Microbial Defense Flashcards
Humoral is most effective for ……
extracellular pathogens
Cellular is most effective for….
intracelluar pathogens
CD8 T cells, Cytotoxic (killer) T cells interacts with which class of MHC
MHC I
What is CTL’s effect on the cell its acting on?
Induces the virus infected cell to undergo apoptosis
TH1 cells interacts with what kind of cell?
Macrophage which has MHC II
TH1’s effect on the cell its interacting with?
Tell Macrophage to kill the bacteria/pathogen it phagocytose
………..both interact with………….
Th1 and TH2 interact with B cell via its MHC II who has BCR bound to toxins
Th1 and Th2’s effect on antigen specific B cell…..
Tells B cell to differentiate in plasma cell, essentially a factory that makes lots of secretory ig
Th17 activates….
1) fibroblasts
2) epithelial cells
Th1 provides protection against
intracellular pathogens
abberations lead to autoimmunity
Th2 provides protection against
extracellular pathogens
abberations lead to
1) asthma
2) allergies
Th17 protects against…
extraceullar pathogens
abberations lead to
autoimmunity
Th17 secretes…
IL-17
IL-17….
1) activates neutrophils
2) promotes inflammation
2) promotes autoimmune responses inhibited by Th1 and Th2
T reg cells act on….
immature dendritic cells
T reg cells act on and inhibit….
immature dendritic cells
Th1’s actions
1) lymphocyte growth
2) Mononuclear Phagocyte activation
3) IgG class switch
4) cytotoxicity
Th2
1) IgG, IgE, IgA class switch
2) inhibit Th1
3) stimulate B cell
Th2
1) IgG, IgE, IgA class switch
2) inhibit Th1
3) stimulate B cell
alpha-defensins aka
cryptdins
1) made by paneth cells at the base of the crypts in SMALL intestine
beta-defensins are made by….
epithelia
primarily in
1) respiratory
2) urogenital tracts
3) skin and tongue
Collectins aka
1) Surfactant proteins A
(acute phase protein)
2) Surfactant proteins D (acute phase protein)
bind and coat the surface of pathogens promoting their phagocytosis by macrophages
What do collectins do
SP-A and SP-D
coat pathogens to promote phagocytosis by macrophages
What are SP-A and SP-D and what’s their role
Surfactant Protein A
Surfactant Protein D
Belong to collectin family
acute phase protein
coat pathogen to promote phagocytosis by macrophages
SP-A and SP-D aka
1) collectins family
2) acute phase protein
Once……complement is activated all three outcomes are stimulated and they are…..
C3 Convertase
1) C3a C5a
recruit
1) peptide mediators of inflammation
2) phagocyte recruitment
2) C3b opsonizes pathogens and bind to phagocyte receptors to promote phagocytosis (also need 5a)
- REMOVAL of IMMUNE COMPELXES
3) C5b, C6-C9
formation MAC and lysis of pathogens/cell
*The type of innate immune reponse triggered…..
determines the type of adaptive immune response generated
PAMP receptors like the TLRs are expressed in different….
cellular compartments relevant to the LIFE CYCLE & MECHANISM of infection by different pathogens
Different signal transduction pathways lead to response effective against….
pathogen expressing conserved molecular pathogenic pattern
…….determines the type of ADAPTIVE immune response generated
The type of innate immune reponse
NO is generated from…. by the enzyme….
L-Arginine
nitric oxide synthase
Three forms of NOS
eNOS:
- need calcium
- endothelial NOS
nNOS
- need calcium
- neuronal NOS
iNOS
- inducible NOS
- do NOT need calcium
- regulated by transcriptional regulation
- expression induced by TNF and other pro-inflammatory CYTOKINES
Nitric Oxide is
1) potent vasodilator
2) REduces platelet aggregation
3) inhibits mast cell inflammation
4) microbial
5) reduce leukocyte adhesion
Oxygen derived free radicle is dependent on activation of …..
NADPH oxidative system
List 3 oxygen derived free radicles
1) superoxide anion production
2) hydrogen peroxide
3) hydroxyl radical
Oxygen derived radicals interact with…..
