Innate Immunity - Hunter Flashcards
(151 cards)
1
Q
Describe colonization vs. infection:
A
Colonization is like having bacteria in your nose but not causing any problems; infection is when bacteria have broken your immune defenses and cause symptoms
2
Q
Describe infection vs. disease:
A
Infection is when bacteria have made it into your body, while disease in when your cells have been damaged AS A RESULT of the infection.
3
Q
What are opportunistic pathogens?
A
Pathogens that are on your body but only cause disease when you are immunosuppresed
4
Q
What are the intrinsic epithelial barriers to infection?
A
Mechanical, chemical, and microbiological
5
Q
Describe the mechanical intrinsic defenses of the skin?
A
epi cells joined by tight junctions
longitudinal flow of air or fluid
6
Q
Describe the chemical defenses of the skin?
A
- fatty acids
- B-defensins (anti-microbial peptide)
- Lamellar bodies (seals the skin)
- cathelicidin (anti-microbial in lysosomes)
7
Q
Describe the mechanical barriers of the gut?
A
- epi cells joined by tight junctions
2. longitudinal flow of liquid
8
Q
Describe the chemical barriers of the gut?
A
- low pH
- enzymes (pepsin)
- alpha-defensins (cryptdins)
- RegIII (lecticidins)
- Cathelicidin
9
Q
Describe the mechanical defenses of the lungs?
A
- epi tight junctions
2. Movement of mucus by cilia
10
Q
Describe the chemical defenses of the lung?
A
- Pulmonary surfactant
- Alpha-defensins
- cathelicidin
11
Q
Describe the mechanical defenses of the ENT cavities?
A
- epi tight junctions
- tears (physically wash away shit)
- nasal cilia
12
Q
Describe the chemical defenses of the ENT cavities?
A
- enzymes in tears and saliva (lysozyme)
- Histatins (antimicrobial/antifungal)
- B-defensins
13
Q
What are the three mechanisms of direct tissue damage by pathogens?
A
- Exotoxin
- Endotoxin
- direct cytopathic effects
14
Q
Microbial pathogenesis involves (direct/indirect) damage of tissues
A
direct
15
Q
Immunopathology involves (direct/indirect) damage to tissues
A
indirect
16
Q
What are the three methods of tissue damage via immunopathology?
A
- Immune complexes
- Anti-host anitbody
- Cell-mediated immunity
17
Q
What are the three antimicrobial ENZYMES?
A
- Lysozyme (tears)
- Pepsin (gut)
- Secretory phospholipase A2
18
Q
How do defensins function?
A
Embeds itself in the bacterial membrane, dimerizes, and opens a pore
19
Q
Defensins, cathelicidins, and histatins can all function because they have what kind of charge?
A
amphipathic
20
Q
t/F: anti-microbial peptides are normally produced as pro-peptides
A
T
21
Q
What cell type initiates inflammation once pathogens breach the epithelium?
A
macrophages
22
Q
what two classes of chemicals do macrophages release to initiate the inflammation cascade?
A
chemokines and cytokines
23
Q
(blanks) like TNF-a, cause vasodilation, increased vascular permeability, and upregulate expression of adhesion molecules to epithelium
A
cytokines
24
Q
Chemokines attract what types of cells?
A
neutrophils (via CXCL8) and monocytes
25
Phagocytic cells, plasma cells, and the complement system engage and eliminate pathogens (before/during) the adaptive response is generated
BEFORE
26
Activation of what two systems during inflammation causes pain and blood clotting?
Kinin and coagulation
27
If the innate system works, is there a need for inflammation?
Nope
28
Macrophages recognize pathogens by (blank) encoded receptors
genome
29
What are the first two lines of defense if bacteria overrun tissue?
macrophages and complement system
30
T/F: neutrophils are more phagocytic than macrophages
true
31
What is on top of the PM in gram positive bacteria?
PDG layer with lipteichoic anchors and surface proteins
32
what is on top of the Pm in gram negative bacteria?
small PDG layer, then lipoprotein layer, then LPS layer
33
Do we want macrophages to recognize specific pathogens or patterns?
patterns
34
What are the four PAMPs for bacteria?
