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Immunology > Final Exam Immunology > Flashcards

Final Exam Immunology Flashcards

1
Q

eosinophil

A

kills antibody coated parasites through release of toxic granule contents

  • combats multicellular parasites or heminths
  • 1-6% of WBC
  • Granules contain toxic enzymes and histamine
  • Granules stain brightly with dye; Eosin - acid loving
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2
Q

basophil

A
  • Controls immune response to parasites
  • least common granulocute (0.01%-3%)
  • Granules contain histamine, proteoglycans (heparin and chondroitin)
  • IL4 - central to many allergic reactions
  • Express IgE
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3
Q

Mast cells

A
  • Expulsion of parasites from the body by release of granules containing histamine + other active agents
  • Major mediator of type I hypersensitivity
  • Express IgE
  • Granules contain histamine and heparin
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4
Q

Macrophage

A

Phagocytosis and killing of microorganisms

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5
Q

Dendritic cells

A

activates T cells to initiate the adaptive immune system

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6
Q

Macrophages and dendritic cells

A
  • Both phagocytic
  • Macrophages: bactericidial activity
  • Dendritic: No bactericidial activity
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7
Q

“professional antigen presenting cells”

A

dendritic cells

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8
Q

Neutrophils

A
  • phagocytosis and killing of microorganisms
  • PMN (polymorphonuclear cells)
  • 40-70% of leukocytes
  • short life span: 24hr half life
  • Migrate from blood to sites of infections
    1. phagocytosis
    2. Granules loaded with degradative enzymes
    3. Produce reactive oxygen and nitrogen radicals
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9
Q

Three major funcitons of neutrophils

A
  1. Migrate from blood to site of infection
  2. Phagocytosis followed by intracellular degranulation
  3. Produce reactive oxygen radicals through respiratory burst - NADPH-oxidase
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10
Q

diapedesis

A

leukocyte extravasation - movement of leukocytes out of the circulatory system and toward sites of inflammation or infection

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11
Q

Neutrophil Migration

A

Neutrophils rapidly moves through vessels and it has receptors (selectin and integrin) that allow the neutrophil to bind and interact with several ligands on the surface of endothelium.

  • During an inflammation/infection, these sites of receptors become more sticky and chemokines are released.
  • Neutrophils slow down and the receptors are binding to the vessel with higher affinity.
  • Integrins recieve signal from chemokines

Selectin ligand on neutrophil binds to selectin on the vessel surface, slowing it down, then the integrin binds to integrin ligands in the vessels and the cell performs diapedisis.

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12
Q

LFA-1 + ICAM1

A

low affinity integrin LFA1, binds to ICAM1, when a chemokine receptor and chemokine have interacted.

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13
Q

Bacteria killing process

A
  1. receptor binding
  2. engulfment
  3. phagocytosis

The real killing is when granules fuse with phagosome

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14
Q

Killing of microbes process

A
  1. microbes bind to phagocyte receptors
  2. phagocyte membrane zips up around membrane
  3. microbe ingestedin phagosome
  4. fusion of phagosome with lysosome

Killing of microbes by ROS, NO, and lysosomal enzymes in phagolysosomes.

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15
Q

enzymes

A

degrade bacterial components

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16
Q

defensins

A

poke holes in bacterial membranes

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17
Q

lactoferrin

A

sequester iron away from bacteria

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18
Q

Respiratory burst

A
  • When NADPH oxidase is activated, and production of bactericidal compounds begin
  • Superoxide + Hydrogen peroxide
  • ## HOCl - hypochlorous acid
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19
Q

Neutrophil death: two fates

A

Macrophage ingestion

Exits the body as Pus

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20
Q

DIseases with Neutrophil dysfunction

A

CGD
Chediak Higashi
LAD

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21
Q

CGD

A

NADPH oxidase defects

No respirator burst , greatly reduced bacterial killing

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22
Q

Chediak Higashi syndrome

A

phagocytosis and granule defects

unable to engulf and kill bacteria

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23
Q

LAD deficiency

A

deficiency in adhesion molecules, migration into tissue is minimal

Very high # of neutriphils in blood, but they cannot migrate to site of infection. Infection goes unchecked

