IHO Week 1 Diebel Flashcards

1
Q

Major Functions of Innate Immunity

A
  1. Complement activation 2. Inflammation 3. Cell activation (cytokine and chemokine production, phagocytosis and other killing microbes) 4. priming of the adaptive immune response
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2
Q

3 Things Recognized by the Innate Immune System

A
  1. Foreign molecular structures called PAMPs 2. stress or damage indicators aka DAMPs 3. absence of certain ‘self’ MHC1marker molecules by NK cells
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3
Q

PRRs

A

pattern recognition receptors; 13 TLRs are included in this

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4
Q

PRRs that recognize PAMPs do not activate phagocytosis and do trigger cell signaling leading to gene transcription events to foreign material

A

TLRs

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5
Q

C-Type Lectin Receptors

A

Mannose, Dectin 1, DC-SIGN

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6
Q

Scavenger Receptors

A

SR-A and SR-B

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7
Q

Steps Phagocytosis

A
  1. bacterium attaches to membrane and evaginations called pseudopodia 2. ingested to form phagosome 3. fuses with lysosome 4. bacterium is killed and digested by lysosomal enzymes 5. digestion products released from cell
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8
Q

Phagocytosis Oxidative Attack from:

A

Reactive Oxygen Species (O2, OH, H2O2, HClO) and Reactive Nitrogen Species (NO, NO2, ONOO-)

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9
Q

Alternative Pathway to activate the complement system

A

innate immune defense strategy which results in opsonization and facilitated uptake of the coated microorganism by phagocytosis

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10
Q

Classical Pathway to Activated by

A

Antibodies or mannose binding lectin

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11
Q

Complement activation is a cascade reaction leads to:

A

opsonization, chemotaxis of phagocytes, increased blood flow, increased permeability, damage to plasma membranes on cells, G(-) bacteria, enveloped viruses, and other organisms, release of inflammatory mediators from mast cells

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12
Q

Classical Pathway (Adaptive Immunity) direct destruction

A
  1. C1q binds to antigen: antibody complex; cleaves and activates downstream complement components 2. C5b binds to the membrane associated with the antigen:antibody complex which leads to the formation of the membrane attack complex
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13
Q

Lectin Pathway (Innate Immunity) direct destruction

A
  1. Mannose binding protein bound to bacterial carbohydrates mimics C1q -> cleavage and activation of downstream complement components 2. C5b binds to the membrane to form attack complex
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14
Q

Alternative Pathway (Innate Immunity)

A

C3 is spontaneously cleaved or cleaved by C3b by serum proteases activated by bacteria; C3b binds to bacterial and yeast cell walls and viral envelopes; bound C3b leads to the downstream activation of the complement components

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15
Q

A Components-C3a, C4a and C5a action

A

-chemotactic factors that direct migration of/degranulation of PMNs and macrophages and degranulate mast cells and basophils to large amounts of histamine

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16
Q

Potency of A Complement Components

A

C5a»C3a»C4a

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17
Q

What complement deposits on any surface with an exposed amine or hydroxyl ie bacteria cell

A

C3b and C4b

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18
Q

What complement acts as opsonins and further cleaves C3 to ramp up signaling at the surface

A

C3b and C4b

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19
Q

What are inactivated when bound to host cells by decay accelerating factor

A

C3b and C4b

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20
Q

What complement binds to microorganisms or host body cells

A

C5b

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21
Q

What complement acts as a focal point for the deposition of the membrane attack complex?

