Week 1 Flashcards
(103 cards)
1
Q
bacterial LPS is recognized by what 3 things
A
TLR4, MD2, and CD14
2
Q
which domain does CD8 bind to
A
α3 of MHC I
3
Q
which domain does CD4 bind to
A
β2 of MHC II
4
Q
positive thymic selection vs negative
A
positive: T cells need to be able to recognize self
negative: T cells can’t be TOO reactive to self; occurs by dendritic cells/macrophages
5
Q
epitope
A
where the Ab binds to the Ag (aka antigenic determinant)
6
Q
papain
A
cleaves Ab into Fab (contains variable region for Ag binding) and Fc regions (class switching occurs here)
7
Q
Abs can fight infections by 3 ways. What are they?
A
- neutralization: binds directly to toxin/ inhibits it from binding to pt
- opsonization: Abs coat bacterium then a macrophage eats it
- complement activation
8
Q
what Igs do complement?
A
IgG and IgM
9
Q
what Ig is for sensitization of mast cells?
A
IgE
10
Q
What Ig is for sensitization for killing by NK cells?
A
IgG
11
Q
what Ig does opsonization?
A
IgG
12
Q
what Ig is for transport across epithelium?
A
IgA
13
Q
What Ig can cross placenta?
A
IgG
14
Q
what part of an Ab determines the isotype?
A
Fc
15
Q
ADCC (antibody dependent cell cytotoxicity)
A
Ab binds to Ag on target cells
Fc receptor on NK cells recognizes the bound Ab
Cross linking of Fc R tells NK cell to kill target cell → apoptosis
16
Q
bias definition
A
any systemic error in design, conduct, or analysis of study that results in mistaken estimate of exposure on risk of disease
can occur at any stage of study and in all studies (more often in retro
17
Q
selection bias
A
error due to differences in those who are selected/participate in a study and those that don’t
18
Q
information bias
A
flaw in measuring exposure/outcome that may result in differential accuracy of info. between comparison groups
19
Q
selection bias non response
A
rates of refusal to participate differ in those with disease who are exposed vs those without disease who are exposed
*to combat: keep recogrds of non-responders/analyze data
20
Q
info. bias: diagnostic
A
validity of diagnosis altered by knowledge of exposure
ex. OC and DVT
21
Q
nondifferential misclassification of exposure
A
amount/direction of misclassification is similar b/t cases and controls
always results in underestimating OR - can result in false negatives
22
Q
differential misclassification of exposure
A
amount of misclassification differs b/t cases and controls - having outcome alters exposire history/recall
23
Q
confounding
A
estimate of exposure distorted because mixed with extraneous factor; is the factor on which the exposed and unexposed differ
must be a risk factor in the unexposed group/associated with the exposure
24
Q
opsonization process
A
- Ab binds to bacterium
- Ab coated bacterium binds to Fc receptors on cell surface (MACROPHAGES AND NEUTROPHILS, IgG NOT IgM)
- macrophage endocytoses bacterium coated
- lysosomes fuse with phagosome creating phagolysosome
25
Humira and Embrel are MoAb to what
TNFα
26
hapten
has 1 epitope
27
affinity vs. avidity
**affinity**: strength of single Ag combining site of an Ab and a single epitope of an Ag
**avidity**: strength of binding of an Ab for an Ag (ex. IgM has greater avidity than IgG because it has more binding sites)
28
toxoid
altered protein toxin used in tetanus vaccine; good becasuse it is a cross reacting Ag that induces an immune response that protects
29
when does maximum precipitation occur?
at equivalence with with molar ratio of Ag to Ab is in slight Ag excess giving maximal crosslinks
30
agglutination
what Ab is best at that?
combination of an Ab with a particulate Ag (RBC, latex particle, bacteria). Works with insoluble (particulate) Ag - see visible clumps in minutes
IgM\>IgG because more binding sites
more sensitive than precipitation
31
titer
1/highest dilution of anti-serum that still gives a positive agglutination reaction
32
precipitation
soluble antigen, only precipitates at optimal AgAb ratios. IgG best at this.
