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Immuno > Innate Immunity > Flashcards

Innate Immunity Flashcards

1
Q

Describe the definition of innate immunity.

A

-natural/native immunity
-from birth
-protect body from infection without prior contact with the infectious agent

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2
Q

Describe the mucosal surfaces infection for pathogens.

A
  1. airway = inhaled (COVID), spores:
    -meningitidis -> meningitis
    -bacillus anthracis -> inhalation anthrax
  2. GI = contaminated water/food
    -salmonella -> typhoid fever
    -rotavirus -> diarrhea
  3. repro tract = physical contact
    -brucellosis
    -EHV1
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3
Q

Describe the external epithelia infection for pathogens.

A
  1. external surface
    -physical contact -> trichopyton -> athletes foot
  2. wounds & abrasions
    -skin abrasion -> bacillus athracis -> cutaneous anthrax
    -puncture wound -> clostridium tetani -> tetanus
    -infected animals ->francisella tularenis -> tularemia
  3. insect bites
    -mosquito (aedes aegypt) -> flavivirus -> yellow fever
    -deer tick -> borrelia burgdorferi -> lyme disease
    -mosquito (anopheles) -> plasmodium -> malaria
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4
Q

Describe the mechanism of infection.

A
  1. adhere to epithelium -> flora, phagocytes, local chemical
  2. local infection & penetration of epithelium -> antimicrobial, peptides, phagocytes, complement
  3. local infection of tissues -> complement, cytokines, chemokines, phagocytes, NK cells, macrophages, DCs to lymph nodes (start adaptive), blood clots
  4. adaptive immunity -> infection cleared by T cells
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5
Q

Describe the phases of initial response to infection.

A
  1. innate immunity (0-4hr)
    -recognition, nonspecific, broad effectors
  2. early induced (4-96hrs)
    -PAMPS & DAMPS
    -inflammation & activate effector cells
  3. adaptive (>96hrs)
    -antigen to lymphoid organs
    -recog by native B & T cell
    -clonal expansion & differentiation to effector cells
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6
Q

Describe the difference between innate & adaptive immunity.

A

Innate = nonspecific, immediate, no memory
Adaptive = specific, delayed, memory

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7
Q

Describe the 3 lines of defense.

A

Innate = nonspecific
1st: skin, mucous membrane, chemical
2nd: phagocytosis, complement, interferon, inflammation, fever
Adaptive = specific
3rd: lymphocytes, antibodies

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8
Q

Describe physical barriers (mechanical).

A

-skin
-ciliary movement of respiratory tract
-peristaltic movement of intestinal tract
-washing via tears, saliva
-mucus layer in vag, digestive tract, respiratory tract

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9
Q

Describe physical barriers (chemical).

A

-fatty acids (sweat) -> inhibit bacterial growth
-lysozyme & phospholipase (tears, saliva, nose) -> inhibit growth of infectious agents
-low pH -> antibacterial
-surfactants -> enhance phagocytosis

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10
Q

Describe physical barriers (microbiological).

A

-normal biota prevents infection vs inhibitory substances

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11
Q

Describe nonspecific mechanisms involved in protection of host during pathogen elimination.

A

-acidification (pH = 3-4)
-toxic oxygen derived products & nitrogen oxide
-antimicrobial peptides (defensins & cationic proteins)
-enzymes (lysozyme - target gram pos & acid hydrolases - digest bacteria)
-competitors (lactoferrin & VitB)

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12
Q

Describe the humoral barrier.

A

*breach of physical barrier = penetration & inflammation
-complement system = 30 proteins in serum to prevent infection

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13
Q

Describe the coagulative system.

A

-activation = blood coagulation
-chemotactic factors
-beta lysine made by platelets = bactericidal against G+
-lactoferrin & transferrin = bind iron (bacteria cant grow without iron)
-lysozyme = digest bacterial cell wall
-interferons = inhibit infection & replication of viruses
-IL1 = increase temp & induce acute phase proteins (bactericidal)

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14
Q

Describe the 4 cell barriers.

A
  1. *Neutrophil = (PMN) phagocytose microorganisms
  2. *Macrophages = phagocytize microorganism & infected cells intracellularly
    >APC
  3. NK cell = kill infected & tumor cells
  4. Eosinophils = eliminate parasites
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15
Q

Describe neutrophils two types of granules required for the intracellular killing process.

A

*CD66 on surface
1. Azurophilic (primary) granules:
-defensins = kill bacteria
-proteolytic enzymes = elastase & cathepsin G -> degrade bacteria protein
-lysozyme = degrade bacterial cell wall
-myeloperoxidase = generate bactericidal substance
2. Secondary granules: (in mature PMN only)
-lysozyme
-lactoferrin
-NADPH oxidase = toxic radicals

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16
Q

Describe the signals to induce chemotaxis of macrophage toward microbe entry. (4)

A

*CD14, CD11b, F4/80
-lysosomes = intracellular killing
1. N-formyl-methionine = secreted by bacteria
2. Peptides = cog system
3. Complement system
4. Cytokines = secreted by macrophages at site

17
Q

Describe the receptors needed for phagocytosis. (4)

A
  1. Complement - C3b
  2. Scavenger - on macrophage & bind polyamines on bacterial surface
  3. Fc - on macrophage
    >antibodies bound to antigen expose Fc region
    >Fc region = bind Fc receptor on phagocytes
    >phagocyte binding of Fc region = enhances metabolic activity of the phagocyte
  4. TLR - recognize PAMPs
    >macrophage bind an antigen (activated) -> secrete cytokines (IL1, TNF, IL6) -> inflammatory reaction
18
Q

Describe the purpose of phagocytosis.