A

C5b

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22
Q

What complement associated with CD59 protectin and homologous restriction factor to prevent formation of membrane attack complex

A

C5b

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23
Q

Phagocytosis-Opsonin Receptors: Collagen-domain receptor examples and ligands

A

examples: CD91/calreticulin
ligands: collectins SP-A, SP-D, MBL; L-ficolin; C1q

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24
Q

Phagocytosis-Opsonin Receptors: Complement Receptors examples and ligands

A

ex: CR1, CR3, CR4, CRig, C1qRp
ligands: complement components and fragments

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25
Q

Phagocytosis-Opsonin Receptors: immunoglobulin Fc receptors

A

ex: FcalphaR and FcgammaRs
ligands: specific IgA or IgG antibodies bound to antigen and CRP

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26
Q

Hallmarks of Inflammation

A

-edema, hyperthermia, local hypoxia, extravasation (influx of WBC via IL-8)

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27
Q

What increases vascular permeability besides Leukotriene D4

A

histamine-complement C5a stimulation of basophil and mast cell degranulation

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28
Q

What causes vasodilation and increased vascular permeability

A

prostaglandin E2-complement C5a stimulation of basophil and mast cell degranulation

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29
Q

What causes neutrophil chemotaxis, increased vascular permability

A

Leukotriene-complement C5a stimulation of basophil and mast cell degranulation

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30
Q

What besides histamine increased vascular permeabillity

A

Leukotriene D4-complement C5a stimulation of basophil and mast cell degranulation

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31
Q

Macrophages Triggers of Inflammation: 3

A

TNF, IL-1 and IL-8

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32
Q

can cause a fever, stimulates expression of E-selectin

A

TNF

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33
Q

induction of local inflammation; activates endothelial cells to express adhesion molecules; induces the production of chemokines to recruit leukocytes and role in fever

A

IL-1

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34
Q

chemotaxis

A

IL-8

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35
Q

activation of phagocytic cells and NK cells in trigger of inflammation

A

IFNgamma

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36
Q

Name 3 changes in tissue during acute inflammation

A
  1. increased blood supply 2. increased capillary permeability 3. increased leukocyte migration
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37
Q

Cells in acute inflammation

A

more neutrophils and activated helper T cells

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38
Q

Cells in chronic inflammation

A

more macrophages, cytotoxic T cells and B cells

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39
Q

Important Inflammatory Cytokines (3)

A

TNFalpha, IL-1 and IFNgamma

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40
Q

More migration in high shear or low shear

A

low shear

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41
Q

3 Step Model of Leukocyte Adhesion

A
  1. Tethering with CD15 and E-selectin 2. Triggering with direct signal and chemokines 3. Adhesion-activation of integrins and CR3/LFA-1, ICAM-1
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42
Q

histamine main source and action

A

mast/basophils: increased permeability, smooth muscle contraction, chemokinesis

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43
Q

5HT

A

platelets/mast cells: increased permeability, smooth muscle contraction

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44
Q

platelet activating factor main source and action

A

basophils/neutrophils/macrophages: mediator release from platelets, increased perm., smooth muscle contraction, neutrophil activation

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45
Q

IL-8 main source and action

A

mast/endothelium/monocytes and lymphocytes: polymorph and monocyte localization

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46
Q

C3a main source and action

A

C3: mast cell degranulation, smooth muscle contraction

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47
Q

C5a main source and action

A

C5: mast cell degran, neutrophil and macrophage chemotaxis, neutrophil activation, smooth muscle contraction, increased capillary perm

48
Q

bradykinin main source and action

A

kinin system: vasodilation, smooth muscle contraction, increase capillary perm, pain

49
Q

fibrinopeptides and fibrin breakdown products main source and action

A

clotting system: increased vasc perm, neutrophil and macrophage chemotaxis

50
Q

PGE2 main source and action

A

cycolo-oxygenase pathway, mast cells: vasodilation, potentiates vasc. perm produced by histamine and bradykinin

51
Q

leukotriene B4 main source and action

A

lipoxygenase pathway, mast cells: neutrophil chemotaxis, syngergizes with PGE2 in increasing vascular permeability

52
Q

leukotriene D4 main source and action

A

lipoxygenase pathway: smooth muscle contraction, increasing vascular permeability

53
Q

PMN signaling differentiation

A

(IL3+GMCSF)->(IL-3 + GMCSF +GMCSF)

