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Flashcards in Immunology Deck (326):
1

Positive selection location

thymic cortex

2

Negative selection location

Thymic medulla

3

MHC class II deficiency

/defect in development of CD4+ cells in the thymus. /no MHC class II so helper cells cannot be selected by positive selection mechanisms in the thymus but CD8 cytotoxic cells can be produced. /also known as type II bare lymphocyte syndrome.

4

Positive selection mechanism

T cells expressing TCRs capable of binding self-MHC on cortical epithelial cells survive.

5

Negative selection mechanism

T cells expressing TCRs with high affinity for self antigens undergo apoptosis. Tissue-restricted self-antigens are expressed in the thymus due to the action of autoimmune regulator (AIRE).

6

Autoimmune polyendocrine syndrome-1

deficiency of negative selection.

7

Lymph drainage of head and neck

cervical

8

Mediastinal lymp nodes drain

trachea and esophagus

9

Axillary lymph node drainage

Upper limb, breast, skin above umbilicus

10

Celiac lymph node drainage

Liver + stomach + spleen + pancreas + upper duodenum

11

Superior mesenteric lymph node drainage

lower duodenum + jejunum + ileum + colon to splenic flexure

12

Inferior mesenteric lymph node drainage

Colon from splenic flexure to upper rectum

13

Internal iliac drains

Lower rectum to anal canal (above pectinate line) + bladder + vagina (middle third) + cervix + prostate

14

Para-aortic drains

testes + ovaries + kidneys + uterus

15

Superficial inguinal node drains..

anal canal (below pectinate) + skin below umbilicus (except popliteal area) + scrotum + vulva.

16

popliteal drains

dorsolateral foot + posterior calf

17

thoracic duct drains into..

junction of left subclavian + internal jugular veins

18

Function of medullary sinus of lymph node

Outside near capsule. Houses reticular cells and macrophages, which perform nonspecific filtration.

19

Location of B-cells in lymph node

Outer cortex.

20

lymph node follicle

Site of b-cell localization and proliferation

21

Difference between primary follicles and secondary follicles.

Primary follicles are dense and dormant, secondary follicles are activated and have pale central germinal centers.

22

Function of medulla of lymph node and composition

Consists of medullary cords and medullary sinuses.

23

Medullary cords

Closely packed lymphocytes and plasma cells.

24

medullary sinuses

Communicate with efferent lymphatics and contain reticular cells and macrophages.

25

Where are T cells located in lymph node?

paracortex

26

Paracortex

region between follicles and medulla. Contains high endothelial venules through which T and B cells enter from blood.

27

Sinusoids of spleen

Long, vascular channels in red pulp with fenestrated "barrel hoop" basement membrane.

28

Where are T cells found in the spleen?

periarteriolar lymphatic sheath (PALS) within the white pulp.

29

Where are B cells found in the spleen?

Follicles within the white pulp.

30

Marginal zone of spleen.

Zone between the red pulp and white pulp that contains macrophages and specialized B cells.

31

Marginal zone of spleen function

Where APCs capture blood-borne antigens for recognition by lymphocytes.

32

GBS encapsulated or nonecapsulated?

encapsulated

33

Mechanism for increased susceptibility to encapsulated organisms with splenic dysfunction

Decreased IgM --> decreased complement activation --> decreased C3b opsonization.

34

Postsplenectomy hematologic findings

1) Howell-Jolly bodies (nuclear remnants)
2) Target cells
3) Thrombocytosis (loss of sequestration and removal)
4) lymphocytosis (loss of sequestration).

35

Spleen follicle organization

Germinal center surrounded by mantle zone surrounded by marginal zone.

36

Thymus location

Anterosuperior mediastinum

37

Thymus organization

Cortex is dense with immature T cells; medulla is pale with mature T cells and Hassall corpuscles

38

Hassall corpuscles

Contain epithelial reticular cells

39

T cell and B cell origin

T cells = Thymus (mature in thymus, originate in bone marrow), B cells = Bone marrow.

40

Thymic hypertrophy seen in...

MG

41

Innate immunity components

Neutrophils, macrophages, monocytes, dendritic cells, NK cells (lymphoid origin), complement.

42

Mechanism of innate immunity

Germline encoded

43

What physical barriers does innate immunity have?

epithelial tight junctions + mucus

44

Proteins secreted by innate immunity

lysozyme, complement, CRP, defensins.

