Innate Immunity

Question 1

What are barriers?

Answer 1

The first line of defence

Can be physical, chemical, physiological, or probiotic

Question 2

What are examples of physical barriers?

Answer 2

Epithelial surfaces

Skin and mucous membranes (mouth, eyes, respiratory tract, GI tract, UT, Vagina)

Question 3

What are examples of low chemical barriers?

Answer 3

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

Question 4

What are examples of physiological barriers?

Answer 4

Diarrhoea, vomiting, coughing, and sneezing

Question 5

What are examples of probiotic barriers?

Answer 5

• Competition for nutrients
• Blocking adhesion sites
• Immune stimulation
• Direct anatgonism

Question 6

What are examples of barriers in the oral cavity?

Answer 6

• 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

Question 7

How does the apical junctional complex work as a pathogenic barrier?

Answer 7

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

Question 8

Bacterial toxins can disrupt the protective adhesion complexes, attacking the epithelial barrier. What is one such bacteria that produces these toxins?

Answer 8

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

Question 9

What are the different cells that act as components of innate rersponses (first responders)?

Answer 9

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

Question 10

What are the down sides of using APCs and phagocytci cells when fighting infection?

Answer 10

• 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

Question 11

What do toll-like receptors (TLRs) do, in brief?

Answer 11

Recognise and bind to PAMPs (pathogen associated molecular pattern)

Recognise things that aren’t common to our microbiome

Question 12

What are the effcts of TLRs?

Answer 12

Cytokine production = fever, inflammation
Chemokine production = cell recruitment
Activation of bacterial killing mechanisms
Activation of dendritic cells

Question 13

What are the key reactions creating an acute inflammation?

Answer 13

1. Stasis = slowing of blood via vasodilation and fluid exudation to allow chemical mediators and inflammatory cells to colelct and respone to stimulus
2. Increased vascular permeability allowing plasma to flow out of the blood vessel
3. Leukocytes attach to endothelium and migrate to site of injury

Question 14

What are the 6 elements required to produce an inflammatory reaction?

Answer 14

1. Actual inflammatory response (stimulus)
2. Inflammatory mediators (mast cells)
3. Vascular permeability and dilaton
4. Chemotaxis (neutrophils and macrophages)
5. Phagocytosis (the point at which the antigen is removed)
6. Proinflammatory cytokine release

Question 15

What are the 4 types of polymorphonuclear (PMN) cells and their purpose?

Answer 15

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

Question 16

What are the different types of lymphocytes and their uses?

Answer 16

T cells, B cells, and NK cells
Specific immunity, viral immunity, and tumout protection
Sceond most prevalent leukocyte

Question 17

What are the key features of neutrophils?

Answer 17

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

Question 18

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?

Answer 18

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

Question 19

What is opsonisation?

Answer 19

The use of opsonins in an immune process to tage foreign pathogens for elimination by phagocytes

Question 20

How does opsonisation work?

Answer 20

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

Question 21

What is phagocytosis and how is this process helped along?

Answer 21

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

Question 22

How does phagocytosis occur in oxygen indepenent pathways?

Answer 22

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)