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24
Q

the complement system is a grouo of _ found in serum involved in:

A

zymogens

  1. Control of inflammation - Recruitment of phagocytes
  2. Enhanced pathogen uptake and clearance - Opsonization
  3. Lyttick attack of cell membranes (killing bacteria)
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25
Q

Classical Pathway

A

Antigen: Antibody complex

  • Initiated by antibody or C reactive protein (CRP) binding to pathogen surface
  • C1 (C1q, C1r, C1s)
  • C1 binding + CRP (phosphocholine) on pathogen surface
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26
Q

Perfect ligand for C1q in the classical pathway

A

IgM

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27
Q

MBL pathway

A
  • Initiated by MBL binding to mannose and fucose residues on pathogen surface
  • Initiating complex –> MASP1 and MASP2 and MBL

Ligand recognition molecules from classical and MBL are structurally similar

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28
Q

Classical pathway mechanism

A
  • C1 binds to IgM
  • C2 and C4 bind forming C2aC4b
  • C3 binds to C2aC4b
  • C3a leaves, C3b stays on pathogen surface

Cr1 = phagocytosis
C5-9 = lysis of pathogen

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29
Q

MBL initiation and after

A
  • Activated MASP2 cleaves C4 to C5a and C4b. Some C4b binds covalently to the microbial surface
  • Activated MASP2 also cleaves C2 to C2a and C2b
  • C2a binds to surface C4b forming the classical C3b convertase C4b2a
  • C4b2a binds C3 and cleaves it to C3a and C3b. C3b binds covalently to microbial surface

‘/[

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30
Q

how is the alternative pathway activated?

A

Spontaneously. Without the help of a ligand-binding molecule

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31
Q

Spontaneous activation of C3 in plasma

A

C3 spontaneously hydrolyzed
1. C3b attach to the bacterial membrane and liberation of C3a which acts as a chemoaatractant (anaphylatoxin) to phagocytes)

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32
Q

example of anaphylatoxin

A

C3a

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33
Q

C3 convertase classical

A

C4b2a

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34
Q

Alternative C3 convertase

A

C3bBb

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35
Q

How complement activation induces phagocyte recruitment

A
  1. anaphylatoxins (C3a, C5a) act on blood vessels to increase vascular permability
  2. Increased permeability - increased leakage from blood vessels and extravasation of complement and other plasma proteins to the site of infeciton
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36
Q

opsinization basics

A

I. complement activation leads to deposition of C3b on the bacterial cell surface

  • CR1 on macrophage binds C3b on bacterium
  • Endocytosis of the bacterium by macrophage
  • Macrophage membranes fuse, creating a membrane bounded vesicle, the phagosome
  • Lysosomes fuse with phagosomes, forming a phagolysosome
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37
Q

C3 cleavage

A

C3a - recruits phagocyte s
C3b - tags bacterium for destruction (opsonization or membrane attack)

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38
Q

lyttick membrane attack

A

C5-C9

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39
Q

C1 inhibitor

A

Binds to activated C1r, C1s, removing them from C1q and to activated MASP2, removing it from MBL

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40
Q

Factor H

A

binds C3b, displacing Bb for cofactor I

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41
Q

Factor I

A

Serine protease that cleaves C3b and C4b

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42
Q

CD59 (protectin)

A

Prevents formation of membrane attack complex

binds to C5b678, preventing recruitmen of C9 from the pore

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43
Q

Acute phase response

A

IL6 goes into liver, producing CRP (C reactive protein).

