Flashcards in Pathogens and Hosts Deck (41)
Describe some host defence mechanisms
• Innate immunity - Phagocytic mechanisms
• Acquired immunity - Antibody and complement (cell mediated immunity)
Describe some physical barriers to infection
Describe the process of phagocytosis
• Phagocytosis (ingestion) of a particle
• Organism held in phagosome
• Fusion with lysosome
• Phagolysosomeis formed
• Intra-cellular killing
Describe briefly the process and function of opsonisation
• Organism coated with antibody or complement
• Phagocytic cell has receptors for both
• Efficiency of phagocytosis greatly improved
What type of reactions are involved in the adaptive immune response?
What antibody is typically found in primary infections?
What antibody is typically found in secondary infections?
What antibody is typically found in mucosal immunity?
What antibody is typically found in allergy or parasite infections?
Briefly describe the complement system
The complement system is a part of the innate immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promotes inflammation, and attacks the pathogen's plasma membrane. The complement system consists of a number of small proteins found in the blood, in general synthesized by the liver, and normally circulating as inactive precursors (pro-proteins). When stimulated by one of several triggers, proteases in the system cleave specific proteins to release cytokines and initiate an amplifying cascade of further cleavages. The end result of this complement activation or complement fixation cascade is stimulation of phagocytes to clear foreign and damaged material, proxy inflammation to attract additional phagocytes, and activation of the cell-killing membrane attack complex.
How many complement proteins are there?
What is the use of antibodies in infections?
• Neutralises bacterial toxins (e.g. tetanus, diphtheria)
• Neutralises viruses in viraemic stage
• Prevents adherence of microorganisms
• Opsonises capsulate organisms (Strep pneumoniae, Haemophilus influenzae)
• Useful means of diagnosis (serology)
What are the three main functions of the complement system?
Phagocytosis – by opsonizing antigens. C3b has most important opsonizing activity
Inflammation – by attracting macrophages and neutrophils
Membrane attack – by rupturing membranes of foreign cells and gram negative bacteria
Whats the primary functions of the two CD4+ T cell subtypes?
Both release specific cytokines related to the type of infection to cause either:
– Th1 - cell mediated immunity (macrophages, CD8+)
– Th2 - control B cell antibody response
Whats the importance of cell mediated immunity?
• Important in the clearance of:
• Most viral infections and fungal infection
• Intra-cellular infection
• Lymphocytosis - increased WBC during infection
Describe some signs of clinical infection
– Inflammation can be cause by infection or AI ailment
– Pyrexia (fever)
– Tachycardia (increased HR)
– Rigors (whole body shaking uncontrollably >5mins, body desperately trying to create a fever and fight infection)
– Increased white cell count
– Increased C reactive protein (CRP) – marker of inflammation
– Note that infection can also be latent or sub-clinical
Whats the difference between a pathogen and a commensal?
• A pathogen is an organism which can cause disease
• A commensal is an organism which is part of normal flora e.g. E. coli in the gut, Staph aureus in the nose, axilla
• The distinction between these is not always clear e.g. during immunosuppression, antibiotic treatment or infection, opportunistic infections can occur when commensals take over
How can you tell if an organism is a pathogen or a commensal?
o Koch’s Postulates - organism must be found in all cases of the disease, be able to be cultured outside the body for several generations and should reproduce the disease on inoculation
o Sterile vs. non-sterile sites - knowledge of normal flora for site, the organism’s pathogenicity and its clinical context
What is Koch's postulate?
Koch’s Postulates - used to see if an organism is pathogenic or a commensal. The organism must be found in all cases of the disease, be able to be cultured outside the body for several generations and should reproduce the disease on inoculation
Describe some sterile sites in the human body
Bone and bone marrow
What are the two requirements of an organism needed to be pathogenic and cause an infection?
