Immune Response to Infection (1) Flashcards
What routes to pathogens use to infect the body?
- External epithelia
- External surfaces
- Wounds and abrasions
- Insect bites
- Mucosal surfaces
- Airway
- GI tract
- Reproductive tract
What are the constitutive barriers to infection in the skin?
- 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 are the constitutive barriers to infection in the mucosal surfaces?
- Secreted mucous
- Physical barrier traps invading pathogens
- Secretory IgA (prevent entry/attachment into epithelia)
- Lysozyme and antimicrobial peptides directly kill invading pathogens
- Lactoferrin starves bacteria of iron
- Cilia – trap and remove pathogens, assisted by physical manoeuvres such as sneezing and coughing
What are the constitutive barriers to infection by commensal bacteria?
- 100tn bacteria
- Compete for resources (scarce) with pathogenic microorganisms
- Produce fatty acids & bactericidins to inhibit growth
Name the cells and soluble 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
What are the features of 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
What are the features of polymorphonuclear cells?
- Polymorphonuclear cells (neutrophils, eosinophils, basophils/mast cells)
- 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 monocytes and macrophages of these organs.
What are the features of the mononuclear cells?
- Mononuclear cells (monocytes, macrophages, lymphocytes) – monocytes produced in bone marrow and circulate in blood to migrate to tissues to differentiate into macrophages
- 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
Describe phagocyte recruitment.
- 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)
Describe the recognition of micro-organisms.
- Recognition of micro-organisms
- 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
Describe opsonisation and endocytosis.
- Opsonisation & endocytosis (phagolysosome = phagosome & lysosome fusion)
- Endocytosis is facilitated by opsonisation
- Opsonins act as a bridge between the pathogen. And the phagocyte receptors
- E.G. Antibodies –> Fc receptors; complement –> complement receptors; Acute Phase Proteins (i.e. CRP)
Describe the formation of phagolysosomes
- Phagosome and lysosome fuse to form phagolysosome
- Protected compartment in which killing of the organism occurs
What are the types of microbial killing?
- Oxidative
- Non-oxidative
Descrive oxidative killing.
Oxidative killing (HOCl acts as an oxidant and anti-microbial)
(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 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
What happens after a neutrophil has completeled phagocytosis?
- 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 –> pus formation
- Extensive pus formation causes abscess formation
What do macrophages do after phagocytosis?
Become antigen presenting cells and communicate with the adaptive immune response
Name features of natural killer cells.
- Present within blood and migrate to inflamed tissues (kills ‘altered self’ or virus-infected)
- Express inhibitory receptors for self-HLA molecules to prevent mal-activation by normal-self
- Express a range of activator receptors (i.e. natural cytotoxicity receptors to recognise heparan sulphate proteoglycans)
- Integrate signals from inhibitory and activator receptors
- Secrete cytokines to regulate inflammation (promote dendritic cell function)