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Flashcards in Immunology Test 2 Deck (344):
1

T Cells vs B Cells

T cells must be present at site of interaction with antigen presenting molecule; secretions are short range. B cells secrete antibody and don’t have to be present to see the result.

2

What activates T-Cells?

antiogen + Antigen presenting Molecule

3

Th0

is the precursor to all Helper T cells

4

Where do Th0 cells exist?

when presented by DC they move from afferent lymph to paracortex to show T-cells to cause them to divide and differentiate.

5

Th1

delayed hypersensitivity T-Cells; proliferate rapidly in lymph node; react with antigen precession cells and secretes cytokine to attract macrophages in Classically activate M1.

6

What does Th1 secrete when it encounters an APC?

IFN-gamma (a lymphokine and cytokine), as well as IL-2

7

IFN-gamma

is a pro-inflammatory cytokine that is chemotactic for macrophages

8

macrophages activated by IFNgama

classically activated to ingest bacteria and kill it.

9

Why does Th2 secrete IL-2?

help activate killer T-cells

10

What do the macrophages activated by Th1 secrete?

TNFalpha and IL-1

11

Th17

very similar to Th1, produces inflammatory IL-17 a more ferocious inflammatory agent than Th1.

12

what types of infection is Th1 involved in?

bacteria

13

what types of infection is Th17 involved in?

fungal infections, and autoimmunity

14

what method of activation does Th17 utilize for its macrophages?

Classic M1 macrophages

15

lymphokines are a subset of..

cytokines

16

Th2

leave node and circulate through blood and lymph to encounter antigen in tissue; secretes IL-4 t activate M2 macrophages

17

what does Th2 secrete?

IL-4

18

IL-4

chemotactic for eosinophils

19

What type of macrophages are activated by Th2?

Alternative activated or M2

20

M2 vs M1 activation

M1 = classical and it is involved in inflammtaion; M2 = healing (debris removal, scar, walling-off)

21

What does Th2 help to target?

Macrophages that target eosinophils

22

When does Th1 show up compared to Th2?

Th1 is first then Th2 takes over in repair and healing

23

Tfh

Follicular Helper T-Cells; migrate into follicle in cortex when activated by DC; help B cells to recognize antigen and activate into antibody secreting plasma cell

24

Two functions of Tfh

1) help B cells recognize antigen and activate antibody secretion 2) Class switching from IgM

25

Treg

Regulatory T-Cell; very small population (only 5%) that suppress activation of other T-helper cells.

26

Treg in the gut

Secretes IL-10 and TGF-Beta to avoid immune response to food.

27

Phenotype of regulatory T-cells

CD4+/CD25+

28

Cytotoxic TCells (CTL)

signal target cell to activate apoptosis by engaging CD95 (death receptor) and secrete lytic granules (granzymes) and Perforins to allow penetration of granzymes.

29

Granzymes

lytic granules secreted by CTL

30

Perforins

secreted by CTL to allow penetration of granzymes.

31

Viral Hepatitis

CTLs kill the body’s own liver cells, but not the virus itself

32

Memory Cells

after response to antigen, the number of T-cell declines. These cells have same attributes of stem cells in that they can rapidly replicate in response to antigen (low concentrations)

33

Subpopulation markers

CD3, CD4, CD8 - surface markers on T cell population; involved in Tcell activation

34

CD3 is on..

virtually all cells

35

CD4 is on…

only T-helper cells

36

CD8 is on…

only CTL cells

37

MHC Restriction

T cell will only recognize peptide antigen when it is bound to body’s own MHC molecule; A t cell is antigen specific and MHC restricted.

38

MHC

Major Histocompatibility Complex - fruit bowl on surface of APC that contains the epitope piece

39

Antigen Presentation - extrinsic

Antigen is broken down by lysosomal enzymes in DC, vesicles fuse with surface with MHC on inner surface —> fusion causes MHC on surface to express partially broken own antigen.

40

What are the antigen presenting cells?

Macrophages, dendritic cells, B-cells

41

Epitopes for T-cells must be

continuous epitopes (B cells can be continuous or discontinuous)

42

T-Cell Receptor

same structure as antibody, except two chains called Alpha and beta which a constant and variable region.

43

Do T-cells have variable regions?

Yes - they have special VDJ regions that recombine and have 3 CDRs.

44

Where does T-cell development take place?

Thymus

45

CD3 is associated with..

the TCR and it transmits signal when the Th cell binds to correct antigen and MHC

46

TCR-pMHC

when antigen interacts with TCRR, this becomes activated and activates a cascade of accessory molecular interaction that modify, enhance, diminish activation.

47

what CD types are on MHC Class II?

CD4 (shut off CD8); all Th cells

48

What CD types are on MHC class I?

