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Flashcards in Immuno CCOM 1 Deck (129):
1

What do cells of the innate response recognize during an immune response?

structural motifs common to many pathogens: PAMPs
Pattern Recognition Receptors are responsible for this:
Toll receptors - CD14 binds w LPS and complexes with TLR4

2

What condition might exhibit an elevated CD14 level?

kawasaki disease

3

What are Nod-like receptors used for?

they can form inflammasomes that result in the initiation of cell death and cytokine release
CYTOSOLIC

4

What are some example of PAMPs?

LPS
mannose residues
f-met-leu-phe
bacterial peptidoglycan

5

What does Mannose binding lectin bind to specifically on bacteria?

repetitive oligosacchardies

6

What do scavengar receptors recognize?

anionic polymers
acetylated low density lipoproteins
old and dying host cells
ex: PSR for phosphatidyl serine during apoptosis

7

What are some factors in the innate immunity?

Type 1 interferons-cytokines
phagocytes
complement proteins
NK cells
gamma-delta T lymphocytes
pyrogens (exo/endogenous)

8

What other cell may have similar function to NK cells?

gamma-delta T lymphocytes

9

What are exogenous and endogenous pyrogens?

exo: products of microorganisms that induce or act directly on hypothalamus
endo: IL1, IL6, TNFa - cause release of arachidonic acid that metabolizes to PGE2 which acts on hypothalamus

10

Describe active and passive immunity vs natural and acquired

active natural: pt acquires disease and recovers
active acquired: pt vaccinated
passive natural: mother passes immunity
passive acquired: pt given preformed IGs

11

Where do all leukocytes originiate from?

bone marrow

12

Where do lymphocytes first encounter pathogens?

secondary lymphoid tissues

13

Which cell type does the spleen have the most?

B lymphocytes

14

What is the more accurate view of the function of lymph nodes?

trap foreign molecules
concentrate these molecules in same location as appropriate WBC to increase opportunity

15

How do lymph node cells constantly recirculate?

about 2% of the lymphocyte pool recirculates every hour
to feel out the environment
-surveillance and communication
-80% lymphocytes end up in diff node by end of day

16

What are properiteis of MALT?

non-encapsulated
MALT cells recirculate to only other mucosal tissues

17

describe the markers for T cells

All are CD3
some are CD4 (helper)
somer are CD8 (ctotoxic)

18

What types of cells do hematopoeitec stem cells give rise to?

RBCs
WBCs
platelets

19

What are cytokine made of?

protein or glycoprotein
they act locally

20

What are the only cells that produce antibodies?

B cells

21

What is biological activity of Abs?

phagocytose
help lyse organisms
clump organisms together

22

What are some reducing agents of Abs?

mercapto: breaks apart 4 chains at disulfide bonds
Papain: breaks hinge to yield 3 fragments
Pepsin: yields 2 F(ab)2 (divalent)

23

After papin digests Abs, describe the properties of the fragments

Fab can still bind Ag
Fc cannot bind Ag but is:
crystallizable
complementable C1q
phagocytes
placenta mediator

24

What is the order of concentraion of Igs in descending order?

GAMDE

25

What determines the type of heavy chain? What does the heavy chain define?

a.a sequence
heavychain defines isotype of Ig

26

What is the hypervariable region

Where there is contact with the epitope of the antigen. The regions that contact epitope is the idiotype

27

How many constant domains are on the light chain and heavy chain?

light: 1
heavy: 3

28

Which is the only Ab to cross the placenta?

IgG

29

What are the fucntions of IgG?

neutralizes toxins...
opsonizes antigens/bacteria
complement activation

30

IgM

secreted as pentamer
Ag receptor as a monomer
J chain joins units together
no hinge region
extra constant domian in heavy
agglutinizes
complements strong

31

What is the first Ab type formed in the primary immune reponse?

IgM

32

IgA

a dimer linked by J chain
has a secretory component in secretions-protects from protease
protects on mucosal surfaces

33

What is the predominant Ab found in bodily secretions?