CRP is a common clinical readout of infection or inflammation

CRP binds phosphocholine on bacterial surfaces
MBL binds carbohydrates on bacterial surfaces

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44
Q

C1,C2,C4 deficiency

A

Immune complex disease

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45
Q

C3 deficiency

A

Susceptibility to Capsulated bacteria

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46
Q

C5-C9 deficiency

A

Susceptibilty to Neisseria

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47
Q

Facor I deficiency

A

Similar to C3 (susceptbility to capsulated bacteria)

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48
Q

Which complement components are associated with which functions?

A

C3a, C5a = recruitment
C3b = opsonization
C5b,6,7,8,9 = membrane attack

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49
Q

immediate innate response

A

0-4 hrs

Very minor tissue damage is repaired

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50
Q

Induced innate immune response

A

4hrs - 4 days

minor tissue damage is soon repaired

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51
Q

Adaptive immune response

A

4 days +

Major tissue damage is gradullay repaired

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52
Q

Gram +

A

peptidoglycan, lipotheichoic acid

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53
Q

gram -

A

Lipopolysachharide

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54
Q

PAMP

A

hypomethylated CpG DNA

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55
Q

Microbes contain genetically conserved patterns called

A

PAMPS - pathogen associated molecular patterns

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56
Q

PAMPS are recognized by

A

PRR (pattern recognition receptors) of the innate immune system: Macrophages, NK cells, neutrophils, DC

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57
Q

Types of PRRs

A

TLRs and Cytosolic receptors

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58
Q

Uptake receptors

A

Facilitate uptake of particles
- complement receptors
- scavenger
- mannose

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59
Q

Signaling recepotrs

A

recognize bacterial PAMPs and inducde activation of the cell through signaling cascades leading to changes in gene expression

TLR
NOD like
RIG-I-like

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60
Q

TLR structure

A

Amino end - pathogen recognition domain outside of the cell

carboxyl end: TIR domain on cytosolic side of cell

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61
Q

TLR structure

A

Amino end - pathogen recognition domain outside of the cell

carboxyl end: TIR domain on cytosolic side of cell

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62
Q

TLR2 + TLR6

A

Lipoteichoic acid

Gram positive bacteria

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63
Q

TLR4

A

Lipopolysachharide

Gram - Bacteria

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64
Q

TLR7

A

ss viral RNA

RNA virus

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65
Q

TLR8

A

ss viral RNA

RNA

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66
Q

TLR9

A

Unmethylated CpG rich DNA

Bacteria + DNA virus

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67
Q

TLR3

A

DS viral RNA

RNA VIRUS

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68
Q

TLR5

A

Flagellin

Bacteria

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69
Q

which TLR are on plasma membrane

A

TLR2+6

TLR4

TLR5

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70
Q

Which TLR are on endosomes

A
  • TLR3,7,8,9
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71
Q

TLR4 needs help from other molecules to access

A

LPS

  • Complex of TLR4, MD2, Cd14 and LPS assembled on surface
  • MyD88 binds TLR4
  • Leads to release of NFkB which enters the nucleaus
  • NFkB activates transcription of genes for inflammatory cytokines, which are synthesized in the cytoplasm and secreted via ER
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72
Q

TLR4 SIGNALING by the TRIF and MyD88 cascade

A

Synthesis and secretion of TNF-alpha and other inflammatory cytokines

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73
Q

NOD like receptors recognize

A

bacterial cell wall

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74
Q

inflammasomes recognize

A

pathogens as well as intracellular damage or injury

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75
Q

RIG I , MDA5 recognize

A

Viral nucleic acids

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76
Q

activation of NfkB results in

A

gene transcription

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77
Q

proinflammatory cytokines

A

IL6
IL1
TNF
IL12
IFNy

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78
Q

IL1/IL6/TNF-alpha

A

Liver
- activation of complement
- Acute phase proteins

BM endothelium
- phagocytosis
- Neutrophil mobilization

Hypothalamus
- decreased viral and bacterial replication
- Increased body temperature

