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ABAI > Review Book > Flashcards

Review Book Flashcards

1
Q

TCR complex

A

TCR (alpha/beta or gamma/delta)
Cd3 (epsilon/delta and gamma/epsilon),
2 zeta chains

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2
Q

NKT cell recognize

A

Lipids in context of Cd1

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3
Q

Costimulatory signal in t cell activation

A

Cd28 (T cell receptor) with B7-1 (cd80) or B7-2 (cd86)

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4
Q

T cell survival signal

A

IL-2 with its receptor CD25

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5
Q

Cd80/86 increased/decreased by:

A

Increased by PAMPs/bacterial products detected by dendritic cells

Decreased by CTLA-4 that pushes out cd28 and binds cd80/86, downregulating it

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6
Q

Mutation causing x-linked lymphoproliferation syndrome (XLP)

A

Mutation in SAP
SAP binds SLAM and links SLAM to Fyn (linked to cd3 proteins) on activated T cells

EBV in boys with XLP can develop HLH

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7
Q

Zap-70 deficiency cell enumeration

A

No Cd8 cells
No T cell function
Normal B cells
Normal NK cells

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8
Q

T cell activation signaling sequence

A
  1. Antigen binds TCR (via MHC)
  2. Lck phosphorylates cd3 and zeta proteins, recruiting zap-70
  3. Zap-70 phosphorylates LAT
  4. Lat becomes docking site for PLC-1 and Grp2
  5. Grp2 recruits sos that catalyzes GDP to GTP on RAS —> Mek>erk>Fos>ap-1 transcription factor
  6. PLC converts pip > DAG and ip3, activates:
    A. DAG -> PKC -> NFkB
    B. IP3 -> increased intracell Ca via CRAC on cell membrane -> calmodulin >calcinuerin > NFAT > cytokine transcription
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9
Q

BCR complex components

A

Surface immunoglobulin
Ig alpha and Ig beta chains

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10
Q

BCR signaling cascade

A
  1. Lyn P itam (Igalpha/beta), docking for Syk
  2. Syk (~zap-70 analogue) P BLNK
  3. BLNK activates ras, rac, plc, btk, grb-2
  4. Btk + Syk activate PLC -> PIP2 into ip3/DAG
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11
Q

How complement enhances BCR

A

Antigen opsonized with c3b > degraded to c3d
C3d ligand for cd21(cr2) on B cells
Forms complex - cd21-cd19-cd81
- when binds c3d, complex goes to BCR and activates cascade with enhanced response

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12
Q

Inhibitory receptors in T, B, and NK cells

A

T cells - ctla-4, pd-1
B cells - fcgammaRIIbeta
NK cells - KIRs

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13
Q

NFkB activators

A

IL-1, TNF, IL-17, TLR activation

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14
Q

Antiviral Cytokines

A

Type I interferon (IFNalpha/beta), IL-28A, IL-28B, IL-29

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15
Q

Cellular immunity cytokines

A

IL-2, , ifn gamma, IL-15, IL-17

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16
Q

Humoral immunity cytokines

A

IL-7, IL-11

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17
Q

Anti-inflammatory cytokines

A

TGF-beta, IL-10, il-37, il-38

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18
Q

Cytokines in isotope switching

A

IL-4 and -13 — IgE
Tgf-beta, il-5 — IgA
Il-10 — igg4
IFN-g - IgG

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19
Q

TNF actions

A

Acute inflammation (esp GNR)
Recruits neutrophils/monos
Stimulates endothelial cells to express adhesion molecules and induce chemotaxis

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20
Q

Lymphotoxin action

A

Activates endothelial cells and neutrophils

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21
Q

BAFF action

A

Survival signals to maturing B cells
Upregulates anti-apoptotic Bcl-2 activation of NFkB

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22
Q

APRIL cytokine action

A

Upregulates anti-apoptotic Bcl-2 activation of NFkB

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23
Q

Il-1 action at high and low concentrations

A

Low - local inflammation, endothelial cells increase surface molecules for leukocyte adhesion

High - fever, synthesis acute phase reactants in the liver, neutrophil/plt production in bone marrow

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24
Q

IL-18 source

A

Macrophages
Dendritic cells
Pro-molecules cleaved by caspase-1
NOT made by T, B, or NK cells

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25
Q

Il-18 actions

A
  • IFN-gamma production by T and NK cells
  • inhibits IgE synthesis
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26
Q

IL-33 actions

A

Alarmin (w/ TSLP, Il-25)
T cells - Th2 development
ILCs - activate group 2 ILCs

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27
Q

Il-37 action

A

With SMAD3 in nucleus - inhibits transcription pro-inflammatory mediators

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28
Q

Anakinra target

A

Binds IL-1R (IL-1Ra) to prevent Il-1 pro-inflammation in autoinflammatory syndromes

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29
Q

IRAK-4 deficiency infections

A

Pyogenic infections, esp strep pneumonia

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30
Q

Il-19 action

A

Activates monocytes to release il-6, TNF-alpha, ROS

promotes Th2

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31
Q

Il-22 action

A

From Th-17 cells
Epithelial cells increase defensins and barrier function

Induces MHC class I antigen expression

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32
Q

IL-12 actions

A
  • Stim ifn-gamma production by T and NK cells
  • promotes Th1 cells (that produce ifn-gamma)
  • increases production il-18 receptor (il-18 aka ifn-gamma inducing factor)
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33
Q

Il-23 actions

A
  • important in protection klebsiella PNA
  • promotes differentiation/maintenance Th17 cells (that produce il-17)
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34
Q

Il-27 action

A
  • Promotes Th1
  • promotes ifn-gamma production by t cells
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35
Q

Type I ifn action
(Ifn-alpha, -beta)

A
  • inhibit viral replication
  • increase class I MHC expression
  • stimulate Th1 cells
  • promote sequestration lymphocytes in LNs
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36
Q

Il-7 action

A

Survival of T cells (esp cd4)

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37
Q

Il-21 action

A

Class switching and Ig production by B Cells

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38
Q

IL-2 action

A
  • required for survival/function Tregs
  • proliferation of NK cells
  • induces Bcl-2 expression
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39
Q

IFN-gamma action

A
  • Promotes Th1 differentiation
  • Inhibits Th2 differentiation
  • Inhibits class switch IgE, IgG4
  • increases MHC on APCs
  • promotes macrophage inflammation and inhibits IgE-dep eosinophil rich reactions
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40
Q

il-16 action

A

Promotes Th1/dampens Th2

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41
Q

Il-17 action

A
  • increases th17
  • increases chemokines/cytokines
  • increases gm-csf and g-csf
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42
Q

Il-25 action

A

Alarmin
Increases il4, 5, 13

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43
Q

Il-4 action

A
  • th2 differentiation
  • class switch to IgE and IgG4
  • it’s receptor, il-4R signals through Jak-stat (stat6)
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44
Q

Il-5 action

A
  • activates eos
  • B cell proliferation and IgA production
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45
Q

Il-13 action

A
  • fibrosis as tissue repair of chronic inflammation
  • mucus by lung epithelial cells
  • IgE and IgG4 class switching
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46
Q

Il-6 action

A
  • pro-inflammatory
  • stimulates acutely phase protein synthesis in liver
  • production neutrophils in BM
  • T cells to produce il-17
  • signaling involves jak1/stat3
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47
Q

Il-15 action

A
  • survival of memory CD8 T cells, NK cells, NKT cells
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48
Q

TGf-beta

A
  • anti-inflammatory cytokine
  • inhibits proliferation/function T cells
  • inhibits macrophage activation
  • induces apoptosis
  • regulates tissue repair and activates fibrosis
  • uses Smad receptors
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49
Q

Gm-csf action

A

Promotes granulocytes, monocytes, macrophage activation

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50
Q

M-csf action

A

Promotes monocytes maturation

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51
Q

G-csf action

A

Granulocyte maturation

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52
Q

IL-33 action

A

Th2 development
Activates group 2 ILCs

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53
Q

Il-3 action

A
  • promotes mast cell development BM
  • basophil-differentiating cytokine
  • eos development
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54
Q

C-kit ligand action

A
  • mast cell growth factor
  • sustains viability T cells in thymus
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55
Q

Castleman’s disease

A

Overproduction Il-6
LN hyperplasia,
Fever, microcytic anemia, LAD, hypoalbuminemia, high CRP

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56
Q

Role of cytokines IL-1 -5

A

Hot T-Bone stEAk
Il-1 - fever
Il-2 - stimulates T cells
Il-3 stimulates bone marrow
Il-4 stimulates IgE
Il-5 stimulates IgA

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57
Q

X-linked SCID receptor mutation

A

GammaC, part of IL-2R. Important for il-2r, il-4r, il-7r, il-9r, il-15r, -il-21r

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58
Q

Il-2R components

A

Il-2Ralpha
Il-2R beta
GammaC
Engages jak3-stat5

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59
Q

Source of chemokines

A

Epithelial cells, endothelial cells, leukocytes, fibroblasts

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60
Q

Chemokines assoc w/ atopy

A

CCL2, CCL5, ccl7, ccl11
Cxcl8

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61
Q

WHIM syndrome

A

Warts
Hypogamm
Infections
Myelokathexis (retention neutrophils in BM)

Assoc w/ defects in CXCR4

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62
Q

CC chemokines

A

Recruits eos, monos, basos
Lymphocytes for ALLERGY

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63
Q

CXC chemokines

A

Recruits Neutrophil
Lymphocytes for INFLAMMATION

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64
Q

Ccl5 (RANTES) receptor

A

CCR 1,3,5

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65
Q

CCL11 (eotaxin) receptor

A

CCR3

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66
Q

CCL17 (TARC) receptor

A

CCR4

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67
Q

CXCL8 (IL-8) receptor

A

CXCR 1,2

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68
Q

Selectins role

A

Rolling of leukocytes and binding carbs

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69
Q

P-selectin summary

A

Aka CS62P
On Platelets,
ligand PGSL (and sialyl-lewis),
binds Pmns, T cells, monocytes

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70
Q

E selectin summary

A

Aka CD62E and ELAM
On Endothelium
Binds ESL-1, cd15, pgsl, sialyl lewis
Homes T cells to sites inflammation

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71
Q

L selectin

A

Aka LAM-1, CD62L
On Lymphocytes Leukocytes
Ligands gLycsm-1, madcam-1, cd34, Sialyk-lewis
Homes to LN HEV (via Glycam) and PMN rolling (via madcam)

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72
Q

LAD-2 deficiency and selectins

A

PMNs can’t express carb ligands for E and P selectin

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73
Q

Role beta integrin family (alpha4beta7)

A

Gut homing
Binds madcam

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74
Q

Chemokine in heparin induced thrombocytopenia

A

Cxcl4

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75
Q

HIV chemokinea

A

CCR5
if homozygous mutation - no HIV infection
If heterozygous - slow infection progression

CXCR4

CCL3L1
- if low level, higher HIV acquisition and worse disease

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76
Q

Atherosclerosis chemokine

A

CXC3CL1

CX3CR1
- v249I mutation —> increased risk acs
- T280M —> protects against plaque

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77
Q

Glanzmann’s thrombasthenia chemokine

A

GIIbIIIa defect leads to plt defect

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78
Q

Alternative pathway C3 convertase

A

C3bBb

Stabilized by properidin

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79
Q

Alternative pathway activation

A

C3 tick-over to C3b in microbial surfaces

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80
Q

Only known positive regulator of complement system

A

Properidin
Stabilizes factor B

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81
Q

Classical pathway activation

A

Antigen-Ab complex binds C1
(Binds CH2 domain IgG or CH3 of IgM)

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82
Q

Classical pathway c3 convertase

A

C4b2a

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83
Q

Binding affinity order of c1q for immunoglobulin

A

IgM > IgG3 > IgG1 > IgG2

Cannot bind IgG4

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84
Q

Involved pathway if love C3 and C4

A

Classical pathway activation

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85
Q

Lectin pathway activation

A

MBL binds mannose on microbial polysaccharides and MBL-assoc protease 1 (MASP-1, and MASP-2)

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86
Q

Lectin pathway enzyme that cleaves to create c3 convertase

A

MASp-2 cleaves c4 and c2

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87
Q

Lectin pathway convertase

A

C4bC2a
(Same as classical)

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88
Q

C5 convertase

A

C3bBbC3b in AP
C4b2aC3b in CP and LP

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89
Q

MAC

A

C5b-c8 polyC9

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90
Q

Inhibitors of MAC formation on complement cascade

A

S protein and CD59

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91
Q

Complement anaphylotoxins

A

C5a
C4a
C3a
Induce inflammation and vascular permeability

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92
Q

C5a role

A

Most potent mediator basophil and citaneois mast cell degranulation
(>c3a>c4a)