1. f-Met-Leu-Phe receptor
2. Mannose receptor
3. Scavenger receptor
4. LPS binding protein, TLR-4, and CD14
35
what are the two PAMPs for fungi?
Mannose recetpros and Dectin-1-glucan receptor. (if you leave sugary stuff out you will get mold)
36
What is the PAMP for viruses
Mannose
37
What is the scavenger receptor?
acetylated lipoproteins
38
LPS binding protein, TLR-4 and CD14 receptors are for gram (blank) bacteria
negative
39
How many human TLR genes are there?
10
40
TLR proteins are (blank) receptors
PAMP
41
T/F: TLR can be on the cell surface or endosomal
True
42
TLR activation engages transcription factor (blank) and induces production of inflammatory mediators
NF-Kb
43
Nucleoside Oligomerization Domain (NOD)-like proteins are similar to (blank) proteins
TLR
44
What do NODs do?
detect cytoplasmic bacteria and signal inflammation
45
What do retinoic acid inducible Gene (RIG) like proteins do?
detect viral RNA in the cytoplasm and signal inflammation
46
Are TLRs highly conserved?
yes
47
What is another name for LPS?
endotoxin
48
If pathogens invade the cytoplasm, (blanks) kick in and take over the job of TLRs
NODs
49
Where are RIGs located?
in the cytoplasm
50
What is the general cascade of PAMP producing danger signals?
1. PAMP recognition
2. TLR dimerization
3. Intracellular signaling
4. Gene expression
51
What protein is recruited by dimerized TLRs?
IRAK4 and IRAK1
52
How is NF-Kb produced?
IRAK4 mediated scaffolding releases TAK1 which leads to degradation of IkB and release of NF-Kb
53
IRAK-1 deficiency is a rare autosomal (blank) disease
recessive
54
How do you diagnose IRAK1 deficiency?
clinical suspicion and demonstation of poor response of monocytes to TLR agonists
55
What happens if you have no IRAK4?
No immune response via no inflammatory response via no cytokine release
56
A functioning inflammatory resposne is critical in host defense against (blank) bacterial infections, as evidenced in IRAK1 deficiency
pyogenic
57
What are the two major categories of defects in neutrophil function?
Defects in intracellular killing and adhesion defects
58
CGD, Chediak Higashi, and Type I integrin deficiency are all (blank)
defects in neutrophil function
59
CGD and G6PD deficiency are types of (blank)
abnormal respiratory burst
60
MPO deficiency, specific granule deficiency, and Chediak-Higashi are types of (blank)
granule abnormalities
61
Type I integrin deficiency and type 2 E-selectin ligand deficiency are types of (blank)
leukocyte adhesion deficiency
62
What is the most important means of defense against extracellular bacteria, fungi, and protozoan parasites?
Phagocytosis and intracellular killing
63
What are the two methods in which particulate microbes are engulfed?
endocytosis and micropinocytosis
64
What are the most important phagocytic cells?
macrophages and neutrophils
65
Invagination of the cell membrane creates the (blank)
phagosome
66
Lysosomes filled with antimicrobial substance fuse with the phagosome to form the (blank)
phagolysosome
67
T/F: most micbrobes are killed and digested in the phagolysosome
True
68
what type of G-protein receptor is needed to form NADPH oxidase
GPCR C5a receptor
69
where is NADPH in the phagolysosome?
membrane bound
70
what does NADPH oxidase make that kills bacteria? What is this process called?
superoxide and hydrogen peroxide; the RESPIRATORY BURST--needs lots of oxygen to synth these molecules
71
pH of the lysosome is lowered to...
activate hydrolases and antimicrobial peptides that kill the microbes
72
What allows protons to be pumped into the phagolysosome to lower the pH?
NADPH oxidase
73
what X-linked protein can cause NADPH oxidase defects if its is not present?
gp91
74
What are the mechanisms of phagolysosome hostility?
