S2 Innate Immune System Flashcards
What are the 3 factors determining the outcome of the host-pathogen relationship? Which part of the infection model does each effect?
- infectivity (pathogen)
- host’s immune response (patient)
- virulence (mechanism of infection)
What does infectivity mean?
Ability of microbe to establish itself within/on the host
What does virulence mean?
Capacity of the microbe to do damage
Which 3 groups are at increased risk of infection?
- Elderly
- Children
- Pregnant women
What is the immune system?
Cells and organs that contribute to immune defences against infectious and non-infectious conditions (self vs non-self)
What is an example of a non-infectious condition the immune system targets?
Cancer
What is an infectious disease?
When the pathogen succeeds in evading and/or overwhelming the host’s immune defences
What are the 4 roles of the immune system?
- Pathogen recognition (cell surface and soluble receptors)
- Containing/eliminating the infection (killing and clearance mechanisms)
- Regulating itself (minimum damage to host)
- Remembering pathogens (preventing reoccurrence of the disease)
What are the two types of immunity?
- innate immunity
* adaptive immunity
What is innate immunity?
- first immunity
- immediate protection
- fast (seconds)
- lack of specificity
- lack of memory
- non change in intensity
What is adaptive immunity?
- second immunity, if any pathogen gets through innate
- long lasting protection
- slow (days)
- specificity
- immunologic memory
- changes in intensity
What are the first lines of defence?
Factors that prevent entry and limit growth of pathogens
- physical barriers
- physiological barriers
- chemical barriers
- biological barriers
What are the physical barriers?
- skin
- mucous membranes (mouth, respiratory tract, GI tract, urinary tract)
- bronchial cilia
What are the physiological barriers? Give an example of an infectious disease that causes each
- diarrhoea (food poisoning)
- vomiting (hepatitis)
- coughing (pneumonia)
- sneezing (sinusitis)
What are the chemical barriers?
- low pH e.g. on skin, in stomach and vagina
* antimicrobial molecules - IgA, lysozyme, mucus, gastric acid and pepsin, beta-defensins
What are the biological barriers?
- normal flora (non-pathogenic microbes) that become pathogenic if get into wrong location
What are the benefits of the human microbiome?
- they compete with pathogens for attachment sites and resources
- produce antimicrobial chemicals
- synthesis vitamins
- lead to immune maturation
Give examples of some normal flora that inhabit the skin.
- staphylococcus aureus
- staphylococcus epidermidis
- streptococcus pyogenes
- candida albicans
- clostridium perfingens
Give examples of some normal flora that inhabit the nasopharynx.
- streptococcus pneumoniae
- neisseria meningitidis
- haemophilius species
When do clinical problems arise from normal flora?
Displacement of normal flora by e.g. breaching of the skin integrity, fecal-oral route or fecal-perineal-urethral route, poor dental hygiene/dental work, depleted by antibiotic therapy or overgrown and becomes pathogenic
Who are high-risk patients to serious infections?
- asplenic patients
- patients with damaged or prosthetic heart valves
- patients with previous infective endocarditis
What are the second lines of defence?
Factors that will contain and clear the infection
- phagocytes
- chemicals
- inflammation
What are the 3 main phagocytes?
- macrophages (in all organs) - produce cytokines/chemokines and phagocytose microbes
- monocytes (in blood) - differentiate into macrophages at infected tissue
- neutrophils (blood) - increase during infection, recruited by chemokines to infection site
What are the other key cells of the innate immunity (minus phagocytes)?
- basophils/mast cells
- eosinophils
- natural killer cells
- dendritic cells - present microbial antigens to T cells (acquired immunity)
How do phagocytes recognise microbes?
Phagocytes have pathogen recognition receptors (PRRs) e.g. TLR4 that recognise and bind to pathogen-associated molecular patterns (PAMPs) on the microbe
Microbes also have proteins called opsonins on their surface that bind to opsonin receptors on phagocyte
Two attachments increases recognition - more enhanced
What are examples of opsonins? Why are they important?
- complement proteins
- antibodies e.g. IgG
- acute phase proteins e.g. CRP
Essential in clearing encapsulated bacteria
What do phagocytes do?
Ingest and destroy (phagocytosis)
In which two pathways do phagocytes kill microbes?
- oxygen dependent pathway (respiratory burst) - toxic oxygen products
- oxygen-independent pathways - enzymes
What is the antimicrobial action of C3a and C5a complement serum proteins?
Recruitment of phagocytes
What is the antimicrobial action of C3b-C4b complement serum proteins?
Opsonisation of pathogens
What is the antimicrobial action of C5- C9 complement serum proteins?
Killing of pathogens
Membrane attack complex
What are the 2 activating pathways of complement serum proteins?
- alternative pathway
* MBL pathway
What are clinical problems that arise if phagocytosis is reduced?
- decrease spleen function
- decrease neutrophil number
- decrease neutrophil function
What are the antimicrobial actions of macrophage-derived cytokines like TNFalpha/IL-6/IL-1
- systemic actions - liver (CRP and MBL - complement activation), bone marrow (neutrophil mobilisation), hypothalamus (increased temp)
- local inflammatory actions - blood vessels (vasodilation, vascular permeability, expression fo adhesion molecule to attract neutrophils)
What is the summary of the innate immune response?
- Innate barrier breached
- Complement, mast cells and macrophage activation
- Cytokine/chemokine production causes vascular changes and chemoattraction
- Hypothalamus and liver cause fever and acute phase response
- Redness, heat, swelling and pain due to local inflammation