Chemoattractant

C3a chemotactic for eos only

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93
Q

CR2 (cd21) role in complement

A

Binds c3d and is a 2nd signal for B cell activation
Decreases antigen any needed for B cell activation.
Hemos trap ag-ab complexes in germinal centers

Receptor for EBV

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94
Q

Complement receptor CR1(cd35)

A

Binds c3b, c4b
Regulates c3 convertase dissociation
Phagocytosis of c3b and c4b coated particles
Clears immune complexes (cr1 on RBCs)

HIV uses to infect monocytes

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95
Q

Complement receptor cr2 (cd21)

A

Binds c3d
Keeps ag-an complexes in terminal centers for B cell activation

EBV uses to facilitate cell entry

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96
Q

Complement receptor cr3 (cd11b/cd18)

A

Binds iC3b, Icam-1
Phagocytosis and leukocyte adhesion to endothelial cells

LAD 1

Mediates phagocytosis M tuberculosis

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97
Q

Complement receptor cr4 (cd11c/cd18, gp150/95)

A

Bjnds iC3b
Phagocytosis
Lad type 1

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98
Q

Cd46 (mcp)

A

Cofactor to factor I, inactivated C3b and C4b

Assoc w/ aHUS

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99
Q

CD55 (DAF)

A

Binds c3b c4b
Prevents Bb binding c3b
Prevents 2b binding c4b

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100
Q

CD59

A

Prevents c9 binding C5b-8

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101
Q

C3 nephritic factor

A

Autoantibodies that stabilize c3bBb
Consumption of c3

Assoc w/ c3 glomeruloneohropathy and partial lipodystrophy
- subendothelial deposits Ig and C3

Lipodystrophy - adipose source of factor D, completes formation c3bBb

(Lipodystrophy affects waist up, where more adipocytes)

Clue - low c3/nml c4 (alternative pathway)

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102
Q

Anti-c1q autoantibodies

A

Auto ab to c1q
In hypocomplementemic urticarial vasculitis (huvs)
Immune complex deposition skin, joints, kidneys, lungs
Tx = hydroxychloroquine, dapsone steroids

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103
Q

Infxn assoc w/ terminal
Complement deficiency

A

Neisseria

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104
Q

Issues w/ early classical complement pathway deficiency

A

Encapsulated orgs (strep pneumonia!)
Lupus
Accelerated atherosclerosis
(Early mi second cause death)

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105
Q

Deficiency if:
Ch50 absent
Ah50 ok

A

Low C1q, c1q, c1q, c2, c4

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106
Q

Deficiency if
Ch50 nml
Ah50 absent

A

Low factor D, factor b, properidin

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107
Q

Deficiency if
Ch50 absent
Ah50 absent

A

Low c3, c5-c9

If c3 absent —> low factor H or I

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108
Q

Complement deficiency in sle

A

C1q&raquo_space;>
Also see low c1/s, c4, c2

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109
Q

MBL deficiency infxns

A

Pyogenic

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110
Q

Demographic c9 and c2 deficiencies

A

C9: 1/1000 Japanese
C2: 1/10,000 caucasian

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111
Q

Complement deficiency assoc w/ age related macular degeneration

A

Factor H

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112
Q

Inhibitor factor XIIa

A

C1 inhibitor
Therefore inhibits kallikrein production and bradykinin

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113
Q

Factor XIIa inhibitor

A

C1 inhibitor, therefore decrease kallikrein and bradykinin

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114
Q

Factor XIIa inhibitor

A

C1 inhibitor, therefore decrease kallikrein and bradykinin

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115
Q

Type II hypersensitivity examples

A

Cell antigens
Hemolytic anemia
Good pastures

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116
Q

Type III hypersens examples

A

Sle
GN
Serum sickness
Arthur’s rxn

Immune complexes

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117
Q

Mediators type II hypersens

A

IgG and IgM
+ complement/phagocytes

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118
Q

3 mechanisms type II hypersensitivities

A

1- opsonization (IgG) and phagocytosis (FcepsilonRI) (eg hemolytic anemia)
2 - complement activation (eg goodpasture) - IgG/M activate classical complement
Anti-basement membrane
3 - abnormal response w/o injury (MG, Graves)

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119
Q

Arthus rxn

A

Local vasculitis from immune complexes deposition (type III hypersens)
Local edema, neutrophil infiltration, hemorrhage, necrosis
Peak intensity 4-10hrs

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120
Q

Serum sickness rxn

A

Type iii hypersens
Rash, joint swelling, LAD, fever
7-12d after trigger start

Kidneys, liver, hemolysis

Re-exposure, sx onset 12-36 hrs

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121
Q

Type iii hypersens

A

Immune complex deposition
- vasculitis
- sle
- GN
- serum sickness

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122
Q

Type iv hypersens (cell-mediated)

A

Iva - cd4 th1 (ifn-gamma), TNF a, il2); macrophages, NK cells — contact dermatitis, TB

IVb - cd4 Th2 — eos, B cells — DRESS, morbillifirm drug rash

IVc — cd8, perforin, granzyme — psoriasis, drug induced Hep B

IVd — T cells — neutrophils — contact derm, agep

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123
Q

2 types NK cells

A

Cd56bright - 10%, cytokine producing
Cd56dim - 80%, activated

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124
Q

Antimicrobial peptide examples

A

Cathelicidins
Defensins
Produced by keratinocytes

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125
Q

Cytokines released from neutrophils

A

Il-1a, Il-12, -23, APRIL, BAFF

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126
Q

Cytokines from monocytes

A

TNF-alpha, Il-1, Il-6, Il-8, il-12

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127
Q

Dendritic cell cytokines

A

Il-1, il-6, il-23, TNF

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128
Q

Eosinophil proteins

A

Major basic protein
Eosinophil cationic protein

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129
Q

Mast cell cytokines

A

Ifn gamma, il6, TNF alpha, tgf beta, PAF, tryotase

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130
Q

Basophil cytokines

A

Il-4, il-6, BAFF, tslp

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131
Q

NK cell cytokines

A

TNF alpha, il-10, ifn-gamma

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132
Q

DAMPs

A

Damage associated molecular patterns
Endogenous molecules released by injured cells (NOT from apoptosis)

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133
Q

PRR (patent recognition receptors)

A

In APCs
Recognize DAMPs and PAMPs

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134
Q

Cytokines that require cleavage by inflammasome to be activated

A

Il-1 and Il-18

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135
Q

TLR ligands

A

PAMPs
Activate innate immunity

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136
Q

TLR that recognizes RSV and rhinovirus

A

TLR 2, 6, 7

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137
Q

TLR 4 ligands

A

GNR (lipopolysaccharides) , GP bacteria (peptidoglycans), rsv, acute phase proteins (Hsp 70, 90)

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138
Q

Adaptor protein involved in all TLR signaling (except TLR3)

A

MyD88

Activates NFkB and AP-1

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139
Q

TLR3 signaling mediators

A

TRIF, TRAF

Activates IRF3 and IRF7, induce type I IFN

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140
Q

Endosomal TLRs

A

Live in a NEST
Nine
Eight
Seven
Three

Play big role in viral recognition

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141
Q

TLR affected with hav encephalitis

A

TLR3

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142
Q

TLR pathway with Pyogenic infections

A

MyD88, IRAK4

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143
Q

NEMO deficiency

A

Canonical incisors, ectodermal dysplasia, recurrent bacterial infections
IKKgamma

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144
Q

Chronic mucocutaneous candidiasis deficiency

A

CARD9 - (cascade activation and recruitment domain), part of inflammasome

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145
Q

Cryoporin associated periodic syndromes (caps) mutation

A

NLRP3 - inflammasome

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146
Q

Central tolerance T cells

A

Via AIRE in MTEC

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147
Q

B cell central tolerance (negative selection)

A

Receptor editing with help RAG1/2 and light chain rearrangement

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148
Q

Thymus develops from which branchial arch

A

3 and 4

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149
Q

T cell positive selection

A

If bind strongly enough to peptides bound by MHC on cortical Thu if epithelial cells

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150
Q

T cell negative selection

A

AIRE induces expression self antígena
Occurs in medulla
(Negative selection in cortex)

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151
Q

When do T cell lose double positivity (cd4+cd8+)

A

When leave cortex and go to medulla

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152
Q

How do naive T cells home to parafillocular zone in T cells

A

Their CCR7 (on mature naive T cells) binds ccl19/21 from dendritic cells/stromal cells

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153
Q

How do T cells leave LN?

A

Via S1P gradient

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154
Q

What do Gamma delta T cells recognize

A

Lipids and heat shock proteins

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155
Q

Where are Gamma delta T cells found?

A

Gut tissue

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156
Q

NK T cell recognize and produce?

A

Recognize glycolipids

Produce ifn gamma, IL-4, -3, -17

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157
Q

What cytokines induce, are produced by, transcription factors of Th1

A

Induced by il12, ifn gamma
Produce ifn gamma
Txn factor Tbet, stat4
For intracellular defense

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158
Q

What cytokines induce, are produced by, transcription factors of Th2

A

Induced by il4,
Produce il4, 5, 13
Txn factors gata3, stat6

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159
Q

What cytokines induce, are produced by, transcription factors of Th17

A

Induced by il-6
Produces il-17,
Txn factor RORgammaT, stat3
Extracellular defense
Psoriasis

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160
Q

What cytokines induce, are produced by, transcription factors of Th9

A

Induced by tgf beta
Produces il9

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161
Q

What cytokines induce, are produced by, transcription factors of Tfh

A

Induced by/produces il-21
Txn factor bcl-6
Helps B cells make antibodies

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162
Q

What cytokines induce, are produced by, transcription factors of Tregs

A

Induced by tgf-beta
Produces tgf-beta, Il-10
Txn foxp3, stat5

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163
Q

3 types Treg

A

Natural T regs in thymus - mediate self tolerance
Induced Treg (Tr1) in periphery - suppress effector cells
iTreg (Th3) - in periphery, help IgA production in gut

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164
Q

Where are B cells first produced in fetus

A

Fetal liver @7eks

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165
Q

How mature naive B cells enter LN

A

Express cxcl5 that binds cxcl13 expressed by follicular dendritic cells i

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166
Q

How follicular naive B cells in LN follicles move to border with T cells

A

Activated by antigen presenting dendritic cells, increase ccr7 expression

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167
Q

Which interaction needed to stimulate B cell switch recombination (class switching)

A

Cd40 (b cell) with cd40L (follicular helper T cell)

Also need AID and UNG

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168
Q

HyperIgM causes

A

Deficiencies in cd40, cd40L, AID, UNG

Ig gets stuck in IgM form (doesn’t have tools for class switching

CD40L on T cells affected

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169
Q

Somatic hypermutation (affinity maturation)

A

T cell dep (need cd40-cd40L)
In germinal center
Point mutations in V regions

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170
Q

Peripheral B cell survival signals

A

BLYSS, APRIL, BAFF

receptors on B cells are BR3, TACI, BCMA

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171
Q

Role of Tdt
Terminal deoxynucleotidyl transferase

A

Adds nucleotides randomly during vdj recombination At hairpins

Responsible for heterogeneity

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172
Q

B 1 B cells

A

In peritoneal cavity and fetus

Independent of T cells

Doesn’t need antigen - constitutive secrete Ig

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173
Q

What has vdj recombination

A

Ig Heavy chains and TCR beta

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174
Q

12/23 rule

A

In vdj recombination, a gene segment flanked by 12 nt spacer can only be joined by gene segment flanked by 23 nt spacer

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175
Q

RSS

A

Recombination signal sequences
12 or 23nt long

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176
Q

Role rag1/2

A

Align 2 RSSs
Cleave dsDNA between coding segment and RSS

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177
Q

Artemis

A

Opens hairpins at coding ends (with DNA-pk
Vdj rearrangement

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178
Q

DNA ligase IV /XRCC4

A

Ligate coding and rss joints

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179
Q

Lymphocyte pro-apoptotic proteins

A

Intrinsic - Bim binds Bax and bak to activate caspase 9

Extrinsic - FasL binds Fas, activates caspase 8

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180
Q

Lymphocyte apoptosis pathways converge on ___ to lead to apoptosis

A

Caspase 3

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181
Q

Cytokines that stimulate NK cells

A

Ifn alpha, beta, il12

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182
Q

Cytokine needed for NK cell development

A

IL15

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183
Q

ILC in allergy

A

Ilc2 recruited to lung and skin after allergen, il5 dep eos recruitment, il13 smooth m contraction, mhc II th2 enhancement —> allergy and fibrosis