1. Acidification
2. toxic oxygen species
3. toxic nitrogen oxides
4. antimicrobial peptides
5. enzymes
6. competitors
75
What are the ROS?
superoxide, hydrogen peroxide, singlet oxygen, hydroxyl radicla, and hyphohalite OCl-
76
What are the macrophage antimicrobial peptides?
1. cathelicidin
| 2. elastase-derived peptide
77
What are the neutrophil antimicrobial peptides?
1. a-defensins (HNP1-4)
2. b-defensins HBD4
3. cathelicidin
4. azurocidin
5. bacterial permeability inducing protein (BPI)
6. lactoferrin
78
lysozyme digests the cell wall of some gram (blank) bacteria
positive
79
What are the phagolysosome competitors and what makes them?
neutrophils; make lactoferrin and B12 binding protein
80
CGD is caused by the failure of (blank) in the phagolysosome
NADPH oxidase
81
What causes the x-linked variant of CGD?
gp91
82
What are the two modes of inheritance of CGD?
X-linked recessive and autosomal recessive
83
Pyogenic bacteria and fungi cause (blank) on the skin and various organs in CGD
granulomatous lesions
84
Flow cytometry using (blank) reveals a defect in the respiratory burst
dihydrorhodamine
85
What is the treatment of CGD?
long term antibacterial and antifungal prophylaxis
86
Is there a cure for CGD?
Tx with IFNg or bone marrow transplant
87
What is the mode of inheritance of Chediak-Higashi?
autosomal recessive
88
What is the molecular defect in Chediak-Higashi?
defect in microtubule polymerization; decreases phagolysosome formation
89
When does C-H present and what how does it present?
Early childhood with recurrent pyogenic infections (staph and strep), especially GINGIVAL INFECTIONS
90
Partial albinism is a sign of (blank)
Chediak-Higashi
91
What is abnormal with neutrophils and eosinophils in C-H?
large lysosomal vesicles
92
What is the Tx for C-H?
prophylactic antibiotics and bone marrow transplant
93
Pt's with (blank) also present with pyoderma
C-H
94
what is the golden test for diagnosis of Chediak-Higashi?
peripheral blood smear, looking for humungous granules in neutrophils and eosinophils
95
What is the most common defect in granulocyte-mediated defenses?
Neutropenia
96
What are the causes of acquired neutropenia?
drug induced (especially chemo) and autoimmune (anit-neutrophil Abs)
97
What are the three hereditary causes of neutropenia?
1. Familial (benign, ethnic)
2. Infantile genetic agranulocytosis (severe congenital neutropenia)
3. Cyclic neutropenia
98
Neutropenia leads to recurrent (blank) infections
pyogenic
99
How do you measure neutropenia?
decreased absolute neutrophil count
100
What is the lower limit for ANC?
1500-2000cells/mm3 blood
101
Stapah, gram (blank) bacteria, fungi, and (blank) bacteria are common in neutropenia
gram negative and encapsulated
102
Pyogenic bacteria and fungi can lead to life threatening neutropenic (blank)
sepsis
103
What is a common source of infection while in the hospital in pts with neutropenia?
in-dwelling catheter
104
How do you treat neutropenic infections?
Broad spectrum antibiotics followed by targeted antibiotics once the bacteria is ID'd
105
Pt's with neutropenia are treated with (blank) before subsequent rounds of chemotherapy
human recombinant granulocyte colony stimulating factor (hrG-CSF)
106
Severe Congenital Neutropenia (aka SCN or Kostmann Disease) presents at what age?
in infants
107
How does SCN present?
recurrent infections of the skin, soft tissues, lungs, deep organs, and sepsis.
108
What is the ANC level in SCN?
below 200
109
SCN is caused by impaired (blank)
myelopoiesis
110
Dx of SCN is supported by blockage of neutrophil differentiation at the (blank or blank) stage
promyelocyte or myelocyte stage
111
rhG-CSF is used to treat patients with (blank), but risks myelodysplasia and acute myeloid leukemia
SCN
112
Bone marrow transplants to treat SCN are only used when?
in infants refractory to rhG-CSF treatment
113
neutrophils are called to sites of inflammation by tissue (blanks)
macrophages
114
What are the four types of adhesion molecules?