Fat, muscle
- Decreased viral and bacterial replication
- Protein and energy mobilization to generate increased body temperature

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79
Q

immature DC

A
  • Tissue resting
  • Highly endocytic
  • Low expression
  • poor stimulators of T cells
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80
Q

Mature DC after exposure to inflammatory stimuli, PAMPS

A
  • Homes to lymph node
  • endocytosis shuts down
  • High level coexpression
  • Highly stimulatory for T cells
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81
Q

antiviral acts in both

A

autocrine and paracrine

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82
Q

MDA5 + RIG-I

A

cytoplasmic pattern recognition receptors

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83
Q

Type I interferons are very helpful for

A

Viral infections

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84
Q

Antiviral immune response

A
  • Type I interferons! (alpha and beta)
  • work in both autocrine and paracrine manner
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85
Q

after viral infection…

A

TLRs or cytoplasmic receptors can acativate transcription factors

  • IRF –> move to nucleus and activate IFN alpha and beta
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86
Q

anti viral state by type I interferons

A
  • inhibition of viral protein synthesis
  • degradation of viral RNA
  • inhibition of viral gene expression and virion assembly
87
Q

RIG I facilitates activation of

A

IRF3 and NFkB

IRF3 - type I interferon
NfkB - inflammatory cytokines

88
Q

TLRs that have strong type I interferon response

A

TLR7 and TLR3

89
Q

only TLR that doesnt associate with MyD88

A

TLR3, it associates with TRIF

90
Q

interferon responses from virus infected cells

A
  • increase expression of ligands for receptors on NK cells
  • Activate NK cells to kill virus infected cells
91
Q

NK cells (lymphocytes)

A

A balance of activation and inhibition determines the fate of target cells

INNATE immune system

Type I interferon drives the proliferation of NK cells

Type I interferon drives the differenctation of NK cells into cytotoxic effector cells

92
Q

Important functions of NK cells

A
  1. killing of infected or damaged cells
    - activating (killing) /inhibitory receptor (no killing)
    - whichever one has stronger signal determines the fate of the cell
  2. production opf cytokines to activate macrophages
    - NK produce IFNy to stimulate activation of macrophages and their killing
93
Q

KIRs

A

killer cell immunoglobin like receptors

Can be activating or inhibitory, depending on their tail

94
Q

Inhibitory receptors (KIR) have

A

long cytoplasmic tails

95
Q

activating receptors (KIR) have

A

short, cytoplasmic tails which interact with adapter molecules to facilitate signaling

96
Q

NK cell delivery of toxic molecules (synapses)

A

Formation of NK killing “synapse” thrpigh tight association with NK cell

  • perforin: poreforming molecule, much in common with C9 complement cascade
  • granzymes: delivered through the pore, activate an apoptotic cascade, activate caspases

DNA cleavage, nulcear fragmentation, membrane blebbing

Apoptosis of target cell

97
Q

rebuck skin window

A

measures migration of leukocytes to sites of inflammation/injury

98
Q

CD18 deficiency

A

integrin beta 2

99
Q

LAD

A

subject to recurrent bacterial infections
- PMN + minocytes unable to emigrate to tissues that are infected and are trapped in crirculation
- very high WBC count

100
Q

Factor I deficiency

A

inhibits C3 convertase

Leads to C3 depletion

101
Q

CH50 assay

A

Not testing MAC on bacteria, but engineering the attack of red blood cells as a measure of complement activity

Red blood cells are being lysed

Tests Patients Serum
RBC must be present (deosnt matter the source)
Antibody against RBC - bind to RBC

CH50 = 0
- C5-C9 = membrane attack complex. A deficiency in these leads to susceptibility to Neisseria. Because doctor suspected she had a deficiency in one of the MAC molecules.

102
Q

innate immunity expl.

A

distinguish host from infectious agents bu recognizing conserved motifs
- activated within min to hrs of exposure
- not significanlty increased by previous exposure

103
Q

adaptive immunity expl.