ILC3s -> increased in BAL of asthmatics

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184
Q

FCepsilonRI is expressed on 2/3:
Mast cells
Basophils
Eosinophils

A

Not on eosinophils

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185
Q

Cytokines stimulating differentiation of mast cells, basos, eos

A

Stem cell factor - mast cells
Il-3 to basos
Il-5 to eos

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186
Q

Mast cell progenitors and where develop

A

Ckit+ (cd117), cd34+ stem cells
Develop after arrival in tissue

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187
Q

Progression of mast cell mediator release

A

<15 mins - preformed mediators (tryptase, histamine, heparin, chymase)

10-30mins - lipid mediators (PGD2, LTC4, LTB, paf)

Hrs-days - cytokines and chemokines

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188
Q

FCeRI binding IgE

A

Mast cell activation
Alpha, beta, and 2 gamma chains

IgE binds via alpha chain

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189
Q

Peak IgE in relation to pollen season

A

4-6wks after peak pollen season

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190
Q

Immunodeficiency with high IgE

A

Bullous pemphigoid
WAS
Omenn
IPEX
Atypical incomplete DiGeorge
Netherton

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191
Q

MRGPRX2 receptor

A

Susceptible mast cells activated by this receptor with certain medications - cipro, atracurium, vanco, narcotics (except fentanyl)

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192
Q

Basophil receptor

A

CD123 (il-3 receptor)
Il-3 important for expansion/differentiation

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193
Q

Eosinophils preformed mediators

A

Mbp, eos cationic protein, eos peroxidase, eos-derived neurotoxin

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194
Q

Markers on eos (flow cytometry)

A

Siglec-8, CCR3, EMRI

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195
Q

Eos Txn factor

A

GATA1

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196
Q

Chemokines that draw eos to tissues

A

RANTES (ccl-5) and eotaxin (eot-1/ccl11 and eotaxin-2/ccl24)

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197
Q

Eosinophilia level

A

> 500 cells/ul

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198
Q

Eosinophilia ID ddx

A

Hyper-IgE
Omenn
IPEX
Zap70 def
Netherton synd

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199
Q

Most common cause eosinophilia in US worldwide

A

US - drug reactions
WW - parasites (NOT protozoa - giardia, amoeba)

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200
Q

Eos suppressed by

A

Fever, steroids, most viral/bacterial infxn (HIV raises eos)

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201
Q

Hyper eosinphilic syn criteria

A

eos >1500 x2 at least 4 wks apart
AND
end-organ damage OR tissue involvement

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202
Q

Causes eosinophilia

A

NIAAA
Neoplasm
Infection
Allergic
Autoimmune
Adrenal insufficiency

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203
Q

Monocyte surface marker

A

CD14 (part of TLR4 and a LPS receptor)

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204
Q

Macrophage surface molecules

A

CD14, CD16, CD11b/CD18, CD33

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205
Q

Macrophage activation

A

Classical M1: Induced by LPS or Th1 cytokines (IFN-gamma), phagocytose and present antigen, secrete Th1 cytokines (TNFa, IL6, IL1beta _> T cell activation

Alternative M2: induced by steroids and Th2 cytokines, reponse to parasitic infections

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206
Q

Macrophage activation syndrome/HLH

A

uncontrolled activation macrophages with increased cytokines. Predisposing ID and low NK cells + immune activation –> damage

High fever, HSM, high ferritin and TG, low fibrinogen, hepatitis

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207
Q

HLH dx criteria

A

> /5 of the following:
fever splenomegaly
cytopenia in 2+ lines, hyperTG
hypofibrinogenemia hemophagocytosis
low/absent NK cels ferritin <500
soluble CD25 >2400 (activated T cells)

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208
Q

Plasmacytoid dendiritic cells

A

Marker CD123, secrete IFNa and are in viral infxn
(unique dendritic cell subset, as no CD11c expression)

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209
Q

Langerhans cells

A

dendritic cell subset, marker CD11c, Birbeck granules
Prime CD8 T cells

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210
Q

Dendritic cell maturation

A

Immature in the tissue, where uptake antigen
Mature in lymphoid organ

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211
Q

CD1 isoforms

A

class I MHC like molecules that present nonpeptide molecules to T cells

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212
Q

Langerhans cell histiocytosis markers

A

Confirm LC identity on bx with CD1a and CD207

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213
Q

chemokines attracting neutrophils in tissue

A

IL-8 (CXCL8), LTB4
Also with sialyl-lewis, e-/p-selectings, LFA1/ICAL1

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214
Q

Color of basos, eos, neutrophils on H&E stain

A

Basos - basic blue
Eos acidic, bright red
Neutrophils neutral pink

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215
Q

ELANE mutation

A

affects CD11b in granulocyte elastase in neutrophils

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216
Q

Neutrophil granules

A

primary - MPO, defensins, cathelicidin/cathepsin

Secondary - lysozyme, collagenase, elastase, lactoferrin, Cd11b

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217
Q

Chediak Higashi neutrophil granule change

A

Enlarged primary granules

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218
Q

heparin induced thrombocytopenia antibodies

A

against plt antigen PF4

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219
Q

WAS

A

eczema, infections, thrombocytopenia
defective WASp gene

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220
Q

Steroid resistant asthma role smooth muscle

A

Airway smooth muscle unregulates glucocorticoid receptor (GR)-beta, a negative inhibitor

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221
Q

Required for B and T cell development

A

IL-7

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222
Q

B cell negative selection

A

Auto reactive/nonfunctional B cells removed

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223
Q

Parts of thymus

A

Subcapsular zone - lymphocyte progenitors

Cortex - lymphocytes in division, expression, TCR section
- positive selection with TCR re-arrangement compatible with MHC
- negative selection begins in cortex - auto reactive/nonfunctional T cells/TCRs apoptose

Medulla - where final stages selection/maturation
- most of negative selection
- has Hassles corpuscles

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224
Q

Cryopatches

A

T cell precursors that go to cryopatches instead of thymus - lymphoid aggregates under intestinal
epithelium to form specialized T cell populations

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225
Q

2 follicle types in LNs

A

Primary - site resting B cells
Secondary - germinal center of B cell proliferation

Ratio primary to secondary LNs defines LN activity

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226
Q

Area of spleen where lymphocytes are

A

White pulp

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227
Q

Which cells only undergo negative selection

A

B cells

T cells undergo positive and negative

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228
Q

Nasal airway resistance regulated by

A

Nasal valve, which is controlled by swelling inferior turbinate

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229
Q

Sinus development

A

Maxillary/ethmoid present at birth
Sphenoid develop at 3yo
Frontal at 6yo

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230
Q

Sinuses listen to
FM AM PS SS

A

Frontal, maxillary, ant ethmoid drain into middle meatus

Posterior ethmoid, sphenoid drain into sphenoethmoidal recess above superior turbinate

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231
Q

Lower airway changes asthma vs copd

A

Asthma: smooth m enlarged in LARGE airways, have increased cd4 and eos, increased il-5/4,

Copd: enlarged smooth m in SMALL airways, increased acidic glycoproteins, cd8, NO increased il5

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232
Q

Mast cells in dermis express

A

Cd68

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233
Q

Homing cells to skin via

A

CCR4/ccl17 and ccr10/ccl27

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234
Q

Pemphigus vulgaris ab

A

IgG ab to desmoglein 1/3

Blisters flacid - erupt

IgG and C3 staining on suprabasal layers

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235
Q

Bullous pemphigoid

A

Tense
Prominent pruritus
IgG BP180, bp230
Linear basement membrane IgG and C3

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236
Q

Dermatitis herpetiformis

A

Small bullae elbows/knees
Pruritic
Assoc w celiac
IgA to epidermal transglutaminase

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237
Q

Fpies lab value acute episode

A

Increase neutrophils, elevated methemoglobin

Friable mucosal with villous atrophy

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238
Q

EOE cytokines

A

Il-5, eotaxin -3

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239
Q

Labs to diagnose celiac

A

Gliadon sensitivity
Anti-tTG IgA (tissue transglutaminase)

Total IgA (if IgA deficient, false neg anti-ttg iga

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240
Q

Study type and statistic

A

Cross-sectional - prevalence
Case-control - odds ratio
Cohort (subjects with common characteristic - who develops dz) - relative risk
Rct - absolute risk reduction, suggest causality

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241
Q

Type I (alpha) error

A

Falsely reject null hypothesis

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242
Q

Type II (beta) error

A

Falsely accept null (commonly from underpowered studies)

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243
Q

Odds ratio

A

Axd/ b x c

(True pos x true neg) / (false pos x false neg)

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244
Q

Relativ risk

A

Incidence in exposed / inc unexposed

Ppv / c/ c+d

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245
Q

Absolute risk

A

Number events in treated or control group / number people in the group

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246
Q

Elements informed consent

A

Competence, disclosure, understanding, voluntariness, consent

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247
Q

Risk factors allergic rhinitis

A

FHx atopy
IgE > 100 before age 6
Increased SES
Maternal smoking

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248
Q

Immediate allergic response
Sx and their mediators

A

Histamine - itch, sneeze, rhinorrhea
PGD2 and leukotrienes - nasal congestion
Kinins- nasal congestion/blockage

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249
Q

Priming

A

Chronic inflammation leads to lower dose of allergen to elicit sx (AR)

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250
Q

First line tx perennial and seasonal AR

A

Perennial - intranasal steroids
Seasonal - inteanasal antihistamines

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251
Q

Most effective med rhinorrhea

A

Jntranasal ipratropium

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252
Q

NARES

A

No allergic rhinitis w eosinophils

Eos>20% on nasal smear
Middle aged men
Yr-rnd sx
Abnml PG metabolism
Tx - topical steroids

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253
Q

Gustatory rhinitis nerves

A

Stimulation sensory c-fibers
Parasympathetic reflex,
Chokinergic muscarinic receptors
Tx - ipratropium

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254
Q

Atrophic rhinitis

A

Noninflammatory
Progressive atrophy in middle aged men in warm countries (Saudi Arabia)
Klebsiella colonization
Foul smell nasal vault

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255
Q

Secondary atrophic rhinitis

A

Causes: multiple ess empty nose syndrome
granulomatous disease

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256
Q

Rhinitis of pregnancy Tx

A

Intranasal corticosteroids are ineffective

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257
Q

AFRS

A

Eosinophilic process (mbp, Il-5, etc)
Asymmetric?
Peanut butter mucus (brown and viscous)
Ct - central hypoattenuation
Bony demineralization
MRI - hyper intense areas in mucin (heavy metals iron mgn within mucin) - heterogenous opaciticTikn)

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258
Q

AFRS criteria

A

All 5:
1. Hypersens to fungi confirmed
- asp., alternaría, curvularia, penicillium, fusarium, bipolaris
2. Nasal polyposis
3. Ct findings
4. Noninvasive fungus in mucin or in cx
5. Eosinophil mucin w/o invasión into sinus tissue

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259
Q

Vernal conjunctivitis

A

Sight threatening
chronic conjunctiva inflammation
Young males in warm dry climates
Severe photophobia, intense itching
Worse with antihistamines (increased dryness)
+verna;/spring sx

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260
Q

Atopic keratoconjunctivitis

A

Sight threatening
Commonly with a topic dermatitis
Keratoconus
Anterior subcapsular cataracts
Gritty photophobia

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261
Q

Giant papillary conjunctivitis

A

From contacts
mechanical trauma - protein buildup on lenses - allergic reaction
Get redness, itching after contact removal, morning mucus discharge
Tx - remove contacts and use artificial tears

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262
Q

Hordoleum versus chalazion

A

Hordoleum (stye) = pain
Chalazion = not painful

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263
Q

Granulomatosis with polyangiitis eye findings

A

50% ocular sx
Conjunctivitis, corneal ulcers, pain

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264
Q

Adult with new onset ad

A

Be concerned about cutaneous T cell lymphoma (ctcl)

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265
Q

Itch cytokine

A

Il-31
Induced by staph a

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266
Q

Cytokines reflective of AD severity

A

Cutaneous t-cell attracting chemokine (CTACK and ccl27)
Thymus and activation regulated Chemokine (TARC)

267
Q

Cytokines in acute and chronic AD

A

Acute - IL-4, -13 — th2, also il25 and -33
Chronic - Il-5, Il-12, ifn-g
Il-17, -22
“Education is chronic starting at 5 through Grade 12
— th1