54
Q

have Fc receptors to bind antibodies which makes them able to kill by antibody-dependent cellular cytotoxicity

A

PMN

55
Q

Eosinphils signaling

A

(IL3 +GMCSF)->(IL3+GMCSF +IL5)

56
Q

what activates C5a and C3a to degranulate

A

Eosinophils and Basophils

57
Q

Basophils signaling

A

(IL3+GMCSF)->(IL3 + GMCSF + IL4)

58
Q

Macrophages signaling

A

(IL3 + GMCSF)-> (IL3 + GMCSF +MCSF)-> (GMCSF +MCSF)

59
Q

Cytokines and lymphokines produced by macrophages

A

IFNalpha, IL1beta, IL6, TNFalpha, IL8, IL12

60
Q

Dendritic Cell Signaling

A

from myeloid: (IL3 +GMCSF)-> (IL3 +GMCSF+MCSF)-> (GMCSF+ IL4)

61
Q

process and present foreign protein antigens to T cells

A

Classical dendritic cells

62
Q

passively present foreign antigen in the form of immune complexes to B cells in lymphoid follicles

A

Follicular dendritic cells

63
Q

NK signaling for differentiation

A

(IL-7)->(IL-2)

64
Q

2 markers of NK cells

A

CD16 (FcyRIII) and CD56 (NCAM)

65
Q

What activates NK cells to secrete cytokine INFgamma

A

IL-12 and TNFalpha

66
Q

signal transduction element of T cell; Th and Tc

A

CD3

67
Q

adhesion molecule that binds to class II MHC molecules; signal transduction; Th

A

CD4

68
Q

low affinity receptor for Fc region of IgG; NKcell

A

CD16(FcyRIII)

69
Q

signal transduction; CD21 co-receptor; Bcell

A

CD19

70
Q

receptor for complement (C3d and EBV); B cell

A

CD21 (CR2)

71
Q

receptor for costimulatory B7 molecule on APC; Th and Tc

A

CD28

72
Q

receptor for Fc region of IgG

A

CD32 (FcgammaRII)

73
Q

signal transduction; Bcell

A

CD40

74
Q

adhesion molecule; NK cell

A

CD56

75
Q

IgG

A

main antibody in blood and tissue fluids; neutralized toxins and blood borne viruses, binds bacteria and facilitates destruction via complement

76
Q

How long for activation of B and T lymphocytes?

A

7-10 days

77
Q

T cell job versus B cell job

A

Tcell (cell mediated) survey surfaces of body’s cells for parasites within or dangerous mutations and release lymphokines while Bcells (humoral) protect extracellular spaces of the body with antibodies

78
Q

Residence of B and T cells

A

can be in blood or lymph nodes and spleen

79
Q

Can mature B and T cells travel from one lymph node to another or to and from the spleen?

A

yes

80
Q

Primary Lymphoid Organs

A

Thymus and Bone Marrow

81
Q

Secondary Lymphoid Organs and Tissues

A

-waldeyer’s ring (tonsils and adenoids), bronchus associated lymphoid tissue (lymph nodes, bone marrow, spleen), lymphoid nodules, peyer’s patch, urogenital lymphoid tissue

82
Q

anther name for epitopes

A

antigenic determinants

83
Q

a cytokine made by a lymphocyte

A

lymphokine

84
Q

What 2 things do all T cells express

A

CD3 and T cell receptors created through DNA arrangement

85
Q

what couples with CD3 complex to make up the TCR

A

alpha beta peptides in alpha beta T cells

86
Q

alpha beta T cells function by binding what

A

MHCI or MHCII molecules

87
Q

gamma delta can function with binding what

A

MHC

88
Q

Job of Type 1 Helper T cells; Th1 (CD4)

A

recognize antigen and make a lymphokine that attracts MACROPHAGES

89
Q

job of Th17 Helper T cells; Th17 (CD4)