33
radioimmunoassay RIA
an inhibition assay - radioative Ag gets displaced by unlabeled and then measure that
34
ELISA
coat plates with Ag, add serum. if Ab is present it will bind and then give second Ab linked to enzyme that gives color
can quantitate by testing dilutions - the last dilution that still gives measurable color is the titer
35
direct vs. indirect fluoresence
**direct**: Fl labeled Ab to T cell marker (CD3), then T cells with it will fluoresce
**indirect**: looking for Ab in patients serum: incubate serum with test tissue; if Ab present, will bind (invisible) then add Fl labeled anti-Ig
36
how many loci are there for Ig genes
3: 2 light chain (kappa and lambda, chromosomes 2 and 22)
1 heavy chain (chromosome 14)
37
VDJ recombinase
lymphocyte specific enzymes RAG1 and RAG2 recognize and cleave unique recombination signal sequences that flank Ig gene segments - same for B and T cells
defect = SCID
38
TdT (terminal deoxynucleotidal transferase)
adds extra nucleotides when joining of Ig gene segments is imprecise
39
allelic exclusion
normal B cell has single functional heavy chain rearrangement and single functional light chain rearrangement - means 1 B cells makes a single tupe of Ab with single Ag specificity
40
what is class switching controlled by? what enzyme is used?
T cells and Ag; rearrangements occur @ DNA level without RAG1/2
AID = enzyme for class swtich
occurs in germinal centers of 2° lymphoid organs
41
affinity maturation
during course of immune response, random mutations occur within rearranged variable regions; if they result in inc. affinity for the Ag, the b cells will be positively selected and expanded
42
structural proteins in virus
non-structural proteins in virus
**structural:** capsid, nucleocapsid (NA and capsid), matrix
**non-structural**: polymerase, TFs
43
capsid
protein shell surrounding nucleic acid genome in viruses
44
nucleocapsid
"core" of virus
nucleic acid/protein assembly packaged in virion
45
tegument
regulatory proteins in the virion located between the nucleocapsid and envelope
46
are enveloped or non-enveloped viruses more sensitive to heat, drying, detergents?
enveloped are more sensitive!
transmitted by direct contact (blood/sex) and transmitted via respiratory
non-enveloped are tougher droplets (influenza, measles, rubella, VZV); can be fecal-oral route
47
structure of the following virses:
HSV (HSV1 and 2, EBV, CMV), HBV, smallpox
DNA enveloped
48
structure of the following virses:
adenovirus, papillomaviruses, parvovirus
DNA nucleocapsid virus
49
structure of the following virses:
influenza, RSV, measles, mumps, rabis, HTLV, HIV, HCV
RNA enveloped viruses
50
structure of the following virses:
enteroviruses (polio, coxsackie, echovirus, HAV), rhinovirus, rotavirus, norovirus, HEV
RNA nucleocapsid viruses
51
segmented RNA genoma
influenza virus made of 8 segments of viral RNA that carry the info needed to make virus particles; each segment can make at least 1 protein
52
what does influenza recognize and on what types of cells
sialic acid on epithelial cells; mediates entry and delivery of virus
53
what does HIV recognize and on what types of cells
recognizes CD4/CXCR4 on T cells
54
replication of DNA viruses:
1. where?
2. what polymerase does it use?
3. examples
nucleus
uses host DdRp to make viral mRNA
ex. parvovirus, papillomavirus, adenovirus, HSV (poxvirus is weird and replicates in cytoplasm by carrying its own polymerase)
55
replicaton of (+)ssRNA viruses
1. where?
2. what polymerase does it use?
3. examples
1. cytoplasm
2. can be used directly as mRNA but carries RdRp for making more virions
3. poliovirus
56
replication of (-)ssRNA viruses
## Footnote
1. where?
2. what polymerase does it use?
3. examples
1. cytoplasm
2. RdRp using the **negative strand as template**
3. influenza, measles, rabies
57
replication of dsRNA virses
## Footnote
1. where?
2. what polymerase does it use?
3. examples
1. cytoplasm
2. RdRp uses - strand as template; can unwind dsRNA
3. rotavirus
58
replication of retroviruses (HIV)
reverse transcriptase (RdDp) → DNA unwinding then hydrolysis of RNA in RNA-DNA hybrid by RNAse H
DNA viral copy is transcribed into viral mRNA by host RNA pol
59
infectious nucleic acid
purified viral DNA or RNA without protein that can carry out entire viral growth cycle → production of complete virus particles
only in virses that don't require polymerase
60
can RdRp proofread?
no! leads to diversity in RNA viruses
61
what type of viruses do budding vs lysis?
