Innate Immunity Flashcards
What are barriers?
The first line of defence
Can be physical, chemical, physiological, or probiotic
What are examples of physical barriers?
Epithelial surfaces
Skin and mucous membranes (mouth, eyes, respiratory tract, GI tract, UT, Vagina)
What are examples of low chemical barriers?
Low pH = skinn (5.5), gastric acid (1-3), vagina (4.4)
Antimicrobial molecules eg mucosal immunoglobulins, lysozyme (sebum, perspiration, urine), mucus, beta-defensins (epithelia), and pepsin
What are examples of physiological barriers?
Diarrhoea, vomiting, coughing, and sneezing
What are examples of probiotic barriers?
- Competition for nutrients
- Blocking adhesion sites
- Immune stimulation
- Direct anatgonism
What are examples of barriers in the oral cavity?
- Saliva washes the mucosal surfaces
- Lining epithelia have junctional complexes and express toll-like receptors which detect microorganisms and release mediators of inflammation
- Epithelial cells release antimicrobial peptides
- Local blood vessels respond to alarm signals by releasing migrating phagocytic white blood cells
- These move in a directional manner towards the microbial threat and attempt to engulf and destroy microbes
How does the apical junctional complex work as a pathogenic barrier?
Apical junctional complex is made up of tight junctions followed by adherens junctions
Tight junctions make it difficult for pathogenic bacteria and viruses in lumen to enter due to proximity
Adherens junctions are made up of E-cadherin intracellular and extracellular domains which form protective adhesion complexes
Bacterial toxins can disrupt the protective adhesion complexes, attacking the epithelial barrier. What is one such bacteria that produces these toxins?
Poryphromonas gingivalis (p. gingivalis) produces a toxin with structural similarity to intercellular adhesion molecules
Toxin corrups adhesion complexes allowing access of microbial products to the underlying tissue, there the toxin increases permeability
What are the different cells that act as components of innate rersponses (first responders)?
Antigen presenting cells (APCs) such as dendritic cells, macrophages, and B cells. These live realtively longer than granulocytes.
Phagocytic cells which are subdivided between oxygen independent pathways (lyosomal enzymes) and oxygen dependent pathways (oxidative bursts)
Oxygen independent = various enzymes important for presenting antigens (APCs)
Oxygen dependent = reaxtice oxygen and nitrogen species (RONs) such as neutrophils and macrophages
What are the down sides of using APCs and phagocytci cells when fighting infection?
- APCs can’t present antigens to many cells due to short life span
- Oxygen independent phagocytic cells are ONLY antigen presenting, they cnanot KILL bacteria; however, they can dismantle and present them elsewhere
- Oxygen dependent phagocytic cels CAN kill bacteria
What do toll-like receptors (TLRs) do, in brief?
Recognise and bind to PAMPs (pathogen associated molecular pattern)
Recognise things that aren’t common to our microbiome
What are the effcts of TLRs?
Cytokine production = fever, inflammation
Chemokine production = cell recruitment
Activation of bacterial killing mechanisms
Activation of dendritic cells
What are the key reactions creating an acute inflammation?
- Stasis = slowing of blood via vasodilation and fluid exudation to allow chemical mediators and inflammatory cells to colelct and respone to stimulus
- Increased vascular permeability allowing plasma to flow out of the blood vessel
- Leukocytes attach to endothelium and migrate to site of injury
What are the 6 elements required to produce an inflammatory reaction?
- Actual inflammatory response (stimulus)
- Inflammatory mediators (mast cells)
- Vascular permeability and dilaton
- Chemotaxis (neutrophils and macrophages)
- Phagocytosis (the point at which the antigen is removed)
- Proinflammatory cytokine release
What are the 4 types of polymorphonuclear (PMN) cells and their purpose?
Neutrophilic PMNs = kills bacteria, pus formation, most prevalent leukocytes
Basophilic PMNs = becomes mast cells, early response to injury, contributes to allergy
Eosinophilic PMNs - parasitic infections
Monocytes OMN = kills bacteria and eats debris, intracellular pathogens, wide role in controlling immunity and inflamamtion, becomes macrophages
What are the different types of lymphocytes and their uses?
T cells, B cells, and NK cells
Specific immunity, viral immunity, and tumout protection
Sceond most prevalent leukocyte
What are the key features of neutrophils?
Most numerous WBC and increase in numbers in acute inflammation
Short lifespan once activated in tissues
Ameboid (able to move from vessels to tissues)
Movement can be directional due to chemotaxin attraction
Actively phagocytic
Generated free radicals kill phagocytised bacteria
Increased produciton in bone marrow caused by cytokines generated in the inflammatory response
During growth and metabolism, bacteria release distinctive low molecular weight products such as a small peptide called fmlp and a core unit of peptidoglycan unique to the bacterial cell wall. How is this related to chemotaxis?
Neutrophils have surface receptors that detect certain products and enable the cell to move towards the source
This directional movement in response to the concentration gradients of extracellular signals is called chemotaxis
Products of inflammation assist in the directional locomation, or chemotaxis, of neutrophils
What is opsonisation?
The use of opsonins in an immune process to tage foreign pathogens for elimination by phagocytes
How does opsonisation work?
Microorganisms must normally be coated before being bound and engulfed by phagocytic cells
Common bacterial products such as cell wall peptidoglycan and surface lipoplysaccharide of -ve bacteria can activate the complement system.
(These are the same common determinants that are recognised by toll-like receptors)
Complement system coats the microrganism and the coating material is recognised by special receptors on the phagocytic cells
What is phagocytosis and how is this process helped along?
Phagocytosis is the capture and digestion of foreign particles
Chemokines are cytokines that attract macrophages and neutrophils to infected tissues
Opsonins attach to microbes to increase the ability of phagocytes to adhere (opsonisation)
Once phagocytosis is complete, neutrophils can kill the phagocytised bacteria
How does phagocytosis occur in oxygen indepenent pathways?
A bacterium engulfed by a macrophage is encased in a vacuole
Lyosomes fuse with the vacuole and digest the bacterium
Antigens from the digested bacterium are presented with MHC II on the cell surface (attracts neutrophils to finish the job)