CD8 (shut off CD4); all CTL cells

49

MCH Class II

used by DC, macro, B-cells; selective for Th cells; antigen presenting cleft is made up of two peptides

50

MCH Class I

present on all nucleated cells; antigen presenting peptide is composed of one single peptide with stabilization constant peptide. Dependent on intrinsic pathway.

51

Intrinsic APC

when contents uptake via the extrinsic pathway leak out of the vesicle and are put on the surface of MCH class cells.

52

what types of cells react to MCH Class i?

CTL

53

Cross Presentation

cells can bring samples in from periphery and arranged not only for Th response, but also for CTL

54

CD4

is on helper T cells and helps strengthen the binding between MHC class II and APC

55

B-cell as antigen presenting molecule

B cell binds to antigen and takes into cell and loads into Clas II MCH. Tfh recognizes MHC II and hopes B cell to release antibody. Epitope that the B cell sees is not the same as the Tfh epitope.

56

To activate B cell, is the epitope the same as the Tfh?

no! there is digestion in between.

57

what if you block B-cell endocytosis?

cannot be activated by T cells to make antibody

58

Which is a better APC DC or B cell?

DC because B cells don’t produce cytokines

59

T-Independent Antigens

don’t get help from T-cell for activation; it is a carbohydrate antigen with a large backbone. This clustered binding is enough signal for activation, but DOES NOT signal for class switching.

60

Lectin

proteins that recognize simple sugar sequences (mannose Binding protein) and bind to T-cell and B Cells to simulate binding to an antigen when they are not.

61

Mitogens

a type of lectin that causes mitosis.

62

cytokine storm

when a bunch of T-cells are activated at same time and leads to lethal pro-inflammatory response

63

Where does the thymus originate?

Epithelial from pharyngeal cleft, macrophages from marrow; thymocytes from bone marrow

64

Notch receptor

lymphoid cells from marrow get into cortex and interact with these receptors who guide them into the T-cell differentiation pathway

65

Pre-T cells

large in size, double negatives (CD4-/CD8-) that have activated Rag1 and Rag2 for VDJ rearrangement.

66

General process of T-cell maturation

Double negative to double positive to mature phenotype with single positive.

67

How selective is the T-cell development?

Very selective and the majority of T-cells are double positive; fewer than 2% are exported from thymus.

68

A T-cell must meet there requirements…

1) not recognize self to cause autoimmunity (MCH alone or MHC with self peptide) 2) not recognize free antigen 3) recognize antigenic peptide plus self MHC

69

Thymic Epithelial Cells

the cells responsible or secretion of T-cells in the thymus. The cells express on their surface MHC class I and II.

70

T-Cell selection has three options

Non-selection, positive selection, negative selection

71

Non-selection

no binding to MHC because it does not recognize self MHC and leads to apoptosis.

72

Positive Selection

CDR1 and CDR2 bind to alpha helices of MHC groove, but CDR3 does not interact with the endogenous peptide. This cell survives.

73

Negative Selection

TCR binds to MHC with self peptide with TOO high of affinity that results in T-cell activation.

74

if developing T-cell binds with all 6 CDRs…

it becomes an autoimmune

75

Fate of negative selection..

apoptosis or regulatory T-cells -(thymic or natural regulatory-Tcell)

76

Histocompatibility

outcome of grafts of living tissues between two individuals

77

Histocompatibility -2

Mouse; found on Ch17 that encodes tissue rejection factors (histocompatibility antigens).

78

What is the histocompatibility complex on human cells?

Human Leukocyte Antigen that has four importan loci A, B, D, and DR with incredible genetic polymophism.

79

What chromosome is HLA located on?

Ch6

80

What is the order of HLA?

closest to centromere Class II, Class III and then Class I (furthest from centromere)

81

Class II loci on HLA?

DP, DQ, DR (DR most important)

82

Class I loci on HLA?

B, C, A (most important A and B)

83

what loci do we need to know for transplants?

HLA A, B, DR

84

who are you more likely to match for antibodies with, your sister or your parent?

sister

85

Linkage disequilibrium

not much recombination in HLA genes!

86

anchor position

Sites of coordination in amino acid sequence between epitope and MHC

87

how many CDRs does T cell receptor use to bind to MHC?

4

88

how many CDRs does Tcell receptor use to bind to epitope?

2

89

Synergeic

isografts - grafts between genetically identical individuals

90

Allogeic

allografts - grafts between non-identical membrane of same species

91

Zenogeneic

Xencografts: grafts between members of different species

92

Hyperacute rejection of graft

graft is given to patient with pre-existing antibody. Antibody binds to endothelial cells on grafts blood vessel and activate complement and vasospasm. Graft never perfuses with blood.

93

Graft Rejection

Th1 recognizes MHC with foreign antigen (class II - DR); and secrete IFNgamma and bring in macrophages from the graft recipeient. Th1 secrets nearby CTL that is bound to MHC antigen of Class I (HLA-A and HLA-B) to kill target graft.