45

Key features of pathogen recognition in innate immunity

Toll-like receptors (TLRs).

46

TLRs

Pattern recognition receptors that recognize pathogen-associated molecular patterns (PAMPs) (eg LPs, flagellin, nucleic acids (viruses))

47

Components of adapative immunity

T cells, B cells, circulating antibodies

48

MHC 1 loci

HLA-A, HLA-B, HLA-C (all have 1 letter)

49

MHC 1 expression

Expressed on all nucleated cells. Not expressed on RBCs.

50

MHC I vs. MHC II function

MHC 1 present endogenously synthesized antigens (eg viral or cytosolic proteins) to CD8+ T cells. MHC II prsent exogenously synthesized antigens (eg bacterial proteins to CD4+ helper T cells).

51

protein associated with MHC 1

Beta2-microglobulin

52

Antigen loading in MHC 1

Antigen peptides loaded onto MHC I in RER after delivery via TAP (transporter associated with antigen processing).

53

MHC II loci

HLA-DP, HLA-DQ, HLA-DR (all have 2 letters)

54

MHC II expression

Expressed on APCs

55

protein associated with MHC II

Invariant chain

56

Mechanism of MHC II

Antigen loaded following release of invariant chain in an acidified endosome.

57

HLA A3

hemochromatosis

58

Addison disease HLA association

B8

59

MG HLA association

B8

60

MS HLA association

DR2

61

RA HLA association

DR4

62

Addison's HLA association

DR3 + DR4

63

Hashimoto's HLA association

DR5

64

DM1 HLA association

DR3 + DR4

65

MS HLA association

DR2

66

Goodpasture's HLA association

DR2

67

SLE HLA association

DR2 + DR3

68

Pernicious anemia HLA association

DR5

69

Hay fever HLA association

DR2

70

Graves HLA association

DR3

71

NK cell mechanism

Use perforin and granzymes to induce apoptosis of virally infected cells and tumor cells

72

What enhances NK cell activity?

IL-2 + IL-12 + IFN-alpha + IFN-beta

73

What induces NK cells?

Exposure to a nonspecific activation signal on target cell and/or to an absence of class I MHC on target cell surface.

74

NK cell other mechanism

antibody-dependent cell mediated cytotoxicity

75

antibody-dependent cell mediated cytotoxicity mechanism

CD16 binds Fc region of bound Ig, activating NK cell

76

Process of B cell antigen specificity

somatic hypermutation

77

CD4+ vs. CD8+ cells

CD4 help b cells make antibodies and produce cytokines to recruit phagocytes and activate other leukocytes. CD8 directly kill virus-infected cells.

78

Where are mature and immature T cells found?

immature in cortex, mature in medulla.

79

What activates Th1 cells?

IL-12

80

What activates Th2 cells?

IL-4

81

What activates Th17 cells?

TGF-beta + IL-6

82

What are cytotoxic T cells activated by?

Th1 cells

83

What induces differentiation of Th1 cells?

IFN-gamma and IL-12

84

What inhibits TH1 cells?

IL-4 + IL-10 (from Th2 cell)

85

What do Th2 cells secrete?

IL-4, IL-5, IL-10, IL-13

86

Th2 cell function

Recruit eosinophils for parasite defense and promote IgE production by B cells

87

What induces differentiation of Th2 cells?

IL-4

88

What inhibits Th2 cells?

IFN-gamma from Th1 cells

89

macrophage-lymphocyte interaction mechanism

Macrophages and other APCs release IL-12, which stimulates T cells to differentiate into Th1 cells. Th1 cells release IFN-gamma to stimulate macrophages.

90

Cytotoxic T cell mechanism

1) kill virus-infected, neopalstic, and donor graft cells by inducing apoptosis.
2) release cytotoxic granules containing preformed proteins (eg perforin, granzyme B)

91

Regulatory T cell mechanism

Maintain specific immune tolerance by suppressing CD4 and CD8 T-cell effector functions.

92

Regulatory T cell markers

CD3, CD4, CD25, FOXP3

93

What do activated regulatory T cells produce?

anti-inflammatory cytokines (IL-10 + TGF-beta)

94

APCs

B cells + macrophages + dendritic cells

95

Caveat about T and B cell activation

Two signals are required for T-cell activation, B-cell activation, and class switching.

