infection - innate immune system Flashcards

1
Q

what are the factors determining the outcome of the host-pathogen relationship?

A

infectivity (pathogen)
virulence (mech of infection)
patient (host immune response)

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2
Q

what is the immune system?

A

cells & organs that contribute to immune defences against infectious & non-infectious conditions (self VS non-self)

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3
Q

what are infectious diseases?

A

when the pathogen succeeds in evading and or overwhelming the host’s immune defences

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4
Q

what are the roles of the immune system?

A
  1. pathogen recognition - cell surface & soluble receptors
  2. containing / eliminating the infection - killing & clearance mechanism
  3. regulating itself - minimum damage to host (resolution)
  4. remembering pathogens - preventing the disease from recurring
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5
Q

what are the features of innate immunity? (1st line)

A

immediate protection:
fast (within seconds)
lack of specificity / memory
no change in intensity

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6
Q

what are the features of adaptive immunity?

A
long lasting protection:
slow (days)
specific - gram neg or positive
immunologic memory - circulating memory B cells / T 
changes in intensity
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7
Q

what are the first lines of defence in immune response?

A

factors that prevent ENTRY and limit GROWTH of pathogens:

physical, physiological, chemical & biological barriers

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8
Q

what are the physical barriers?

A

skin
mucous membranes (mouth, resp tract, GI tract, urinary)
bronchial cilia

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9
Q

what are physiological barriers?

A

D&V

coughing & sneezing

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10
Q

what are chemical barriers?

A
low pH (skin, stomach, vagina)
antimicrobial molecules:
IgA (tears & saliva)
lysozymes (urine)
mucus (mucous membranes)
gastric acid
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11
Q

what are biological barriers?

A

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)

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12
Q

what are examples of normal flora on skin?

A
staph aureus
staph epidermis
strep pyogenes
candida albicans
clostridium perfringens
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13
Q

what are examples of normal flora on nasopharynx?

A

PIM - ALL encapsulated
strep Pneumoniae
haemophilus Influenza
neisseria Meningitidis

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14
Q

what are examples of when normal flora is displaced from normal to sterile location and causes problems?

A
  1. breaching skin integrity: skin loss, surgery, injection drug users, IV lines
  2. faecal-oral route
  3. faecal-perineal-urethral route (UTI women)
  4. poor dental hygiene (dental extraction, brushing/flossing, gingivitis)
  5. high-risk patients: asplenic / hyposplenic, damaged / prosthetic valves, previous endocarditis
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15
Q

examples of when normal flora overgrows and becomes pathogenic when host becomes IMMUNO-COMPROMISED?

A

diabetes
aids
malignant diseases
chemotherapy

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16
Q

example of when normal flora is depleted by antibiotics?

A
  1. intestine - severe colitis (C. diff)

2. vagina - thrush (candida albicans normally suppressed by lactobacilli)

17
Q

what are second line defence of innate immunity?

A

factors that will CONTAIN & CLEAR the infection:

phagocytosis, chemicals, inflammation

18
Q

what are the main phagocytes & their functions?

A
  1. macrophages: all organs, phagocytosis, present microbial antigens to T cells, produce cytokines / chemokines
  2. monocytes: in blood, go to site of infection - differentiate to macrophage
  3. neutrophils (pus): in blood, increased in infection, recruited by chemokines to site of infection, ingest pyogenic bacteria (staph a & strep pyogenes)
19
Q

what are other key cells of innate immunity?

A

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

20
Q

how does pathogen recognition occur?

A
  1. microbial structures: PAMPs (carbohydrates, lipids, proteins, nucleic acids)
  2. phagocytes: PPRs (toll like receptors - TLR)
21
Q

what are examples of PAMPs?

A

gram neg bacteria: lipopolysaccharide (TLR4), lipoproteins (TLR2)
gram Pos bac: Peptidoglycan (TLR2)
all Mycobacteria: Mannose-rich glycans (TLR2)
bacterial flagella: flagellin (TLR5)

22
Q

what is opsonisation of microbes?

A

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)

23
Q

what are examples of opsonins?

A
  1. complement proteins (C3b, C4b)
  2. antibodies: IgG, IgM
  3. acute phase proteins: CRP, MBL (mannose binding lectin)
24
Q

what is a brief overview of phagocytosis?

A

phagocytes: recognise PAMPs & opsonins
engulfment
degradation of infectious microbes

25
Q

describe the process of phagocytosis: killing of pathogens

A
  1. chemotaxis & adherence
  2. ingestion
  3. formation of phagosome
  4. fusion with lysosome (phagolysosome) - acidic
  5. digestion with enzyme
  6. formation of residual body with indigestible material
  7. discharge of waste (residual body) - exocytosis?
26
Q

what are the phagocyte intracellular killing mechanisms?

A
  1. oxygen-dependent pathway (resp burst) - toxic O2 products e.g. H2O2, OH radical, NO, superoxide
  2. oxygen-INdependent pathways: lysozyme, transferrin, proteolytic & hydrolytic enzymes
27
Q

what are the proteins involved in the complement system?

A

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

28
Q

what are the activating pathways of the complement system?

A
  1. alternative pathway: initiated by cell surface microbial constituents (e.g. endotoxins by E. coli)
  2. MBL pathway: initiated when MBL binds to mannose containing residues of proteins on many microbes (salmonella, Candida albicans)
29
Q

what is the function of cytokines / chemokines? (produced by macrophage)

A

chemoattraction
phagocyte activation
inflammation

30
Q

what are the anti-microbial actions of MACROPHAGE-derived TNF-a, IL-1, IL-6?

A
  1. liver (opsonins): CRP, MBL (complement activation)
  2. BM: neutrophil mobilisation - increase WBC production
  3. inflammatory actions: vasodilation, vascular permeability, adhesion molecules (attract neutrophils)
  4. hypothalamus: increase body temperature
31
Q

give an overview of innate immunity

A
  1. innate barrier breached
  2. complement, mast cells & PRR (macrophage activation) - phagocytosis, chemokines/cytokines
  3. vascular changes: vasodilate, vascular permeability
    chemoattraction: neutrophils, monocytes
  4. hypothalamus: fever, liver: CRP, MBL
  5. redness, heat, swelling & pain: local inflammation
32
Q

what causes reduced phagocytosis?

A
  1. decreased spleen function: asplenic, hyposplenic
  2. decreased neutrophil number: chemotherapy, drugs, leukaemia, lymphoma
  3. decreased neutrophil function: chronic granulomatous (no respiratory burst)