94

what if donor has identical Class I, but different class ii?

Th1 is activated, but not CTL. graft is still rejected but slower

95

What if donor is different Class I, but identical Class II?

no TH1 is activated, IL-2 will not be generated and few CTL is activated.

96

which match is more important Class I or II?

II

97

why do we respond more strongly to something that is not a pathogen (graft?)

receptor interacts with MHC in a slightly skewed position, and it thinks that the MHC is foreign and leads to destruction. The response is much slower if it is completely foreign (ie horse skin vs human)

98

HLA linked Diseases

modifications of self proteins create novel epitopes that associate strongly with MHC alleys.

99

natural, active immunity

immunity from exposure to a pathogen; longest lasting

100

Natural, passive immunity

enjoying the products of someone else immune response, pregnancy with IgG

101

Artifical Active immunity

immunization with vaccines, toxioid or antigen preparations

102

what does a dirty vaccine indicate?

more complex the mixture of molecules, the more likely to have unpleasant side effects

103

which provide better immunity - live or killed?

Live - infectious but attenuated.

104

Artificial, Passive Immunity

immune serum or purified antibodies to protect pt at risk of disease. We have antiwar for tetanus, rabies, hepatitis, chicken pox.

105

Toxoid

inactivate toxin that is almost always as effective at eliciting an immune response

106

Rabies Vaccine

active immunization with vaccine growth on human diploid cells; onset is slow so immunization can occur after exposure.

107

Diphtheria Vaccine

another toxoid

108

Pertussis vaccine

whooping cough; old vaccine was ineffective and has been replaced with acellular pertussis. But vaccine is present for strains in 1950, so not completely effective

109

Measles Vaccine

Rates increase significantly when immunizations go down; has extremely high heard immunization

110

Conjugate Vaccines

capsular carbohydrates are T-independent,b ut fail to generate an immune response. So if you couple a complex carb with a protein “carrier” to which Tfh cells could respond and aid B cell in making anti-carbohydrate IgG antibody.

111

what type of antibodies to B-cells make that are simulated by complex carbohydrates?

IgM only

112

what kind of antibody do the B-cells make when stimulated by conjugate vaccine?

IgG

113

what deos the protein antigen from a conjugate vaccine get loaded onto?

MHC Class II

114

Rotasheild

a vaccine against rotavirus that was taken off the market because it caused intussusception leading to necrosis and peritonitis due to hypertrophy of Peyer Patch.

115

Intussusception

telescoping of the bowel, risking blood supply loss causing necrosis and peritonitis

116

Adjuvants

substances added to vaccines to make them more immunogenic

117

how to adjuvants work?

cause an innate immune response that leads to more effect adaptive response.

118

most common adjuvant?

Alum

119

Alum

potassium aluminum sulfate adjuvant that mimics PAMPs to stimulated DC that drive Tfh.

120

Herd Effect

decrease in infection rate in the non-immune part of the herd.

121

Bacterial Immunity

extracellular bacteria are mostly combated by antibody; some are destroyed by C9 of the MAC; intracellular bacteria can survive in the macrophage but are killed if activated by Th1 cells.

122

Most important principle of immunity

humoral immunity may prevent illness, but once ill, T cell immunity is necessary for recovery.

123

Viral Immunity

local immunity (IgA) prevent the invasion of a virus; if it gets into blood it is stopped by IgG; if virus infects cells, T-Cell response is required and virus stimulates cytokine and chemokines to activate DC cells to pick up debris and process the peptides. Presented on Class II and cross-presented on Class I (for CTL)

124

what viruses are the hardest to deal with?

viruses that never appear in blood or lymph, but go latent (herpes)

125

Titer

reciprocal of the maximal diluation of patient’s serum that is still positive in some defined test.

126

DNA Vaccines

immunizing for the DNA that the antigen is encoded from so it would be translated in cell; advantages is quicker vaccine production, more stable faccine, and antigen would be made in body cells producing a natural, active immunity.

127

Monocytes/Macrophage - Time in marrow

Short time - 7 days

128

Monocytes/Macrophage - days in intravascular compartments

3-5 days

129

Monocytes/Macrophage - presence in tissues

days-months

130

Monocytes/Macrophage - histology

gray cyto, kidney shaped nulcues, changing morphology with tissues

131

Monocytes/Macrophage - function

1)move to sites of infec/inflam 2) filter (splenic macrophage) 3) processing and presenting antigens 4) clearance of apoptotic cells

132

why is clearance of apoptotic cells important

could cause severe inflammation and devastating tissue injury if not removed.

