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Host Defense > Test 1, deck 1 > Flashcards

Test 1, deck 1 Flashcards

1
Q

specific characteristics of innate immunity

A
  • inherited in the genome
  • expressed by all cells of a particular type (e.g. macrophages)
  • triggers immediate response
  • recognizes broad classes of pathogens (NOT SPECIFIC)
  • no memory
  • interacts with a range of molecular structures
  • modified epigenetically
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2
Q

specific characteristics of acquired immunity

A
  • encoded in multiple gene segments
  • requires gene rearrangement
  • lag between exposure and response
  • clonal expansion of immune cells for efficient response
  • able to discriminate between closely related molecular structures (SPECIFIC)
  • immunologic memory
  • modified epigenetically
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3
Q

key advantage of innate system? disadvantage?

A
  • adv: activated instantaneously

- disadv: lack of ability to precisely target pathogens and limit collateral damage

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4
Q

key advantage of adaptive system? disadvantage?

A
  • adv: memory & precise specificity

- disadv: takes more than a week to become fully operational

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5
Q

what are 2 initial barriers to infection, what mechanisms do they employ, and where are they found?

A
  • mucosa (gut, lungs, eyes/nose) & skin

- mechanical, chemical, microbiological

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6
Q

how does the innate immune system recognize danger?

A
  • patterns called PAMPs and DAMPs which activate receptors on the innate cells called TLRs (“on” switch for immune response)
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7
Q

2 pathways innate immunity uses to neutralize threat

A

1) soluble proteins made in liver (mannose-triggered phagocytosis)
2) immune effector cells

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8
Q

what are cytokines? fundamental concepts?

A
  • small messenger peptides
  • two peptide chains encoded by separate genes
  • develop as families, exhibit redundancy
  • are expressed by immune and non-immune cells
  • mediate communication between humoral and cellular immunity
  • regulate the intensity of immune response; act as yin and yang
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9
Q

cells of adaptive (acquired) system

A

1) macrophages and dendritic cells given new functions

2) small lymphocyte (B (antibodies) and T (killer,helper) cells)

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10
Q

4 features that determine immunogenicity of acquired immune system

A

1) recognizes antigens with very specific receptors
2) can distinguish between self and non-self
3) can clonally expand antigen specific cells after their activation
4) can remember specific encounters

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11
Q

what are the effector molecules of the adaptive system?

A
  • cytokines

- recognition molecules (antibodies, complement system)

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12
Q

what are HSCs?

A

hematopoietic stem cells- multi-potent, self-renewing sources of WBCs, RBCs & platelets

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13
Q

where are the HSC niches in bone marrow? what is their purpose?

A
  • osteoblasts and sinusoidal endothelial cells
  • Even though stem cells have the ability to self-renew, they must be
    surrounded by this niche in order to do so. This is because the niches supply growth factors and other regulatory molecules that support HSC self-renewal.
    \
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14
Q

what are stromal cells and where are they found?

A
  • found in niches; provide factors needed for HSC maintenance
  • can push HSCs to differentiate into peripheral blood progenitors
  • importance for replenishing of peripheral blood
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15
Q

T/F HSCs are found in the peripheral circulation

A

T- may return to circulation in circadian manner, but chemical signals encourage them to go home (to the bone marrow)

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16
Q

HSCs differentiate into ____; what growth factors/cytokines (ILs) induce these changes?

A

common myeloid (IL-3 and GM-CSF) & lymphoid (IL-7) progenitors

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17
Q

common myeloid progenitors differentiate into ____

A

RBCs (thrombocytes), mast cells (granulocytes) and

  • N (G-CSF)
  • M (GM-CSF, M-CSF)
  • E (IL5)
  • B (IL4)
  • dendritic cells- Flt3L
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18
Q

common lymphoids differentiate into _____

A

NK cells & lymphocytes (b cells (IL3 and IL7) & t cells (IL2 & 7))

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19
Q

where are the lymphoid organs?

A

1- lymph nodes
2- mucosal tissue- intestines
3- spleen
4- tonsils and adenoids

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20
Q

5 types of leukocytes

A 
neutrophils
lymphocytes (Bs and Ts) 
monocytes
eosinophils
basophils
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21
Q

general route of the immune response

A

naive lymphocytes travel in blood to lymph nodes where they may run into dendritic cells presenting matching pathogen; activated lymphocyte then goes back into blood via thoracic duct & left subclavian vein; is called to site of injury by cytokines

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22
Q

which cells are most important front line defense of the innate immune system? where are they normally found?

A
  • neutrophils- have LOTS

- normally found circulating, not in tissue

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23
Q

what is pus?

A

dead neutrophils

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24
Q

3 neutrophil killing mechanisms

A

phagocytosis, degraulation, neutrophil extracellular traps (NETs)

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25
Q

what is the distinction between macrophages and monocytes?

A

monocytes are in blood, macrophages are in tissue

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26
Q

what is sepsis a result of?

A

bystander effects of macrophage recruitment

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27
Q

2 ways dendritic cells take up an antigen

A

1- phagocytosis

2- macropinocytosis

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28
Q

which type of WBCs are known to be able to sustain allergic reactions?