Infectivity - Ability to become established
Virulence - Ability to cause harmful effects once established
Describe some factors which can increase infectivity of an organism, giving some examples
Attachment mechanisms - E.Coli and P-fimbrae
Acid resistance - helicobacter pylori and urease
Describe some virulence factors
Virulence factors - genetically determined microbial components that can influence:
• Toxin production
• Evasion of immune system
Describe some pathologies caused by Streptococcus pyogenes and how it plays a role in its invasiveness
Streptococcus pyogenes (Group A streptococci) causes:
Connective tissue breakdown by enzymes:
What enzymes does Streptococcus pyogenes produce to increase its invasiveness?
Hyaluronidase - breaks down HA (glycosaminoglycan)
Collagenase - breaks down collagen
What is the difference between exotoxins, enterotoxins and endotoxins?
• Exotoxins are released extracellularly by the micro-organism
• Enterotoxins are exotoxins which act on the GI tract
• Endotoxin is structurally part of the Gram-negative cell wall (LPS) which are usually intracellular and only revealed after cell lysis
Describe the toxin involved in tetanus
Exotoxin produced by Clostridium tetani
Toxin binds to nerve synapses and inhibits inhibitory NTs
Death by respiratory paralysis
How do you treat tetanus infections?
Debridement - removal of damaged tissue or foreign objects from the wound
Antibiotics - clears toxin producing organism
Antitoxin - clears pathogenic toxin
Describe the toxin found in Cholera infections
Vibrio cholerae - Colonises small intestine
Enterotoxin production - Increases cAMP levels, which inhibits uptake of Na+ and Cl- ions
Stimulates secretion of Cl- and HCO3- ions causing passive (massive) outflow of H2O
Causes death by dehydration, treated by rehydration
What are superantigens?
Superantigens are a class of antigens that cause non-specific activation of T-cells resulting in polyclonal T cell activation and massive cytokine release, which can result in toxic shock.. SAgs are produced by some pathogenic viruses and bacteria most likely as a defense mechanism against the immune system
Describe some examples of superantigens
Certain exotoxins of Strep pyogenes and Staph aureus (TSS)
What lipid component of an endotoxin is responsible for the toxicity of gram negative bacteria?
Lipid A (component of lipopolysaccharide)
Describe some viral pathogenic mechanisms
Cell destruction following virus infection.
o Death of T4+ cells by HIV.
Virus-induced changes to cellular gene expression.
o Cellular transformation by tumour viruses.
o Influenza A virus.
o Coxsackievirus-induced myocarditis.
Can also be latent (overt vs. unapparent disease) e.g. TB
Name some sites of viral entry
• Respiratory tract
• Alimentary tract
• Urinogenital tract
• Arthropod (vector?)
Whats the difference between antigenic drift and antigenic shift?
o Gradual minor evolution of viruses to generate antigenic variants through natural mutations = antigenic drift
o Significant abrupt changes in virus antigenic structure = antigenic shift
How many enterovirus species are known? Name some examples of enterovirus infections
70+ enteroviruses known, transmitted through GI tract and are excreted in faeces
o Poliomyelitis (poliovirus) – iron lung
o Aseptic meningitis (many enteroviruses)
o Myocarditis (coxsackie B viruses)
o Pancreatitis (coxsackie B viruses)
o Respiratory infections (many enteroviruses)
Describe the latent period of TB infections
Primary infection of epithelial cells.
Virus migration to the ganglia.
Virus remains latent in nucleus of neural tissue
No Virus Replication.
Stimuli (e.g. sunlight, stress, infection, steroids) reactivates virus.
Virus migration to epithelial cells leading to virus replication.
How can retrovirus infections cause tumours?
Virus infects cell.
Virus nucleic acid, as DNA, integrates into cellular genome.
Virus causes changes in cellular gene expression.
Uncontrolled cell multiplication and tumour formation
Colonisation - the formation of compact population groups of the same type of microorganism, such as the colonies that develop when a bacterial cell begins reproducing
Latent - the ability of a pathogenic virus to lie dormant (latent) within a cell, denoted as the lysogenic part of the viral life cycle. A latent viral infection is a type of persistent viral infection which is distinguished from a chronic viral infection.