Innate Immunity Flashcards
Describe the definition of innate immunity.
-natural/native immunity
-from birth
-protect body from infection without prior contact with the infectious agent
Describe the mucosal surfaces infection for pathogens.
- airway = inhaled (COVID), spores:
-meningitidis -> meningitis
-bacillus anthracis -> inhalation anthrax - GI = contaminated water/food
-salmonella -> typhoid fever
-rotavirus -> diarrhea - repro tract = physical contact
-brucellosis
-EHV1
Describe the external epithelia infection for pathogens.
- external surface
-physical contact -> trichopyton -> athletes foot - wounds & abrasions
-skin abrasion -> bacillus athracis -> cutaneous anthrax
-puncture wound -> clostridium tetani -> tetanus
-infected animals ->francisella tularenis -> tularemia - insect bites
-mosquito (aedes aegypt) -> flavivirus -> yellow fever
-deer tick -> borrelia burgdorferi -> lyme disease
-mosquito (anopheles) -> plasmodium -> malaria
Describe the mechanism of infection.
- adhere to epithelium -> flora, phagocytes, local chemical
- local infection & penetration of epithelium -> antimicrobial, peptides, phagocytes, complement
- local infection of tissues -> complement, cytokines, chemokines, phagocytes, NK cells, macrophages, DCs to lymph nodes (start adaptive), blood clots
- adaptive immunity -> infection cleared by T cells
Describe the phases of initial response to infection.
- innate immunity (0-4hr)
-recognition, nonspecific, broad effectors - early induced (4-96hrs)
-PAMPS & DAMPS
-inflammation & activate effector cells - adaptive (>96hrs)
-antigen to lymphoid organs
-recog by native B & T cell
-clonal expansion & differentiation to effector cells
Describe the difference between innate & adaptive immunity.
Innate = nonspecific, immediate, no memory
Adaptive = specific, delayed, memory
Describe the 3 lines of defense.
Innate = nonspecific
1st: skin, mucous membrane, chemical
2nd: phagocytosis, complement, interferon, inflammation, fever
Adaptive = specific
3rd: lymphocytes, antibodies
Describe physical barriers (mechanical).
-skin
-ciliary movement of respiratory tract
-peristaltic movement of intestinal tract
-washing via tears, saliva
-mucus layer in vag, digestive tract, respiratory tract
Describe physical barriers (chemical).
-fatty acids (sweat) -> inhibit bacterial growth
-lysozyme & phospholipase (tears, saliva, nose) -> inhibit growth of infectious agents
-low pH -> antibacterial
-surfactants -> enhance phagocytosis
Describe physical barriers (microbiological).
-normal biota prevents infection vs inhibitory substances
Describe nonspecific mechanisms involved in protection of host during pathogen elimination.
-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)
Describe the humoral barrier.
*breach of physical barrier = penetration & inflammation
-complement system = 30 proteins in serum to prevent infection
Describe the coagulative system.
-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)
Describe the 4 cell barriers.
- *Neutrophil = (PMN) phagocytose microorganisms
- *Macrophages = phagocytize microorganism & infected cells intracellularly
>APC - NK cell = kill infected & tumor cells
- Eosinophils = eliminate parasites
Describe neutrophils two types of granules required for the intracellular killing process.
*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
Describe the signals to induce chemotaxis of macrophage toward microbe entry. (4)
*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
Describe the receptors needed for phagocytosis. (4)
- Complement - C3b
- Scavenger - on macrophage & bind polyamines on bacterial surface
- 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 - TLR - recognize PAMPs
>macrophage bind an antigen (activated) -> secrete cytokines (IL1, TNF, IL6) -> inflammatory reaction
Describe the purpose of phagocytosis.
-detect & destroy microorganisms
-remove damage/foreign cells
-make cytokines for inflammatory response
-present antigen to induce immune response by lymphocytes
Describe the steps of phagocytosis.
- Chemotaxis = phagocytes move to target to be phagocytosed
- Phagocytes detect & bind target
- Surround target via pseudopodia & engulf via endocytosis
- Endocytosed target is enclosed in phagosome
- Phagosome fuses with lysosome = phagolysosome
- Lysosome contents released into phagolysosome
- Digestion begins
Describe the 2 pathways of intracellular killing.
*neutrophils, monocytes, macrophages
1. Oxidative pathway = ROS & RNS
-O2 & glucose increase = ‘respiratory burst’
2. Nonoxidative pathway = depends on lysosomal toxic substances
Describe the generation of ROS.
- Glucose metabolized thru pentose-phosphate pathway = makes NADPH
- Cytochrome oxidase activate NADPH
- Activate NADPH uses O2 = makes superoxide anion
- Superoxide anion reduced to H2O2 & O2 by superoxide dismutase
- OR superoxide anion react with H2O2 = hydroxyl radicals (-OH) & ions (OH-)
Describe myeloperoxidase dependent intracellular killing.
-released during fusion of azurophilic granules with phagosome
-uses H2O2 & Cl = hypochlorous acid
Describe the generation of RNS.
-superoxide anion interact w (RNS) NO to make peroxynitrite (RNS)
-NO = oxidation to make RNS nitrogen dioxide
Describe the antimicrobial action of NO.
-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
Describe the non oxidative intracellular killing pathway.
*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
Describe pathogen recognition by cells of innate immunity.
-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
Describe the 5 diff classes of PRRs.
- TLR
- NOD like receptor (NLR)
- RIG like receptor (RLR)
- C type lectin receptor (CLR)
- Peptidoglycan recognition proteins (PGP)
Describe TLRs.
-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
Describe NOD-like receptors. (NLR)
-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
Describe RIG like receptors. (RLR)
-in cytoplasm
-detect viral RNA (antiviral)
-make IFNs & inflammatory cytokines
Describe C-type lectin receptor (CLRs).
-receptors that bind to carbohydrates (Ca dependent)
-fungal recognition of innate
-expressed by macrophages & DCs
Describe peptidoglycan-recognition proteins (PGRPs).
-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
