What is the difference between infectivity and virulence?
Infectivity is the capacity of a pathogen to establish itself within a host. Virulence is the capacity of a microbe to damage the host
Define immune system
Cells and organs that contribute to immune defences against infectious and non-infectious conditions
Define infectious disease
When the pathogen succeeds in evading and/or overwhelming the host’s immune defences
What are the four main roles of the immune system?
- pathogen recognition
- containing/eliminating the infection
- regulating itself
- remembering pathogens
Describe some key differences between innate and adaptive immunity
Innate immunity:
- fast (seconds)
- lack of specificity and memory
- no change in intensity
Adaptive immunity:
- slow (days)
- specific
- has immunologic memory
- changes in intensity
What are ‘barriers’ in immunity?
Factors that prevent entry and limit growth of pathogens
Give some examples of physical barriers in innate immunity
- skin
- mucous membranes (mouth, respiratory tract, GI tract, urinary tract)
- bronchial cilia
Give some examples of physiological barriers in the innate immune system
- diarrhoea
- vomiting
- coughing
- sneezing
Give some examples of chemical barriers in the innate immune system
- low pH (skin is 5.5, stomach is 1-3, vagina is 4.4)
- antimicrobial molecules
Give some examples of antimicrobial molecules that form part of the innate immune system
- IgA (tears, saliva, mucous membrane)
- lysozyme (sebum, perspiration, urine)
- mucus (mucous membranes)
- beta-defensins (epithelium)
- gastric acid and pepsin
What are ‘biological barriers’?
Non-pathogenic normal flora found in strategic locations, eg. nasopharynx, mouth/throat, skin, GI tract, vagina. They are not found within internal organs/tissues
Give some benefits of the body having ‘normal flora’ (non-pathogenic microbes)
- compete with pathogens for attachment sites and resources
- produce antimicrobial chemicals
- synthesise vitamins (K, B12, other B vitamins)
Give some examples of normal flora that inhabit the skin
- staphylococcus aureus
- staphylococcus epidermidis
- streptococcus pyogenes
- Candida albicans
- clostridium perfringens
Give some examples of normal flora that inhabit the nasopharynx
- streptococcus pneumoniae
- neisseria meningitidis
- haemophilus species
How could normal flora be displaced from its normal location to a sterile location?
- breaching skin integrity (skin loss, surgery, injected drugs, IV lines)
- faecal-oral route (foodborne infection)
- fecal-perineal-urethral route (UTI infection)
- poor dental hygiene/dental work
Which groups of patients are seen as high risk for infections from normal flora?
Patients who are/have:
- asplenic/hyposplenic
- damaged or prosthetic valves
- previous infective endocarditis
Give some examples of conditions that may cause a host to become immunocompromised, allowing overgrowth of normal flora
- diabetes
- AIDS
- malignant diseases
- chemotherapy
What is thrush caused by?
Vaginal yeast infection (candida albicans) that can occur when normal flora is depleted by antibiotics
What are macrophages?
Phagocytes which are present in all organs. They ingest and destroy microbes via phagocytosis, and present microbial antigens to T cells (part of adaptive immunity). They produce cytokines/chemokines
What are monocytes?
Phagocytes which are present in the blood. They are recruited at the infection site where they differentiate into macrophages
What are neutrophils?
Phagocytes which make up 60% of blood leukocytes. They are increased during infection, when they are recruited by chemokines. They ingest and destroy pyogenic bacteria
What is the function of basophils/mast cells?
Early actors of inflammation (vasomodulation) which are important in allergic responses
What are eosinophils used for?
Defence against multi-cellular parasites (worms)
What are natural killer cells for?
They kill all abnormal host cells (either infected with virus or malignant)
What are dendritic cells for?
Present microbial antigens to T cells (in acquired/adaptive immunity)
How does the phagocyte recognise the pathogen to be consumed?
Pathogen will have microbial structures (pathogen-associated molecular patterns or ‘PAMPs’) and phagocyte has pathogen recognition receptors
What is opsonisation of microbes?
Coating proteins called opsonins bind to the microbial surfaces, leading to enhanced attachment of phagocytes
Give some examples of opsonins
- complement proteins (C3b, C4b)
- antibodies (IgG, IgM)
- acute phase proteins (C-reactive protein and mannose-binding lectin)
These are all essential in clearing encapsulated bacteria
What are the two phagocyte intracellular killing mechanisms?
- oxygen dependent pathway
- oxygen independent pathway
What is the oxygen-dependent killing pathway?
Reactive oxygen-containing molecules are produced by the phagocyte which are anti-microbial
What are the different methods of oxygen-independent destruction of pathogens?
- production of lysozymes which break down bacterial cell wall
- production of lactoferrins which are present in neutrophil granules and remove the essential iron from bacteria
- electrically charged cationic proteins damage the bacterium’s membrane
- proteolytic/hydrolytic enzymes digest the proteins of destroyed bacteria
What is the difference between the alternative pathway and the MBL pathway of complement activation?
- alternative pathway is initiated by cell surface microbial constituents (endotoxins on E.coli)
- MBL pathway is initiated when MBL binds to mannose containing residues of proteins found on many microbes
What are complement proteins C3a and C5a responsible for?
Recruitment of phagocytes
What are complement proteins C3b-C4b responsible for?
Opsonisation of pathogens
What are complement proteins C5-C9 responsible for?
Killing of pathogens, membrane attack complex
What are the antimicrobial actions of macrophage-derived TNF-alpha (and where do they take place)?
- liver (CRP and MBL activate complement/opsonisation)
- bone marrow (neutrophil mobilisation)
- inflammatory actions (vasodilation, vascular permeability, adhesion molecules lead to attraction of neutrophils)
- hypothalamus (increased body temperature)
What three things can lead to reduced phagocytosis?
- decreased spleen function (asplenic/hypersplenic patients)
- decreased neutrophil number (chemotherapy, certain drugs, leukaemia and lymphoma)
- decreased neutrophil function (chronic granulomatous disease, Chediak-Higashi syndrome)