IgA

34

Which Ab is passed along through breast milk?

IgA

35

IgE

simliar to IgM structure
allergic reactions (T1 hypersens)
releases histamines
parasitic infections

36

IgD

similar in structure to IgG
not sure of function really
might serve as marker of B cell differentiation

37

How can Igs be antigens?

because they are glycoproteins
ex: human Ig in mouse Igs.
ex: autoimmune

38

Do plasma cells produce IgD?

No

39

Half life of Igs?

G: 23 days
A: 5.5
M: 5
D: 2.8
E: 2

40

Where is the site of hematopoeisis throughout life?

until 6 mo gest: yolk sac and liver
after: marrow

41

What is the cell marker for a hematopietic stem cell?

CD34

42

What is the order of B cell development?

HSC Cd34
pro B cell
pre B cell
immature B cell
mature B cell

43

Which cytokines interact w pro B cells to continue differentiation?

IL 7
IL 3
(also stromal cells)

44

What happens when IL 7 and IL 3 interact w pro B cell?

Ig genes for variable heavy chain rearranges

45

Define the Pre B cell

expression of ruly rearranged Ig heavy chain and initiation of light chain rearrangement

46

Describe the first checkpoint in B cell dev

surrogate light chain interacts w rearranged heavy chain. It goes to cell surface. If they dont interact-> death
if they do-> live/allelic exclusion

47

What is allelic exclusion?

even though B cell encodes for 2 heavy chains and 2 light chains, only one of the loci will be expressed

48

Define the immature B cell

expression of surface IgM (sIgM)

49

What happens if the sIgM interacts w a soluble antigen? an insoluble antigen?

soluble: clonal anergy
insoluble: deletion/apoptosis

50

Define the mature B cell

expression of both sIgM and sIgD

51

Describe the specificities of sIgM and sIgD on the developing b cell

they have the same specificity
(different isotype but same idiotype?)

52

Which transmembrane proteins does Ig associate with in the developing B cell?

Ig-alpha
Ig-beta
(all form BCR)

53

What must occur for the B cell to develop beyond the matrue B cell?

crosslinking of BCRs through antigen epitopes in secondary lymphoid tissues

54

What is the Clonal Selection Theory?

differentiating stem cells rearrange their genes for the hypervariable region to produce clones of B cells that respod to a specific epitope. Produces plama cells or memory B cells

55

What is tolerance?

specific unresponsiveness
prevents reaction against self
checkpoint

56

What are T-independent Ags?
examples?

Can activate B cells without help from T cells
LPS
flagellin
dextran
polysaccharides
any with multiple epitopes
any that crosslinks sIg

57

What are Type 1 T-indep Ags?
What response do you see?
ex?

activate B cells without using BCr
stim polyclonal activation
heterophile Abs-many specificities
B cell mitogens
LPS
Ebstein-Barr

58

What are Type 2 T-indep Ags? What response do you see? ex?

activate B cell by using BCR (sIg), and crosslinking sIg's
capping- moves to one pole
Monoclonal Activation
B cells with only 1 specificity
ex: carb, peptides, dextran

59

What class of Ab is synthesized in a Type 2 T-indep response?

only IgM

60

What happens if a Type 2 T-indep antigen becomes conjugated to a protein?

Switches to a T-dependent response
IgG2 is major Ab made

61

Describe the memory response for a T-indep antigen?

there is no memory response
identical to primary response

62

What are characteristice os T-dependent Ags

proteins, glycoproteins, or conjugated to proteins

63

Which age group responds poorly to T-indep Ags?

children under 2 years

64

Describe T-depedend responses

isotype switch occurs
but specificity stays same!
APC, T cell, B cell needed

65

Which cell surface ligand mediates the development from mature/naive cells to memory or plasma cells?

CD40 (on B cell)
CD40L (on T cell)

66

Why are memory cells faster to react to second exposure of antigens?

