1. Host Defences Flashcards
What is a disease?
The result of a host interaction with a pathogen
Is disease a rare or common outcome of host-pathogen interaction?
Very rare
What 3 factors are taken into account for disease?
Host (human), pathogen (bacterium), environment/circumstances
Examples of ways the host can interact with the pathogen
Vectors (insects), food, sexually transmitted
If a pathogen affects a host, it is more virulent if…
it is transmitted to the host directly
What is responsible for 70-80% of infections?
Zoonosis
What must be overcome in order for disease to occur?
Host defences
What part of the immune system is responsible for non-specific defence mechanisms?
Innate
What part of the immune system is responsible for specific defence mechanisms?
Adaptive
What is the first line of the defence (innate)?
Constitutive - skin, mucous membrane, secretions of skin & mucous membrane
What is the second line of defence (innate)?
Inducible - phagocytosis, antimicrobial proteins, inflammatory response
What is the third line of defence (adaptive)?
Lymphocytes, antibodies
The innate immune system deals with __ infections.
Acute
The adaptive immune system deals with…
Reinfection
What are constitutive defences?
- Provide general protection against invasion by normal flora, or colonisation/infection/infectious disease caused by pathogens
- “Natural Resistance”
- Always on
- Skin, mucosal surfaces, tears, saliva, sweat, urine, stomach acid etc.
- Non - specific
What are inducible defences?
- Must be induced by host exposure to a pathogen
- Only triggered after host is appropriately exposed to pathogen
- Immune responses
- Usually specifically directed against an invading pathogen
- Can be part of innate or acquired immune system e.g. cytokines, antibodies
What are the 4 components of the constitutive defences?
- Anatomical defences
- Microbial antagonism
- Phagocytosis
- Tissue bactericides (incl. complement)
What are the conditions of the skin that bacteria do not like?
- Dry
- Acidic (pH 5.0)
- Low temperature
Are resident microflora in the skin mainly Gram positive or negative?
Positive
What connects the skin to the immune system of the host?
SALT = skin associated lymphoid tissue
Where in the body would you find mucous membranes?
GIT, respiratory tract, urogenital tract
What is the main function of epithelial cells?
Absorption of nutrients
What are ‘M’ cells?
Naturally phagocytic specialised epithelial cells that are continuously sampling the bacterial population in gut & transferring that info to immune cells
Why do many pathogens target M cells?
Because they know they will get across the gut barrier naturally
Why do many pathogens target M cells?
Because they know they will get across the gut barrier naturally
What epithelia is found mainly in the lungs & GIT?
Simple columnar epithelial
What facilitates the joining together of epithelial cells to form a barrier?
Tight junctions
What happens when pathogens target tight junctions?
Pathogen destabilises the tight junctions, you then get water & sometimes blood in the inside moving between the cells and into the gut lumen. This causes bloody diarrhoea e.g. Clostridium perfringens
Where are M cells located?
In follicle associated epithelium, that covers Peyer’s patches
M cells stimulate the production of which antibody?
sIgA
What do Goblet cells secrete?
Mucus
What do entero-endocrine cells secrete?
Sodium and other gut-localised hormones
What do Paneth cells secrete, and where do they stay localised?
Secrete antimicrobial peptides (defensins)
Paneth cells stay localised in the crypt at the base of the villus
What are defensins?
Antimicrobial peptides that form pores in bacterial membranes
What is another term for microbial antagonism?
Colonisation resistance
What is microbial antagonism?
Protection of the surfaces afforded by an intact normal flora (commensal flora) in a healthy host
Name 3 ways that the normal flora can protect mucosal surfaces
- Competition for binding (colonisation) sites
- Antagonism against non-indigenous species - highly specific proteins called bacteriocins produced by normal flora to kill/inhibit other species
- Immunomodulation - normal flora interact with immune system to stop pathogen growth/survival
What are the first to arrive at a site of infection in response to chemokine signals produced in that locality?
Neutrophils, followed by monocytes which will develop into macrophages in tissue
What is neutropenia and what are sufferers very prone to?
Neutropenia is depressed polymorphonuclear leukocyte levels (low neutrophil levels) - sufferers very prone to infection
What is an example of a bacterium that lives in macrophages and hijacks the normal macrophage function?
Salmonella - uses macrophages as a privileged niche for its replication because they are a great source of nutrients
What are examples of tissue bactericides?
Transferrin
Interferon
Lysozyme antimicrobial molecule
Complement
What is the Red Queen Hypothesis?
Bacteria produce their own iron-binding molecules, called siderophores, that compete with the body for iron.
What does Interferon do?
Anitviral molecule
It inhibits viral replication and activates other cells which kill pathogens
Where would you find lysozyme and what does it do?
Lysozyme is an antimicrobial molecule that is found in serum and tears. It breaks down the bacterial cell wall (peptidoglycan).
What is complement?
A set of serum (blood) proteins (C1-C9) which provide a form of constitutive defence
Where would you find complement, and what does it do?
Serum proteins which cause destruction of microorganisms directly or with the help of phagocytic cells. Complement opsonises microorganisms, which makes them more susceptible to phagocytosis.
Where would you find complement, and what does it do?
Serum proteins which cause destruction of microorganisms directly or with the help of phagocytic cells.
Complement opsonises microorganisms, which makes them more susceptible to phagocytosis.
Briefly describe the complement cascade, that eventually leads to phagocytosis
- Antibody binds bacteria in blood → activation of C1/2/3 complex → creates an active enzyme (C3 convertase) → cascade
- C3 convertase cleaves C3 into 2 active subunits (C3a & C3b)
- C3b binds bacterial cell wall → opsonisation
- C3b also cleaves C5 into 2 subunits (C5a & C5b)
- C5a attaches to macrophages & increases their activation
- C3a & C5a attract & activate macrophages → engulf & destroy opsonised bacteria
What is the Classical Pathway?
When the complement cascade is triggered by an antibody
What is the Alternative Pathway?
When the complement cascade is not not triggered by the presence of an antibody i.e the body has never seen the bacteria before.
What makes up the membrane attack complex (MAC), and what does it do?
MAC = C5b, 6, 7, 8, 9
Forms pores in Gram negative cells
What immune functions does complement trigger?
- Phagocytosis
- Inflammation
- Membrane attack
Which complement protein has the most important opsonising activity?
C3b
What is the main aim of complement?
To keep the blood sterile and free of microorganisms