nitric oxide to produce cytotoxic reactive nitrogen intermediates
list 6 phagocytes mechanisms to kill pathogen
1) acidification
- bacteriostatic
- bactericidal
2) Toxic oxygen-derived products
3) Toxic nitrogen oxides
4) defensin and cationic proteins
5) lysozyme dissovles gram positive bacteria’s cell wall. Acid hydrolases further digests bacteria
6) Lactoferrin (binds Fe) and vitamin B12-binding protein act as competitors
5 cytokines and chemokines that macrophage secretes
1) IL-1B
- activates vascular endothelium
- activates lymphocytes
- local tissue desctruction
- increases access of effector cells
Systemic effects
- fever
- production of IL-6
2) TNF-alpha
- activates vascular endothelium
- increases vascular permeability leading to increased entry of IgG, complement, and cells to tissues
- increase fluid drainage to lymph nodes
Systemic effects
- fever
- mobilization of metabolites
- shock
3) IL-6
- lymphocyte activation
- increased antibody production
Systemic effects
-induces acute-phase protein production
4) CXCL8
- chemotactic factor
- recruits
1) neutrophils
2) basophils
3) t cells to site of infection
5) IL-12
- activates Nk cells
- induces differentiation of CD4 T cells in Th1 cells
Activates NK cells
induces differentiation of Cd4 T cells into TH1 cells
IL-12
Systemic effects
- fever
- mobilization of metabolites
- shock
TNF-alpha
Sytemic Effects
- fever
- induces acute-phase protein production
IL-6
Sytemic effects
- fever
- production of IL-6
IL-1beta
Cytokines have ….. and …..actions in directing immunity
local & Systemic
Local effects
- lymphocyte activation
- increased ab production
IL-6
Local effects
- activates vascular endothelium
- increases vascular permeability leading to increased entry of IgG, complement, and cells to tissues
- increased fluid drainage to lymph nodes
TNF-alpha
Local effects
- activates vascular endothelium
- activates lymphocytes
- local tissue destruction
- increase access of effector cells
IL-1Beta
CXCL8 local effects
1) chemotactic factor
2) recruite neutrophil, basophil, and T cells to site of infection
local effects
- activates NK cells
- induces differentiation of CD4 to Th1 cells
IL-12
TH17 cells enhance…..
NEUTROPHIL RESPONSE
IL-1/IL-6/TNF-alpha’s effect on hypothalamus
1) increase body temperature
IL-1/IL-6/TNF-alpha effect on Fat, muscle
1) protein & energy mobilization to allow increased body temperature
What cytokine activates NK cells?
IL-12
What chemokine is a chemotactic factor that recruits neutrophils, basophils, and T cells to infection?
CXCL8
TNF-alpha stimulates…..cells migration to……
DENDRITIC CELLS migration to LYMPH NODES to ACTIVATE ADAPTIVE RESPONSE
A patient has a defect that compromises their macrophages’s ability to produce IL-12 what are the effects of this….
- decrease activation of NK
- low Th1 cells, since CD4 can’t differentiate into TH1 cells
What cytokine increases antibody production and lymphocyte activation?
IL-6
Activation of macrophages by bacterial components leads to production of pro-inflammatory cytokines invoved in systemic defense which has to the potential for something bad….
systemic septic shock
What cytokine helps with CD4 T cells differentiating into Th1 cells?
IL-12
List five acute phase proteins
1) Mannose Binding Lectin
2) fibrinogen
3) SP-A, SP-D
4) SAP
5) CRP
…………and………..are inducible in many cell types
IFN-alpha & IFN-Beta
TLR3 recognizes….
dsRNA
dsRNA is NOT generally found in mammalian cells
True
……….and……….interfere with viral replication
IFN-alpha and IFN-beta
………..and…….activate NK cells that produce IFN-gamma
IFN-alpha and IFN-beta
…….is a strong inducer of IFN synthesis
TLR3
How are infected cells able to help their neighbor cells resist infection?
Infected cells activated by their OWN TLR3 induces IFN synthesis providing protection to neighboring cells
IFN alpha and IFN beta list 3 things
1) induce resistance to viral replication in all cells
2) Increase MHC I expression and ag presentation in all cells
3) activate NK cells to kill virus-infected cells
CD4 Th1 cells activate infected… and provide help to…..for……production
INFECTED MACROPHAGES
help B cells for ANTIBODY PRODUCTION
CD4 TH2 cells aid …..for…..production ESPECIALLY switching to Immuno globulin….
B cells
ANTIBODY PRODUCTION
IgE
TH2 CD4 T cell responses support ……
antibody development
what influnces Ig isotype produced?
CYTOKINE
…..and……are effective for…..
neutralizing bacterial toxins
PROTECTS CELL FROM PATHOGEN’s toxic secretions/byproducts
IgG and IgA antibodies can inhibit bacterial infectivity by blocking………
CELLUAR ADHESION
T/F CD8 T cells can selectively kill infected cells without damaging neighboring cells
True
cytotoxic T cells 3 protein granules
1) perforin
aids in delivering granules’ contents into the CYTOPLASM of target cell
2) serine proteases activate apoptosis once in CYTOPLASM
3) Granulysin - antimicrobial action and INDUCE APOPTOSIS
NK is triggered by ……..and………..
1) expression of stress/viral proteins
2) abscence of MHC I inhibitory signals
What inhibits NK killing?
EXPRESSION OF MHC I
What’s the cell’s solution for pathogens that decrease MHC I expression?
increased NK killing since MHC I isn’t there to inhibit it
Why doesn’t NK kill normal cell?
