innate immunity

Question 1

innate immunity

Answer 1

1) skin and mucosal barriers
2) activation of residential immune cells
- recognition of microbes by DCs
- cytokine and chemokine secretion
3) increased vascular permeability
- leakage of biochemical factors
- migration of phagocytic cells at the site of injury
4) microbial destruction (phagocytic and non phagocytic)

Question 2

how to recognize self from nonself

Answer 2

1) microbes carry patterns
- pathogen associated molecular patterns
- ex. LPS, LPP, PGN, flagellin, etc.
2) the host cells recognize PAMPs by receptors
- pattern recognition receptors (PRR)

Question 3

PRR are present on

Answer 3

1) cell surface
- TLRs, CLRs
2) endosome
- TLRs
3) cytosol
- NLRs

some are located on microbe surface and some on the cytoplasm, and some in endosomes

Question 4

TLRs

Answer 4

1) homologous to a drosphila protein called toll
2) tend to form homodimer except for TLR-2
- can make heterodimers
3) recognizes gram - , peptidoglycan, lipopeptides, LPS, flagellin
4) TLRs that recognize nucleic acids are in endosomes!!
- very important for viral infections

Question 5

TLRs ligation

Answer 5

1) TLR signalling activates transcription factors that stimulate expression of cytokines and chemokines
2) other proteins involved in the inflammatory response and in the antimicrobial functions of activated phagocytes and other cells

Question 6

cellular communication

Answer 6

1) cytokines and chemokines induce inflammation
2) direct
- juxtacrine
3) indirect
- paracrine and autocrine
- endocrine
- synaptic

Question 7

cytokines

Answer 7

1) small, water soluble
2) both innate and adaptive cells (ex. T cells)
3 )chemical messengers to regulate innate and adaptive immune system
4) PAMP and PRR interactions major driving force for cytokine production

Question 8

chemokines

Answer 8

1) cytokines that enable leukocyte migration
2) ex. IL-8 and MCP-1

Question 9

cytokine induction of inflammation

Answer 9

1) IL-1, IL-6
- cause inflammation
- increase vascular permeability
2) leakage of biomolecules, fluid and complement proteins
3) accumulation of materials cause swelling => push nerves => pain
4) TNF-alpha cause vasodilation => NO production => blood flow => erythematous (redness)

Question 10

systemic effects of inflammatory cytokine

Answer 10

1) TNF-alpha, IL-1,6
2) can migrate to target organs
- hypothalamus, liver
3) in liver, induce c reactive protein
- activate complement and opsonization
4) in hypothalamus
- FEVER!!!

Question 11

complement system

Answer 11

1) one of the major soluble elements of the immune system
2) operated by 30 serum proteins
3) tightly regulated

Question 12

complement activation

Answer 12

1) alternative pathway
- cell surface constituents that are foreign, like LPS
2) classical
- IgG and IgM bind to an antigen and then to C1 component
3) lectin
- binding of MBL (mannose binding lectin) to mannose residues of microbes

results in cascade which forms C2 convertase (C3a and C3b are formed)

Question 13

functions of complement

Answer 13

1) opsonization and phagocytosis (C3b and C4b)
2) stimulation of inflammatory rxn
3) cell lysis

Question 14

oposonization

Answer 14

1 )C3b and c4b are opsonins
2) bind to microbial surfaces and target the microbes for phagocytosis

Question 15

stimulation of inflammatory reactions

Answer 15

1) C5a, C4a, and C3a stimulate mast cells and basophils
- degranulation, releasing histamine
2) histamine causes vasodilation and vascular permeability
3) also cause anaphylactic shock
4) C5a and C3a function also in chemotaxis

Question 16

membrane attack complex

Answer 16

1) C5b, C6,7,8,9
2) form cytotoxic pores on surface of microbes
3) Gram + are resistant because of thick cell wall
4) neisseria is Gram - and susceptible

Question 17

phagocytosis

Answer 17

1) neutrophils and macrophages
2) effector molecules
- ROS
- NO
- lysosomal enzymes

Question 18

phagocytosis steps

Answer 18

1) engulfment of microbes
- different membrane receptors of phagocytes bind to microbes, others bind to opsonized microbes
2) internalization of bacteria
- phagosomes and phagolysosomes
3) kill of bacteria
- proteolytic enzymes
- ROS
- NO

Question 19

killing by ROS

Answer 19

1) rapid release of ROS (superoxide anion, radicals, H peroxide) produces by macrophages and PMNs

Question 20

killing by NO

Answer 20

1) NO synthesis and superoxide anion produce highly toxic peroxynitrite (ONOO)

Question 21

killing by proteolytic enzymes

Answer 21

1) destroy internalized microorganisms in phagolysosomes

Question 22

INF gamma

Answer 22

1 )secreted by NK and Th1 cells
2) induce phosphatases and activates macrophages and enhance microbicidal activity

Question 23

non phagocytic microbial killing by neutrophils

Answer 23

1) neutrophils release granules to kill extracellular microbes
- cathepsin, defensin
2) neutrophil extracellular traps
- cell dealth and non cell death associated

Question 24

NET formation pathway

Answer 24

1) chromatin and granule concentration occurs
2) cell undergoes apoptosis
3) proteolytic enzymes and chromatic are explused to form NET

Question 25

NKcell mediated killing

Answer 25

1) both innate and adaptive immunity
2) main function is to kill target cells
3) activating signal and inhibitory signals
4) normal cells
- normal NHC 1 bind to kiler cell inhibitory receptor
5) NK cell activating ligand binds to activating receptor

Question 26

NK cells encounter defective MHC1

Answer 26

1) inhibitory cell signal will NOT occur
2) so sustained NK cell activation signalling

Question 27

NK cell enzymes

Answer 27

1) perforin
- disrupt cell membrane
2) granzyme
- proteolytic

Question 28

CD8+

Answer 28

1) eliminating cells with altered MHC class-1

Question 29

dendritic cells

Answer 29

1) mature with increased expression of co-receptors
2) microbial antigens from MHC2 class molecules activate?

Question 30

mature dendritic cells

Answer 30

1) enter circulation and go to lymph nodes
2) stimulate T cells and cause adaptive immunity
- co-stimulatory signal