A

cells with exquisitely specific receptors for a potentially unlimited number of targets
- effective only after several days
- possess immunological memory, enhanced responsiveness upon reencounter of same pathogen.

104
Q

What is antigen processing?

A

series of intracellular events in which antigen presenting cells make antigens available to T cells

Involves uptake of antigens, their degradation to peptides, binding of the peptides to MHC class. Ior MHC class II and transport to the cell surface

Presentation of MHC peptide complex on the cell surface for the stimulation of T cells

105
Q

What are antigen presenting cells?

A
  • Dendritic Cells
  • Macrophages
  • B cells
106
Q

CD8 T cells bind

A

A3 of MHC class I

107
Q

CD4 T cells bind

A

Beta2 of MHC class II

108
Q

Endocytic antigen processing

A

exogenous or MHC class II

109
Q

Cytosolic antigen processing

A

endogenous or MHC class I

110
Q

Endocytic antigen processing

A
  • Antigen is taken up from the ECS into intracellular vesicles
  • In early endosomes of neutral pH, endosomal proteases are inactive
  • Acidification of vesicles activates proteases to degrade antigen into peptide fragments
  • Vesicles containing peptides fuse with vesicles containing MHC class II molecules
111
Q

Invariant chain

A

blocks binding of peptides to MHC Class II in the ER

in vesicles, invariant chain is cleaved, leaving the CLIP fragment bound.

112
Q

CLIP blocks

A

binding of peptides. toMHC class II in vesicles

HLA-DM facilitates release of CLIP, allowing peptides to bind

113
Q

KEY players of MHC class II pathway

A
  • MHC class II - presents antigens
  • Invariant chain - Directs class II away from typical secretory pathway to endocytic pathways and blocks peptide loading in the ER
  • HLA-DM - acts as a chaperone or catalyst to facilitate exhange of clip with antigenic peptides
  • pH - low pH and degradative environment facilitate denaturation of antigenic proteins
  • Proteases - Cathepsins and other degradative enzymes chew up antigens into peptides
114
Q

KEY players of cytosolic (MHC class I) pathway

A
  • MHC class I - presents antiugenic peptides to T cells
  • Proteasome: multicatalytic enzyme complex that degrades proteins into peptides
  • TAP: transporter that shuttles peptides from cytosol to ER
  • Calnexin, tapasin, Erp57: stabilize MHC class. Iand facilitate association with TAP to enable peptide loading (peptide loading complex)
115
Q

Class I heavy chain is stabilized by

A

clanexin, until b2 microglobulin binds

Peptide loading complex formed

A peptide delivered by TAP binds to the CLass I heavy chain, forming the mature MHC class I molecule

Then the class I molecule ddissociates from. thepeptide loading complex

116
Q

peptides produced in the cytosol are transported into the

A

ER

117
Q

Cytosolic pathogens

A
  • degraded in: Cytosol
  • Peptides bind to MHC class I
  • Presented to CD8 T cells
  • effect on APC: Cell death
118
Q

Extracellular pathogens and toxins/Intravesicular pathogens

A

Endocytic vesicles (low PH)
MHC class II
CD4 T cells
- Activation to lill intravesicular bacteria. and parasites
- Activation of B cells to secrete Ig to eliminate extracellular bacteria/toxins

119
Q

End result of antigen processing

A

display of MHC peptide complex for TCR recognition

120
Q

MHC - Major histocombatability Complex

A
  • Present peptides derived from pathogens to T cells
  • HLA in humans
  • MHC I and II
121
Q

MHC class I structure

A

1 transmembrane region
CD8 binds to Alpha3
Peptide binding cleft: Alpha 1 and Alpha 2

122
Q

MHC class II structure

A

Peptide binding cleft: A1 + B1

2 transmembrane regions

CD4 binds to Beta2

123
Q

MHC class II structure

A

Peptide binding cleft: A1 + B1

2 transmembrane regions

CD4 binds to Beta2

124
Q

Pwptide binding cleft MHC I

A

Alpha 1 + Alpha 2

Strict binding site: 8-10 aa in length

125
Q

Peptide binding cleft MHC class II

A

Alpha 1 + beta 1

Flexible binding site - 10-24+aa in length

126
Q

Where is the variability in MHC class I ?