268
Q

AD cell staining

A

Cd3, cd4, cd45ro,
Activated eos
Increased RANTES and TSLP
decreased antimicrobial peptides

269
Q

Lanngerhans cells

A

FcepsilonR1 lack classic beta chain
Have Birbeck granules

270
Q

Mucus plugs

A

Composed of serum, proteins, inflammatory cells, mucus and cellular debris

271
Q

Asthma predictive index
Risk school- aged asthma

A

> /4 wheeze episodes past yr PLUS

1 major
- parent w/ asthma
- AD
- aeroallergens

OR 2 minor
- food sensitivity
- peripheral eos (>/4%)
- wheeze not related to infection

272
Q

Aeroallergen sensitization to which is assoc w/ asthma pathogenesis

A

Cat, DM, cockroach, Alternaria

273
Q

Post-bronchodilator response in asthmatics

A

Increase in fev1 and/or fvc > 12%

274
Q

Methacholine challenge

A

PC <4 mg/ml diagnostic 4-16 suggestive

275
Q

FeNo increasers/decreasers

A

Increase
- viral uri
- allergic rhinitis
- nitrate-rich foods

Decrease foods
- caffeine
- smoking
- CF
- alcohol
- spirometry

Eos stimulate epithelial cells to produce NO

276
Q

Exercise induced bronchospasm

A

Sx onset after 10mins activity
Resolves 15-30mins after
Fev1 decrease at least 15% after exercise challenge

277
Q

Egg allergen heat stable

A

Ovomucoid, gal d 1

278
Q

Peanut allergen assoc w OAS

A

Ara h 8 (bet v 1 homologue)

279
Q

Peanut allergens assoc w severe anaphylaxis

A

Ara h 12, 13

280
Q

Soybean allergen w/ severe rxn

A

Gly m 5/6

Gly m 3/4 = bet v 1 homologues

281
Q

Wheat allergen assoc w anaphylaxis

A

Tri a 19

282
Q

Latex fruit syndrome fruits

A

Food allergies in 30-50%

BACK
banana, avocado, chestnut, kiwi

283
Q

Birch OAS allergens

A

Stone, fruits, apple, almond, hazelnut, so I’ve been some peanuts, celery, carrots, fennel, coriander

284
Q

Ragweed OAS

A

Melons, zucchini, banana

285
Q

Mugwort OAS

A

Celery, carrot, parsley, mustard, cauliflower, cabbage, garlic, onion

286
Q

Rate of food allergy outgrowth

A

Cows milk, soy, wheat, egg — 85% by age 5

Peanut - 20%

Tree nuts - 9%

287
Q

FPIES most common triggers

A

Milk, soy, rice, oat

50% outgrow after 2 yrs

288
Q

Cellular changes in FPIES

A

Increased neutrophils and Il-10, TNF-g

Decreased eos

289
Q

FPIES dx

A

1 major + 3 minor

Major:
- vomiting 1-4 hrs after w/o IgE sx

Minor
- 2nd episode when eaten again
- repetitive vomiting 1-4 hrs after eating different food
- lethargy, pallor, ed visit requiring ivf
- diarrhea, hypotn, hypothermia

290
Q

Celiac genetics

A

HLA-DQ2
HKA-DQ8

291
Q

Heiner’s syndrome

A

Recurrent PNA, pulm infiltrates, hemosiderosis,Fe def anemia, FTt
Peripheral Eosinophilia
Lung bx
Milk precipitans
Elimination diet

292
Q

Leading causes anaphylaxis children and adults

A

Children - food and venom

Adults - meds and venom

293
Q

MRGPRX2

A

Receptor on mast cells. Can be directly activated by small molecular weight drugs - NBMAs, morphine, fluiriquinolone, vanco
-> mast cell degranulation and non-IgE anaphylaxis

294
Q

Cytokines that correlate with hypotn in anaphylaxis

A

Il-6 and -10,
Tnf receptor 1
Mast cell tryptase
Histamine
C3a

295
Q

Compound that correlates with anaphylaxis severity

A

PAF

296
Q

Risk factors biphasic reactions

A

Severe initial reaction,
Multiple doses epi
Wide pulse P
Delay in epi administration
Unknown trigger

297
Q

Drugs that prolong effect epi

A

TCAs - prevent catecholamine re-uptake
MAOIs - prevent epi degradation

298
Q

Ratio total tryptase to mature

A

Total/mature > 20 —-> mastocytosis

Total/mature < 10 —-> other

299
Q

Tryptase in anaphylaxis

A

Peaks 60-90’
Falls after 5 hrs
Check 15’-3hrs after reaction

Can confirm but not r/o anaphylaxis

300
Q

Histamine peak in anaphylaxis

A

Rises w/in 5 mins, falls in 30-60’

301
Q

Histamine receptors anaphylaxis

A

H1 - coronary artery vasoconstriction, bronchial construction, GI smooth m contraction

H2 - coronary vasodilation, increased cardiac inotropy/chronotropy (rate, force)

H1 and H2 - systemic vasodilation, flushing HA

302
Q

Anaphylaxis treatment in patients on b-B

A

Epinephrine
Glucagon and IVF if not responding
- glucagon has inotropic and chronotropic effects not mediated by beta receptors

303
Q

Most common peri operative anaphylaxis cause us

A

Antibiotics
Europe - nmba

304
Q

Latex allergens

A

Hev b 1-13
Hev b 2 - bell pepper, olive
Hev b 5 - kiwi, potato, beet
Hev b 6 - avocado, banana, chestnut, sweet pepper
Hev b 7 - tomato potato
Hev b 14 - potato

5-7 most common healthcare workers

305
Q

Food-dep exercise induced anaphylaxis most common triggers

A

Celery
Wheat (omega 5 gliadin),

Avoid exercise 4-6hrs of ingesting food

306
Q

Vespid species

A

Very aggressive

Insects around garbage cans/food —> yellow jackets
Common in autumn
Most common cause of stings

Hornets sting when vibration sensed

307
Q

Hornet allergen

A

Dol m 5 - antigen 5

308
Q

Polistinae

A

Paper wasp
Narrow waist, dangling legs
Pol a

309
Q

Risk factor severe reaction to sting

A

No urticaria/angioedema

Only 50% chance if reacted to prior sting will react to subsequent sting

310
Q

VIT safety

A

50% have rxn in buildup phase
5-15% with systemic rxns
<5% require epi

311
Q

VIT efficacy

A

Reduces risk subsequent rxn to <5%

312
Q

VIT indications

A

Anaphylaxis
Can consider in large local reactions f impaired life, frequent exposures

Not indicated:
Large local rxn (4-10% risk systemic rxn)
Urticaria/angioedema

313
Q

Maintenance dose VIT

A

Adults - 100ug (can be increased to 200)
Children - 59 if
300ug for mixed vespid

Fire ants - whole body extracts

314
Q

Skeeter syndrome

A

Large local reactions to mosquitos + fever

315
Q

Chronic urticaria duration

A

At least six weeks

316
Q

Cholinergic urticaria versus exercise induced anaphylaxis

A

EIA will not react with passive heating

317
Q

Treatment of cold and local heat urticarial

A

Cold – cyproheptadine
Heat – hydroxyzine

318
Q

Urticarial vasculitis

A

Associate with a fever and or arthritis
Typically painful and leave markings

319
Q

Hypocomplementemic urticarial vasculitis syndrome (HUVS) criteria

A

Major (have both):
- urticaria > 6 months
- hypocomplementemia

AND
Minor (at least 2)
- venulitis of dermis
- arthralgia/arthritis
- mild glomerulonephritis
- uveitis/episcleritis
- recurrent abdominal pain
- positive c1q precipitan with assoc suppressed c1q

(Anti-c1q ab)

320
Q

Occupational asthma, versus reactive airway dysfunction syndrome

A

OA - latency period,
Reactive - subset OA, occurs after single high level exposure, sx w/in 24 hrs. Eg gases

321
Q

Common associations for occupational asthma

A

Carpenters/woodworkers - plicatic acid (activates complement)
roofers/insulators/painters - isocyanates
Nail salon/dental hygienists/plastics - acrylates, epoxy
Manufacturers of paint, plastic, epoxy — anhydrides

322
Q

OA dx

A

Measure pft at work and at home
Fev1< 20% after exposure suggestive
Methacholine challenge (neg test excludes OA)
Gold standard - inhalation challenge

323
Q

Three stages of hypersensitivity pneumonitis

A

Acute - hrs after exposure,
- NONproductive cough, fever, chills malaise,
- diffuse fine crackles
- cr nml

Subacute/intermittent - wks-mo
- PRODUCTIVE cough, dyspnea, fatigue, wt loss
- diffuse crackles
- ct micronodules, air trapping, mild fibrosis

Chronic - mo-yrs
- cough, dyspnea, wt loss
- digital clubbing
- ground glass, emphysema, honeycombing, fibrosis

324
Q

Farmers lung antigen

A

Thermophilic actinomycetes
In moldy hay, grain, compost

325
Q

Cigarette smoking, and hypersensitivity pneumonitis

A

Smoking decreases risk of HP

326
Q

HP labs

A

CD8 predominance (cd4:8 < 1)
Lymphocytosis>20%
Increased eos, neutrophils, mast cells, IgA/G/M
Noncaseating granulomas

Decreased fev1, fvc, dlco

327
Q

Organic dust, toxic syndrome (ODTS, pulmonary mycotoxicosis)

A

Noninfectious
Febrile illness after exposure to dust with toxin-producing fungi (grain, hay, textiles)
30-50x more common than HP
Complete recovery

328
Q

ABPA dx

A

Need sensitivity to A fumigatus (Asp f 1)
Elevated total IgE > 1000

When not responsive to abx

329
Q

ABPA flare

A

Doubling of baseline IgE

330
Q

COPD

A

FEV1/FVC < 70% after bronchodilation

331
Q

GOLD criteria COPD

A

Gold 0 (at risk): sx but nml spiro
Gold 1 (mild): fev1>/80% pred
Gold 2 (moderate): 50-80% pred fev1
Gold 3 (severe): 30-50% pred fev1
Gold 4 (v severe): fev1<30% or <50% + chronic resp failure

332
Q

Cells in copd

A

Neutrophils, macrophages, cd8 T cells

Neutrophils/macrophages destroy alveolar attachments that help keep airway open and elastic recoil

333
Q

Pan lobular emphysema

A

Copd type, assoc w alpha1 antitrypsin deficiency
- think in young non-smokers with copd

334
Q

Only disease modifying treatment and COPD

A

Smoking cessation

335
Q

Life prolonging treatments, and COPD

A

Smoking cessation, supplemental oxygen 24 hours per day and lung volume reduction surgery

336
Q

Copd vs ild

A

Copd
- decreased Fev1/fvc
- increases tlc
- increased frc
- clubbing uncommon
- wheezing

ILD
- nml/increased fev1/fvc
- decreased tlc
- decreased frc
- clubbing common
- Velcro rales

337
Q

Drug related ILD

A

Chemo - busulfan, bleomycin
Abx - nitrofurantoin, sulfa
Antiarrhythmics - amiidarone, procainamide
Immunosuppressives - mtx, cyclophosphamide, azathioprine

338
Q

IgG4-related lung dz

A

Increase IgG4 plasma cells and lesions in lung, liver, pancreas
IgG4>135
Fibrosis

339
Q

Contact hypersensitivity histology

A

Lymphocytes and spongiosis in upper dermis

340
Q

Contact testing delayed tiggers

A

Corticosteroids, nickel, neomycin, gold

341
Q

Allergic contact dermatitis vs irritant

A

Acd more pruritic, reactions increase between 1st and 2nd readings

Icd - more prevalent, more stinging, reaction almost immediate and decrease between 1st and second readings

342
Q

Mediators in contact dermatitis

A

IL1 alpha, IL1 Beta, TNF alpha, GM- CSF, IL8

343
Q

Poison ivy dermatitis

A

Toxicodendron dermatitis
To urushiol (an oleoresin)
Cross reactivity to mango peels

344
Q

Paraphenylenediamine

A

Most common cause Cd on hairdressers and henna tattoo

345
Q

4 types corticosteroid classes

A

Group A - hydrocortisone type
Group B - triamcinolone type
Group C - betamethasone tupe
Group D - hydrocortisone-17-butyrate type

346
Q

Resins in ACD

A

Epoxy - sensitizing only when not cured
Colophony - from pine trees, in cosmetics, topical meds, industrial products
Ethylenediamine dihydrochloride - in topical creams, aminophylline
Paraphenylenediamine (ppd) - from benzene, in henna