133

Neutrophil - Storage pool

10-14 days

134

Neutrophil - peripheral blood

6h

135

Neutrophil turnover

1-2 days

136

Neutrophil - function

innate immune system, non-specific defense against microbes, response to injury

137

what happens with neutrophils in tissue?

look for sights of potential infection and either kill the infection source or die themselves and get turned over my monocytes

138

what do neutrophils recognize?

they have no memory, but look for pattern recognition on microbes

139

Eosinophil - Bone marrow

influenced by IL-5

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Eosinophil - histological features

large eosinophilic granules, bi-lobed nuclei

141

where doe eosinophils reside?

external surfaces (tracheobronchial tree, GI tract

142

how long do eosinophils survive in periphery?

weeks

143

Eosinophil - Function

Phaocyte, role in allergy, paraste infection, response to tumor, immunoenhancing or immune suppressive

144

Basophil - histology

similar size to eosinophils, bi lobed nulcue, prominent purple/blue granules

145

what receptors are on basophils?

IgE

146

Basophil - function

pathophysiology hypersensitivity reactions

147

what cells make up cells in the progenitor compartment?

stem cells

148

what compartment are the myeloid precursors in?

mitotic compartment

149

what cells make up the myeloid precursors in the mitotic compartment

myeloblast, premyelocye, myelocyte

150

Process of myeloid precursors

proliferation and maturation

151

Percentage of myeloid precursors in mitotic compartment?

Myelocyte 16%>promyelocyte 4%> myeoblast 1%

152

How long to myeloid precursors stay in the mitotic compartment

10-14 days

153

what myeloid precursors are in the storage compartment?

Metamyelocytes, Band and sets

154

what process occurs in the storage compartment?

maturation

155

what is the % of the myeloid precursors in the storage compartment?

Band 30%> metamyelocyte 22% > Seg 21%

156

which is larger the mitotic compartment or storage compartment?

storage with 73%, while mitotic has 21%

157

what is the role of the myeloid precursors?

terminal cells of the neutrophil line. They are active and their job is not to proliferate, but finish maturing and form the storage compartment.

158

what is the function of the storage pool?

a collection of cells that can be localized to fight infection quickly.

159

Marginating pools

pools of neutrophils that hang on the edge of post capillary venules

160

What is the ration of neutrophils in peripheral blood and marginating pool?

1 to 1

161

how long do neutrophils live in peripheral blood

9-12 hours

162

how long to neutrophils live in the tissue?

around 24 hours. Before they undergo apoptosis and are turned over by monocytes

163

where are neutrophils depleted in neutropenia?

storage compartment

164

neutropenia - definition

decrease in absolute neutrophil count (including band and set polymorphonuclear leukocytes) below accepted age norm

165

General pattern for neutrophil count

greatest at newborn, but decrease after 1 week and up until 2 years, then increase during childhood to adulthood. 3000- 1,1000 — 1500

166

What things affect neutrophil norms

ethnic and racial groups have lower norms, and altitude above 5,000 Ft lowers the norm in infants

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implications of neutropenia

decreased delivery of neutrophils to tissue causes inability to resolve bacterial and fungal infections and localized infection

168

ANC of 1,500-1,000

No risk

169

AND of 1,000- 500

moderate to mild neutropenia

170

ANC 500-250

Moderate to severe neutropenia

171

what are the symptoms of moderate to severe neutropenia

skin, mucous membrane infections

172

ANC

severe neutropenia

173

Symptoms of severe neutropenia

sepsis, pneumonia

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what sites should you focus your physical exam on in neutropenia

teeth and gums, lymph nodes, hepatoslenomegaly, infected sites.

175

why should we look carefully at gums in neutropenia?

they are the only place on the body with direct penetration of mucosal barrier

176

how often would you perform a CBC and why in neutropenia

2x a week for 6 weeks; to see if neutropenia is persistent or intermittent. If it cycles, want to see how low the cycles and evaluate their absolute risk

177

What laboratory tests should you perform for neutropenia?

CBC (with retic), Bone marrow aspirate/biopsy, blood chemistries with LDH, uric Acid, alkaline phosphate, anti-neutrophil antibodies

178

primary decreased bone marrow reserve

all cells have gone away as in Kostmann, Scwachman-Diamond, cyclic neutropenia

179

Potions for a decreased marrow reserve?

primary disorders, part of complex phenotype combined with other diseases, Secondary disorders, or idiopathic

180

Secondary decreased bone marrow disorders

decrease in marrow due to chemo, drug induced, nutritional, viral infection

181

Normal Marrow Reserve

usually indicates an increased or normal production of neutrophils;. Due to immune or non-immune causes

182

Immune - normal marrow reserve

chronic benign neutropenia in childhood, autoimmune, alloimmune, drug induced, infection

183

Non-Immune normal marrow reserve

infection, hypersplenism, excessive margination

184

Infection associated neutropenia

a secondary cause; most common cause

185

Mechanisms of Infection associated neutropenia

Increased utilization, excessive complement mediated margination, marrow suppression/failure, unusual cytokine/chemokine induced margination, antibody production

