Immuno 1S: Immune Response to Infection / Primary Immune deficiencies Flashcards
What are the constitutive barriers to infection?
- skin barrier
- Mucosal Surface Barrier
- Commensal Bacteria Barrier
What defence mechanisms does the skin barrier have?
- Tightly packed keratinised cells
-
Physiological factors
- Low pH
- Low O2 tension
-
Sebaceous glands
- Hydrophobic oils repel water/microorganisms
- Lysozyme destroys cell walls
- Ammonia/defensins have anti-bacterial properties
What defence mechanisms does the mucosal surface barrier have?
-
Secreted mucous
- Physical barrier
- Secretory IgA (prevent entry/attachment into epithelia)
- Lysozyme
- Lactoferrin starves bacteria of iron
- Cilia – trap and remove pathogens
What are the components of the innate immune system?
-
Cells
- Polymorphonuclear cells (neutrophils, eosinophils, basophils)
- Monocytes and macrophages
- Natural killer cells
- Dendritic cells
-
Soluble components
- Complement
- Acute phase proteins
- Cytokines and chemokines
Features of the cells of the innate immune system?
- Identical in all individuals
- Cells express receptors that allow them to detect and home to sites of infection
- Cells express genetically encoded receptors (pattern recognition receptors) that allow them to detect pathogens at site of infection
- Cells have phagocytic capacity that allows them to engulf the pathogens
- Cells secrete cytokines and chemokines to regulate immune response
Name the Polymorphonuclear cells
neutrophils, eosinophils, basophils/mast cells
How do Polymorphonuclear cells carry out their function?
- Produced in bone marrow
- Migrate rapidly to site of injury
- Express receptors for cytokines/chemokines (to detect inflammation)
- Express pattern recognition receptors – to detect pathogens
- Express Fc receptors for Ig (to detect immune complexes)
- Capable of phagocytosis / oxidative & non-oxidative killing – particularly neutrophils
- Release enzymes, histamine, lipid mediators of inflammation from granules
- Secrete cytokines and chemokines to regulate inflammation
Name the Mononuclear cells
monocytes, macrophages, lymphocytes
Where are the Mononuclear cells produced and where do they differentiate?
- monocytes produced in bone marrow and circulate in blood to migrate to tissues to differentiate into macrophages
How do mononuclear cells carry out their function?
- Present within tissue
- Express receptors for cytokines and chemokines (to detect inflammation)
- Express pattern recognition receptors –to detect pathogens
- Express Fc receptors for Ig (to detect immune complexes)
- Capable of phagocytosis / oxidative and non-oxidative killing
- Secrete cytokines and chemokines to regulate inflammation
- Capable of presenting processed antigen to T cells
How do macrophages differ from neutrophils in terms of their capabilities?
Capable of presenting processed antigen to T cells
What are macrophages called in each of these organs?
Liver
Kidney
Bone
Spleen
Lung
Neural tissue
Connective tissue
Skin
Joints
Organ
Name for macrophage cells
Liver = Kupffer cell
Kidney = Mesangial cell
Bone = Osteoclast
Spleen = Sinusoidal lining cell
Lung = Alveolar macrophage
Neural tissue = Microglia
Connective tissue = Histiocyte
Skin = Langerhans cell
Joints = Macrophage-like Synoviocytes
Describe the process of phagocyte recruitment carried out by macrophages
- Cellular damage and bacterial products -> local production of cytokines and chemokines
- Cytokines -> activate vascular endothelium -> enhanced vascular permeability
- Chemokines attract phagocytes (not macrophages as they are already present, mainly neutrophils)
Describe the process of microorganism recognition by macrophages and neutrophils
- Pattern-recognition receptors (PRR) – e.g. Toll-like Receptors (TLRs), Mannose Receptors
- Recognise generic motifs (Pathogen-Associated Molecular Patterns – PAMPs)
- PAMPs = bacterial sugars, DNA, RNA
- Fc receptors bind to the Fc portion of Ig to allow for recognition
Which process facilitates macrophages in phagocytosis?
Opsonisation
What do opsonins do?
- Opsonins act as a bridge between the pathogen and the phagocyte receptors
Give 2 examples of opsonins
- Antibodies -> Fc receptors;
- complement -> complement receptors;
- Acute Phase Proteins (APP) i.e. CRP
What is the name of the structure within the macrophage into which the pathogen is taken up into?
Phagosome
What happens once the pathogen is taken up into the macrophages’ and neutrophils’ phagosomes?
Phagosome fuses with lysosome –> phagolysosome
Where in the macrophage and neutrophil does killing of the pathogen occur?
phagolysosome
What are the 2 types of killing mechanisms (of pathogens) in a macrophage and neutrophil?
Oxidative killing
Non-Oxidative killing
What is oxidative killing?
HOCl acts as an oxidant and anti-microbial
Describe the process of oxidative killing
- (1) NADPH oxidase converts O2 –> O·
- (2) Superoxide dismutase converts O· –> H2O2
- (3) Myeloperoxidase converts H2O2 (+ Cl-) –> hydrochlorus acid (HOCl)
- Requires H2O2 and chlorine
Describe the process of non-oxidative killing
- Release of lysozyme and lactoferrin into phagolysosome
- Enzymes present in distinct specific granules which can provide coverage against many bacteria and fungi
How is pus formed in a site of infection?
- The phagocytosis depletes neutrophil’s glycogen reserves and is followed by neutrophil death
- As the cell dies, residual enzymes release and liquify local tissues
- Accumulation of dead/dying neutrophils in tissues à pus formation
- Extensive pus formation causes abscess formation
Summarise the process of killing pathogens in tissue
- Expression of endothelial activation markers
- mobilisation of phagocytes and (granulocyte) precursors from bone marrow or within tissues i.e. neutrophils
- increased neutrophil adhesion and migration into tissues
- phagocytosis of pathogens by macrophages and neutrophils
- oxidative and non-oxidative killing by macrophages and neutrophils
- macrophages then communicate with T cells & neutrophils die (forming pus)
What is the main difference between macrophages/neutrophils and NK cells
Natural killer (NK) cells recognize infected or defective cells in context of MHC class. Thus, NK cells engage with the autologous cells, and will not engage with the cells of a different organism (microbial pathogens or parasites). NK cells are not phagocytic cells; they kill target cells by secreting biologically active compounds (such as granzymes) or inducing a cell suicide by apoptosis.
Macrophages are phagocytic cells, that remove dead cells and cell debris; they may also attack microbial cells, if these cells carry molecules that macrophages can recognize, or if the cells are opsonized by antibodies or complement.
Neutrophils are phagocytic cells that are primarily involved in combating bacterial or yeast infections. They are very sensitive to certain bacterial compounds (such as formylated peptides) and can also recognize opsonized cells.