Immunology - First Aid Flashcards Preview

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Flashcards in Immunology - First Aid Deck (339):
1

LN Follicle is the site of...

B-cell localization and proliferation.

2

In the outer cortex, primary follicles are...

dense and dormant.

3

Secondary follicles have...

pale central germinal centers.

4

The LN medulla consists of...

medullary cords (closely packed lymphocytes and plasma cells and medullary sinuses).

5

Medullary sinuses communicate with...

efferent lympmhatics and contain reticular cells and macrophages.

6

The LN paracortex houses...

T cells. It is the region of the cortex between the follicles and medulla.

7

The paracortex contains high endothelial venules through which...

T and B cells enter from the blood.

8

The paracortex is not well developed in...

pts with DiGeorge syndrome.

9

The paracortex enlarges in...

an extreme cellular immune response (ex. viral infection).

10

Cervical LNs drain...

the head and neck.

11

Hilar LNs drain...

the lungs.

12

Mediastinal LNs drain...

the trachea and esophagus.

13

Axillary LNs drain...

the upper limb, breast, and skin above the umbilicus.

14

Celiac LNs drain...

the liver, stomach, spleen, pancreas and upper duodenum.

15

Superior mesenteric LNs drain...

the lower duodenum, jejunum, ileum, and colon to the splenic flexure.

16

Inferior mesenteric LNs drain...

the colon from the splenic flexure to the upper rectum.

17

Internal iliac LNs drain...

the lower rectum to teh anal canal (above pectinate), bladder, vagina and prostate.

18

The para-aortic LNs drain...

testes, ovaries, kidneys and uterus.

19

The superficial inguinal LNs drain...

the anal canal (below pectinate), and skin below the umbilicus (except popliteal).

20

The popliteal LNs drain...

the dorsolateral foot and posterior calf.

21

The right lymphatic duct drains...

the right side of the body above the diaphragm.

22

The thoracic duct drains...

everything else into the junction of the left subclavian and internal jugular veins.

23

The sinusoids of the spleen are...

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

24

In the spleen, T cells are found in...

the periarterial lymphatic sheath within the white pulp.

25

In the spleen, B cells are found in...

follicles within the white pulp.

26

The marginal zone of the spleen is in between the...

red pulp and white pulp, contains APCs and specialized B cells, and is where APCs present blood-borne antigens.

27

Macrophages in the spleen act to...

remove encapsulated bacteria.

28

Splenic dysfunction (postsplenectomy, sickle cell) leads to...

decreased IgM which leads to decreased complement activation, which leads to decreased C3b opsonization which leads to increased susceptiblity to encapsulated organisms.

29

Encapsulated organisms

SHiNE SKis
1. Strep pneumo
2. H. influenzae
3. N. meningitidis
4. E. coli
5. Salmonella
6. Klebsiella
7. group B Strep

30

Postsplenectomy Findings

1. Howell-Jolly bodies (nuclear remnants)
2. target cells
3. thrombocytosis

31

The thymus is the...

site of T-cell differentiation and maturation. It is encapsulated.

32

The thymus comes from the...

epithelium of the 3rd pharyngeal pouches. Contains lymphocytes of mesenchymal origin.

33

The thymus cortex is...

dense with immature T cells.

34

The thymus medulla is...

pale with mature T cells and Hassall corpuscles containing epithelial reticular cells.

35

Components of Innate Immunity

-neutrophils
-macrophages
-monocytes
-dendritic cells
-NK cells
-complement

36

Components of Adaptive immunity

-T cells
-B cells
-circulating antibodies

37

Innate immunity resistance

-germline encoded
-resistance persists through generations, does not change within an organism's lifetime

38

Adaptive immunity resistance

-variation through VDJ recombination during lymphocyte development
-microbial resistance not heritable

39

Innate immunity response to pathogens

-nonspecific
-occurs rapidly (mins to hrs)

40

Adaptive immunity response to pathogens

-hihgly specific, refined over time
-develops over long periods; memory response is faster and more robust

41

Physical barriers of the innate immune resposne

-epithelial tight junctions
-mucus

42

Innate immunity secreted proteins

lysozyme
complement
CRP
defensins

43

Adaptive immunity secreted proteins

immunoglobulins

44

Innate immunity key features in pathogen recognition

-TLRs: pattern recognition receptors that recgonize PAMPs

45

examples of PAMPs include...

LPS (gram negative bacteria)
flagellin (bacteria)
ssRNA (viruses)

46

Adaptive immunity key features in pathogen recognition

Memory cells: activated B and T cells; subsequent exposure to a previously encountered antigen leads to a stronger, quicker immune response

47

MHC is encoded by...

HLA genes and presents antigen fragments to T cells and binds TCRs.

48

MHC I loci

HLA-A
HLA-B
HLA-C

49

MHC II loci

HLA-DR
HLA-DP
HLA-DQ

50

MHC I Binding

TCR and CD8

51

MHC II Binding

TCR and CD4

52

MHC I Expression

expressed on all nucleated cells; not expressed on RBCs

53

MHC II expression

only on APCs

54

MHC I Function

present endogenously synthesized antigens (viral) to CD8 cytotoxic T cells

55

MHC II Function

present exogenously synthesized protesin (bacterial proteins, viral capsid proteins) to T helper cells

56

MHC I Antigen loading

antigen peptides loaded onto MHC I in RER after delivery via TAP peptide transporter

57

MHC II Antigen loading

antigen loaded following release of invariant chain in an acidified endosome

58

MHC I mode of transport to cell surface

Beta-2-microglobulin

59

HLA-A3 association

hemochromatosis

60

HLA-B27 association

Psoriatic arthritis
Ankylosing spondylitis
arthritis of IBD
Reactive arthritis

61

HLA-DQ2/DQ8 association

celiac disease

62

HLA-DR2 association

MS
hay fever
SLE
Goodpasture

63

HLA-DR3 association

T1DM
SLE
Graves

64

HLA-DR4 association

Rheumatoid arthritis
T1DM

65

HLA-DR5 association

Pernicious anemia (leading to B12 deficiency)
Hashimoto

66

NK cells use...

