Host Defence Mechanisms Flashcards
Describe the skin as a part of innate defence.
Skin is composed of epidermis (keratin), which is virtually impregnable.
Infections may result when there are breaks in the epidermis, e.g., abrasions, puncture wounds and insect bites.
The skin lacks moisture and has a high salt concentration.
Sebaceous glands secrete fatty acids and lactic acids, which decrease the pH of the skin and inhibit the growth of microorganisms.
Furthermore, genes encoding antimicrobial peptides (e.g., Dermcidin) are expressed in sweat glands, and the antimicrobial peptides are secreted into sweat and transported to the epidermal surface.
Describe the upper respiratory tract as part of innate defence.
The URT (which includes the nose, throat and ears) is exposed to >104 bacteria/day; that is, approximately 7 bacteria/minute!
The major barriers to microbial infection in the URT include the mucous membranes that contain mucoussecreting cells and ciliated cells, i.e., the mucociliary system.
The mucous traps the bacteria and the cilia beating sweeps them up and out of the URT.
Furthermore, this area is heavily colonized with microbiota.
This may include opportunistic pathogens e.g., Neisseria meningitidis.
This area is partly protected by antimicrobial peptides in body secretions (tongue, throat).
Describe the lower respiratory tract as part of innate defence.
The LRT includes the trachea, bronchial tubes and alveoli in the lungs.
This area of the body is normally sterile, i.e., it does not contain bacterial as a microbiota.
The host defence mechanisms here are very effective and include:
- the mucociliary system which moves particles up toward throat where they are swallowed (or coughing expels them). Smoking, alcohol consumption and old age affect the functioning of the ciliated epithelium and may increase susceptibility to infections.
- the lungs, i.e., the alveoli lack a ciliated membrane and are protected by alveolar macrophages and antibodies
- antimicrobial proteins (lactoferrin, lysozyme) and peptides (defensins, LL-37) are evident.
Discuss the gastrointestinal tract as part of innate defence.
The GI tract contains the majority of the microbiota.
Nevertheless, the physical and chemical barriers of the GI tract are a deterrent to infectious organisms.
These include stomach acidity, the peristaltic movements of the intestinal contents (which tends to expel potential pathogens before they can colonize), and microbial antagonism from the microbiota.
What does host immune defence include?
non-specific innate immune defence mechanisms
specific adaptive immune response
What are key features of the non-specific host defence?
- effective against a variety of potential pathogens by recognizing general features shared by all bacteria (such as peptidoglycan of the bacterial cell wall)
- innate – not dependent on prior exposure to a pathogen but can be up-regulated upon pathogen exposure
- effective immediately or rapidly (0–4 hours, this is in contrast to the specific immune response which takes days to be elicited).
What antimicrobial substances are found in tears, saliva, mucus, blood and lymph?
- an anti-microbial enzyme called lysozyme
- iron-binding proteins such as lactoferrin
- enzymes such as lactoperoxidase that generate singlet oxygen to kill bacteria
- antimicrobial peptides (ß-defensins, LL-37)
What do blood and lymph contain that tears and saliva do not?
Blood and lymph contain phagocytic cells (neutrophils, monocytes) that can move into the tissues to phagocytose infecting bacteria.
Many organs also contain resident phagocytes, in the form of macrophages, e.g., the lung contains alveolar macrophages.
What is the major antimicrobial component of the body fluids?
complement
Complement proteins constitute 10% of the total protein content of the serum (and are also present in tissues).
What do they do when activated?
- Attract phagocytic cells to the infection site
- Stimulate the release of histamine during inflammation
- Promote the binding of bacteria to phagocytes by a process known as opsonisation
- Can cause cell lysis of certain bacteria
What is inflammation and how is it recognized?
Inflammation is the coming together of the innate immune host defences as the body’s response to infection and injury.
Inflammation is recognised by 4 classic signs; redness, swelling, heat and pain.
With regard to bacterial infections, what purpose does inflammation serve?
Inflammation serves to limit the spread of bacteria, recruit phagocytes, enhance phagocyte effectiveness, and repair tissue damage
Describe acute inflammation.
- Bacteria invade and cause cell damage, resulting in the activation of complement and recruitment of the tissue macrophages.
- Components from the complement pathway, which act as anaphylatoxins, bind to basophils (in the blood) and mast cells (in the tissue) resulting in histamine release.
- The release of histamine leads to an increase in the diameter of the blood vessels locally. This is termed vasodilation.
- The increased diameter of the blood vessels results in an increased blood flow locally, bringing more fluid, phagocytes and proteins (e.g., antibodies) into the infected tissues. This fluid, which results in local swelling, is termed pus.
- Among the proteins that enter into the tissues is fibrinogen. Through a pathway, analogous to the complement pathway, this results in the formation of a fibrin clot. The fibrin clot forms a ‘wall’ around the damaged host cell, thus localizing the infection.
When does chronic inflammation ensue?
If the infection and accompanying inflammatory response are not resolved
Describe chronic inflammation.
- Chemotaxins produced by lymphocytes result in an influx of monocytes into the infected tissue where they differentiate into macrophages. The macrophages are responsible for the degradation of tissue/cellular debris as well as microbial debris.
- In an extreme case of chronic inflammation, the macrophages are activated by cytokines giving rise to activated/inflammatory macrophages. Activated macrophages secrete toxic oxygen intermediates, and tissue-damaging enzymes, which results in damage to the surrounding tissues.
- Cytokines produced during chronic inflammation can result in fever.
- Chronic inflammation that becomes prolonged can lead to extensive tissue damage.
