Immuno CCOM 1 Flashcards

1
Q

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

A

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

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2
Q

What condition might exhibit an elevated CD14 level?

A

kawasaki disease

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3
Q

What are Nod-like receptors used for?

A

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

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4
Q

What are some example of PAMPs?

A

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

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5
Q

What does Mannose binding lectin bind to specifically on bacteria?

A

repetitive oligosacchardies

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6
Q

What do scavengar receptors recognize?

A

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

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7
Q

What are some factors in the innate immunity?

A
Type 1 interferons-cytokines
phagocytes
complement proteins
NK cells
gamma-delta T lymphocytes
pyrogens (exo/endogenous)
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8
Q

What other cell may have similar function to NK cells?

A

gamma-delta T lymphocytes

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9
Q

What are exogenous and endogenous pyrogens?

A

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

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10
Q

Describe active and passive immunity vs natural and acquired

A

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

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11
Q

Where do all leukocytes originiate from?

A

bone marrow

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12
Q

Where do lymphocytes first encounter pathogens?

A

secondary lymphoid tissues

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13
Q

Which cell type does the spleen have the most?

A

B lymphocytes

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14
Q

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

A

trap foreign molecules

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

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15
Q

How do lymph node cells constantly recirculate?

A

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

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16
Q

What are properiteis of MALT?

A

non-encapsulated

MALT cells recirculate to only other mucosal tissues

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17
Q

describe the markers for T cells

A

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

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18
Q

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

A

RBCs
WBCs
platelets

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19
Q

What are cytokine made of?

A

protein or glycoprotein

they act locally

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20
Q

What are the only cells that produce antibodies?

A

B cells

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21
Q

What is biological activity of Abs?

A

phagocytose
help lyse organisms
clump organisms together

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22
Q

What are some reducing agents of Abs?

A

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

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23
Q

After papin digests Abs, describe the properties of the fragments

A
Fab can still bind Ag
Fc cannot bind Ag but is:
crystallizable
complementable C1q
phagocytes
placenta mediator
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24
Q

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

A

GAMDE

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25
Q

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

A

a.a sequence

heavychain defines isotype of Ig

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26
Q

What is the hypervariable region

A

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

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27
Q

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

A

light: 1
heavy: 3

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28
Q

Which is the only Ab to cross the placenta?

A

IgG

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29
Q

What are the fucntions of IgG?

A

neutralizes toxins…
opsonizes antigens/bacteria
complement activation

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30
Q

IgM

A
secreted as pentamer
Ag receptor as a monomer
J chain joins units together
no hinge region
extra constant domian in heavy
agglutinizes
complements strong
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31
Q

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

A

IgM

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32
Q

IgA

A

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

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33
Q

What is the predominant Ab found in bodily secretions?

A

IgA

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34
Q

Which Ab is passed along through breast milk?

A

IgA

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35
Q

IgE

A

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

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36
Q

IgD

A

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

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37
Q

How can Igs be antigens?

A

because they are glycoproteins

ex: human Ig in mouse Igs.
ex: autoimmune

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38
Q

Do plasma cells produce IgD?

A

No

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39
Q

Half life of Igs?

A
G: 23 days
A: 5.5
M: 5
D: 2.8
E: 2
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40
Q

Where is the site of hematopoeisis throughout life?

A

until 6 mo gest: yolk sac and liver

after: marrow

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41
Q

What is the cell marker for a hematopietic stem cell?

A

CD34

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42
Q

What is the order of B cell development?

A
HSC Cd34
pro B cell
pre B cell
immature B cell
mature B cell
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43
Q

Which cytokines interact w pro B cells to continue differentiation?

A

IL 7
IL 3
(also stromal cells)

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44
Q

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

A

Ig genes for variable heavy chain rearranges

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45
Q

Define the Pre B cell

A

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

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46
Q

Describe the first checkpoint in B cell dev

A

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

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47
Q

What is allelic exclusion?

A

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

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48
Q

Define the immature B cell

A

expression of surface IgM (sIgM)

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49
Q

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

A

soluble: clonal anergy
insoluble: deletion/apoptosis

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50
Q

Define the mature B cell

A

expression of both sIgM and sIgD

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51
Q

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

A

they have the same specificity

different isotype but same idiotype?

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52
Q

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

A

Ig-alpha
Ig-beta
(all form BCR)

53
Q

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

A

crosslinking of BCRs through antigen epitopes in secondary lymphoid tissues

54
Q

What is the Clonal Selection Theory?

A

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
Q

What is tolerance?

A

specific unresponsiveness
prevents reaction against self
checkpoint

56
Q

What are T-independent Ags?

examples?

A
Can activate B cells without help from T cells
LPS
flagellin
dextran
polysaccharides
any with multiple epitopes
any that crosslinks sIg
57
Q

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

A
activate B cells without using BCr
stim polyclonal activation
heterophile Abs-many specificities
B cell mitogens
LPS
Ebstein-Barr
58
Q

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

A
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
Q

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

A

only IgM

60
Q

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

A

Switches to a T-dependent response

IgG2 is major Ab made

61
Q

Describe the memory response for a T-indep antigen?

A

there is no memory response

identical to primary response

62
Q

What are characteristice os T-dependent Ags

A

proteins, glycoproteins, or conjugated to proteins

63
Q

Which age group responds poorly to T-indep Ags?

A

children under 2 years

64
Q

Describe T-depedend responses

A

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

65
Q

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

A

CD40 (on B cell)

CD40L (on T cell)

66
Q

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

A

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

67
Q

What is affinity maturation?

A

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

68
Q

Describe the Lag phase of a primary resopnse

A

B cells undergo clonal selection

7-10 days

69
Q

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

secondary repsonse?