A

eosinophils

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29
Q

what is the function of mast cells?

A
  • have lots of histamine which causes vasodilation, allowing WBCs to enter the site of infection
  • cause increased local blood flow & leaky vessels
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30
Q

what do NK cells do?

A
  • go after cells that don’t look right- virus infected & tumor cells
  • can target viruses when slow adaptive response is gearing up
  • induce apoptosis
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31
Q

What are the 2 key phagocytic cells in the innate system?

A

macrophages and neutrophils

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32
Q

What are the differences between the 2 key phagocytic cells in the innate system?

A

macrophages- mature, long lived, increase at sites of infection, 1st to encounter pathogen
neutrophils- abundant in circulation (not tissues), short lived, rapid responders

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33
Q

Two ways phagocytes counter threats

A

1) phagocytosis- use receptors to recognize PAMPs when sampling the environment
2) mediator production- release factors to activate other responses (cytokines, chemokines)

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34
Q

What are the four signs of inflammation?

A

redness, pain, heat, swelling

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35
Q

What are the 3 things inflammation does?

A

1) alters blood flow
2) increases permeability of vascular system
3) gives infiltration of WBCs

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36
Q

how is the inflammation response initiated?

A
  • by recognizing PAMPs and DAMPs (pathogen associated molecular pattern) and activate an immune response best suited towards eliminating the infected organism; takes minutes from exposure
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37
Q

what are the 4 classes of pathogen recognition receptors (PRRs)?

A
  • toll like
  • c-type lectin
  • Rig-I like receptor
  • NOD-like receptor
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38
Q

Where are the two places PRRs can be expressed?

A

transmembrane (TLRs CTLRs) or soluble intracytoplasmic (Rig and NOD)

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39
Q

What does TLR-4 recognize?

A

LPS (on gram negative bacteria)

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40
Q

What is the TLR4 pathway?

A

receptor binds MyD88, binds IRAK, releases NFKB and initiates transcription

41
Q

What happens if TLR is missing?

A

get unrestricted replication of bacteria

42
Q

what are the critical cells in the innate response that interface with the adaptive system?

A

** dendritic cells

NK cells

43
Q

what are some key characteristics of dendritic cells?

A

1) roam freely in all tissues/organs
2) have lots of PRRs
3) interact with NK cells and GDTs (gamma delta t-cells)

44
Q

how do NK cells interact with the adaptive system?

A
  • bind to antibody coated cells and degradulate

ADCC- antibody dependent cytotoxicity

45
Q

what are 2 innate-like lymphocytes?

A
  • NKT cells - subset of T cells with molecules found on NK cells ; recognize lipid antigens, provide immediate help for adaptive system
  • GDTs- recognize phosphoantigens (metabolic intermediate produced by fungi & bacteria)
46
Q

where are GDTs commonly found?

A

mucosal sites

47
Q

which type of innate cells can establish memory phenotype?

A

GDTs, NKTs, ILCs

- macrophages- epigenetic changes which train them for faster response

48
Q

what is the sequence like at the N-terminal end of the light & heavy chains?

A
  • it is the variable terminal, the sequence is very specific
49
Q

what are the 5 antibody isotopes?

A 
"MADGE" 
IgM- mu
IgA- alpha
IdD- delta 
IgG- gamma
IgE- epsilon
50
Q

Which two antibodies have extra long heavy chains?

A

IgM and IgG

51
Q

what is the predominant antibody induced in the secondary response?

A

IgG

52
Q

what is the predominant antibody in external secretions?

A

IgA

53
Q

What is the predominant antibody induced in the primary response?

A

IgM

54
Q

Which antibody is found mainly on the surface of B cells?

A

IgD

55
Q

Which antibody is involved in allergic hypersensitivities?

A

IgE

56
Q

How are isotopes classified?

A

in the constant region of their heavy chain

57
Q

What are the two types of light chains?

A

kappa (60) & lambda (40)

58
Q

what kind of bond holds the heavy chains together? light chains?

A

both are disulfide

59
Q

What are the two fragments above and below the disulfide bond called?

A

Fab (fragment antigen binding) &

Fc (crystalizing fragment)

60
Q

which is special about IgM

A

comes together as a pentamer in blood; is predominant antibody induced in the primary response; is 5x larger

61
Q

what is special about IgA

A

found in blood as monomer & in mucosal secretions as dimer

62
Q

what is the major Ig in blood?

A

IgG

63
Q

what is the half-life of IgG?

A

21 days (3 weeks)

64
Q

what do mast cells have receptor for?

A

Fc part of IgE (allergies) = FCeR

Fc= crystalized fragment

65
Q

3 functions of antibodies

A

1) neutralization (prevents bacterial adherence)
2) opsonization (promotes phagocytosis)
3) complement activation (complement enhances opsonization)

66
Q

what is the IgE mediated allergy response?

A

have two IgEs bound to Fc receptor specific for IgE side by side; allergen binds to both IgEs, cross linking promotes degranulation of histamine packets

67
Q

what is Fc receptor-mediated killing?