347
Q

HAE type I Vs type II

A

Type I - decreased c4, low/absent c1 inh with decreased function; 85% cases

Type ii - deceased c4 and increased/nml c1 inh that’s nonfunctional; 15% cases

348
Q

Acquired c1-inh deficiency

A

Ab to c1-inh
Assoc w nonhodgkins lymphoma

Low c4
Low c1q
C1 inhibitor low/normal
C1 inh function decreased

349
Q

T- B+ NK- SCID

A

Il2rg - gamma c def, x-linked, 50-60% of scids, cd132-

Jak3 def - AR, cd132+

350
Q

T- B+ NK+

A

IL7R - AR, 5% scids, no thymus
Cd3E - ar, no game m/delta T
Cd45 (ptprc gene) - ar, normal gamma/delta T cells, no thymus
Coronin 1a def - coro1a - normal thymus

351
Q

T-B-NK-

A

Ada def - ar, 20% scids, rachitic rosary, abnormal iliac bones, deafness

Activated rac2 def - defective hematopoietic energy metabolism

Reticular dysgenesis (ak2) - severe neutropenia, sensorineural deafness

352
Q

T- B- NK+

A

Xlf def (nhej1) - microcephaly, facial dysmorphism, radiation sensitivity

Artemis - DCLRE1C (Artemis), no microcephaly, AR

353
Q

Omenn syndrome

A

RAG1/2 mutation, can’t rearrange Ig genes
Decreased B cells
Erythroderma
Increased lymphoid tissues
HSM
Eosinophilia, increased IgE
Neonatal red rash

354
Q

HyperIgE type I
(Job synd)

A

Stat3 GOF
AD
triad: 1. recurrent skin/lung infections (a aureus, a pneumonia, H flu, C albicans)
2. Severe eczema
3. IgE >2000

Retained teeth, scoliosis
Absent Th17

355
Q

Hyper IgE type II

A

DOCK8
Severe eczema
Cutaneous viral and bacterial infxns (hpv, hsv, vzv, molluscum)
Decreased IgM, NK cells, TRECs
Increased eos, B cells, Tregs

356
Q

Hyper IgE type III

A

Tyk2
- similar to type II with disseminated BCG lymphadenitis, salmonellosis

(Tyk2 in il12 signaling to produce ifn-g)

357
Q

Cd40 ligand def
(X-linked hyper IgM)

A

X-linked recessive
Biliary tract and liver dz
No germinal centers
Cryptosporidium
Neutropenia
IgM normal or high, others decreased

Cd40 deficiency is AR

358
Q

Wiscott Aldrich synd

A

X-linked recessive,
Triad: immune def (bacterial/viral), eczema, small plts
EBV lymphoma

359
Q

WIP SYnd

A

WIPF
WAS protein absent
Thrombocytopenia

360
Q

Hyper IgE syndrome

A

STAT3 LOF
AD
cold skin abscesses, pneumatoceles
Scoliosis
Hard to differentiate from AD STAT3 GOF

361
Q

Netherton syndrome

A

SPINK5
Icchthyosis
Bamboo hair

362
Q

No B cells with enteroviral infections

A

XLA

363
Q

XLA

A

Btk gene
Sinopulm infxns, GI (enteroviruses)
No germinal centers - BTK req’d for survival
All Ig decreased
Nml T cells
Nml pro-B cells
- Boys with BTK will have monocytes, but no BTK expression in them

364
Q

AR agammaglobulinemia

A

Several forms, occur in pre-B cell stage when heavy chain recombines

365
Q

Aid and ung deficiency

A

High IgM, low IgG/IgA

366
Q

Good syndrome

A

Adult onset hypogamm, thymoma
Decreased B, T, eos, neutros, panhypogamm
Thymenctomy does not help immunodeficiency

367
Q

WHIM syndrome

A

Warts
Hypogamm
Infections
Myelokathexis (neutros retained in BM)

368
Q

Herpes encephalitis genes

A

Tlr3
Unc93b19
HSE with primary hsv infection
Usu 3-6yo
Decreased ifn-a and -b

369
Q

Ifn-g mutations

A

Complete absence = AR + affects extra cellular domain
AD = heterozygous, intracellulat domain

370
Q

Osteo w NYB mycobacteria

A

IFNgR1/2 deficiency

371
Q

C1q leading causes death

A

Infection, atherosclerosis and MI
(C1q plays role in cholesterol clearance)

372
Q

Complement mediated (atypical) HUS

A

Complement activated on epithelium

Treated with c5 blockers (eculizumab and ravilozumab)

Microangiopathic hemolytic anemia, thrombocytopenia, kidney injury

Disseminated neisserial ingections

373
Q

Receptors HIV uses to enter cells

A

CCR5 - monocytes/macrophages, acute infection
CXCR4 - T cells, advanced hiv dz

374
Q

Western blot hiv testing

A

Requires 2/3 bands present for + result:
Anti-p24, anti-gp41, anti-go160/gp

375
Q

HIV exposed infants tested

A

At birth, 2-3wks, 1-2mo, 4-6mo

376
Q

Elisa antibody hiv test

A

High sensitivity/mod specificity
Requires confirmatory
False + from multiple pregnancies, autoimmune dz, multiple blood
Transfusion

False -: window period

377
Q

Ritonavir and fluticasone

A

Ritonavir, inhibits cyp3a4 and cyp2dg,
Causing increased levels ICS (fluticasone) to systemic levels
Cause Cushing syndrome

378
Q

HLA B5701 and abacavir

A

Life threatening allergic reaction

379
Q

Immune reconstitution inflammatory syndrome

A

Decrease in clinical status 4-8wks after ART initiation
Reaction of reconstituting immune system and it’s reaction to opportunistic infection with cytokine storm

380
Q

EOE cytokines

A

IL-5, IL-13, eotaxin-3 (ccl26)
Eotaxin3 most overexpressed gene in EoE, receptor is CCR3. Chemotactic for eos

381
Q

Triggers EoE

A

Milk, wheat, egg, soy

382
Q

Dupilumab effect on EoE

A

May reverse esophageal dysmotility/dilation

383
Q

FIP1L1-PDGFRA fusion

A

Myeloproliferative variant HES
Mainly men
Higher risk cardiac cx
Increased serum B12, tryptase
Sensitive to imatinib

384
Q

T cell lymphocytic variant (L-HES)

A

Prominent skin findings (eczema, urticaria)
May progress to T cell lymphoma
- hypergamm
Elevated TARC/CCL17
Aberrant il5 producing T cells
Cd3-cd4+ T cells

385
Q

Dx criteria systemic masyocytosis

A

1 major + 1 minor or 3 minor:
Major: bx w dense infiltrates >15 mast cells
Minor:
- bx >25% mast cells with spindle shape
- c-kit mutation (kit D816V)
- expression CD2 and/or CD117+ mast cells
- tryptase >20

386
Q

Mast cell activation syndrome criteria (mast cell activation not meeting systemic mastocytosis criteria)

A

3 criteria needed:
A- typical s/s systemic mast cell activation (eg anaphylaxis)
B - involvement MC with biochemical studies (elevated baseline typtase, urinate metabolites, etc)
C- symptomatic response to mast cell stabilizers

387
Q

Ehrlichiosis

A

Lone star tick
SE, south central, mid Atlantic
Can trigger HLh
Smear showing intreukocytic morulae
Tx / tetracyclineor chloramphenicol

388
Q

Mendelian susceptibility to mycobacterial disease (msmd)

A

Mycobacterial disease clearance depends in ifn-g activating T cells

Defects in il-12/-23/ifn-g cause msmd

389
Q

Hep B marker infectivity/viral
replication

A

HBeAg

390
Q

Syphilis stages

A

Primary - painless chancre o genitals, skin, mucosa

Secondary - rash on palms/soles, condyloma lata (warts) in genitals, malaise, fever

Tertiary - cv, neuro

391
Q

Syphilis screening

A

Nontreponemal ab (vdrl, rpr) tests reactivity to antigen
followed by more specific treponemal test looking for antibodies (fta-abs, EIA)

392
Q

False positive syphilis testing

A

Pregnancy
Iv drug use
Tb, nonsyphillus treponemal, rickettsia, hiv
Endocarditis

393
Q

Treating AOM

A

Any signs in those <6mo
B/l involvement in those 6-23mo
Rest - shared decision making

First line uncomplicated - high dose amox x 10d
Other - augmentin

394
Q

Rhinosinusitis acute v subacute v chronic

A

Acute - up to 4wks
Subacute - 4-12wks
Chronic - >12 wks

395
Q

Bacterial causes ars

A

Strep pneumonia
Moraxella
H flu

396
Q

ARS dx criteria

A

2 major or 1 major +2 minor

Major:
Purulenta rhinorrhea
Nasal congestion/obstruction
Facial congestion/fullness
Facial pain/pressure
Fever
Hyposma/anosmia

Minor:
Headache
Ear ache/pressure/fullness
Bad breath
Dental oaon
Fatigue
Cough (post nasal drip)

397
Q

Treatment abrs

A

Augmentin (amox-clavulanate)
High dose augmentin for those at higher risk/higher risk areas

Alternative - fluoriquinolone/doxy
Alternative children - clinda + ceohalosporin

398
Q

Recurrent sinusitis

A

> 4 episodes/yr

399
Q

Th17 cells

A

Produce il-17, -22, and synergies with TNF-a and il-1b to enhance inflammation

Induced by il-6, tgf-b

Survival increased by il-23

Cytokines recruit neutrophils and enhance local innate response

400
Q

CREST

A

Calcinosis cutis
Raynaud’s
Esophageal dysmotility
Sclerodactyly
Telangectasia

Sx of sclerosis/crest synd

401
Q

Sjogrens ab

A

Ana, SS-A (Ro), SS-B (La)

402
Q

Progressive sclerosis and crest syndrome Ab

A

Anticentromere Ab

403
Q

Rheumatoid arthritis Ab

A

RF, anti-CCP

404
Q

RF meds

A

NSAIDs
Steroids
Dmards - mtx, sulfasalazine, hydroxychloroquine
Jak inhibitors (tofacitinib, baricitinib)
TNF-a blockers (infliximab, adalimumab)
Anti-Il-6 - tocilizumab
Ctla-4-Ig - abatacept
- ritux

405
Q

Macrophage activation syndrome (mas) and systemic JIA

A

10% of those with JIA have MAS

406
Q

Chediak Higashi synd

A

Oculocutaneous albinism
Neuro defects, infxn (cutaneous, sino-pulm) with GNR, staph, strep

Trafficking protein defect, granules in neutrophils fuse make enlarged granules, can’t move granules

407
Q

Familial HLH screening markers

A

Perforin and cd107a

408
Q

APECED

A

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy

Chronic mucocutaneous candidiasis, recurrent thrush, dystrophic nails, endocrineopathies (DM, alopecia…)

AIRE mutation

Anti-interferon omega Ab very specific for test

409
Q

ALPS

A

Autoimmune lymphoproliferative syndrome
- AI cytopenias, LAD, HSM, lymphomas
Genes: FAS
Dx - high double neg T cell - TCR alpha/beta (CD3+CD4-CD8-), high B12, il-10

410
Q

IPEX

A

Immunodysregulation polyendocrinopathy enteropathy x-linked

Severe diarrhea, for allergy, early onset DM, cytopenias, skin lesions foxp3 (in Tregs)
AR

411
Q

Sezary syndrome

A

Older patients with chronic nonspecific dermatitis or generalized erythroderma

Need:
Erythroderma >/80% body
Clonal TCR rearrangement
Sezary count >/1000 or increased cd4 cells with loss cd26 cells

412
Q

Waldenstroms macroglobulinemia

A

High IgM
Assoc w chromosome 6 abnormalities

413
Q

Castlemans disease

A

Giant cell LN hyperplasia
Angiofollicular LN hyperplasia
HHV-8 implicated in pathogen

May have POEMS syndrome
(Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin abnormalities)

414
Q

Acute hemolytic transfusion reactions (htr)

A

IgM and complement

415
Q

Delayed htr

A

Minor blood group antigens (eg Rh)
5-10d after transfusion
Increased LDH, indirect bili

416
Q

TRALI

A

Severe resp distress 1-4hrs after

Donor Ab directed at recipient neutrophil antigens or HLA determinants

417
Q

Warm reactive AIHA

A

IgG against RBCs

Positive DAT

418
Q

Cold reactive AIHA

A

IgM binds to I antigen on RBCs at cold temperatures, activates complement

419
Q

Evans syndrome

A

ITP + AIHA w/o underlying etiology

Assoc w PID (eg cvid, alps)