96

Naive T-cell activation

Dendritic cell samples and processes antigen --> dendritic cell migrates to draining lymph node --> T-cell activation (signal 1): antigen is presented on MHC II and recognized by TCR on Th (CD4+) cell. Endogenous antigen is presented on MHC I to Tc (CD8+) cell --> Proliferation and survival (signal 2): costimulatory signal via interaction of B7 proteins (CD80/86) and CD28 --> Th cell activates and produces cytokines. Tc cell activates and is able to recognize and kill virus-infected cell.

97

B-cell activation and class switching mechanism

1. Th-cell activation.
2. B-cell receptor-mediated endocytosis; foreign antigen is presented on MHC II and recognized by TCR on Th cell.
3. CD40 receptor on B cell binds CD40 ligand (CD40L) on Th cell.
4. Th cell secretes cytokines that determine Ig class switching of B cell. B cell activates and undergoes class switching, affinity maturation, and antibody production.

98

Fab

region of antibody containing variable/hypervariable regions.

99

What fixes comploment

Fc region of IgM and IgG

100

Idiotype

unique antigen-binding pocket; only 1 antigenic specificity expressed per B cell.

101

carbohydrate side chains

Expressed on Fc region

102

What determines isotype (IgM, IgD, etc)?

Fc region

103

neutralization

Antibody binding and preventing bacterial adherence.

104

VJ

light-chain genes

105

V(D)J

heavy-chain genes

106

How is antibody diversity generated?

1) Random recombination of VJ (light-chain) or V(D)J (heavy-chain) genes.
2) random addition of nucleotides to DNA during recombination by terminal deoxynucleotidyl transferase (TdT)
3) Random combination of heavy chains with light chains

107

How is antibody specificity achieved?

1) Somatic hypermutation and affinity maturation (variable region)
2) Isotype switching (constant region)

108

Affinity maturation mechanism

Process by which Th cell-activated B cells produce antibodies with increased affinity for antigen. With repeated exposures to the same antigen, host produces antibodies of successively greater affinities.

109

Immunoglobulins expressed on mature, naive B cells prior to activation...

IgM and IgD

110

What mediates isotype switching?

CD40L and cytokines

111

Immunoglobulin responsible for neutralizing bacterial toxins and viruses

IgG

112

Main antibody in secondary (delayed) response to an antigen

IgG

113

Which immunoglobulins have J chains?

IgA and IgM

114

IgA in circulation

Exists as a monomer

115

How does IgA cross epithelial cells?

Transcytosis

116

IgA caveat

Most produced antibody overall, but has lower serum concentrations.

117

What contains IgA

Tears, saliva, mucus, and breast milk.

118

What is secretory component?

Portion of IgA that IgA picks up from epithelial cells, and which protects Fc portion from luminal proteases.

119

What is produced in the immediate response to an antigen?

IgM

120

IgM forms

Monomer on B cell, pentamer with J chain when secreted.

121

Why does IgM exist as a pentamer?

Pentameric form enables avid binding to antigen while humoral response evolves.

122

IgD

Unclear function. Found on surface of many B cells and in serum.

123

What immunoglobulin has the lowest concentration in serum?

IgE

124

Thymus-independent antigens

Antigens lacking a peptide component. Thus, they can't be presented by MHC to T cells and are weakly immunogenic.

125

Example of thymus-independent antigen

LPS

126

Critical function of CD40L

Class-switching. Expressed on helper T cells

127

What activates acute-phase reactants?

IL-6

128

What produces acute-phase reactants

liver

129

CRP function

Opsonin; fixes complement and facilitates phagocytosis

130

CRP clinical significance.

Sign of ONGOING inflammation.

131

Function of ferritin

Binds and sequesters iron to inhibit microbial iron scavenging.

132

Functions of fibrinogen

1) coagulation factor
2) promotes endothelial repair
3) correlates with ESR.

133

Function of hepcidin

1) decreases iron absorption (by degrading ferroportin)
2) decreased iron release (from macrophages)
*

134

anemia of chronic disease mechanism

Increased hepcidin due to chronic inflammation.

135

Serum amyloid A

acute phase reactant

136

Transferrin mechanism

Internalized by macrophages to sequester iron.

137

Why is albumin downregulated with inflammation?

Reduction conserves amino acids for positive reactants.

138

MAC target

gram negative bacteria

139

What activates classic complement pathway?

IgG or IgM

140

What activates alternative complement pathway?

Microbe surface molecules

141

What activates Lectin complement pathway?