Isotype switch already ocured
At a higher activation state
more precursors
higher affinity Ag receptors

67

What is affinity maturation?

increased Ab binding strength somatic mutations in variable
'survival of fittest'
BCRs on B cells are better too
(remember specificity does not change)

68

Describe the Lag phase of a primary resopnse

B cells undergo clonal selection
7-10 days

69

What is the first type of Ab produced in a primary response?
secondary repsonse?

primary: IgM
secondary: IgG is predominant

70

What is linked recognition?

eptiopes must be physically linked on same anithgen

71

What are examples of conjugated vaccines?

influenze type b
pneumococcal conjugate vaccine

72

What protects infants from disease?

maternal Ig
infant Ig after 6 mo
normal gut flora

73

What types ofinfections does breast feeding protect from

respiratory
GI

74

How many V, D, J and C chains in heavy and light chaings?

light: Vk=40 ; Jk=5 ; Vl=40 ; Jl=4
heavy: Vh=50 ; Dh=20 ; Jh=6 ; Ch=9

75

Desribe how you use a paired sera test

collect serum sample 1 durin illness
and sample 2 after recovery
If titer is 4X increase, then disease
ex: SARS

76

What is sensitivity?

a measure of ability to identigy diseased cases
Most helpful when negative-to rule out
there are false positives
good for screenings

77

What is specificity?

measure of ability to test non-diseased
Best when it is positive-to rule in
there are false negatives
good for confirmatory

78

What are the primary binding tests?

1) ELISA
2) IF
3) Blotting
4) Flow Cytometry

79

Describe ELISA

Add known antigens to well
Add diltued uknown serum
Add 2nd Ab conjugated w enzyme
Add chromagen for color

80

Descfribe Direct IF

Add tissue specimen to slide
Add Ab w conjugated flourescent
Look under UV scope to see it

81

Describe Indirect IF

When you dont have tissue, but you have serum (Abs)
Add 2nd Ab w Fluorescent

82

Immunoblotting

Separate Proteins
Transfer/Blot
Nitrocellulose
Detect bound Abs

83

Compare ELISA and blotting specificities and sensitivities

ELISA: high sense, low spec
Blot: low sense, high spec

84

What are ELISAs used?

pregnancy tests
viral hepatitis
RIST/RIA

85

When is IF used?

DFA: rabies, herpes
IFA: assay Abs

86

When is blotting used?

HIV, confirmatory
Alzheimer's

87

FACS

measure number of cels w certain surface markers
CD4:CD8 ratios of HIV pts
tumor cells w markers
PBL populations

88

What is the CD4:CD8 ration in normal patients?

2:1
less in AIDS patients. Treatment returns to normal

89

What is the prozone effect?

insoluble precipitates:
antibody excess zone-none
equivalence zone- formed
antigen excess zone-none

90

Describe the Ouchterlony test

3 wells: 1) pt sample 2) known lab sample w tested Ag 3) Ab against Ag

3 interpretations: 1) complete identity-rainbow 2) Non-Identitiy- X 3) Partial Identity-spur

for fungal diseases

91

Which molecules are opsonins?

C3b
C4b

92

Which molecules are anaphylatoxnis? What do they do?

C5a > C3a > C4a
degranulation of mast cells and release of histamine/vasoactive

93

Which molecules are for margination? What do they do?

C5a
allows WBCs to adhere to vessels

94

Which is for chemotaxis?

C5a > C3a

95

What is the function of the membrane attack complex?

permeablizing membranes by adding pores to break it down via osmotic pressure

96

Which molecules regulate vascular tone?

C2a
C2 kinin

97

How are immune complexes removed in the complement cascade?

in plasma: via RBCs (via CR1)
in liver: phags

98

Describe the stains of basopphils, eosinophils, and neutrophils

basophil: dies w basic dyes
eosinophil: dyes w acid dyes
neutro: noes not stain w either

99

What are cells of the mononuclear phagocytic system?

monocytes, macrophages and their derivatives

100

What is the main signal to activate monocytes for phagocytosis?