420
Q

Thrombotic microangiopathy

A

Triad: hemolytic anemia (non immune), thrombocytopenia, renal disease

421
Q

TTP clinical features

A

Adamts13 deficiency

FAT RN
fever
Anemia (microangiopathic hemolytic)
Thrombocytopenia
Renal failure
Neuro changes

422
Q

Graves dz

A

TSH receptor Ab

Assoc w autoimmune polyglandular syndrome type 2

423
Q

Hashimoto dz

A

Ab to TPO, TG, TSH receptor

Assoc w APS-2

424
Q

Membranous nephropathy

A

Most common nephrotic syndrome adults
Subepithelial Ig deposits activate complement

Thickening glomerular basement membrane

425
Q

MPGN

A

Thickening GBM

Assoc w hep c

426
Q

RPGN

A

Crescentic GN with focal necrotizing lesions

Can progress days-wks

Adults - pauci-immune
Kids - immune complex mediated more common

427
Q

Anti-glomerular basement membrane (anti-gbm) dz

A

In RPGN or part of Goodlasture’s synd (pulm-renal vasculitic syn)

Ab (IgG1 and IgG4) against alpha3 chain of type IV collagen
1/3 perinuclear antineutrophil cytoplasmic ab (pANCA) and cytoplasmic antineutrophil cytoplasmic ab (c-anca)

428
Q

Pemphigus vulgaris

A

Target desmogleins-1 and -3 and/or desmosome with IgG and C3
In EPIdermis

Life threatening

Flaccid bullae

429
Q

Bullous Pemphigoid

A

60-80yo
SUB-epidermis

Tense bullae on urticarial base
Target BPs - BP180 and BP230, hemidesmosome

Eosinophilic infiltrate and increased IgE

430
Q

Epidermokysis bullosa acquisita

A

In areas of trauma
Target type VII collagen

431
Q

Celiac dz genetics
And testing

A

HLA DQ2 and DQ8

IgA to tissue transglutaminase or endomysium

432
Q

AI hepatitis Ab types 1 and 1

A

Type 1:
Ss- or dsDNA
Smooth muscle
Actin
Soluble liver or pancreas Ag

Type 2:
Anti-liver-kidney-microsomes-1 (ALKM-1)
Liver-cytosol antigen (ALC-1 or LC1)

433
Q

Primary biliary cirrhosis

A

Middle aged women
HLA A 0201 and HLA DR8
Progressive inflammation of intrahepatic ducts —> chronic cholestasis, fibrosis, cirrhosis, failure

434
Q

Primary sclerosing cholangitis (PSC)

A

Inflammation, fibrosis, bile duct stricture
Affects Intra and extrahepatic ducts
Men>women
Genetics - HLA B8, DR3
Assoc w UC
Increased risk cholangiocarcinoma
Dx- ercp

435
Q

Autoimmune vs autoinflammatory conditions

A

Autoinflammatory - innate immune system, no autoantibodies or auto reactive T cells
- early age onset
- recurrent bouts similar in severity

Autoimmune
- later onset, have autoantibodies and auto reactive T cells, worse outbreaks over time
- activation adaptive immune system

436
Q

FMF

A

MEFV gene (codes pyrin)
- severe mutations - M694V
- Tx = daily colchicine which can decrease likelihood amyloidosis
Tonsillectomy can be curative

437
Q

TRAPS

A

Tumor necrosis factor receptor associated periodic syndromes
- AD, in TNFRSF1A gene
- febrile episodes can last weeks, periorbital swelling, conjunctivitis, pleuritis, HA
- amyloidosis
- Tx = Il 1 blockers, anakinra, steroids

438
Q

PFAPA

A

Tx steroids, tonsillectomy
Fevers last 3-6d, occur q3-8wks

439
Q

Mevalonate kinase deficiency (Hyper-IgD)

A

Mutation MVK gene - cholesterol and steroid synthesis pathway
Fevers 3-7d, painful LAD, apthous ulcers, and pain, arthritis

Flares from stress and vaccinations
Tx - steroids, anakinra prn

440
Q

Cryoporin assoc periodic syndromes (CAPS)

A

Mutations in NLRP3
3 diseases: cinca/nomid = most severe
Muckle wells - moderate
Familial cold induced autoinflammatory syndrome (FCAS) - mildest

Fever, rash, arthralgia, amyloidosis
Nomid with dysmorphism, dev delay, bony overgrowth, sensorineural hearing loss

441
Q

CAPS Tx

A

Il-1 blockade - anakinra, canakinumab

442
Q

Pyogenic sterile arthritis, pyoderma gangrenous, and acne syndrome (PAPA)

A

AD, mutation in CD2 binding protein 1– prolonged inflammasome activation

Early life arthritis
Then sterile pyoderna gangrenosum, cystic acne, Pyogenic sterile arthritis

Tx - il-1 blockade

443
Q

DIRA deficiency of IL- receptor antagonist

A

Uninhibited Il-1 activity -> skin and bone disease
skin and bone disease
Tx - anakinra (anti-il-1) replace lost protein

444
Q

Majeed syndrome

A

Lipin2 gene
Chronic recurrent multi focal osteomyelitis
Pain, fever, psoriatic appearing rash and acne
Tx - nsaids and steroids

445
Q

Blau syndrome
Juveline Systemic granulomatosis

A

Nod2 GOF - involved in nfkb activation
Triad: granulomatous poly arthritis
Uveitis
Pustular skin lesions
Later in life joint swelling and contractures

446
Q

NFkB -opathies

A

Related to ubiquitous dysregulation
Granulomas
Oral ulcers
Uveitis
Immunodeficiency

447
Q

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome

A

Interferonopathy - mutations in proteasome system (PSMB8, PSMG2, etc).
Proteasomes clear ubq waste proteins

Sx - daily fevers, skin plaques, eyelid swelling, ftt, lipodystrophy

Autoimmunity - hemolytic anemia, hypothyroid
Tx - jak inhibitors interrupt interferón signaling, some success

448
Q

Deficiency of adenosine deaminase 2 (DADA2)

A

Mutations cecr1 - gene codes for ada2
Def -> adenosine accumulation, neutrophil activation, increased m1 macrophage polarization and inflammatory cytokine production

Fevers, lacunar strokes (before age 5), organomegaly, cytopenias, hypogamm, polyarteritis nodosa

Tx - steroids, tnf blockade, cyclophosphamide,

Def ada1 -> T-B-NK- SCID

449
Q

Amyloidosis

A

Native proteins that are misfolded and aggregate as insoluble, then accumulate and cause end organ damage

450
Q

Cryoglobulinemia

A

Immunoglobulins that undergo reversible precipitation at low temps

451
Q

Mixed cryoglobulinemia sx

A

Meltzers triad:
Purpura
Arthralgia
Weakness

452
Q

Granulomas labs

A

Macrophage secrete molecules after activation that promote granuloma formation :
ACE
calcitriol (1,25dihydroxyvitamine d3)
Osteopontin
Tnf-a

453
Q

Lofgrens syndrome

A

Self acute limited form sarcoidosis
Triad:
B/l hilar adenopatía
Erythema nodosum
Polyarthritis

454
Q

Granulomatosis with polyangitis

A

Triad sx:
Sinus involvement - ulcers, cobblestoning
Lungs - nodules, cavities lesions, pulm hemorrhage
Kidneys - focal segmental crescentic GN, pauci-immune

+/-c-anca, may have p-anca

455
Q

Egpa

A

Starts with asthma and allergic rhinitis
2- peripheral eosinophilia
3 - small vessel vasculitis dz

Eos>1500
P-anca

Tx mepolizumab
Asthma persists even after vasculitis improved
Most common cause mortality - cardiac dz

456
Q

Hyperacute rejection.

A

Pre-existing Ab
Mins-hours

457
Q

Acute cellular rejection

A

7d-3mo
CD8 T cells (type 4 hypersensitivity)

458
Q

Acute antibody mediated

A

Days-months
Antibodies trigger complement, endothelial injry, thrombosis
C4d deposition in capillaries (type II and iii hypersens)

459
Q

Chronic rejection

A

Months-yrs
T cells, cytokines
Ongoing acute rejection
Vascular smooth muscle proliferation, fibrosis, occlusion
- cd4 vasculopathy or accelerated graft atherosclerosis

460
Q

Tolerance transplanted graft

A

Via Tregs

461
Q

Engraftment neutrophils and platelets

A

Neutro- 3 consecutive days with anc>0.5x10^9 or 1 day >1x10^9

Plt - >20x10^9 in 3 consecutive days

462
Q

Gvhd cells

A

Donor t cells
Il-10, ifn-g, tnf-a

463
Q

Chronic GVH

A

Cd4 T cell mediated
B cells, Th17

Prevent with T cell depletion

Occurs >100 days (usu >6mo)

Fibrosis and scarring

464
Q

Acute gvh

A

<100 days

Cd45RO T cells

Ppx mtx, cyclosporine, tacro, steroids

Tissue injury - red angry rash, diarrhea, abd pain, weight loss

465
Q

Sos syndrome

A

Sinusoids obstruction syndrome
After transplant
Most often with hematopoietic cell transplantation
W/in 29 d transplant:
Bili >2
Hepatomegaly/RUQ pain
>2-5% wt gain from fluid retention

466
Q

Sweat test result

A

Cf unlikely sweat Cl </29
Indeterminate 30-59
Positive >/60

467
Q

Ivacaftor
Lumacaftor
Tezecaftor

A

Ivacaftor - increases probability cftr channel opening (gating)
Lumacaftor - Phe508del corrector, increases production cftr
Tezecaftor - F508del corrector facilitates delivery of cftr to cell surface

468
Q

Cockroach allergen

A

Bla g 1, 2, 4 5 6 9 11
Per a 1

469
Q

Standardized extracts

A
  1. Dust mite
  2. Short ragweed
  3. Cat
  4. Grasses - Bermuda and northern
    5 Hymenoptera

Extracts standardized by Center for Biologics Evaluation & Research/FDA

470
Q

Dose range allergen proteins in IT

A

1000-1500 AU/BAU

471
Q

Immuno increases seen in IT

A

Increase:
IgG blocking Ab (first IgG1 then IgG4)
IgA in resp secretions
Cd4+cd25+ regulatory cells (il-10, tgf-b,) and % cd8 cells
Initial increase and then decrease specific IgE
Th1 cytokines (Ifn-g, il-12)
Increased ifn-g:IL-4 ratio
Histamine2 receptor
Breg Dc4reg

472
Q

Immune decreases in IT

A

Seasonal rise specific IgE
Low affinity IgE receptor FceRII (cd23)
B cell activation markers
Basophil hyper reactivity
Recruitment eos, basos, mast cells in nose/lung
Allergen specific lymphocyte proliferation
Th2, Th17, il-2 receptor, NFkB activation, il-8 secretion

473
Q

What slows loss of potency in IT vials

A

Glycerine - inhibits proteolytic activity

474
Q

Antibacterial in IT vials

A

Phenol

475
Q

Extracts with proteolytic activity that degrade pollen

A

Mold, cockroach

Don’t mix with pollens, hdm, dander

476
Q

Effective maintenance scit dose aero allergen

A

5-20ug of major allergen

Aka 1000-4000 BAU/AU

477
Q

Maintenance dose venom

A

Single venom 100ug
Mixed vespid 300ug

478
Q

Rate of systemic rxns scit

A

0.2% of shots end in reaction
In 2% of patients
2% severe
2 fatalities/yr

479
Q

SLIT tab let options

A

5-grass pollen (Northergn grass, Kentucky blue, Timothy, orchard, perennial rye, sweet vernal)
Timothy grass
Short ragweed
HDM

480
Q

SLIT studies

A

first RCT with Ragweed
original studies from Noon & Freemen with timothy grass measuring conjunctival challenges

481
Q

Antihistamines

A

Stabilize histamine receptors in inactive state

482
Q

Antihistamine to be used in renal and liver impairment

A

renal - loratadine
Hepatic - use fexofenadine

Grapefruit juice decreases absorption antihistamines

483
Q

anithistamines with quickest onset

A

cetirizine and levocetirizine

484
Q

beta agonist
ultra long acting

A

carmoterol, indacaterol - onset action 5 hrs, last >/24
Bulkier the side chain - more selective for B2 receptro
larger size terminal amino group - protects from degradation by MAO

485
Q

B agonist adverse effects

A

tremor, tachycardia, prolonged QTc, MI, transient increased hypoxia
hyperglycemia, decreased K+ and Mg++

486
Q

beta agonist resistent

A

B16 arg/arg homozygotes - agonist receptor downregulation and resistance to SABAs