VISI
1. vascular addressin CD34
2. Integrin (LFA-1)
3. Selectin (L-selectin)
4. ICAM-1
115
CD18 is a component of which adhesion molecule?
ICAM1
116
What are the four general steps of neutrophil migration?
1. rolling adhesion
2. tight binding
3. diapedesis
4. migration
117
Is CD18 attached to the endothelium or to the neutrophil?
endothelium
118
What molecule is used during rolling adhesion of neutrophils?
E-selectin
119
What adhesion molecule is used during tight binding?
ICAM1
120
Leukocyte Adhesion Def. type I presents with?
recurrent bacterial infections
121
Adhesion molecule defects in LAD 1 result in (blank) ((3)
bad neutrophil chemotaxis, phagocytosis, and neutrophilia (increased Neuts)
122
Omphalitis, pneumonia, gingivitis, and peritonitis are characteristic of (blank)
LAD type 1
123
what is the inherited molecular defect in LAD type 1
deficiency of the B-2 integrin subunit of CD18
124
How do you diagnose LAD type 1?
CD18 flow cytometry
125
What is LAD type 1 Tx?
bone marrow transplant
126
High levels of CRP indicate what?
an inflammatory process is active
127
The acute phase response is mediated by (blank)
acute phase proteins, duh!
128
CRP is a (blank)
opsonin
129
What binds and sequesters iron to stop bacterial growth?
ferritin
130
Fibrinogen is a (blank) factor
coagulation factor
131
Fibrinogen levels correlate with (blank), an inflammation indicator
erythrocyte sedimentation rate (ESR)
132
T/F: Albumin production is normal during acute phase
FALSE; albumin production is LOW
133
Bacteria induce macrophages to produce IL6 which acts on (blank)
hepatocytes
134
What are the acute phase proteins?
1. serum amyloid protein
2. CRP
3. fibrinogen
4. Mannose binding lectin
5. SPA and SPD
135
CRP binds (blank) on bacterial surfaces
phosphocholine
136
CRP as as a (blank) activating complement when it binds to bacteria
opsonin
137
Mannose binding lectin binds to mannose on bacterial surfaces, acting as a (blank), activating complement
opsonin
138
Viral RNA induces interferon(blank) gene expression
alpha/beta
139
Where does viral mRNA bind to signal for IFN expression?
endosomal TLR-3
| MDA-5/RIG1/CARDIF in the cytosol
140
What are the effects of IFNa and IFNb?
1. induce resistance to viral replication in all cells
2. increase expression of ligands for receptors on NK cells
3. Activate NK cells to kill virus infected cells
141
in an IFNa/b primed cell, viral dsRNA activates (blank), which degrades viral/host mRNA causing apoptosis
RNase L
142
IFNa/b increases the expression of (blank) on nucleated cells
MHC I
143
NK cells are derived from (blank)
lymphoid progenitor cells
144
What activates NK cells?
Type I IFNs and cytokines (TNF-a and IL12)
145
what cytokine do NK cells produce in large quantities?
IFNg
146
What two molecules do NK cells use to kill virus infected cells, cells with intracellular pathogens, and tumors?
perforins and granzymes
147
Can NK cells recognize normal self MHC I?
yes
148
T/F: NK cells will kill cells that express stress molecules
YES
149
(blank) cell deficiencies will lead to severe/recurrent infections of herpes viruses (VZV, HSV, EBV, and CMV)
NK cells
150
What is the name of the process by which NK cells bind and kill antibody-coated pathogens?
antibody dependent cell mediated cytotoxicity
151
Describe the timeline of innate immunity cytokine release and cell response?
1. IFNa/b, TNF-a, and IL12 produced from 0-4 days
2. NK mediated killing of cells from 0-6 days
3. T-cell mediated killing of cells from 2 days onward
4. Virus titer peaks around four days and lowers as T cell response grows