A

inflammation; more powerful than Th1; autoimmunity

90
Q

job of Type 2 Helper T cells, Th2 (CD4)

A

alternatively activated macrophages, function in walling-off pathogens and promoting healing; usually after Th1; parasites

91
Q

job of Follicular Helper T cells, Tfh (CD4)

A

stimulated via antigen and migrate from T cell areas of lymph nodes into the B cell follicles where they help B cells get activated to IgM/IgG/IgE/IgA

92
Q

job of Regulatory T cells, Treg (CD4)

A

make cytokines that suppress the activation and function of Th1, Th17, and Th2 to keep immune response in check

93
Q

job of cytotoxic or killer cells, CTL (CD8)

A

destroy body cell they id as bearing a foreign or abnormal antigen

94
Q

what serves to increase affinity for antigen, activates Th and serves as tag for identification

A

CD4

95
Q

Needed for adhesion

A

LFA-1 on T and ICAM-1/3

96
Q

Needed for Ag Specific activation

A

CD2 to CD58, CD8/4 to MHCI/II

97
Q

Needed for co-stimulation

A

CD28 to B7 (akaCD80/86)

98
Q

Needed for cytokine signals

A

IL-1R to IL-1, CD25 to IL-2

99
Q

2 ways of killing via Killer T cells

A
  1. FAS-FAS ligand interaction (induces caspase to apoptosis) 2. secreting toxic agents as well (TNF or granzymes to apoptosis)
100
Q

Where do T cells differentiate to CD4 or CD8?

A

Thymus

101
Q

Positive versus Negative selection of T cell maturation

A

(+) self restricted, (-) tolerant to self-antigens

102
Q

Most abundant immunoglobulin, 2 adjacent to activate complement

A

IgG

103
Q

only antibody to pass from mother to fetus in humans; valence 2

A

IgG

104
Q

secreted as a pentamer held together by the J chain with 4 constant domains; immunoglobulin; better at activating COMPLEMENT and first to appear in blood after new exposure; then replaced by IgG; valence 10

A

IgM

105
Q

main form of antibody inserted into B cell membranes as their antigen receptor; sits on the membrane; valence 2

A

IgD

106
Q

in secretions (saliva, tears, genitourinary and gi fluids, milk), associated with secretory component that acquires epithelial cells, first line defense in mucous membranes; secreted as dimer; valence 2, 4, 6, or 8

A

IgA

107
Q

immunoglobulin to attach to mast cells in tissues to make PG, leukotrienes, and cytokines to inflammation (histamine); parasites; valence 2

A

IgE

108
Q

4 was antibody as adapter molecules

A
  1. immune complex (C1q) 2. immune complex/pathogen opsonization phagocytosis (FcR) 3. target cell/pathogen (recognition killing-FcR) 4. antigen (sensitization cell activation FcR)
109
Q

If you change the heavy chain from mu to alpha does the light chain change from kappa or lambda or stay the same

A

stays the same

110
Q

what two immunoglobulins when bind change the angle b/w Fab

A

IgG or IgM

111
Q

Angle change with binding of Fab for 2 reasons

A
  1. binding to phagocytic cells via Fc receptors for altered Fc of IgG 2. C1qto bind to 2 adjacent Fcs
112
Q

If lots of IgG around what happens

A

forms a hexamer that allows CH2 landing pad for C1q to complement cascade

113
Q

what is the trade off in IgG hexamer versus monomer

A

complement activation versus opsonization

114
Q

Heavy chain chromosome

A

14; VDJ

115
Q

What germline for VDJ chromosome 14

A

DNA to CH genes

116
Q

what recognizes open sites in the DNA for VDJ recombination?

A

RAG1-RAG2 multimers

117
Q

Stages of VDJ Recombination

A
  1. synapsis: RAG synaptic complex 2. cleavage: RAG post-cleavage complex 3. joining: coding joint (imprecise junction) or signal joint (precise junction)