A

primary: IgM
secondary: IgG is predominant

70
Q

What is linked recognition?

A

eptiopes must be physically linked on same anithgen

71
Q

What are examples of conjugated vaccines?

A

influenze type b

pneumococcal conjugate vaccine

72
Q

What protects infants from disease?

A

maternal Ig
infant Ig after 6 mo
normal gut flora

73
Q

What types ofinfections does breast feeding protect from

A

respiratory

GI

74
Q

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

A

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

75
Q

Desribe how you use a paired sera test

A

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

76
Q

What is sensitivity?

A

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

77
Q

What is specificity?

A

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

78
Q

What are the primary binding tests?

A

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

79
Q

Describe ELISA

A

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

80
Q

Descfribe Direct IF

A

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

81
Q

Describe Indirect IF

A

When you dont have tissue, but you have serum (Abs)

Add 2nd Ab w Fluorescent

82
Q

Immunoblotting

A

Separate Proteins
Transfer/Blot
Nitrocellulose
Detect bound Abs

83
Q

Compare ELISA and blotting specificities and sensitivities

A

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

84
Q

What are ELISAs used?

A

pregnancy tests
viral hepatitis
RIST/RIA

85
Q

When is IF used?

A

DFA: rabies, herpes
IFA: assay Abs

86
Q

When is blotting used?

A

HIV, confirmatory

Alzheimer’s

87
Q

FACS

A

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

88
Q

What is the CD4:CD8 ration in normal patients?

A

2:1

less in AIDS patients. Treatment returns to normal

89
Q

What is the prozone effect?

A

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

90
Q

Describe the Ouchterlony test

A

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
Q

Which molecules are opsonins?

A

C3b

C4b

92
Q

Which molecules are anaphylatoxnis? What do they do?

A

C5a > C3a > C4a

degranulation of mast cells and release of histamine/vasoactive

93
Q

Which molecules are for margination? What do they do?

A

C5a

allows WBCs to adhere to vessels

94
Q

Which is for chemotaxis?

A

C5a > C3a

95
Q

What is the function of the membrane attack complex?

A

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

96
Q

Which molecules regulate vascular tone?

A

C2a

C2 kinin

97
Q

How are immune complexes removed in the complement cascade?

A

in plasma: via RBCs (via CR1)

in liver: phags

98
Q

Describe the stains of basopphils, eosinophils, and neutrophils

A

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

99
Q

What are cells of the mononuclear phagocytic system?

A

monocytes, macrophages and their derivatives

100
Q

What is the main signal to activate monocytes for phagocytosis?

A

IFN-gamma

101
Q

What activates M1 macrophages?

what do they secrete?

A

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

102
Q

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

A

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

103
Q

What are some positive chemotactic signals?

A
C5a
Fibrinopeptide B
Proinflamm. cytokines:IL1, TNF-a
chemokines: IL-8
LTB4 (lipoxygenation/arach acid)
LPS
104
Q

What can cytotixic chemo drugs induce?

A

neutropenias

105
Q

What are the 4 stages of phagosytosis?

A
  1. chemotaxis
  2. adherence
  3. Ingestion
  4. Digestion
106
Q

name some adherence molecules for phagocytosis

A

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

107
Q

What are the 3 mechanisms for digestion in phagocytosis?

A
  1. Respiratory burst
  2. phagosome-lysosome fusion
  3. Toxic nitrogen oxides
108
Q

Describe Respiratory burst

A

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

109
Q

Describe phagosome-lysosome fusion

A

lysosomes from granules
defensins and protegrins disrupt mmbrane
lactoferrin chelates iron

110
Q

Describe toxic nitrogen oxides

A

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

111
Q

What are the main cytokines that induce inflammation?

A
IL-1
IL6
IL-8
TNF-a
IL-12
112
Q

Which cytokines induce fever?

A

IL-1
IL-6
TNF-a

113
Q

Which receptors/ligands are involved in rolling adhesion?

A

sialyl_Lewisx on the neutrophil:

E-selectins on endothelials

114
Q

Which receptors/ligands are involved in tight binding?

A

integrins on neutrophil:

ICAM-1 on endothelials

115
Q

Which receptors/ligands are involved in diapedesis?

A

integrins on neutrophil:

CD31 (PECAM)

116
Q

Which complement pathway inhibitors can cause meningitis?

A

C5-8 deficiency
properdin deficiency
MBL deficiency

117
Q

What cels are the major producers of IFN-gamma?

A

CD4 helper T cells

NK cells

118
Q

What type of surface oplarity of bacteria enhance phagocytosis?

A

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

119
Q

What is the acute phase response?

A
a systemic resopnse to local inlammation
fever
increased hormone (ACTH)
leukocytosis
acute phase proteins
120
Q

name some actue phase proteins

A
C3
CRP
haptoglobin
factor B
\_\_\_\_\_\_\_\_
albumin/prealbumin
fibrinogen
121
Q

What can an elevated CRP level indicate?

A

unstable coronary artery disease

if in healthy: higher risk of CV disease

122
Q

What is ESR?

A

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

123
Q

What is the hallmark of local acute response?

A

influx of PMNs

124
Q

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

A

complement system
blood clotting/kinin system
fibrinolytic system

125
Q

What are matrix metalloproteinases?

A

degrade ECM proteins so free moveement of inflammatroy cells can occur

126
Q

Describe the effedct of adenosine in inflammation

A

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

127
Q

What is the hallmark of chronic inflammation?

A

accumulation/activation of macrophages

-granulomas too

128
Q

Descsribea granuloma

A

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

129
Q

Describe tetanus
incubation period?
causes what?
immune response?

A

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