A

Alpha 1 and alpha 2

127
Q

Where is the variability in MHC class II?

A

Beta. 1

128
Q

MHC is both

A

polymorphic and polygenic

129
Q

genetic polymorphism

A

variants or alternative forms of a gene present in a population at a stable frequency

130
Q

haplotype

allele

A

haplotype - the collective set of MHC alleles present in an inidivudal chromosome

alllele: one type of variant

131
Q

MHC class I isotypes

A

HLA-A
HLA-B
HLA-C

Highly polymorphic

132
Q

MHC class II isotypes

A

HLA-DP
HLA-DQ
HLA-DR

133
Q

MHC I expression

A

Expressed by all cells

Can be upregulated by type I interferon (IFNa or IFNb)

134
Q

MHC class II expression

A

Expressed by antigen presenting cells. (Macorpahges, DC, B cells) can be upregulated by IFN-y + CIITA

135
Q

MHC genes are expressed

A

co-dominantely

136
Q

Immunoproteasome

A

Induced by INF-y

Exhange of beta subunits: improves generation of peptides that bind to MHC class I

Different caps: speed export of peptides

137
Q

Results of innate immune response

A

complement - induces inflammation

Produce inflammatory cytokines (IL1,6 and TNFalpha)

138
Q

Inflammation awakens adaptive immunity through DC

A

Communicates between Innate and adaptive systems

DC at sites of infection become triggered to “mature” in response to PAMPS or inflmmation

DC migrates through lymphatics to draining lymph nodes, interacting with many B and T cells

139
Q

Immature DC

A
  • Tissue resident, resting
  • Highly endocytic , phagocytic
  • **Low level expression **of molecules
  • Poor stimulators of T cells
140
Q

Mature DC

A

Homes to lymph node
Endocytosis shut down
High level expression of costimulatory molecules
Highly stimulatory for T cells

141
Q

Primary lymphoid organs

A

Thymus
Bone Marrow

sites at which leukocytes undergo hematopoiesis (development and differention) and/or selection. Houses naive leukocytes

142
Q

secondary lymphoid organs

A

spleen, lymph nodes etc. Sites at which naive , activated, and memory cells are housed

143
Q

T cell receptor

A

Alpha and beta chain

Variable + constant regions + transmembrane region

Antigen binding site consists of both alpha and beta chains

144
Q

B cell receptor

A

Surface (transmembrane region) or antibody (plasma , no transmembrane region)

Heavy and light chain

Antigen binding site: 1 HC 1 LC
Variable region: 1 HC, 1LC
Constant region: Heavy chain
Transmembrane region: only for Surface B cells

145
Q

Life stages of B and T cells

A
  1. Generating receptor
  2. Selection
  3. Activation
  4. Differentation
146
Q

generating receptor

A

Rearrangement

147
Q

selection

A

making sure the receptor does not react with self

148
Q

activation

A

providing all of the signals needed to cause clonal expansion

149
Q

differentation

A

signals recieved during activation dictate the differentiation of the cell and its specific function

150
Q

Gene rearrangement in somatic cells generate potential

A

for great diversity

151
Q

B cells recognition of antigen :

A

“see” naive antigen through BCR

152
Q

T cells antigen recognition

A

see antigenic peptides (digested or processed pieces of antigens) presented by MHC molecules

153
Q

B and T cells see things very differently

A

Epitopes recognized by T cells are often buried, and the antigen must be broken down into peptide fragments and the epitope peptide binds to MHC molecule. The T cell receptor binds to a complex of MHC molecule and epitope peptide

BCR and antibodies recognize native protein antigens

154
Q

What. areantibodies good for?