186

infections associated with neutropenia

viral, bacterial, fungal, protozoal, rickettsial

187

clinical characteristics of antibiotics induced neutropenia

onset: days to weeks; acute symptoms, recurrence with small dose of antibodies; positive antibody test

188

Clinical characteristics of toxin neutropenia

onset is weeks to months, directly toxic to cells, rechallange with high dose may relapse after latent period

189

toxic drug that causes neutropenia

phenothiazine

190

Hypersensitivity in secondary neutropenia

onset is weeks to months, associcated with rash, fever, lymphadenopathy, hepatitis, nephritis, rarely aplastic anemia

191

drugs that cause hypersensitivity neutropenia

dilantin, phenobarbital

192

hypersensitivity vs. Toxic neutrophilia

toxic is directly toxic to cells; hypersensitivity elicits are more inflammatory response in nature and less toxic.

193

Mechanism of Cancer Chemo on secondary neutropenia

suppression of myelopoiesis

194

Findings of chemo induced neutropenia

other cytopenias present such as anemia, thrombocytopenia

195

Aplastic anemia induced secondary neutropenia mechanism

stem cell failure with other cytopenias present

196

Vitamin B12 and folate deficienty induced secondary neutropenia mechanism

ineffective hematopoeisis; intramedually death secondary to effets of deficient on replication

197

Vit B12 and Folate deficiency neutropenia findings

other cytopenias (thrombocytopenia) with megaloblast changes in marrow

198

Hypersplenism induced neutropenia mechanism

reticuloendothelial sequestration with other cytopennia

199

Causes of secondary neutropenia

Drug/toxin induced, chemo, aplastic anemia, Vitb12 and folate deficiency, hypersplenism

200

management of Secondary neutropenia

withdrawal of drugs or toxins, treatment of underlying disorder, replacement of deficienty, management of infections, support care with prophylactic, G-CSF in some conditions

201

G-CSF in treatment of secondary neutropenia

used in chemotherapy, primary cytokines to cause production in marrow

202

Marrow production in immune neutropenia

Normal to increased

203

Storage pool in immune neutropenia

normal to mildly decreased

204

Mechanism of immune neutropenia

increased turnover of neutrophils, vascular compartment decreased levels

205

Categories of Immune neutropenias

alloimmune, chronic benign childhood neutropenia, autoimmune, drug-induced

206

Fe saturation under 10%

iron deficiency

207

Anemia of Chronic inflammation iron saturation

10-20%

208

autoimmune neutropenia clinical features

may find ITP, AIHA, and other hematologic antibodies, immunodeficiency states, variable ANC, normal cellularity, late maturation arrest

209

Management of autoimmune neutropenia

treat primary autoimmune disorder, G-CSF may be helpful

210

Alloimmune neutropenia - mechanism

maternal: to neutrophil specific antigens, transplacental passage and bidning to neonatal neutrophils

211

Clinical features of alloillumine neutropenia

usually lasts 2-4 weeks; occasionally 3-4 months; may be asymptomatic, but could develop skin infections and rarely sepsis or meningitis. Confused with neutropenia by sepsis; myeloid hyperplasia with arrest at mature; small storage pool

212

In response to EPO injections, you would expect..

increased reticulocyte count, fall if MCV if Fe deficient, treatment is controversial whether it makes them feel better.

213

Management of alloimmune neutropenia

antibiotics and supportive care for infection, IVIG infusion, consider G-CSF for severe infection

214

pancytopenia

abnormal patelets, wbc, Rbc

215

MCV in sickle cell anemai

normal to high; except in sickle Beta than

216

what cells are involved primary neutropenia

stem cells and neutrophil precursors

217

dacryocytes

tear-dropped cells

218

anisocytosis

RBC unequal in size

219

polychromasia

bluish cells in reticulocytes

220

congenital disorders of Stem cells and myeloid precurosors

Congenital Neutropenia (Kostmann’s Syndrome), cyclic neutropenia, Shwachman-Diamond, Glycogenosis Ib, neutropenia with metabolic disease or immune disorders

221

Kostmann’s Syndrome - Mechanism

apoptosis of myeloid precursors associated with Elastase (ELA-2) mutations; sometimes defects in G-CSF receptor

222

Kostmann's Syndrome - inheritance

AD, AR, sporadic

223

Kostmann's Syndrome - Clinical Features

severe neutropenia in infancy, monocytosis, eosinophilia (putting out other cells, but no neutrophils), Myeloid hypoplasia in marrow; tno storage pool; recurrent purulent infections, risk of AML or myelodysplaisa

224

Why does Kostmann’s not have a storage pool?

arrest in maturation in promyelocyte and myelocyte stage (mitotic pool)