487
Q

If patient needs B-blocker, prefer cardioseelctive B-B

A

eg metoprolol, atenolol (not propranolol, etc)

488
Q

how to treat pt on B-b unresponsive to epi

A

glucagon

489
Q

cystinyl leukotrienes

A

LTC4, LTD4, LTE4
Form via 5-LO pathway, from LTA4 via LTC4 synthase

490
Q

leukotriene antagonist responses in AERD

A

1 - improved FEV1
2 - decreased rescue inhaler use
3 - decreased asthma exacerbations

491
Q

what to monitor while on zileuton or zafirleukast

A

liver function

492
Q

mast cell stabilizers action

A

Eg cromolyn, nedocromil
inhibit IgE-mediated Ca channel activation
Increased intracell Ca needed for mast cell degranulation
blocks activation neutrophils, eos, etc

493
Q

Muscarinic receptors

A

M1 - on eos in those w/ copd
M2 - inhibitory R on parasymp nerves; dysfunctional M2 causes increase ACh
M3 - primary mediator smooth m contraction in airways - concentation bronchi >trachea > alveoli >airway epithelium

ACh -> bronchoconstriction, mucus secretion, vasodilation

494
Q

ipratropium bromide use

A

asthma - decreases hospitalizations
COPD - 1st line,
also in rhinitis
Inhibits both M2 and M3 (muscarinic inhibitor/anticholinergic)
quick onset - 7.6mins to 50% maximal broncodilation

495
Q

Tiotropium

A

longer action than ipratropium - dissociates more slowly than ipra

496
Q

oral steroids cellular effects

A

Decrease T > B cells,
CD4>CD8
Upregulate CXCR4
slight decrease IgG/M
Decrease eos, basos, monos
Increase neutros (demargination)
Innate immunity spared

reverse decreased responsiveness to B agonists (increase receptors)

497
Q

STEROID side effects

A

Stunt growth, Subcaspular posterior catacts
Thrush
Eye (glaucoma, cataracts, increased P), Endo (DM)
Rage, raises BP
Osteopenia
Immunosuppresion
Dysphonia, DM

498
Q

ICS in asthma

A

does NOT prevent progressive loss lung function

499
Q

Binding affinity GC receptors

A

mometasone > fluticasone >budesonide > triamcinolone

500
Q

omalizumab indications

A

asthma >/6yo, evidence perennial aeroallergen
(no improved pulm function)

CU >/12

Nasal polyps >/18

Black box - anaphylaxis

501
Q

Mepolizumab

A

Asthma >6yo, eos >150

HES, EGPA, CRSwNP >18yo

Warning - herpes zoster

502
Q

Reslizumab

A

eos asthma >18 (eos >400)

IV only

Better in obese pts

Black box - anaphylaxis

503
Q

Bneralizumab

A

eos asthma >12yo (eos >300)

Kills eos/basos via ADCC

504
Q

TNF-a inhibitors

A

Infliximab, adalimumab, certolizab, golimumab

Block innate system

505
Q

Abatacept, belatacept

A

Blocks cd28 costimulation (b7-1, -2)
Bu

506
Q

Ruxolitinib

A

Jak1/2 inhibitor

507
Q

Tofacitinib

A

Jak 1/3 inhibitors
Used in RA, psoriatic arthritis, UC

508
Q

Baricitinib

A

Jak 1/2 inhibitor
Used in RA

509
Q

Methotrexate

A

Inhibits lymphocyte cell replication

510
Q

Azathioprine

A

Inhibits purine synthesis and metabolism

Causes apoptosis T cells, inhibits t and B cell proliferation

Urticarial vasculitis, chronic urticaria, glild

511
Q

MMF

A

Affects purine nt synthesis and metabolism

Decreased b and T cell proliferation, decreased Ab production
Used in chronic urticaria, organ transplant

512
Q

Cyclosporine

A

Inhibits Th function as calcineurin inhibitor, inhibits transcriptional factors (eg NFAT that is responsible for IL-2

513
Q

Tacrolimus

A

Inhibits txnal factors (eg nfat), inhibits T cell activation

Used in atopic derm >/2

514
Q

Rapamycin/sirolimus

A

Inhibits mTOR
Inhibits T cell activation, proliferation, Ab production

515
Q

Interferons

A

Interfere with viral infections

Type I - ifn a/b - antiviral
Type II - ifn-g - macrophage activating effects; used in CGD

Drugs - adverse effects flu like sx

516
Q

CAR-T cells

A

Chimeric antigen receptor
Have engineered receptors to recognize tumor cells

For B cell malignancies, (cml and all)

Some pts, car T cells become unresponsive over time
Increased T cell activation can also lead to cytokine release syndrome

517
Q

3 types gene therapy

A

1 - gene therapy/addition (introduce gene into cell)
2 - gene editing, site specific (crispr/
Cas9
3 - gene silencing (does not change gene sequencing)

518
Q

IGRT manufacturing method

A

Isolation- Modified Cohn-Oncley cold ethanol fractionation

519
Q

Dose IV igrt

A

0.3-0.6g/kg/mo
400-600mg/kg q3-4wks
For every 100mg increase —> 121mg increase in IgG trough

520
Q

SQ IGRT dose

A

100mg/kg/wk

521
Q

IG dose autoimmune

A

Higher dose - 2g/kg q3-4wks

522
Q

Epi dose

A

0.01 mg/kg of 1:1000 for SC/IM

0.01 mg/kg of 1:10,000 IV

523
Q

Polysaccharide vaccines

A

T indepen
Pneumovax (23-valent)
Meningococcal

524
Q

Conjugated

A

T-dependent
HiB, prevnar-13, meningococcal (menactra, menveo)

525
Q

In functional/anatomical asplenia vaccine recs

A

Separate pcv13 and menactra by at least 4 wks

526
Q

When to give ab-containing product after live vaccine administration

A

At least 2 wks

527
Q

Arthus reactions

A

Severe local reactions after vaccine administration due to high Ab titers
Most common after 4th/5th dose DTaP
Type iii hypersens - immune complex deposition

528
Q

Gelatin allergy vaccines

A

In Mmr, vzv, rabies, yellow fever

529
Q

Yeast is in which vaccines

A

HBV, HPV

530
Q

B cell ID vaccine ppx

A

Strep pneumonia
Flu
Menu gococcal
HPV

531
Q

T cell PID vaccine ppx

A

Live vaccines contraindicated
Likely ineffective otherwise in complete SCID, questionable in partial defects

532
Q

Contraindicated vaccines in phagocyte disorders

A

Love bacterial (can receive live viral)

533
Q

Steroid use and vaccines

A

If >20mg/d x2+wks -> wait 1 mo after stopping steroids

534
Q

Ivig and vaccine administration

A

If live vaccines given first > wait 2 wks for ivig

Ivig given first > wait 8+ months

535
Q

Indications typanostomy tubes

A

OME 3 episodes/6mo or 4/yr
Persistent OME x 3 mo (b/l) or 6 mo (unilateral)
Hearing loss

536
Q

Gell-Coombs classification

A

Type I - anaphylaxis (acute IgE-mediated; requires sensitization)
Type II - antibody depen cytotoxic rxns (cytopenias)
Type III - immune complex (eg serum sickness)
Type 4 - cell-mediated/delayed hypersens

537
Q

Subclassification type 4 gell-Coombs

A

IVa - th1 (ifn-g) - monocytes/macrophages - eczema, ppd
IVb - Th1 (IL-4, -5) - eos - maculopapular, DRESS
IVc - CTL (perforin and granzyme) - cd4/8 - bullous to pustular, increased cd8 in skin, SJS, fixed drug eruption
IVd - T cells and IL8 - involve PMNs - pustular rash - AGEP

538
Q

Prohapten hypothesis

A

Most drugs by themselves no immunogenic, only when metabolized to reactive metabolite

539
Q

P-I drug allergy concept

A

When drug binds to TCR with string enough affinity, esp when interacting with MHC, then may become immunogenic

540
Q

Atopy risk factor for what drug allergies

A

Latex, radiocontrast

541
Q

MHCs and assoc drug rxns

A

HLA-B*5701 - abacavir (test mutation before starting)

HLA-B*1502 - carbamazepine in Han Chinese (SJS/TEN)

HLA-A*3101 - carbamazepine in Europeans

HLA-B*5801 - allopurinol SCAR rxns in Asians

HLA-B*1301 - dapsone

542
Q

Drug induced hemolytic anemia

A

Quinidine, methyldooa, pcn

543
Q

Drug induced thrombocytopenia

A

Vanco, hep (HIT, IgG to hep-plat factor 4)
Sulfonamides, propulthiouracil, quinidine

544
Q

Serum sickness (like) rxns (type iii)
(Immune complexes)

A

Occurs 1-2wjs after first exposure or 1-7d in previously sensitized

With pcns, sulfonamides, phenytoin
Cefaclor most common cause kids

Fever, arthralgia, LAD, erythema multiforme/urticaria

545
Q

Arthus rxn (type iii)

A

Local selling and tenderness, maybe necrosis after vaccination
Typically with boosters
Onset w/in hours , resolves in days

546
Q

Al drug induced cutaneous lupus

A

Anti-ro (ssa) -La (ssb)
Hctz, CCB, ACE-I, antifungals

547
Q

SJS vs TEN

A

SJS <10% epidermal detachment
TEN >30% involvement

Steroids CONTRAINDICATED in TEN

Pcn, sulfonamides, anticonvulsants, nsaids, allopurinol

Fas/fasL mediated apoptosis epidermal cells, cd8 activation, perforin release

Ivig may help (some anti-Fas Ab)

548
Q

DRESS

A

Anticonvulsants, antimicrobiana, sulfonamides, allopurinol, minocycline

Fever, facial edema, LAD, hepatitis

Weeks after therapy and May worsen even after Tx d/c

549
Q

MRGPRX2

A

Mast cell receptor - certain drugs have this as a target, can cause pseudo allergic reactions (anaphylactoid)
Eg nmba, fluiroquinolones

550
Q

AGEP

A

Acute generalized exanthematous pustulosis

Pustular skin rash, fever, neutrophilia, eosinophilia

Onset 24hrs of drug

551
Q

Predictive value neg skin test to PCN major and minor determinants

A

97% rule out anaphylaxis potential

552
Q

Pcn major/minor determinants

A

Major - benzylpenicilloyl polylysine (pre-pen)

Minor - pen G, penicilloate

553
Q

Low risk pcn allergy

A

Mild Non IgE cutaneous sx,
IgE rxn >5 yrs ago
Unknown rxn

554
Q

Cephalosporin with unique r group

A

Cefazolin

555
Q

Major sulfonamide common reaction

A

Tmp/smx in pts with HIV - delayed maculopapular rash - T cell mediated

556
Q

Vanco reaction

A

VAncomycin May cause IgA bullous dermatitis

557
Q

Most common cause peri operative drug rxns

A

Quaternary ammonium muscle relaxants (succinylcholine)

558
Q

Bio marker cytokine release syndrome (drug rxn)

A

IL-6

559
Q

Contraindications desensitizations

A

Severe cutaneous reactions (eg blistering skin) immune complex mediated reactions
- ten/SJS, dress, serum sickness, hemolytic anemia, drug induced hepatitis/nephritis

560
Q

IgE levels for omalizumab

A

30-700

561
Q

Eerily and Kate phase mediators of SPT

A

Early - histamine, tryptase, chymase, carboxypeptidase, substance P, calcitonin gene related peptide (cgrp)

Late - cd4 T cell
Eos

562
Q

Intradermals most useful for

A

Pcn, chemo, muscle relaxants, insulin, heparin

563
Q

Most reproducible pft and primary outcome in most asthma drug trials

A

Fev1

564
Q

Factors affecting DLCO

A

Hgb levels
Increased with exercise, supine position, L-R cardiac shunt

Decreased by copd/emphysema, bronchiolitis obliterans, ild.
May be high in asthmatics

565
Q

Forced oscillation technique

A

Small P oscillations at mouth transmitted to lungs
Measures resistance and reactance
For those unable to cooperate with pft

566
Q

Significant response bronchodilator in adults

A

Increase FEV1 of 12% AND >/200ml

567
Q

Pft in emphysema

A

Decreased FEV1/FVC with decreased DLCO

568
Q

Methacholine challenge

A

Concentration of Methacholine that causes decrease in fev1 by 20% = PC20
PC20 of </ 8 is positive

Antimuscarinics and antichokinergics interfere with testing

569
Q

Mannitol v Methacholine

A

Methacholine with high sensitivity, rules out asthma

Mannitol with high specificity rules in asthma (particularly exercise induced)