Normal Cell has MHC I expressed on surface deliverying inhibitory signals to NK
…….or…….cannot stimulate negative signal in NK. NK is triggered by signals from activating receptors
Altered MHC I or ABSENT MHC I
NK’s effect on affected cell
Granules released induces APOPTOSIS on infected cell
Ig…. exists as a pentamer
IgM
The only Ig that passes through a placenta
IgG
initial early induced phase of reponses is characterized by
1) low affinity IgM
2) early source of pro-inflammatory cytokines
3) NO HYPERSOMATIC MUTATION, no isotype switching
4) no generation of memory cells
1) b Cell binds bacteria component adn receives IL-5 signal
2) B-1 secretes IgM anti-polysacchride ab
3) igM binds polysacchride capsule
4) activation of COMPLEMENT and removal bacteria
read
IgM can activate what… to remove bacteria
COMPLEMENT
Innate immune lymphocyte differ from those in adaptive part
true
List 3 innate like lymphocytes
1) B-1 Cells
2) Epithelial gamma:beta cells
3) NK T cells
B-1 cells make….and has ligands…..and cannot be…..
IgM NATURAL Antibody
ligands NOT MHC assoc
can NOT be boosted
Epithelial gamma:beta cells produce……and ligands are……and cannot be
Cytokines Rapidly
ligands ARE MHC-IB associated
can NOT be boosted
NK T cells……especially……and ligands are…..and cannot be
make cytokines Rapidly
especially IFN-gamma
Ligands ARE lipids bound to CD1d
cannot be boosted
how is IgA trasnported into the gut lumen…..
through EPITHELIAL CELLS at the base of the CRYPTS
…….the dominant isotype protect the gut
IgA
Remember that…..imparts mucosal immunity
IgA
*…..does NOT stimulate complement
IgA
Deficiencies in IgA increase susceptibility to…..
mucosal infections
…..cannot substitute in efficent mucosal defense
IgG
*…..do NOT generate memory
Gamma delta T cells
Naive gamma delta T cells are…..immune T cells activated in the ……and NOT in……..
INNATE
EPITHELIA
NOT LYMPH NODE
Describe the pathway to activating gamma/delta T cells
1) cells infected with bacteria produce STRESS INDUCED PROTEINS
2) infected cell expressed 2 atypical class I molecules known as MIC-A and MIC-B
3) gamma-delta T cells bearing NK receptor
NKG2D bind to MIC-A and MIC-B
4) infected epithelial cell is killed via apoptosis and replaced by adj healthy cells
……..of gamma:delta T cells bind to MIC-A and MIC-B
NKG2D
infected epithelial cells expressed 2 atypical class I molecules:
MIC-A
MIC-B
alpha-defensins aka
cryptdins
alpha-defensins
cryptdins
- made by PANETH cells at the base of the crypts in SMALL INTESTINE
beta-defensins
made by EPITHELIAL primarily in the
1) respiratory
2) urogenital tracts
3) skina dn tongue
Cathelicidin peptides are made by…..and …..
neutrophils
epithelia
Surfactant proteins of the collectin family……and…..bind to and coat the sufaces of pathogens and promote phagocytosis by macrophages
SP-A and SP-D
gamma:delta cells
1) produce cytokines rapidly
2) ligands ARE MHC-IB associated
3) cannot be boosted
B-1 make….
1) natural ab protection against streptococcus penumoniae
2) ligands not MHC associated
3) cannot be boosted
NK T cells
1) make cytokines rapidly especially IFN-gamma
2) ligands are lipids bound to CD1d
3) cannote be boosted
….provides mucosal immunity
IgA
*….does NOT stimulate complement
IgA
deficiencies in…..increases susceptibility to mucosal infections
IgA
…..do NOT generate memory and are activated in the epithelia not in lymph node
gamma:delta T cell
things to remember about gamma:delta T cells
1) do not generate memory
2) MHC-IB associated
3) found in epithelia as opposed to lymph nodes
4) receptor NKG2D reacts to MIC-A and MIC-B protein
Neutrophils and epithelia make…..peptides
Cathelicidin
………made by epithelial primarily in the respiratory, urogenital tracts, skin and tongue
B-defensins
……made by Paneth cells at the base of crypts in the small intestine
Alpha-defensins
…..bind to and coat the surfaces of pathogen to promote macrophage phagocytosis just like C3a
Surfactant protein- A (SP-A)
Surfactant protein-B (SP-B)
…..and…..recruit phagocyte and peptide mediators of inflammation
C3a and C5a
….binds to complement receptors on phagocyte, promotes oposinization of pathoges, removal of immune complexes
C3b
membrane attack complex, lysis of certain pthogens and cells
C5b, C6, C7, C8, C9
What should we know about TLR3
1) TLR3 exist intracellularly in the ENDOSOME
2) activates NK cells producing IFN-gamma
3) STRONG inducer of IFN-alpha and IFN-Beta
what to know about IFN-alpha and IFN-beta
1) induce resistance to viral replication in ALL CELLS
2) INCREASE MHC class I expression and antigen presentation in ALL CELL
3) activate NK cells to kill virus-infected cells
