Lecture 1: Introduction to Module Flashcards
Who developed germ theory?
Robert Koch, Anton van Leeuwenhoek and Louis Pasteur.
What is germ theory?
The theory that disease is caused by pathogenic microorganisms. Replication is the direct cause of disease. As well as the fact that environmental/genetic factors can affect severity of it.
Germ theory also states that disease can be cured by targeting these microorganisms.
It evolved from Koch’s postulates.
Who developed terrain theory?
Claude Bernard, and later Antoine Bechamp.
What does terrain theory state?
That disease is a result of change to internal environment, and inability to maintain homeostasis.
Implies that general health protects against disease.
What functions does a functional immune system perform?
- Protection against pathogens
- Development of body tissues
- Repair and maintenance of tissues
- Removal of ‘worn out’ cells and debris
- Wound healing and subsequent tissue repair
- Maintenance of stem cell niches and pools
What can happen when the immune response is not balanced?
Overreaction can lead to severe consequences such as death and permanent damage such as rheumatoid arthritis.
Underreaction can lead to death by pathogens.
How does the level of protection of the immune system change over time?
Immune system is strong in post-nates, due to maternal antibodies. After dropping swiftly, the immune system will get stronger until it plateaus at around 20. At around 65 years old, immune system will drop drastically.
What sites of infection are there in the human body?
- Interstitial spaces, blood and lymph
- Epithelial surfaces
- Intracellular cytoplasmic
- intracellular vesicular
What are the 5 major groups of pathogens?
Viruses, bacteria, fungi, protozoa, and helminths.
What are the key aspects of the human immune system?
(4R)
- Recognition
- Reaction
- Regulation
- Remembering
Describe “Recognition” (4R)
Occurs through use of receptors.
Innate immune system uses germline encoded receptors to produce immediate or induced response against broad range of potential pathogens.
Adaptive immune system generates specific receptors on T/B cells to respond to repeat infections.
Describe “Reaction” (4R)
The response by the immune system.
This can include:
- Leukocytes and lymphocytes
- Antimicrobial agents (enzymes and peptides)
- Complement system components
- Antibodies (produced by B-cells)
- Cell signalling molecules - Cytokines, chemokines, interferons.
Describe “Regulation” (4R)
The regulation of the immune system to prevent autoimmune response, or insufficient response.
Regulatory cells (Regulatory T cells) and soluble components such as cytokines.
Describe “Remember” (4R)
The ability of the immune system to remember pathogenic antigens from previous infections.
Classical immunological memory is only generated by the adaptive immune system. Mostly consists of B and T cells.
What are the 2 “arms” of the immune system?
The innate immune system and the active immune system.
What 4 general stages are there in infection? And at what time do they roughly take place in an infection?
- Innate responses by non-specific and broadly specific factors. 0-4 hours
- Induced innate response and the activation of the immune response, recruitment of effector cells. 4-96 hours
- Adaptive response (recognition by naive B and T cells and clonal expansion/differentiation to effector cells). >96 hours.
- After infection, memory cells have been created from B and T cell activation, allow for faster and stronger immune response upon reintroduction of pathogen.
What is the first line of defence for the innate immune system?
Barriers, chemicals, and ‘normal’ microbiota.
These factors can prevent attachment of pathogens.
Normal microbiome can affect pathogenic colonisation.
How do epithelial cells and phagocytes respond to infection?
They can produce antimicrobial proteins (AMPs)
AMPs are secreted from cell or into phagosome.
Secreted in an inactivated state, activated by proteolytic cleavage, where pro-region is separated from the amphipathic domain.
Where are alpha and beta defensins produced?
Alpha defensins are produced by both neutrophils and epithelial cells.
Beta defensins are only produced by epithelial cells.
What is the mechanism of action of defensins?
The cationic properties of these molecules allow them to position themselves in the lipid bilayer, creating holes in cell membranes.
What can deregulation of antimicrobial peptides result in?
Chronic inflammatory syndromes such a psoriasis, among other tissue pathologies, beta-defensin gene copy number is increased.
What are interferons?
Interferons, or IFNs are signalling molecules that provide protection against virus and bacterial infections.
They are produced by infected cells.
What effect do interferons have on immune response?
- Prevent viral replication in infected cells
- Alerting ‘uninfected’ cells by cell to cell signalling.
- Enhances immune attack by enhanced action of NK cells, T cells, B cells
- Increased presentation of viral antigen.
- Stimulates interferon stimulated genes on the cells that they bind to, effects can be viral replication prevention, apoptosis, etc.
What are the types of IFNs?
Type 1 IFNs (20 subtypes)
- IFN alpha (13 subtypes - mainly secreted by leukocytes)
- IFN beta (1 subtype - secreted mainly by fibroblasts)
- 6 other subtypes with poorly defined roles
- All type 1 IFNs use IFNAR1 and IFNAR2 heterodimer receptors.
Type II IFNs (1 subtype)
- IFN gamma - secreted mainly by specialised immune cells: natural killer cells, NKT cells and specific T cell subclasses.
Type III IFNs (4 subtypes)
IFN lambda 1, IFN lambda 2, IFN lambda 3 (IL-29, IL-28A and IL-28B) and IFN lambda 4.
- Type II IFNs have similar functions to type 1 IFN family but leukocytes are largely unresponsive to them.
When are interferons released?
When a virus enters a cell and attempts to reproduce, it produces biological markers that can alert a cell. Once a cell is alerted, it will begin producing interferons.