A

macrophages, neutrophils, NK cells, eosinophils, basophils and mast cells all have Fc receptors (FcR’s) on their surface, and the cells can be triggered by cross linking of the receptors (phagocytosis or secretion)

68
Q

when is the critical time for babies with regards to serum Igs?

A

6-9 months

passively protected by maternal IgG for first few months

69
Q

half life of serum antibody titers?

A

tetanus- 11 years

measles- 2014 years

70
Q

what is a monoclonal antibody? when is this useful?

A

antibody from a clone of B cells (B-cells make antibody to 1 epitope); useful for targeting cancerous tumor; any drug that ends in MAB

71
Q

what is a polyclonal antibody?

A

antibody from multiple close of B cells (IVIG treatment, immunizations)

72
Q

what secrete immunoglobulins?

A

terminally differentiated B cells (plasma cells)

73
Q

describe the specificity of antibodies produced by 1 B cell

A

all antibodies produced by same B cell have same variable heavy chain, and same variable light chain

74
Q

describe DNA rearrangement for light chains

A

one of ~40 Vks is rearranged next to one of ~5 Jks; everything in between is deleted

75
Q

describe RNA splicing for light chain

A

an intron after Jk is taken out to connect with Ck sequence

76
Q

what three genes need to be rearranged together for a heavy chain? what is the order re-arrangement occurs in?

A

Vh, Dh, Jh

- DJ rearranged first, then VDJ

77
Q

what is allelic exclusion?

A

only one Vh and one Vl are rearranged per B cell (only one allele is rearranged (and thus expressed))

78
Q

which CD represents HSCs?

A

CD34

79
Q

where do mature B-cell precursors exist?

A

bone marrow

80
Q

what two antibodies must a mature B cell have on the surface?

A

IgM & IgD
(MD!)
** remember the variable regions on these two Igs will be the same!!

81
Q

in which B cell precursor does DJ (heavy chain) rearranging occur?

A

early pro B cell

pro B cells are where there are IgH rearrangements and no light chain arrangements

82
Q

in which B cell precursor does V-DJ (heavy chain) rearranging occur?

A

late pro B cell

pro B cells are where there are IgH rearrangements and no light chain arrangements

83
Q

what happens in pre-B cells?

A

there is a pre-B cell receptor composed of a surrogate light chain and mu heavy chain; this is transiently localized to surface, shuts of rearrangement of other allele OFF, then goes back intracellularly

(** pre-B cells have mu heavy chain)

84
Q

in which B cell precursor does VJ (light chain) rearranging occur?

A

starts in small pre-B cell, completes by immature B cell

85
Q

what happens to make immature B cells?

A

light chain is produced, associate with mu heavy chains, and IgM is expressed on cell surface; called immature b/c they don’t proliferate/ differentiate in response to antigens (will always express the same variable region)

86
Q

what two things is recombination mediated by?

A

RSS (sequence) and RAG1/2 (enzyme)

87
Q

what is a BREC?

A

B-cell recombination excision circle= excised DNA= rings left over when excision occurs, look for them when trying to determine if making new B cells

88
Q

what determines if an antibody will be secreted or left on the membrane?

A

alternative splicing of SC (1st) and MC (downstream) (C-terminal end of transcript)

89
Q

how do you get co-expression of IgM and IgD on same B cell?

A

Vh is the same

Cu and Cd are chosen based on alternative splicing (Cd is downstream (but close) to Cu)

90
Q

what is an isotype switch? where and when does it occur?

A

changing the Ch of an antibody
occurs NOT in bone marrow
happens after the antibody has encountered an antigen

91
Q

what are the equivalents of the RSS & RAG sequences for a class/antibody switch?

A

RSS= switch region

RAG (enzyme)= AID

92
Q

3 ways of generating antibody diversity in bone marrow

A

1) VDJ gene joining
2) N-Nucleotide addition by TdT (adding in random type and # of nucleotides between excision & rejoining)
3) combinatorial association of H & L chains (each have own variable region)

93
Q

Way to generate antibody diversity not in bone marrow

A

4) somatic hypermutation (variable region mutates 1 in 1,000 bps)

94
Q

what is a Tdt?

A

terminal deoxynucleotidyl transferase

enzyme which adds in random NTs

95
Q

what happens to VDJ rearrangements that shift the reading frame?

A

they die

96
Q

what are the two things that happen to VDJ rearrangements that produce self-reactive antibodies

A

1) if the antigen is multivalent (have lots of sites for attachement), they undergo apoptosis
2) if the antigen is soluble, they become anergic (don’t activate)

97
Q

how can multivalent cells be rescued?

A

up-regulate RAG, get “receptor editing”, where the cell choses new V & J sites for the light chain

98
Q

how are T cell receptors (TCRs) analogues of B cell receptors (antibodies)?

A
  • they are analogous to the FAB fragment
  • instead of heavy and light chains, they have alpha and beta chains (or gamma delta)
  • see allelic exclusion
  • use RSS/RAG system to get TRECs
  • have Valpha, Calpha, Vbeta, Cbeta
99
Q

what genes are required for the alpha and beta chains?

A

alpha- V&J (&C)

beta- VDJ (&C)

Host Defense (6 decks)

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