Define infectivity
The ability of a microorganism to establish itself within the host
Define virulence
The capacity of microbes to cause damage to tissues
Define pathogenicity
A combination of infectivity (the ability of a microorganism to establish itself within a host) and virulence (the capacity of microbes to cause damage to tissues).
Define immune system
Cells and organs that contribute to immune defences against infections and non-infectious conditions (self v non-self)
Define infectious diseases
When the pathogen succeeds in evading and / or overwhelming the hosts immune defences.
What roles does the immune system have?
Pathogen recognition: Cell surface and soluble receptors
Containing / eliminating the infection: killing and clearance mechanisms
Regulating itself: Minimum damage to host (resolution)
Remembering pathogens: Preventing the disease from recurring.
What is innate immunity?
This is immediate protection.
- Fast (within seconds)
- Lack of specificity
- Lack of memory
- No change in intensity
What is adaptive immunity?
Long lasting protection:
- Slow (days)
- Specificity
- Immunological memory
- Changes in intensity
What are the first lines of defence in innate immunity?
- Physical barriers
- Physiological barriers
- Chemical barriers
- Biological barriers.
These are all factors that prevent entry and limit growth of pathogens.
What physical barriers are present in innate immunity?
- Skin
- Mucous membranes
- Mouth
- Respiratory tract
- GI tract
- Urinary tract
- Bronchial cilia
- Mouth
- Respiratory tract
- GI tract
- Urinary tract
What physiological barriers are present in innate immunity?
-
Diarrhoea: food poisoning
-
Vomiting: Food poisoning, Hepatitis, Meningitis
-
Coughing: Pnuemonia
-
Sneezing: Sinusitis
What chemical barriers are present in innate immunity?
Low pH
- Skin (5.5)
- Stomach (1-3)
- Vagina (4.4)
Antimicrobial molecules
- IgA (tears, saliva, mucous membrane)
- Lysozyme (sebum, perspiration, urine)
- Mucus (mucous membrane)
- Beta-defensins (epithelium)
- Gastric acid + pepsin
What biological barriers are present in innate immunity?
Normal flora
- Non pathogenic microbes
- Strategic locations
- Nasopharynx
- Mouth / Throat
- Skin
- GI tract
- Vagina (lactobacillus spp)
- Abscent in internal organs / tissues
Benefits
- Compete with pathogens for attachment sites and resources
- Produce antimicrobial chemicals
- Synthesize vitamins (K, B12, other B vitamins)
Give some examples of normal flora that inhabit the skin
Staphylococcus aureus
Staphylococcus epidermidis
Streptococcus pyrogenes
Candida albicans
Clostridium perfringens
BUT some can become pathogenic if they inhabit different areas of the body.
Give examples of normal flora that inhibit the nasopharynx
Streptococcus pneumoniae
Neisseria meningitidis
Haemophilus species
BUT some can become pathogenic if they inhabit different areas of the body.
How could normal flora be displaced from its normal location?
- Breaching the skin integrity:
- Skin loss
- Surgery
- IV drug users
- IV lines
- Fecal-oral route
- Foodborne Infection
- Faecal-perineal-urethral route
- UTI
- Poor dental hygiene / dental work (common cause of harmless bacteraemia -bacteria in the blood)
- Dental extraction
- Gingivitis
- Brushing / Flossing
- Skin loss
- Surgery
- IV drug users
- IV lines
- Foodborne Infection
- UTI
- Dental extraction
- Gingivitis
- Brushing / Flossing
What patients are classified as high risk of getting a serious infection?
- Asplenic (and hyposplenic) patients
- Patients with damaged or prosthetic valves
- Patients with previous infective endocarditis
In Europe, it is recommended that these patients are given antibiotic prophylaxis. However, in the UK, this is not the case.
Apart from being displaced, when else can flora cause clinical problems?
- When host is immunocompromised
- This causes flora to overgrow and become pathogenic.
- E.g. Diabetes, AIDS, Malignant disease, chemotherapy
- When normal flora is depleted by antibiotics
- e.g. In intestine with severe colitis (Clostridium difficile)
- Vagina in thrush (Candida albicans).
- This causes flora to overgrow and become pathogenic.
- E.g. Diabetes, AIDS, Malignant disease, chemotherapy
- e.g. In intestine with severe colitis (Clostridium difficile)
- Vagina in thrush (Candida albicans).
After innate barriers, what are the bodies second lines of defence?
Phagocytes and Chemicals.
These lead to inflammation.
These are factors that will contain and clear the infection.
What are the main types of phagocyte?
- Macrophages
- Monocytes
- Neutrophils (pus)
Other than phagocytosis cells, what other cells are involved in innate immunity?
- Basophils / Mast cells
- Eosinophils
- Natural Killer cells
- Dendritic cells
How do immune cells recognise pathogens?
-
Microbial structures: PAMPs (pattern associated molecular patterns): Carbohydrates, Lipids, Proteins, Nucleic acids
-
Phagocytes: PRRs (Pattern recognition receptors): Toll like receptors.
- Also receptors inside the cell to recognise the viruses
-
Opsonisation of microbes: coating porteins called opsonins that bind to the microbial surfaces leading to enhanced attatchment of phagocytes and clearance of microbes.
PAMPs and PRR binding, it causes phagocytes to release cytokines and generates a local inflammatory response. Whereas, when opsonins bind to an opsonin receptor it activates killing mechanism.
What are some examples of opsonins?
Complement proteins: C3b, C4b
Antibodies: IgG, IgM
Acute phase proteins: CRP, MBL (mannose-binding lectin)
How do phagocytes work?
- They recognise the pathogen (PAMPs / Opsonins)
- Englufment
- Degredation of infections microbes
What are the two intracellular phagocytotic killing mechanisms?
Oxygen dependant pathway (respiratory burst)
Oxygen independent pathwa
What are the complement pathways?
20 serum proteins.
Most important C1-9 2
There are 3 complement pathways: The alternative pathway, the classical pathways and the MBL pathway (homologous to classical pathway).
What is the role C3a and C5a?
Recruitment of phagocytes
What are the roles of C3b - C4b?
Opsonisation of pathogens
What are the roles of C5-C9?
- Killing of pathogens
- Membrane attack complex
What are the anti-microbial actions of macrophage devied TNFa/IL-1/IL-6?
Liver (opsonins): CRP, MBL (complement activation)
Bone marrow: neutrophil mobilisation
Inflammatory actions: vasodilation, Vascular permiability, Adhesion molecules (attraction of neutrophils)
Hypothalamus: Increased body temperature
What causes reduced phagocytosis?
Decreased spleen function
- Asplenic patient
- Hyposplenic patients
Decrease neutrophil number
- Cancer chemocherapy
- Certain drugs
- Leukaemia and lymphoma
Decrease neutrophil function
Chronic granulomatous disease (no respiratory burst)
Chediak-Higashi syndrome (no phagolysosomes formation)