Mannose or other sugars on microbe surface

142

complement proteins involved in anaphylaxis

C3a, C4a, C5a

143

MAC components

C5b-9

144

C3b functions

1) opsonin
2) clears immune complexes

145

Primary opsonins in bacterial defence

C3b and IgG

146

What prevents complement activation of self cells?

1) decay-accelerating factor (DAF, aka CD55)
2) C1 esterase inhibitor

147

C1 esterase inhibitor deficiency mechanism

unregulated activation of kallikrein leads to increased bradykinin

148

DAF deficiency

Causes complement-mediated lysis of RBCs and PNH

149

Other name for IL-1

Osteoclast-activating factor

150

Il-1 functions

1) causes fever, acute inflammation
2) activates endothelium to express adhesion molecules
3) induces chemokine secretion to recruit WBCs

151

IL-6 functions

1) fever
2) stimulates production of acute-phase proteins

152

IL-12 functions

1) Induces differentiation of T cells into Th1 cells
2) activates NK cells

153

TNF-alpha functions

1) sepsis
2) activates endothelium
3) causes WBC recruitment
4) vascular leak

154

Cytokines secreted by macrophages

1,6,8,12,TNF-alpha

155

cytokines secreted by all T cells

IL-2 and IL-3

156

IL-2 functions

Stimulates growth of helper, cytotoxic, and regulatory T cells, and NK cells

157

IL-3 functions

- Supports growth and differentiation of bone marrow stem cells.
- Functions like GM-CSF

158

What secretes interferon-gamma

NK cells and Th1 cells in response to Il-12 from macrophages

159

Interferon-gamma functions

1) stimulates macrophages to kill pathogens
2) inhibits differentiation of Th2 cells
3) activates NK cells to kill virus-infected cells.
4) Increases MHC expression and antigen presentation by all cells.

160

cytokines secreted by Th2 cells

Il-4,5, and 10

161

IL-4 functions

1) induces differentiation of T cells into Th2 cells
2) promotes growth of B cells
3) enhances class switching to IgE

162

IL-5 functions

1) promotes growth and differentiation of B cells
2) enhances class switching to IgA
3) stimulates growth and differentiation of eosinophils

163

IL-10 functions

1) attenuates inflammatory response
2) decreases expression of MHC class II and Th1 cytokines
3) inhibits activated macrophages and dendritic cells

164

What is responsible for attenuating the immune response?

TGF-beta and IL-10

165

NADPH functions

Creation AND neutralization of ROS.

166

NADPH oxidase mechanism

Utilizes NADPH to generate oxygen anions

167

Lactoferrin

Protein found in secretory fluids and neutrophils that inhibits microbial growth via iron chelation.

168

Pyocyanin

enzyme in Pseudomonas that generates ROS to kill competing microbes

169

Interferons

Glycoproteins synthesized by virus-infected cells that act locally on uninfected cells, priming them for viral defense by helping to selectively degrade viral nucleic acid and protein.

170

Proteins found on T cells

1) TCR
2) CD3
3) CD28
4) CXCR4/CCR5

171

CD3 function

Associated with TCR for signal transduction.

172

CD28 function

Binds B7 on APC.

173

Regulatory T cell markers

CD4, CD25

174

B cell markers

1) Ig
2) CD19,20,21,40
3) MHC II
4) B7

175

Ig function

Protein expressed on B cells that binds antigen.

176

Proteins expressed on macrophages

1) CD14
2) CD40
3) CCR5
4) mHC II
5) B7 (CD80/86)
6) Fc and C3b receptors

177

CD14 function

receptor for PAMPs

178

NK cell markers

1) CD16
2) CD56 (unique marker for NK)

179

CD16 on NK cells functions

Binds Fc of IgG

180

Costimulatory signal

T and B cells need 2 signals to become activated. This is a safety mechanism of self-tolerance.

181

Superantigen mechanism

Cross-link Beta region of T-cell receptor to MHC class II on APCs. Can activate any CD4+ T cell --> massive cytokine release.

182

Endotoxins/LPS mechanism

Directly stimulate macrophages by binding to endotoxin receptor TLR4/CD14. No Th cells involved.

183

bacterial examples of antigenic variation

1) salmonella
2) borrelia recurrentis
3) N gonorrhoeae

184

viral examples of antigenic variation

1) influenza
2) HIV
3) HCV

185

parisitic examples of antigenic variation

trypanosomes

186

half-life of antibodies

3 weeks

187

When are patients given preformed antibodies (which bugs?)?