IFN-gamma

101

What activates M1 macrophages?
what do they secrete?

classicaly acitaved
IFN-gamma, TLR ligands
secrete IL-1beta, IL-6, TNF

102

What activates M2 macrophages? What immune responses are they involved in?

alternatively activated
activated by IL-4, IL-13
parasitic immunity, allergies, wounds, tissue remodel

103

What are some positive chemotactic signals?

C5a
Fibrinopeptide B
Proinflamm. cytokines:IL1, TNF-a
chemokines: IL-8
LTB4 (lipoxygenation/arach acid)
LPS

104

What can cytotixic chemo drugs induce?

neutropenias

105

What are the 4 stages of phagosytosis?

1. chemotaxis
2. adherence
3. Ingestion
4. Digestion

106

name some adherence molecules for phagocytosis

opsonins:
C3b
Fc of Abs (IgG1, IgG3)
C-reactive protein

107

What are the 3 mechanisms for digestion in phagocytosis?

1. Respiratory burst
2. phagosome-lysosome fusion
3. Toxic nitrogen oxides

108

Describe Respiratory burst

superoxide formed via NADPH oxidase
H2O2 formed via superoxide dismutase
OCl- formed via myeloperoxidase

109

Describe phagosome-lysosome fusion

lysosomes from granules
defensins and protegrins disrupt mmbrane
lactoferrin chelates iron

110

Describe toxic nitrogen oxides

the cNOS and iNOS pathways produce NO.
No inhibits iron enzymes and damages pathogen DNA.
(iNOS and resp burst form peroxynitrite)

111

What are the main cytokines that induce inflammation?

IL-1
IL6
IL-8
TNF-a
IL-12

112

Which cytokines induce fever?

IL-1
IL-6
TNF-a

113

Which receptors/ligands are involved in rolling adhesion?

sialyl_Lewisx on the neutrophil:
E-selectins on endothelials

114

Which receptors/ligands are involved in tight binding?

integrins on neutrophil:
ICAM-1 on endothelials

115

Which receptors/ligands are involved in diapedesis?

integrins on neutrophil:
CD31 (PECAM)

116

Which complement pathway inhibitors can cause meningitis?

C5-8 deficiency
properdin deficiency
MBL deficiency

117

What cels are the major producers of IFN-gamma?

CD4 helper T cells
NK cells

118

What type of surface oplarity of bacteria enhance phagocytosis?

hydrophobic surfaces enhance phagocytosis
ex: M. tuberculosis
hydrophilic empede
ex: s. pneumoniae

119

What is the acute phase response?

a systemic resopnse to local inlammation
fever
increased hormone (ACTH)
leukocytosis
acute phase proteins

120

name some actue phase proteins

C3
CRP
haptoglobin
factor B
________
albumin/prealbumin
fibrinogen

121

What can an elevated CRP level indicate?

unstable coronary artery disease
if in healthy: higher risk of CV disease

122

What is ESR?

erythrocyte sedimentation rate
Bigrinogen reduces charge on RBC so they clump.
ESR~ level of inflamm response
TB, tissue necrosis, rheumatic, MI, malignancy

123

What is the hallmark of local acute response?

influx of PMNs

124

What are the 3 enzyme cascades that are activated when endothelial cells are damaged?

complement system
blood clotting/kinin system
fibrinolytic system

125

What are matrix metalloproteinases?

degrade ECM proteins so free moveement of inflammatroy cells can occur

126

Describe the effedct of adenosine in inflammation

A1 receptor: enhances inflammation
-activated at low concentrations
A2 receptor: suppresses inflammation
-activated at high concentrations

127

What is the hallmark of chronic inflammation?

accumulation/activation of macrophages
-granulomas too

128

Descsribea granuloma

necrotic center
fibrosis/scar formation
enlargement and replacement of normal tissue
M1 center, M2 periph

129

Describe tetanus
incubation period?
causes what?
immune response?

2 weeks incubation
causes spastic paralysis
pharm active levels but too low for immune response
No natrual active immunity