infection - innate immune system Flashcards
what are the factors determining the outcome of the host-pathogen relationship?
infectivity (pathogen)
virulence (mech of infection)
patient (host immune response)
what is the immune system?
cells & organs that contribute to immune defences against infectious & non-infectious conditions (self VS non-self)
what are infectious diseases?
when the pathogen succeeds in evading and or overwhelming the host’s immune defences
what are the roles of the immune system?
- pathogen recognition - cell surface & soluble receptors
- containing / eliminating the infection - killing & clearance mechanism
- regulating itself - minimum damage to host (resolution)
- remembering pathogens - preventing the disease from recurring
what are the features of innate immunity? (1st line)
immediate protection:
fast (within seconds)
lack of specificity / memory
no change in intensity
what are the features of adaptive immunity?
long lasting protection: slow (days) specific - gram neg or positive immunologic memory - circulating memory B cells / T changes in intensity
what are the first lines of defence in immune response?
factors that prevent ENTRY and limit GROWTH of pathogens:
physical, physiological, chemical & biological barriers
what are the physical barriers?
skin
mucous membranes (mouth, resp tract, GI tract, urinary)
bronchial cilia
what are physiological barriers?
D&V
coughing & sneezing
what are chemical barriers?
low pH (skin, stomach, vagina) antimicrobial molecules: IgA (tears & saliva) lysozymes (urine) mucus (mucous membranes) gastric acid
what are biological barriers?
normal flora: non pathogenic microbes
strategic location (nasopharynx, mouth, throat, skin, vagina)
absent in internal organs
compete with pathogens for attachment sites & resources
produce antimicrobial chemicals
synthesise vitamins (K, B12, thiamine)
what are examples of normal flora on skin?
staph aureus staph epidermis strep pyogenes candida albicans clostridium perfringens
what are examples of normal flora on nasopharynx?
PIM - ALL encapsulated
strep Pneumoniae
haemophilus Influenza
neisseria Meningitidis
what are examples of when normal flora is displaced from normal to sterile location and causes problems?
- breaching skin integrity: skin loss, surgery, injection drug users, IV lines
- faecal-oral route
- faecal-perineal-urethral route (UTI women)
- poor dental hygiene (dental extraction, brushing/flossing, gingivitis)
- high-risk patients: asplenic / hyposplenic, damaged / prosthetic valves, previous endocarditis
examples of when normal flora overgrows and becomes pathogenic when host becomes IMMUNO-COMPROMISED?
diabetes
aids
malignant diseases
chemotherapy
example of when normal flora is depleted by antibiotics?
- intestine - severe colitis (C. diff)
2. vagina - thrush (candida albicans normally suppressed by lactobacilli)
what are second line defence of innate immunity?
factors that will CONTAIN & CLEAR the infection:
phagocytosis, chemicals, inflammation
what are the main phagocytes & their functions?
- macrophages: all organs, phagocytosis, present microbial antigens to T cells, produce cytokines / chemokines
- monocytes: in blood, go to site of infection - differentiate to macrophage
- neutrophils (pus): in blood, increased in infection, recruited by chemokines to site of infection, ingest pyogenic bacteria (staph a & strep pyogenes)
what are other key cells of innate immunity?
mast cells/basophils: allergy, early inflammatory response
eosinophils: multi-cellular parasites (worms)
NK cells: kill ALL abnormal HOST cells (viral infected/malignant)
dendritic cells: present antigens to T cells
how does pathogen recognition occur?
- microbial structures: PAMPs (carbohydrates, lipids, proteins, nucleic acids)
- phagocytes: PPRs (toll like receptors - TLR)
what are examples of PAMPs?
gram neg bacteria: lipopolysaccharide (TLR4), lipoproteins (TLR2)
gram Pos bac: Peptidoglycan (TLR2)
all Mycobacteria: Mannose-rich glycans (TLR2)
bacterial flagella: flagellin (TLR5)
what is opsonisation of microbes?
coating proteins (opsonins) bind to microbial surfaces - leads to enhanced attachment of phagocytes & clearance of microbes
essential in clearance of encapsulated bacteria: PIM nasopharynx normal flora (N. meningitidis, Strep pneumoniae, H. influenza)
what are examples of opsonins?
- complement proteins (C3b, C4b)
- antibodies: IgG, IgM
- acute phase proteins: CRP, MBL (mannose binding lectin)
what is a brief overview of phagocytosis?
phagocytes: recognise PAMPs & opsonins
engulfment
degradation of infectious microbes
describe the process of phagocytosis: killing of pathogens
- chemotaxis & adherence
- ingestion
- formation of phagosome
- fusion with lysosome (phagolysosome) - acidic
- digestion with enzyme
- formation of residual body with indigestible material
- discharge of waste (residual body) - exocytosis?
what are the phagocyte intracellular killing mechanisms?
- oxygen-dependent pathway (resp burst) - toxic O2 products e.g. H2O2, OH radical, NO, superoxide
- oxygen-INdependent pathways: lysozyme, transferrin, proteolytic & hydrolytic enzymes
what are the proteins involved in the complement system?
20 serum proteins, C1-C9 most important
C3a & C5a: recruitment of phagocytes (attact)
C3b-C4b: opsonisation of pathogens (binding)
C5-C9: killing of pathogens, membrane attack complex
what are the activating pathways of the complement system?
- alternative pathway: initiated by cell surface microbial constituents (e.g. endotoxins by E. coli)
- MBL pathway: initiated when MBL binds to mannose containing residues of proteins on many microbes (salmonella, Candida albicans)
what is the function of cytokines / chemokines? (produced by macrophage)
chemoattraction
phagocyte activation
inflammation
what are the anti-microbial actions of MACROPHAGE-derived TNF-a, IL-1, IL-6?
- liver (opsonins): CRP, MBL (complement activation)
- BM: neutrophil mobilisation - increase WBC production
- inflammatory actions: vasodilation, vascular permeability, adhesion molecules (attract neutrophils)
- hypothalamus: increase body temperature
give an overview of innate immunity
- innate barrier breached
- complement, mast cells & PRR (macrophage activation) - phagocytosis, chemokines/cytokines
- vascular changes: vasodilate, vascular permeability
chemoattraction: neutrophils, monocytes - hypothalamus: fever, liver: CRP, MBL
- redness, heat, swelling & pain: local inflammation
what causes reduced phagocytosis?
- decreased spleen function: asplenic, hyposplenic
- decreased neutrophil number: chemotherapy, drugs, leukaemia, lymphoma
- decreased neutrophil function: chronic granulomatous (no respiratory burst)