budding = enveloped; take from host cell membrane
lysis = non-enveloped; break membrane
62
virulence factors
allow invasion from other sites
63
capsule
discrete layer of polypeptide/polysaccharide that masks PAMPs like LPS and peptidoglycan that allow bacteria to avoid the innsane immune system/complement deposition
64
pili
example of antigenic variation; expressed from pilin gene - there are silent genes and can be recombined to escape immune recognition
65
gene slippage
phase variation = turning genes on and off
genes have many repeats in nucleotides early in sequence
66
gene inversion
flagellin encoded by fimA which is recognized by TLR4; recombinase mediates gene inversion at promtor
67
T3SS
type 3 secretion system
* responsible for direct injection of protein into eukarotyotic cells
* proteins are effectors that kill/disable/adapt eukaryotic cells for intracellular bacterial growth
* only in gram negative bacteria
68
T4SS
type 4 secretion system
* secretion system responsible for transfer of DNA during conjugation
* can also secrete proteins/complexes
* in gram negative and gram positive
69
T5SS and T7SS
* uses Tat and Sec to secrete toxins, receptor binding proteins, pili
* T7SS new virulence factor ID'd
* only in gram negative
70
siderophores
iron binding proteins secreted by bacteria; can outcompete human proteins for Fe (needed for rapid bacterial growth)
71
neutrophils
* polylobulate nuclei
* primary (azurophilic) and secondary (specific) granules
* stored in BM and released when need to fight infection
72
C3b and opsonization
enhances phagocytosis (opsonization)
CR1 on macrophage/neutrophil binds C3b on bacterium (from complement deposition) → endocytosis of bacterium by macrophage → phagosome → phagolysosome
73
metabolic consequences of phagocytosis
1. inc. in glycolysis by hexose monophosphate shunt
2. increase in uptake of O2
3. increase in production of peroxide
4. pH of phagolysosome acidifies to 4.7
74
neutrophil microbicidal substances
* bleach (hypochlorite)
* cationic proteins (punch holes in membranes)
* defensins (antibiotic properties)
* lysozyme (breaks down microbial peptidoglycan)
75
chronic granulomatous disease
defects in cytochrome b gene/NADPH oxidase - can't make peroxide and superoxide. staph/e.coli/candida susceptible
76
CRP
APRP in liver; binds phosphocholine on pneumococci and triggers complement; an opsonin
77
mannose binding lectin
APRP made in liver
binds mannose motifs on bacteria, triggers complement
78
lipopolysaccharide binding protein LBP
APRP made in liver
binds LPS from gram neg and helps it bind CD14 receptors on macrophages which triggers TLR4
79
serum amyloid P
binds to several bacteria
80
TLR2 target
gram positive bacteria, mycobacteria, yeasts and other fungi (recognizes peptidocglycans, GPI-linked proteins, lipoproteins, zymosan)
81
TLR4 target and downstream effects
gram negative bacteria, RSV (recognizes LPS and F-protein)
downstream:
* TRIF pathway: type I IFNs
* Myd88 pathway: TNFα thru NFKB
82
cytokine storm of septic shock
macrophages releases tons of TNFα, IL-1, IL-6, and IL-12
83
IL-8
secreted by macrophages; chemoattractant to neutrophils
84
IL-6
induces acute phase liver proteins
85
what is the classical complement pathway initiated by
AgAb complex or CRP
86
C1qrs
in classical pathway of complement;
C1r and s are serine proteases that are activated when C1q binds to AgAb complex (binds 2 IgG molecules or 1 IgM)
C1q only binds to Fc tail of IgG or IgM if they are bound to Ag!
87
does complement get activated when IgM or IgG are soluble?
no!!! 1 IgM or 2 IgG need to be antigen bound thru Fc tail
88
MAC
membrane attack complex
C5b6789m binds sequentially to form complex on cell surface that creates a pore to disrupt cell membrane
89
3 distinct sites of classical complement anchoring
1. C1qrs
2. C4b2a3b
3. C5b6789n (MAC)
90
alternate pathway of complement is triggered by what?
what enzyme/protein complex is on surface?
microbe
C3 convertase → C3bBb then C3b amplification
C3 convertase is stabilized by **properdin**
C5 convertase splits C5
91
lectin pathway of complement
triggered by MBL (protein with 6 helices) part of innate IS that recognizes microbes in absence of Ig
activates mannose binding lectin assoc. serine proteases (MASPs) to initiate complement
92
C3a
chemotactic for neutrophils, causes mast cells to release histamine
93
C3b
major opsonin, leads to inc. phagocytosis
94
Factors H and I
inhibit alternate pathway of complement
95
carboxypeptidase
degrade C3a and C5a
96
C1 esterase inhibitor
absence?
blocks C1r and C1s
absence = hereditary angioneurotic edema
97
decay accelerating factor
breaks down C4b2a and C3bBb
98
membrane co-factor protein MCP
dissociates C4b2 and C3bBb and fcailitates C4b and C3b degradation by Factor I
99
homologous restriction factor/CD59
defect?
block MAC by interfering with C9 attachment/polymerization
defect = paroxysmal nocturnal hemoglobulinuria
100
C4 and C2 deficiency
autoimmunity
101
C5-8 deficiency
susceptibility to gram negative infections
102
C3 deficiency
recurrent life threatening infections
103
factor I deficiency
uncontrolled activation of alternate pathway and depletion of C3