225

Treatment of Kostmann’s

aggressive treatment of infection, G-CSF 3-100 to keep ANC high, consider BMT for poor response to G-CSF

226

Cyclic Neutropenia Mechanism

ELA-2 mutation and apoptosis in precursors and cyclic hematopoesis

227

Inheritance of cyclic neutropenia

AD, Sporadic

228

Symptoms of cyclic neutropenia

fever, pharyngitis, aphthous ulcers, gingivitis, periodontitis

229

ITP

antibodies against platelets

230

how long do cycles last in cyclic neutropenia

21 +/- 3 days; the rest of the time neutrophils are normal

231

ANC in cyclic neutropenia

232

Schisotcytes

fragmented part of red blood cell, jagged with two pointed ends and no area of central pallor

233

Bone marrow in cyclic neutropenia

myeloid hypoplasia, arrest at myelocyte level during neutropenia

234

management of cyclic neutropenia

aggressive antibiotics, G-CSF daily to increase the low value of ANC so risk of infection decreases

235

Shwachman-Diamond Syndrome - mechanism

FAS associated premature apoptosis of marrow precursors; Decreased CD34+, marrow stromal defect

236

Shwachman-Diamond Syndrome - inheritance/genetics

AR, defect in SBDC gene on Ch17

237

Clinical features of sHwachman-Diamond

multisystem - neutropenia, pancreatic insufficiency, metaphyseal chondrodysplasia, dysmorphic features, 25% develop marrow aplasia, 25% develop MDS/AML; neutrophil dysfunction, recurrent infection

238

Management of SHwachman -Diamond

pancreatic enzyme replacement, aggressive antibiotic therapy, BMT for severe

239

Cartilage Hair hypoplasia

AR, short limbed dwarf, fine hair, neutropenia

240

Dyskeratosis Congenita

X linked, nail dystrophy, hyperpigmentation, marrow hypoplasia, neutropenia

241

Chronic idiopathic neutropenia mechanism

myeloid hypoplasia and maturation arrest at myelocyte, metamyelocyte or blast stage, no specific inheritance

242

Clinical features of idiopathic neutropenia

mod to severe neutropenia, recurrent infections, no neutrophil antibodies

243

management of idiopathic neutropenia

G-CSF

244

leukocytosis

increase in total WBC risk of infection, inflammation, malignancy, Increase in neutrophils (segs and band)

245

Neutrophilia causes

increased production, enhanced release of storage pool, decreased egress from ciruculation, reduced migration

246

Eosinophilia causes

Allergic disorder, dematits, parasitic infections, tumor, GI disorder, Hereditary, hyperesinophilic syndromes,

247

Neutrophilia definition

>7,500 cells/ul

248

Eosinophilia AEC

>350 /ul

249

Monocytosis AMC

>1,000 newborn; >500 children, adults

250

Causes of Monocytosis

hematologic disorders, collagen vascular disease, granulomatous disease, infection, malignant disease

251

Causes of monocytopenia

glucocorticoid admin, infection with endotoxemia

252

Basophilia causes

hypersensitivity reactions, inflammation and infection, myeloproliferative disease

253

Basophilopenia causes

glucocorticoid admin, thyrotoxicosis

254

where do lymphocytes enter the lymph node?

through afferent lymphatic vessels and into the sub capsular space.

255

how does lymph lead the lymph node?

efferent lymphatic vessels

256

Traveculae

short connective tissue in the lymph nodes that extend and divide the cortex.

257

Reticular fibers

are located in the cortex and paracortex, used by dendritic cells to hang on as they flow through the lymph node.

258

Lymphoid Follicle

In the cortex that houses B cells and germinal centers

259

Germinal centers

located in the follicle; regions of active cell proliferation and apoptosis. Made up of B cells, dividing B cells, and macrophages.

260

Composition of cortex vs. paracortex lymph node

Cortex is B cells; Parapcortex is T-Cells (with some B)

261

Lymph node Medulla

region of loosely arranged cords of cells containing B cells, a few T cells and plasma cells.

262

High Endothelial Venule

Vessels that have endothelial bulges that act as sites of recognition and diapedesis of lymphocytes from blood into the lymphatic node space. Notable for their rounded protrusions into the lumen

263

Primary Follicle of Lymph Node

also called primary lymphatic nodule; not vernal in center of follicle, but tight knit cells.

264

What are the different layers of the germinal center

inner follicle cells, mantle zone of closely packed lymphocytes and marginal zode of looser packed lymphocytes.

265

What cells are in the follicle center? be specific

Centroblasts and centrocytes (plasma cells)

266

Tingible body macrophages

engulf apoptotic cells

267

where do most macrophages exist in the lymph node?

subcapsular space

268

Trabeculae of the thymus

the bilobed thymus is ensheathed in connective tissue septa that divides the tissue into pseudo lobules

269

Thymus cortex

located closest to the capsular sheath, more densly packed set of developing thymocytes or T-cells (appears darker with nucleus).