"To Be Healed Very Rapidly"
Tetanus, Botulinium, HBV, Varicella, Rabies

188

When are combined passive and active immunizations needed?

Hep B + rabies exposure

189

Only live attenuated vaccine given to HIV patients

MMR

190

Live attenuated vaccine mechanism

organism loses its pathogenicity but retains capacity for transient growth within inoculated host.

191

Live attenuated vaccine pros/cons

Pro: induces strong, often lifelong immunity.
Con: can revert to virulent form.

192

hep A vaccine: live or killed?

killed

193

polio (salk) vaccine: live or killed?

killed

194

BCG: vaccine: live or killed?

live

195

varicella vaccine: live or killed?

live

196

yellow fever vaccine: live or killed?

live

197

measles vaccine: live or killed?

live

198

Rabies vaccine: live or killed?

killed

199

influenza injection vaccine: live or killed?

killed

200

mumps vaccine: live or killed?

live

201

rubella vaccine: live or killed?

live

202

polio (sabin) vaccine: live or killed?

live

203

site of action of histamine

postcapillary venules

204

Type I hypersensitivity mechanism and delayed response.

1) Preformed antibodies on mast cells or basophil (IgE) are cross-linked with free antigens.
2) Delayed response follows due to production of archidonic acid metabolites (eg, leukotrienes).

205

Type II mechanisms

1) opsonization and phagocytosis
2) Complement- and Fc receptor-mediated inflammation
3) Antibody-mediated cellular dysfunction

206

Direct Coombs test

Detects antibodies that have adhered to patient's RBCs (eg test Rh+ infant of an Rh- mother)

207

Indirect coombs test

Detects serum antibodies that can adhered to other RBCs (test an Rh negative woman for Rh positive antibodies)

208

Acute hemolytic transfusion reaction hypersensitivity type

Type II

209

AIHA hypersensitivity type

Type II

210

Type III hypersensitivity mechanism

Immune complexes activate complement, which attracts neutrophils; neutrophils release lysosomal enzymes.

211

Polyarteritis nodosa hypersensitivity type

Type III

212

Serum sickness mechanism

Antibodies to foreign proteins are produced. Immune complexes form and are deposited in membranes, where they fix complement, leading to tissue damage. Usually due to drugs acting as haptens.

213

serum sickness presentation

Fever + urticaria + arthralgia + proteinuria + lymphadenopathy

214

test for arthus reaction

immunofluorescent staining

215

Arthus reaction mechanism

Local subacute antibody-mediated. Intradermal injection of antigen into presensitized (already has circulating IgG) individual leads to immune complex formation in skin.

216

Arthus reaction presentation

edema + necrosis + complement activation.

217

Type IV mechanism

1) Sensitized T cells encounter antigen and release cytokines, leading to macrophage activation.
2) Response does not involve antibodies.

218

Type IV caveat

Not transferable by serum since cell mediated.

219

Transplant rejections hypersensitivity type

Type IV

220

Febrile nonhemolytic transfusion reaction mechanism

Type II hypersensitivity reaction. Host antibodies against donor HLA antigens and WBCs

221

Febrile nonhemolytic transfusion reaction presentation

Fever + headaches + chills + flushing

222

Acute hemolytic transfusion reaction mechanism

Type II hypersensitivity reaction. Intravascular hemolysis (ABO blood group incompatibility) or extravascular hemolysis (host antibody reaction against foreign antigen on donor RBCs).

223

Acute hemolytic transfusion reaction presentation

Fever + hypotension + tachypnea + tachycardia + flank pain + hemoglobinuria + jaundice (extravascular)

224

hemoglobinuria

intravascular hemolysis

225

Intravascular hemolysis

breakdown of RBCs in blood vessels

226

extravascular hemolysis example

host antibody reaction against foreign antigen on donor RBCs

227

drug-induced lupus antibody

anti-histone

228

autoantibodies in polymyositis, dermatomyositis

Anti-Jo-1 + anti-SRP + anti-Mi-2

229

primary membranous nephropathy autoantibody

antiphospholipase A2 receptor

230

scleroderma autoantibody

Anti-Scl-70 (anti-DNA topoisomerase I)

231

Autoimmune hepatitis type I autoantibody

anti-smooth muscle

232

anti-SSA

anti-Ro

233

anti-SSB

anti-La

234

celiac disease autoantibodies

IgA anti-endomysial + IgA anti-tissue transglutaminase

235

p-ANCA also known as

MPO-ANCA

236

c-ANCA also known as

PR3-ANCA

237

Other impt findings in bruton's

Absenct/scanty lymph nodes and tonsils

238

Bruton's gene mutation

BTK (tyrosine kinase)

239

Bruton's presentation

Recurrent bacterial and enteroviral infections after 6 months (after maternal IgG declines).