A

Bacterial toxins - get neutralized = toxins unable to bind to receptors because the antibody binds it.

Bacteria in ECS - get opsonized tagged with C3b for destruction

155
Q

What does it take for a T cell to recognize antigens?

A

DC cells take up pathogens for degradation.
1. pathogen is taken apart inside the DC
2. Pathogen proteins are unfolded and cut into small pieces
3. Peptides bind to MHC and go to cell surface
4. TCR bind to peptide:MHC complex on DC surface

156
Q

Basic structure of an immunoglobin

A
  • Two heavy chains and two light chains
  • Disulfide bonds
  • Contains discrete antigen binding regions in the N terminus from both the heavy and light chains
157
Q

Fab region

A

comsists of both heavy and light chains

158
Q

Fc region

A

consists of only heavy chains

159
Q

antigens bind to what region on antibody

A

variable region of heavy and light chains

159
Q

antigens bind to what region on antibody

A

variable region of heavy and light chains

160
Q

Fab name meaning

A

fragment antigen binding

161
Q

Fc name

A

fragment crystallizable

162
Q

Membrane bound BCR associates with

A

signaling molecules Ig-alpha and Ig-beta

163
Q

antitgen bontact by antibody is mediated through

A

Hypervariable loops of the heavy and light chains CDR

  • antigen is contacted by six hypervariable loops, 3 in the light chan and 3 in the heavy chain
  • Most of the diversity between antibodies is in these regions
164
Q

The most diversity is in _ of CDR

A

CDR3

The highest number of Ab;Ag contacts are usually within the CDR3 region

165
Q

5 major classes of human antibodies

A

IgG
IgM
IgD
IgA
IgE

166
Q

monomeric IgM

A

antibody + J chain, whereas pentameric IgM is just five antibodies together.

167
Q

Dimeric IgA is held together by

A

J chain

168
Q

Valency and avidity

A

Monovalent interactions has a low avidity

pentameric IgM is polyvalent and has very high avidity of interaction

169
Q

IgA specific function

A

transport across mucosa, neutralization

170
Q

IgD specialized function

A

antigen receptor on naive B cells, sensitized basophils

171
Q

IgE

A

immediate hypersensitivity, sensitizes mast cells

172
Q

IgG

A

neutralization, opsonization, complement activation and neonatal immunity (crosses placenta)

173
Q

IgM

A

antigen receptor on naive B cells, complement activation

174
Q

antibody diversity is due to

A

Combinatorial diversity - multiple germ line segments

Junctional Diversity

Somatic hypermutaiton

175
Q

VDJ

A

heavy chain

176
Q

VJ

A

light chain

177
Q

Heavy chain recombination

A

D-J
V-DJ
VDJ

178
Q

light chain recombination

A

V-J
VJ

179
Q

opsonin

A

any molecule that enhances phagocytosis by tagging it for binding to a cell surface receptor
- complement proteins that bind complement receptors
- antibodies that bind Fc receptors on phagocytic cells

180
Q

opsonization

A

the process by which bacteria are altered by opsonins so as to become more readily and more efficiently engulfed by phagocytes

181
Q

two types of light chains

A

Kappa and lambda

182
Q

Recombination process

DETAILED

A
  1. Heavy chain undergoes Rearrangement. D-J
  2. Then V is added to become VDJ
  3. After heavy chain, light chain rearrangement occurs. The only thing that occurs is V-J.
183
Q

Sequence of events during VDJ recombination

A

Synapsis
Cleavage
Hairpin
Joining

184
Q

VDJ synapsis

A

two selected coding segments and their adjacent RSSs are brought together by chromosomal looping