A

-detect & destroy microorganisms
-remove damage/foreign cells
-make cytokines for inflammatory response
-present antigen to induce immune response by lymphocytes

19
Q

Describe the steps of phagocytosis.

A
  1. Chemotaxis = phagocytes move to target to be phagocytosed
  2. Phagocytes detect & bind target
  3. Surround target via pseudopodia & engulf via endocytosis
  4. Endocytosed target is enclosed in phagosome
  5. Phagosome fuses with lysosome = phagolysosome
  6. Lysosome contents released into phagolysosome
  7. Digestion begins
20
Q

Describe the 2 pathways of intracellular killing.

A

*neutrophils, monocytes, macrophages
1. Oxidative pathway = ROS & RNS
-O2 & glucose increase = ‘respiratory burst’
2. Nonoxidative pathway = depends on lysosomal toxic substances

21
Q

Describe the generation of ROS.

A
  1. Glucose metabolized thru pentose-phosphate pathway = makes NADPH
  2. Cytochrome oxidase activate NADPH
  3. Activate NADPH uses O2 = makes superoxide anion
  4. Superoxide anion reduced to H2O2 & O2 by superoxide dismutase
  5. OR superoxide anion react with H2O2 = hydroxyl radicals (-OH) & ions (OH-)
22
Q

Describe myeloperoxidase dependent intracellular killing.

A

-released during fusion of azurophilic granules with phagosome
-uses H2O2 & Cl = hypochlorous acid

23
Q

Describe the generation of RNS.

A

-superoxide anion interact w (RNS) NO to make peroxynitrite (RNS)
-NO = oxidation to make RNS nitrogen dioxide

24
Q

Describe the antimicrobial action of NO.

A

-phagocytes bind TLR -> cytokines like TNFa released -> expression of inducible nitric oxide synthetase (iNOS)
-iNOS oxidizes l-arg to make l-cit & NO
-NO toxic
-IFNy also induces iNOS
*ROS & RNS = peroxynitrite

25
Q

Describe the non oxidative intracellular killing pathway.

A

*dependent on toxic substances (peptides, proteins, enzymes) in lysosomes
Mechanisms:
-cationic proteins = damage bacteria cell wall
-lysozyme = damage mucopeptide in bacteria cell wall
-lactoferrin = sequester iron to inhibit bacterial growth
-proteolytic & hydrolytic enzymes = digest killed bacteria

26
Q

Describe pathogen recognition by cells of innate immunity.

A

-macrophages, dendritic cells, mast cells = use PRRs to detect PAMPs & DAMPs found on pathogens
-PAMP = expressed by pathogens
-DAMPS = endogenous molecules released from damaged cells

27
Q

Describe the 5 diff classes of PRRs.

A
  1. TLR
  2. NOD like receptor (NLR)
  3. RIG like receptor (RLR)
  4. C type lectin receptor (CLR)
  5. Peptidoglycan recognition proteins (PGP)
28
Q

Describe TLRs.

A

-PRRs located on host cell membrane or within host that signal invaders in innate immune response
-signal thru MyD88 for all TLRs except TLR3 (TRIF)
-goal of signaling = production of pro inflammatory cytokines!!!
-extracellular = fungus & bacteria
-intracellular = virus

KNOW TLR3,7,8,9!!!
29
Q

Describe NOD-like receptors. (NLR)

A

-found inside cell
-detect pathogen in cytoplasm (intracellular bacteria)
-22 human, 34 mouse
-NOD1 = bacterial peptidoglycan
-NOD2 = muramyl dipeptides
-detect PAMPs by NLRs = activate transcription factor NF-kB -> transcription of genes for expression of pro inflammatory cytokines
-NLRs signal thru IRF3/7 = IFN production
-NLRs activated by DAMP signals

30
Q

Describe RIG like receptors. (RLR)

A

-in cytoplasm
-detect viral RNA (antiviral)
-make IFNs & inflammatory cytokines

31
Q

Describe C-type lectin receptor (CLRs).

A

-receptors that bind to carbohydrates (Ca dependent)
-fungal recognition of innate
-expressed by macrophages & DCs

32
Q

Describe peptidoglycan-recognition proteins (PGRPs).

A

-peptidoglycan = polymers of N-acetylglucosamine & N-acetyl muraminic acid found on G+ & G- surfaces
-located in lg granules of neutrophils (skin, bone marrow, intestine in pigs)
-detect microbial peptidoglycan by PGRPs = makes antimicrobial peptides:
>defensins Alpha & beta

Immuno (24 decks)

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