240

Most common primary immunodeficiency

Selective IgA deficiency

241

CVD etiology

defect in B-cell differentiation

242

term for cardiac defects in DiGeorge

Conotruncal abnormalities

243

How do you test for 22q11 deletion?

FISH

244

Immunodeficiency that prevents after adiminstration of BCG vaccine...

IL-12 receptor deficiency

245

IL-12 receptor deficiency etiology

decreased Th1 response

246

Labs in IL-12 receptor deficiency

decreased IFN-gamma

247

hyper-IgE syndrome etiology

Deficiency of Th17 cells due to STAT3 mutation, leading to impaired recruitment of neutrophils to sites of infection.

248

labs in hyper-IgE

Increased IgE + decreased IFN-gamma

249

hyper-IgE presentation

Coarse facies, cold (noninflammed) staphylococcal abscesses, retained primary teeth, eczema.

250

SCIDs etiology

either
1) Defective IL-2R gamma chain (x-linked)
OR
2) adenosine deaminase deficiency (AR)

251

Findings in SCIDS

1) Decreased T-cell receptor excision circles (TRECs)
2) absence of thymic shadow on CXR
3) absence of germinal centers
4) absence T cells on flow cytometry.

252

Findings in ataxia-telangiectasia

1) increased AFP
2) decreased IgA, IgG, and IgE
3) lymphopenia
4) cerebellar atrophy

253

Hyper-IgM inheritance

X-linked recessive

254

pathogens in Hyper-IgM

pneumocystis + cryptosporidium + CMV

255

gene mutation in Wiskott-Aldrich syndrome

WAS gene

256

Wiskott-Aldrich syndrome etiology

T cells unable to reorganize actin cytoskeleton.

257

lab findings in Wiskott-ALdrich

- decreased to normal IgG, IgM
- Increased IgE, IgA
- fewer and smaller platelets

258

Wiskott-aldrich association

Increasedd risk of autoimmune disease and malignancy.

259

Chediak-Higashi defect and etiology

- Defect in lysosomal trafficking regulator gene (LYST).
- Microtubule dysfunction in phagosome-lysosome fusion.

260

Chediak higashi presentation

1) Recurrent pyogenic infections by staphylococci and streptococci.
2) Partial albinism
3) peripheral neuropathy
4) progressive neurodegeneration
5) infiltrative lymphohistiocytosis.

261

Findings in Chediak Higashi

1) Giant granules in granulocytes and platelets
2) pancytopenia
3) mild coagulation defects

262

another name for flow cytometry

dihyrorhodamine test

263

Catalase positive organisms

Nocardia
Pseudomonas
Listeria
Aspergillus
Candida
E coli
Staphylococci
Serratia
B cepacia
H pylori

264

Increased risk for... with deficiency in early complement

Encapsulated species.

265

T cell deficiency leads to increased risk of...

sepsis

266

bacterial infections with decreased granulocytes (neutropenia)

Staphylococcus
Burkholderia
Pseudomonas
Serratia
Nocardia

267

viral infections in B cell deficiency

Enteroviral encephalitis
Poliovirus (live vaccine contraindicated)

268

Fungal infections in granulocyte deficiency (neutropenia)

Systemic candida
Aspergillus

269

granulocytes

cells containing granules. Basophils, eosinophils, neutrophils.

270

Syngeneic graft (isograft)

Graft from identical twin or clone

271

Hyperacute graft rejection onset

within minutes

272

Hyperacute graft rejection pathogenesis

Pre-existing recipient antibodies react to donor antigen, activating complement.

273

Hyperacute graft rejection features

Widespread thrombosis of graft vessels --> ischemia/necrosis.

274

Acute graft rejection timeframe

Weeks to months

275

Acute graft rejection pathogenesis

Cellular: CD8+ T cells activated against donor MHcs (type IV
Humoral: similar to hyperacute, except antibodies develop after transplant.

