Flashcards in Bacterial Infections in Immunodeficiency Deck (19):
We are constantly exposed to micro-organisms, yet disease due to micro-organisms (infection) is rare. Why?
We have evolved alongside many micro-organisms and for most bugs, the aim is to replicate, not to kill us! This has led to co-evolution of host immune system (recognition and response or tolerance) and organisms (immune evasion, virulence factors etc.).
When the balance between host immune system and micro-organisms is skewed, disease occurs. Give examples of how the balance can be skewed.
Reduced host immune system/immunocompromise
Increased organism virulence e.g. new strain
Why does a defect in one aspect of the immune system affect susceptibility to some, but not all micro-organisms?
Different aspects of the immune system act against different types of pathogen.
Give examples of physical barriers.
Skin, gut mucosa, respiratory tract, urinary tract, vagina
What cells and processes are involved in the innate immune system?
Phagocytes (neutrophils, macrophages, eosinophils etc)
What cells are involved in humoral immunity?
What cells are involved in cell-mediated immunity?
Uses innate immune cells for effector function
How does the skin act as a physical barrier? (5)
Low pH, low free water, antimicrobial peptides, cell sloughing, resident commensals
How does the respiratory tract act as a physical barrier? (4)
Ciliated epithelium, antimicrobial peptides, cell sloughing, resident commensals
How does the gut mucosa as a physical barrier? (5)
Low pH, antimicrobial peptides, cell sloughing, commensal flora, tight junctions
How does the urinary tract as a physical barrier? (4)
Urethral sphincter, one way flow, antimicrobial peptides, cell sloughing
How does the vagina as a physical barrier? (2)
Commensal flora, pH
What is the main function of physical barriers?
Prevent invasion of micro-organisms – those that live in the environment and those that live in/on us. This includes bacteria, fungi, viruses and parasites.
How do phagocytes (innate immune system) recognise and respond to pathogens?
Phagocytes express pathogen recognition receptors (PRRs) e.g. TLRs, C-type lectins, dectin, and so recognise pathogen-associated molecular patterns (PAMPs) such as lipopolysachharide, peptidoglycan, beta-glucan. They also express receptors for complement & antibodies.
They respond with phagocytosis & intra-cellular killing, using Phago-lysosome fusion, ROS, bleach etc. They also release extracellular substances e.g. antimicrobial peptides, NETs etc.
In other words:
- Chemotaxis of phagocyte to microbes
- Ingestion of microbes by phagocytes
- Killing of microbes by enzymes and other chemicals, elimination
What type of organism(s) do phagocytes defend against?
Extracellular pathogens - bacteria, fungi, parasites
How does complement cascade (innate immune system) recognise and respond to pathogens?
Complement = series of plasma proteins
3 different recognition pathways:
- Classical pathway: C1q binds to antibody-antigen complex
- Mannose binding lectin pathway: binds to repeating sugars
- Alternative pathway: failure to inactivate intrinsic activation
- Opsonisation: phagocyte complement receptors (C3b)
- Chemotaxis: phagocyte complement receptors (C3a)
- Direct killing: C5-9 membrane attack complex
What type of organism(s) does complement system defend against?
Adjunct in the defence against extracellular pathogens - mainly bacteria.
NB – membrane attack complex (C5-9) is an essential component in the response to Neisseria species e.g. Neisseria meningitidis.
How does humoral immunity recognise and respond to pathogens?
Recognition is via B-cell receptors (antibody on surface of B-cell) – they recognise extracellular antigens (in the ‘humors’). This usually requires T-cell help, except polysaccharide antigens (marginal zone B-cells).
They respond by increasing production of antibodies (IgM, IgG, IgA, IgE). Then, neutralisation (bound Abs block binding of pathogens/toxins to cells), complement activation (C1q binds to Ag-Ab complexes), and antibody-dependent cytotoxicity (receptors on phagocytes for Fc portion of antibody).