA- methicillin sensitive staph aureus
Why is staphylococcus aureus commonly penicillin resistant?
due to beta lactamase
Describe clostridium perfringens? (gram positive bacilli)
Found in soil and normal commensal in human and animal gut/faeces
in contaminated food, can cause food poisoning (enterotoxin-producing strains)
in serious wounds (wartime) can cause “gas gangrene”
What are three characteristic ways by which virus causes pathogenesis in the host?
Cell destruction following virus infection
-Death of T4+ cells by HIV
Virus-induced changes to cellular gene expression
-Cellular transformation by tumour viruses
Immunopathogenic disease
-Influenza A virus.
-Coxsackievirus-induced myocarditis
How does virus enter cell?
respiratory tract
alimentary tract
urinogenital tract
arthropod vector
capillary
skin
conjunctiva
Describe an acute infection?
so after person gets infected, there is a peak up and down. Virus production is high and the human response dominates and is able to control infection.
Describe latent infection?
after acute infection, the virus goes and hides away and keeps dormant for ages. After certain stimulus it comes back and attacks exactly the same as original acute infection attack
Describe chronic infection?
after acute infection, the virus load doesn’t go back to basic level (doesn’t disappear) and virus remains above baseline for life.
Describe tumour virus infection?
acute infection is mild or very little and virus remains in very low level in background causing very slow changes in cell until becomes malignant .
Give examples of acute virus infections?
Influenza A virus- respiratory infection
enterovirus- enteric and neurological infections
What is viraemia?
means virus reaches the blood stream
How does pathogenicity occur in Influenza A?
Virus infects cells of the respiratory tract
Destruction of respiratory epithelium
-Secondary bacterial infections
Altered cytokine expression leading to fever
-e.g interleukin-1 and interferon
-Avian influenza virus (H5N1) causes a “cytokine storm”
Describe antigenic drift?
Minor changes (natural mutations) in the genes of flu viruses, occurs gradually over time to generate antigenic variants
Describe antigenic shift?
Abrupt major changes in virus antigenic structure
How is the generation of novel influenza brought about?
non human hosts for influenza A viruses play a key role in generating new virus types e.g. avian influenza, swine influenza
Give examples of enterovirus infections?
Poliomyelitis (poliovirus)
Aseptic meningitis (many enteroviruses)
Myocarditis (coxsackie B viruses)
Pancreatitis (coxsackie B viruses)
Respiratory infections (many enteroviruses)
Mechanisms of enterovirus?
acquired through GI system, goes to gut and from the gut, it goes into the bloodstream by viraemia. Either goes to non neuronal tissue (heart…pancreas) or neuronal tissues (CNS) (that can cause paralysis).
Virus in gut gets excreted in stools
Give example of latent virus infection?
herpes simplex virus- cold sores (type 1 ) and genital lesions (type 2)
Describe the herpes virus infection?
virus infects the epithelium and cold sore happens
after this episode, virus migrates to nerve ganglia and virus latent in nucleus
then a stimulus occurs and virus gets reactivated and migrates to epithelium.
Leads to virus replication
Give examples of virus-induced tumours?
Papillomaviruses (HPV)-cervical carcinoma
Retroviruses- lymphomas and leukemias
Describe the retrovirus replication cycle?
Virus attaches to cell by membrane fusion and uncoating process happens.
Membrane fusion releases the viral nucleic acid material on its own in the infected cell.
By a process of reverse transcription- RNA/DNA hybrid forms and then there is the viral DNA formed- double stranded DNA.
This migrates into nucleus and integrates into host nucleic acid material and through viral DNA integration, provirus is formed.
Describe Human T-lymphotropic virus-1 (HTLV-1) (virus induced tumours)?
Transmission by blood and mother to child.
Infects T cells
Modifies host cell gene expression using a Transactivating protein (tax)
Variety of diseases including leukaemia (Adult T-cell Lymphoma-Leukaemia)
Directly responsible for the tumour.