270

where do mature thymocyte precursors reside in the thymus?

medulla

271

What defines the cortex vs medulla of the thymus?

density of the T-cell packing. Cortex is densly packed with immature thymocytes. Medulla is loosely packed more mature thymocytes

272

Where are the blast cells in the thymus

just beneath the capsular, give rise to the immature thymocytes in the cortex.

273

IF T cells return to the thymus, where do they congregate?

Medulla

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Stromal Cells

Epithelioreticular cells, cells that are epithelial-like, dendritic cells, or macrophages. provide matrix and envelop developing thymocytes in large folds as T-cell matures from cortex towards medulla.

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Stromal cell Role

negative and positive T- cell selection, secrete cytokines and thymic hormones important for thymocyte maturation; DIFFERENTIATIO OF SELF FROM NON_SELF

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Does the thymus contain reticular fibers?

No, because there is no bulk flow through it. Stromal cells provide support and have Hassal’s Corpuscles

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Hassal’s Corpuscles

concentric layers of reticular cells in Thymus medulla. Produce thymic stromal lymphoprotin that suppressing autoimmune events.

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How does blood get into the thymus?

enter through small arteries through outer capsule and penetrate into thymus and spread within CT septa between lobules.

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Blood thymus barrier

Combined layers of ensheathed endothelioreticular cells that are connected by tight junctions in vessels

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Importances of Blood Thymus Barrier

so maturing thymocytes are not exposed to any molecules circulating in blood.

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what is the arteriole blood supply to the thymus?

internal thoracic and inferior thyroid

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Where is the blood thymus barrier in the thymus?

cortex, but not medulla.

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what is unique to the thymus

there is no afferent lymphatics

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what is unique to the spleen

open blood circulation through porous splenic sinuses.

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what artery supplies the spleen?

splenic artery

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what vein drains the sleep?

splenic vein.

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Blood flow in the spleen

in through the splenic artery and then branches to central arterioles that run deeper into the spleen, but as they get deeper then are lined with discontinuous endothelial cells, allowing platelets, RBC and leukocytes to enter sinuses that contain loosely packed arrangements of cells

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periarteriolar lymphoid sheath

lymphocid tissue that is arranged around central arterioles that is composed of T-cells

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Red Pulp

loosely-arrnaged channels/sinuses that blood flow through after leaving central arterioles. (the space)

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White pump

more organized lymphoid tissue in spleen, found directly outside the central arterioles.

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Reticular fibers of spleen

found primarily in red pump

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Macrophages in spleen location

in senescent red cells and platelets

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Macrophages function in spleen

moging senescetn RBCs and platelets, recycing iron, and converting hemoglobin in bilirubin.; removal of debris and bacteria

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Mucosal-Associated Lymphoid Tissue examples

tonsils (palatine, lingual), pharyngeal (adenoids), esophageal nodules, Bronchial nodes and large number of cells might increase in abundance and size as get distal.

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Peyer patch

nodules located in the muscosa and submucosa of the colon

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M cells

involved in MALT, special surface epithelial cells found in small intestine and respiratory tract and deliver antigen to underlying lymphoid tissue.

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what antibodies are involved in MALTs?

IgA; are secreted across mucosal epithelia and in bile. Activated B-cells that were exposed to antigen in MALT, enter lymph, undergo mitotic expansion in mesenteric lymph node, flow out thoracic duct and enter blood, and then pass through underlying CT at any region in intestine to become antibody secreting plasma cells.

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component cells of MALT

T and B cells, plasma cells, macrophages

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Structures of MALTs

lymphoid tissue is not packaged within capsule CT

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distribution of lymphocytes in MALT

larger, dividing immatre lymphocytes in center and smaller,, more dense lymphocytes in periphery.

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Challenged white pulp nodules

clearly visible germinal center in the spleen.

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Periarteriolar lymphatic sheath

consist of T-cells

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Unchallenged White Pulp Nodules

clearly visible nodule in spleen, made of B cells. Non dividing.

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General outline of innate immune system

Infection/tissue damage triggers through TLR receptors inflammatory mediators that case vascular dilation, permeability, and emigration of leukocytes which trigger emigration of phagocytes and monocytes in innate response and EVENTUALLY emigration of monocytes and lymphocytes in adaptive response

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Receptors in Rolling/Adherence

Sialyx LeX, L-Selectin, B2 integrins (CD11b/CD18)

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Biochemical process of the Rolling/Adherence Receptors

PM associated, granule containing store recpetors, actin cytoskeleton and accessory proteins

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Chemotaxis Receptors

C5a, N-formyl oligopeptides, lipid compounds, GM-CSF, IL8, TNFalpha

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Chemotaxis Receptors organlles/biochemical process

PM, actin and accessory proteins, granules (specific), glycolysis as energy source

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Ingestion Receptors

FcR1,2,3; C3b, CR-1

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Ingestion receptors organelles and biochemical process

PM, actin cyto and accessory proteins, glycolysis

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Degranulation/Killin Receptors

FcR1, 2, 3, C3b, CR-1

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Degranulation Killing Organelles and biochemical process

PM, actin ctyoskeleton, Azurophilic and specific granules; phagolysosomal formation, glycolysis

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Respiratory Burst

the processing of taking oxygen and making oxygen radicals that are toxic and can interact with phagocytosed substane for degradation

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Where do the electrons originate to make Superoxide radical?