185
Q

VDJ cleavage

A

RAG1/2 complexes generate double stranded breaks in DNA, forming hairpin loops

186
Q

VDJ hairpin processing

A

Artemis opens hairpins at coding ends

187
Q

VDJ joining

A

non-homologous end joining

Ku70, Ku80, DNA ligase

188
Q

Generation of a functional BCR

A

Early Pro B cell
- Heavy chain rearrangement: D-J

Late Pro B cell
- Heavy chain rearrangement V-DJ

Pre B cell
- Light chain rearrangement
- Rearrange K on 1st chrom
- Rearrange K on 2nd
- Rearrange L on 1st
- Rearrange L on 2nd

189
Q

Junctional diversity

A

Occurs at CDR3 - allowing greater variability than that encoded by gene segments

Diversity is increased by addition of nucleotides

Mediated by TdT

190
Q

what is junctional diversity mediated by

A

TdT

191
Q

antibody deficiency leads to

A

increased susceptibility to extracellular bacterial pathogens - Pyogenic infections

Strep. pneumoniae
Staph. aureus
Strep. Progenies

192
Q

SCID

A

RAG Deficiency –>No B or T cells

193
Q

CD40:CD40L

A

B cells need two signals for full activation by T dependent antigens

194
Q

Hyper IgM

A

AID deficiency

Defect may be in MHC class II - No CD4 T cells to stimulate isotype switch

Only IgM isotype antibodies, reduced diversity of B cell response

195
Q

X linked agammaglobulinemia (XLA)

A

defect in BTK

  • B cells become arrested at the pre B cell stage

NO DETECTABLE B CELLS - No antibody

196
Q

Big picture of B cell development

A

repertoire assembly
negative selection (BM)
positive selection (2ndary organs)
searching for infection
finding infection
attacking infection

197
Q

What does the Pre-B cell receptor do?

A

VpreB + lambda5

Surrogate light chain!

induces allelic exclusion at other heavy chain locus.

Surrogate light chain takes place of rearranged light chain. Allows testing of heavy chain

198
Q

alternative splicing to give both delta and mu chains

A

before activation

199
Q

alternative splicing to secrete Ig

Isotype switching

Somatic hypermutation

A

after activation

200
Q

Somatic hypermutation

A

Induced by AID

Results in point mutations most often within the variable regions of immunoglobins after rearrangement

Leads to affinity maturation

201
Q

mechanism of affinity maturation

A

increased affinity - increased antigen uptake, processing, presentation

Decreased affinity - decreased antigen uptake, processing, presentation . Neglected B cell will not proliferate, antigen specificity will decline in population

202
Q

Isotype switching and somatic hypermutation are dependent on

A

AID

203
Q

Isotype switching

A
  • Causes irreversible changes in DNA, removing intervening C regions
204
Q

Lack of RAG

A

SCID - No T or B cell produced

205
Q

Lack of TdT

A

significantly reduced diversity in B cell repertoire

206
Q

Lack of AID

A

no somatic hypermutation or isotype switching, produce only low affinity IgM, called hyper IgM immunodeficiency

207
Q

events that rely on changes in DNA

A

Somatic recombination
Junctional diversity
Somatic hypermutation
isotype switching

208
Q

Events that rely on changes in RNA

A

dual expression of IgD and IgM

Expression of transmembrane vs secreted forms of IgM

209
Q

Immature B cells co-express IgM and IgD

A

No class switching has yet occurred. these are changes in RNA,

All C regions are maintained at this point

210
Q

B cell - negative selection location

A

bone marrow

211
Q

B cell - positive selection location

A

secondary lymphoid organs

212
Q

Hyper IgM (HIM) Immunodeficiency

A

increased amount of IgM, unable to produce IgG, Ig, and IgE

CD40 ligand defect.

X linked recessive trait

  • isotype switching fails to occur
  • T cell response reduced
  • macrophage activation reduced
  • neutropenia
213
Q

Interaction with FDC provides

A

maturation and survival signals for positive selection

Immunology (18 decks)

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