276

Acute graft rejection features

Vasculitis of graft vessels with dense interstitial lymphocytic infiltrate

277

Chronic graft rejection timeframe

Months to years

278

Chronic graft rejection pathogenesis

CD4+ T cells respond to recipient APCs presenting donor peptides, including allogeneic MHC.
Both cellular and humoral components (type II and IV)

279

Chronic graft rejection features

Recipient T cells react and secrete cytokines --> proliferation of vascular smooth muscle + parenchymal atrophy + interstitial fibrosis + ateriosclerosis.

280

Lung chronic rejection disease

bronchiolitis obliterans

281

heart chronic rejection disease

accelerated atherosclerosis

282

kidney chronic rejection

chronic graft nephropathy

283

liver chronic rejection disease

vanishing bile duct syndrome

284

GVHD pathogenesis

Grafted immunocompetent T cells proliferate in immnocompromised host and reject host cells, leading to severe organ dysfunction.

285

When does GVHD usually occur?

Bone marrow and liver transplants (rich in lymphocytes)

286

When can GVHD be beneficial?

Potentially beneficial in bone marrow transplant for leukemia (graft-versus-tumor effect).

287

Cyclosporine uses

1) transplant rejection prophylaxis
2) psoriasis
3) RA

288

cyclosporine mechanism

Calcineurin inhibitors; binds CYCLOphilin.
Blocks T-cell activation by preventing IL-2 transcription.

289

cyclosporine toxicity

nephrotoxic + HTN + hyperlipidemia + neurotoxicity + gingival hyperplasia + hirsitusm

290

Tacrolimus MOA

- Calcineuron inhibitor; binds FK506 binding protein FKBP.
- Blocks T-cell activation by preventing IL-2 transcription.

291

Tacrolimus SE's

Increased risk of diabetes + neurotoxicity + highly nephrotoxic.

292

Sirolimus aka

Rapamycin

293

Sirolimus MOA

mTOR inhibitor; binds FKBP. Blocks T-cell activation and B-cell differentiation by preventing response to IL-2.

294

Sirolimus toxicity

Pancytopenia + insulin resistance + hyperlipidemia.

295

daclizumab, basiliximab SE's

Edema + HTN + tremor

296

Azathioprine MOA

antimetabolite precursor of 6-mercaptopurine.
- Inhibits lymphocyte proliferation by blocking nucletoide synthesis.

297

Azathioprine uses

1) Transplant rejection prophylaxis
2) RA
3) Crohn's
4) glomerulonephritis
5) other autoimmune conditions

298

azathioprine SE's

leukopenia + anemia + thrombocytopenia

299

azathioprine contraindication

Allopurinol.

300

Other use for mycophenolate mofetil

lupus nephritis

301

mycophenolate mofetil association

Invasive CMV infection

302

mycophenolate mofetil SE's

GI upset + pancytopenia + HTN + hyperglycemia. Less nephrotoxic and neurotoxic.

303

corticosteroid immunosuppression mechanism

1) Inhibit NF-kB.
2) Suppress both B- and T-cell function by decreasing transcription of many cytokines.
3) Induce apoptosis of T lymphocytes.

304

Calcineurin action

NFAT-P--> NFAT, which is a TF

305

aldesleukin

IL-2

306

aldesleukin clinical uses

RCC + metastatic melanoma

307

Filgrastim

G-CSF

308

Sargramostim

GM-CSF

309

IFN-alpha uses

Chronic hep B and C, Kaposi sarcoma, malignant melanoma

310

Romiplostim, etrombopag

Thrombopoietin receptor agonists

311

Oprelvekin

IL-11

312

alemtuzumab clinical use

CLL + MS

313

bevacizumab clinical uses

CRC + RCC + mac degen

314

cetuximab target

EGFR

315

cetuximab uses

Stage IV CRC + head and neck cancer

316

Rituximab target

CD20

317

Rituximab uses

B-cell non-Hodgkin lymphoma + CLL + RA + ITP

318

certolizumab target

soluble TNF-alpha

319

etanercept MOA

decoy TNF-alpha receptor. NOT a monoclonal antibody.

320

Eculizumab clinical use

Paroxysmal nocturnal hemoglobinuria

321

Alpha4-integrin mechanism

WBC adhesion

322

abciximab target

IIb/IIIa

323

denosumab mechanism

inhibits osteoclast maturation

324

omalizumab target

IgE

325

palivizumab target

RSV F protein

326

monocytes

differentiate into macrophages, dendritic cells, and foam cells