NADPH

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what is protective of oxygen radicals

SOD catalase, GHS

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NOX2

Also known as GP91Phox; protein that uses NADPH to transfer electrons to make superoxide

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GP91Phox

works with P22phox on membrane, to interact with cytosolic PHox proteins in complex to take NADPH and electrons to make superoxide.

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Screening of Innate Immune Disorders

CBC, Diff, morphology, Bactericidal activity, chemotaxis activity, Expression of antibodies, DHR oxidation

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Bactericidal Activity

Mix cells with bacteria and see how they kill it

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Chemotaxis Assay

put cells above filter and in bottom chamber, put C5a and incubate and see # and distance through filter

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DHR

A compound that oxidizes dye to fluorescent compound. If you treat with bacteria to enlist more oxygen radicals, fluorescence should increase

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Leukocyte Adhesion Deficiency 1 - clinical

Soft tissue infections (skin, mucosa), gingivitis, mucositis, periodontist, delayed separation of umbilical cord, poor wound healing

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Leukocyte Adhesion Deficiency 1 - Functional Defect

Decreased adherence of neutrophils to endothelial surface, defect in movement of neutrophils to tissue. Neutrophilia

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Leukocyte Adhesion Deficiency 1 - molecular Defect

Complete or partical deficiency of CD18; AR

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Chediak-Higashi Syndrome - Clinical

Oculocuatenous albinism (white forelock), nystagmus photophobia (light bothers eye), recurrent infections, fever, hepatosplenomegaly, hemophagocytic disorder, neurodegenerative syndrome

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Chediak-Higashi Syndrome - Functional defect

Giant granules in leukocytes, defect in movement and decreased degranulation and microbicidal activity. Neutropenia

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Chediak-Higashi Syndrome - Molecular Defect

alterations in membrane fusion by forming leaky granules. Altered MT assembly. CHS1 gene, AR

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Myeloperoxidase Defieciency - Clinical Presentation

Generally healthy; increased fungal infections with diabetics

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Myeloperoxidase Defieciency - Functional Defect

Partial/complete deficiency of myeloperoxidase (converts Superoxide to hydrogen peroxide); defect in killing bacteria, significant defect in killing candida

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Myeloperoxidase Defieciency - Molecular Defect

Post translational modification defect in protein processing; AR

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Myeloperoxidase

enzyme that converts superoxide to hydrogen peroxide

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Chronic Granulomatous Disease - Clinical

Recurrent purulent infections with catalase positive bacteria, fungi on skin and mucosa. Deep infections in lung, spleen, lymph nodes, bones

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CGD - Functional Defect

Neutrophilia, normal adherence and chemotaxis, ingestion and degranulation. Defect in oxidase enzyme. No toxic oxygen metabolites produced, so absent or reduced ability to kill coagulase positive bacteria and fungi.

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CGD - molecular defects

Absent Cyto B558 (Gp91Phox complex); absent P22Phox; Absent p47 Phox; Absent p67Pox; Mild X-linked variant in G-6-PD deficiency in PMNs

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Cyto B558 absence- inheritance

Sex linked recessive

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p22Phox - inheritance

AR

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p47phox

AR

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Characteristics of phagocyte disorder

1) High rate of bacterial or fungal infections 2) infections against atypical pathogens, 3) exception severity of infection; 5) periodontal disease in children 6) infections occur at interface area, more common than deep (though those do occur)

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what activate complement system?

lectins, bacterial protein, surface bound IgG

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Deficiency in C1q, C2, C4 complications

SLE (lupus), autoimmunity, inflammatory vascular disease

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Deficiency in C3 complication

Recurrent bacterial infections

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Deficiency in C5-C9 complications

severe infection with neisseria (meningaococcus)

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Management of innate immune disorders

1) anticipate infection and aggressive attempts to define causative event; 2) surgical procedures to be both diagnostic and therapeutic 3) prompt broad spectrum antibiotics, switch when microbial diagnosis is made 4) some may need 3ug/kg/day 5)some need prophylactic antibiotics

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Transplantation of neutropenia

hematopoetic stem cell might be used to reconstitue myeloid function if good match