570
Q

Factors that increase/decrease FeNO

A

Increase : asthma, atopy, Uris, >12yp, copd exacerbation, Eosinophilic bronchitis

Decrease: bronchiectasis, tobacco smoke, drugs (steroids, antileukotriene, NOS inhibitors), exercise, moderate altitude, hypothermia

571
Q

Ciliary structure

A

Filiar shaft contains fibrils composed of nine outer pairs of microtubules and 2 central microtubules
Adjacent doublets connected by dynein arms
Microtubules composed of tubulin

572
Q

Kartagener’a synd triad

A

CRS
Sitús inversus
Bronchiectasis

Auto R

Saccharine transit test shows slower mucociliary clearance/transit time

Bx preference is from
Carina

573
Q

Asthma sputum smear

A

Charcot Leyden crystals
Curschmamms spirals (corkscrew twists of condensed mucus)
Creola bodies (clumps sloughed epithelial cells)
ECO, MBP

574
Q

Eosinophils in eos asthma
Neutrophils in neutrophilic asthma

A

Eos >3%
Neutros > 76%

575
Q

Degree complement activation by Ig in descending order

A

IgM > IgG3 > IgG2 > IgG2

576
Q

Diagnostic feature ALPS

A

AlphaBeta double negative T cells
(Cd4-cd8-)

577
Q

Cd3- cells

A

B and NK cells

578
Q

Stem cell surface markers

A

Cd34+

579
Q

Treg surface markers

A

Cd3+ cd25+ foxp3+

580
Q

Naive nature B cell surface markers

A

Cd19+ surface IgM+ IgD+

581
Q

Mature B cell surface markers

A

Cd19+ cd21+

582
Q

Memory B cell surface markers

A

Cd19+ cd27+

583
Q

Nk vs NKT cell surface markers

A

NK: cd45+ cd2+ cd16+ cd56+

NKT: cd45+ cd3+ cd16+ cd56+

584
Q

Receptor in mature B cells that binds EBV and HHV8

A

CD21/cr2

also binds rhinovirus

585
Q

Adenovirus cell receptor

A

Cd46

586
Q

Rhinovirus receptor

A

Cd54

587
Q

CD59

A

Inhibits MAC in complement (binds c8, c9)

588
Q

LAD1 defect

A

Defect in common beta chain in CD18

589
Q

LAD2 defect

A

Defect in CD62E and P (NOT L)

590
Q

Inhibitory cell surface marker B cells

A

Cd22

591
Q

A4b7 in T cells bind what

A

MAdCAM-1 in gut

592
Q

Onalizumab binding site

A

CH3 domain on FREE IgE
At FCepsilonRI binding site

593
Q

Core rotors for HIV entry into cells

A

CCR5, CXCR4

594
Q

Prevnar vs pneumovax

A

Prevnar - conjugated polysaccharide, B and T cell

Pneumovax 23 - unconjugated polysaccharide, B cell only

595
Q

Cd56dim vs bright

A

Dim
- mature NK cells
- majority of NK cells, higher cytokinin activity

Bright
- immature NK cell

596
Q

Catalase + organisms

A

Staph aureus
Salmonella
Serrati
Pseudomonas

597
Q

Missing factors when ch50 low/ah50 nml

A

C1q/r/s, c4, c2

598
Q

Missing factors when ch50 nml /ah50 low

A

Factor B/D, properdin

599
Q

Missing factors when ch50 and ah50 absent

A

C3, c5-9

600
Q

Acquired vs hereditary complement deficiency

A

Hereditary - ch50/ah50 absent. Only one component missing

Acquired - levels low, not absent
Multiple components low

601
Q

How to test for infections in those with CVID, XLA, on IGRT

A

Ab testing unreliable
Use PCR

602
Q

Haller cell

A

Extension of ethmoid sinus and air cell
Along medial floor of orbit
Can increase risk acute rhinisinusitis

603
Q

Volumetric sampling methods

A

Impaction - most common; indoor/outdoor sampling
Impingement - liquid impingers draw air particles in; collect bioaerosols
Filtration - suck particles through a filter; detect dust, endotoxins, antigens, fungi, microorganisms

604
Q

Durham sampler

A

Gravitational sampler; simplest method
Slides coated w adhesive, exposed x 24h
Cheap, durable, no power source needed

Biased towards larger particles
Cannot determine air concentration (
Don’t know v of air)

605
Q

Settle plates

A

Sedimentation sampler
Particles settle on agar plate, then incubated and counted (bacteria, molds)
Identified viable airborn organisms
Indoor use only, biased larger particles, can’t determine airborn concentration

606
Q

Slit impactors

A

Burkhard - suction slit, for pollen and spores, frequently on rooftops, efficient for particles <10um, but need consistent wind speed, sampled from 24h-7d; expensive

Allergenico sampler - not wind-oriented, suction sampler collects on lab slides, primarily indoor use

607
Q

Rotating arm impactor

A

Rotorod - Rods sweep through air to collect particles on surfaces with adhesive tape,
Able to calculate air volume and concentration!
Not affected by wind
Not good for small particles (<10um) eg molds (they air stream around the rods)

608
Q

Sieve impactors

A

Anderson sieve impinger - series of sieves, air drawn in and passes through stages/sieves with progressively smaller holes, separated based in size
Used for culture based sampling fungi
Expensive

609
Q

Wind pollen sizes

A

20-60um

610
Q

Grass pollen

A

20-45um
Smooth surface with one pore

611
Q

Northern grasses

A

Timothy - Phl p 1-14
orchard
rye - Lol p 1-14
fescue
bluegrass - Poa p 1-14

612
Q

Southern grasses

A

Bermuda- cyn d 1-14
Bahia - Pas n 1, 13
Johnson - Sor h 1-14

613
Q

Ragweed

A

Amb a 1-10, profilin, cystatin

Spiny exine (outer surface),
15-25um

Pollen-food allergy with banana, cantaloupe, watermelon

614
Q

Mugwort/sage allergen

A

Art v 1-3, profilin

Smooth surface, tricolporate

OAS - celery spice, peach, mustard

Mugwort celery spice syndrome - celery, coriander, peppers, parsley, fennel

615
Q

Cockleburs

A

25-30um
Similar to ragweed with external spikes, but larger and smaller spines

616
Q

Nettle

A

One of smallest pollens
12-16um
Tri-tetraporate

Look wrinkled/air been sucked out of cell

617
Q

Plantain

A

20-40um
Many pores
Pore cap makes it look like doughnut

618
Q

Dock/sorrell

A

20-30um
Tricolporate
Starch inclusion granules - looks bubbly

619
Q

Ash pollen

A

Fra a 1
Furrows make square/pentagon appearance

620
Q

Birch

A

Bet v 1-7
Triporate
Looks like lemon when only 2 pores visible

Oas - Apple, apricot, carrot, celery, cherry, coriander, fennel, hazelnut, kiwi, nectarine, parsley, parsnip, pear, pepper, plum, peach, potato, walnut

621
Q

Birch OAS mneumonic

A

Pal, remember the ABC

Pear, peach, plum, potato
As well as apricot, apple
are linked to Birch
Along with Celery, cherry, And carrot

622
Q

Mountain cedar

A

Jun a 1-3

With cypress, juniper

Thick outer layer, granular inside, outer layer can break, look like PAC man

623
Q

Oak

A

Que a 1

Oak, beech, chestnut
Triangular, 3 white furrows slightly protruding from surface
25-35um

Oak - O with corners - triangle

624
Q

Syacamore

A

Pla a 1
Round, tricolpate, thin exine (outer covering)

625
Q

Pine

A

Mickey Mouse
Large - 50-100um

626
Q

Maple and box elder

A

Tricolpate
Look like beach balls with coloring

627
Q

Elm

A

4-7 oval shaped pores
Outer surface looks wavy

628
Q

Poplar, willow, cottonwood

A

Poplar/cottonwood - round, outer granular surface; no furrows

Willow - furrows

629
Q

Sweetgum

A

Soccer ball with many white pores

630
Q

Mulberry

A

Small 11-20um
2 pores,
Look like a lemon from the side (more granular than birch)

631
Q

Walnut hickory pecan

A

Walnut - Periporate - 9-15 pores

632
Q

Acacia pollen

A

Covered in nerf pads

633
Q

Alternaria

A

Club shaped
Dry day mold - in hay, grains

Alt a 1-12

634
Q

Cladosporium

A

Sausage chain, budding off
Delray day spore - inside and out
6-25um

Cla h 1-12

635
Q

Aspergillus

A

Indoor mold
Looks very similar to penicillin
Like dandelion puff

Asp f 1-22

636
Q

Penicillium

A

Paintbrush
Hypersens pneumonitis

Pen ch 13,18,20

637
Q

Helminthosporium, bipolaris

A

Single spores with thick walls
Look like worm
Allergic fungal sinusitis

638
Q

Epicoccum

A

Round multicell dry day spore
Dark brown, circular, warts on surface

639
Q

Fusarium

A

Colorless
Wet day spore
20-50um
Spindle shaped and curved with tapered ends - string bean

640
Q

Ascomycota

A

Lots of shapes and sizes
8 ascopores to an ascus

641
Q

Dry day mold spores - on dry, sunny, windy days

A

ACE
Alternaria
Cladosporidium
Epicoccum

642
Q

Molds at night and high humidity

A

Ascopores
Basidiospores

643
Q

Dust mite cross reacts with shrimp

A

Der p 10

644
Q

Group 1 dust mite allergens

A

Der p 1 and Der f 1
89% homology
Cysteine proteases

Der p/f2 - 80% homology
Lipopolysaccharise binding proteins

645
Q

Cockroach allergen

A

Bla g
Per a

646
Q

AQI values standardized for

A

Ozone, NO2, SO2, CO, PM

647
Q

AQI zones

A

0-50 - good
51-100 - mod
101-150 - unhealthy for sensitive groups
151-200 - unhealthy
201-300 - v unhealthy
301-500 - hazardous

648
Q

Nitrogen dioxide pollutant

A

Precursor to o3
Decreased in lung function, increased airway neutrophils, pro inflammatory cytokines
Allergen response at 0.4ppm

649
Q

Ozone pollutant

A

Peaks summer and in afternoon
In asthmatics, increases sx, hospitalizations, b agonist use
Decreased lung function acutely and chronically,
Increases neutrophils in airway, Il-6, Il-8, leukotrienes,
Increased airway reactivity and inflammation

Antioxidants (alpha-tocopherol, ascorbate) can help decrease ozone response, esp in gtsm1 def children

650
Q

So2 pollutant

A

Decreased lung function in children
Bronchospasm in asthmatics at 0.5ppm, reverses with beta agonists

651
Q

PM pollutant

A

Increased allergen sensitization
Airway inflammation
Asthma
CV disease
Strep pneumonia binding to airway epithelium

Pollutants activate innate immunity, increase TLRs and DAMPs -> inflammasome -> il-6, il-8

652
Q

Tobacco smoke

A

Assoc w recurrent OM, uri, lri, wheezing, cancer
Increases th2 and eos

653
Q

Allergens extracts with proteolytic activity

A

DM, cockroach, mold

Can’t mix mold/cockroach with pollens (DM ok with pollen)

654
Q

Dupilumab

A

eos asthma >6yo

AD >/6months. (can cause conjunctivitis)

CRSwNP > 18

EOE >12

655
Q

Catalase positive organisms
(CGD)

A

Staphylococcus aureus,
Serratia marsescens,
Burkholderia cepacia,
Nocardia,
Aspergillus.

656
Q

HAE ppx in pregnancy

A

pdC1-INH, subcutaneous

657
Q

Short term HAE ppx prior to sx

A

pdC1-INH, subcutaneous

658
Q

Epi dosing adults

A

0.3-0.5 of 1:1,000

659
Q
A
660
Q

Nemo part of which pathways

A

NF-KB
Ub of Nemo allows IKK-beta to become active —> P inhibitory component and allows NFkB to local size to nucleus

661
Q

Complement deficiency and macular degeneration

A

Factor H deficiency

662
Q

Stat4, stat6, stat3, stat5 involved with which t cells

A

TH1 – STAT3, Tbet
TH2 - STAT6, GATA3
TH17 - RORgT, STAT3
Tfh - BCL-6
Treg - STAT5

663
Q

Relative risk formula

A

Incidence among exposed/incidence unexposed
A/(a+b)
————
C/(c+d)

664
Q

Relative risk reduction formula

A

1-RR

(ARC-ART)/ARC

ABAI (1 decks)

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