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

67

Activity of NK cells is enhanced by...

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

68

NK cells are induced to kill when exposed to...

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

69

NK cells also kill via...

antibody-dependent cell-mediated cytotoxicity (CD16 binds Fc region of bound Ig, activating the NK cell).

70

Major functions of B cells (3)

1. recognize antigen
2. produce antibody
3. maintain immunologic memory

71

To recognize antigen, B cells...

undergo somatic hypermutaiton to optimize antigen specificity.

72

To proudce antibody, B cells differentiate into...

plasma cells to secrete specific Igs.

73

To maintain immunologic memory, memory B cells...

persist and accelerate future response to Ag.

74

CD4 T cells function to...

help B cells make antibody and produce cytokines to activate other cells of the immune system.

75

CD8 T cells function to...

kill virus-infected cells directly.

76

Other T cell functions

-delayed cell-mediated hypersensitivity (type IV)
-acute and chronic cellular organ rejection

77

Positive selection occurs in the...

thymic cortex. T cells expressing TCRs capable of binding surface self MHC molecules survive.

78

Negative selection occurs in the...

medulla. T cells expressing TCRs with high affinity for self antigen undergo apoptosis.

79

Antigen presenting cells (3)

1. B cells
2. macrophages
3. dendritic cells

80

Two signals are required for (3):

1. T cell activation
2. B cell activation
3. class switching

81

Naive T cell activation (4 steps)

1. Foreign body is phagocytosed by the dendritic cell.
2. Foreign Ag is presented on MHC II and recognized by TCR on Th (helper) cell. Ag is presented on MHC I to Tc (cytotoxic) cells. (signal 1)
3. Costimulatory signal is given by interaction of B7 and CD28. (signal 2)
4. Th cell activates and produces cytokines. Tc cell activates and is able to recognize/kill virus-infected cells.

82

B cell activation and class switching (4 steps)

1. Helper T cell activation
2. B cell receptor-mediated endocytosis; foreing antigen is presented on MHC II and recognized by TCR on Th cell (signal 1).
3. CD40 receptor on B cell binds CD40 ligand on Th cell (signal 2).
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.

83

Th1 cell secretes...

IFN-gamma.

84

Th1 cell activates...

macrophages and cytotoxic T lymphocytes.

85

Th1 cell is inhibited by...

IL-4 and IL-10 (from the Th2 cell).

86

Th2 cell secretes...

IL-4, IL-5, IL-6, and IL-13.

87

Th2 cell recruits...

eosinophils for parasite defense and promotes IgE production by B cells.

88

Th2 cell is inhibited by...

IFN-gamma (from the Th1 cell).

89

Macrophage-lymphocyte interaction

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

90

Cytotoxic T cells kill..

virus-infected, neoplastic, and donor graft cells by inducing apoptosis.

91

Cytotoxic T cells release...

cytotoxic granules containing preformed proteins:
1. perforin that helps deliver content of granules into target cell
2. granzyme B = a serine protease that activates apoptosis inside a target cell
3. antimicrobial that induces apoptosis

92

Regulatory T cells help maintain specific immune tolerance by...

suppressing CD4 and CD8 T-cell effector functions.

93

Regulatory T cells are identified by expression of...

cell surface markers CD3, CD4, CD25 (alpha chain of IL-2 receptor) and transcription factor FOXP3.

94

The part of antibody that recognizes antigen is...

variable part of L and H chains.

95

Fc portion of IgM and IgG acts to...

fix complement.

96

Heavy chain contributes to...

Fc and Fab fractions.

97

Light chain contributes to...

Fab fraction only.

98

Fab is the...

antigen binding fragment.

99

Fab determines...

the idiotype: it is a unique antigen-binding pocket. Only 1 antigenic specificity is expressed per B cell.

100

Fc is the...

constant region with a carboxy terminal. It binds complement and has carbohydrate side chains.

101

Fc region determines...

isotype (IgM, IgD, etc.)

102

Antibody diversity is generated by (4):

1. random recombination of VJ (light chain) or VDJ (heavy chain) genes
2. random combination of heavy chains
3. somatic hypermutation (following Ag stimulation)
4. addition of nucleotides to DNA during recombination by terminal deoxynucleotidyl transferase

103

Mature lymphocytes express...

IgM and IgD on their surfaces.

104

Mature B lymphocytes may differentiate in...

germinal centers of LNs by isotype switching (gene rearrangement; mediated by cytokines and CD40 ligand) into plasma cells that secrete IgA, IgE or IgG.

105

IgG is the main antibody in...

secondary (delayed) response to an antigen. It is the most abundant isotype in the serum.

106

Actions of IgG

-fixes complement
-crosses placenta to provide infants w/ passive immunity
-opsonizes bacteria
-neutralizes bacterial toxins and viruses

107

IgA prevents...

attachment of bacteria and viruses to the mucous membranes. It does NOT fix complement.

108

IgA crosses epithelial cells by...

transyctosis. It is a monomer in circulation and a dimer when secreted.

109

IgA is the most..

produced antibody overall but is released into secretions (tears, saliva, mucus) and early breast milk (colustrum).

110

IgA picks up a...

secretory component from epithelial cells before secretion.

111

IgM is produced in...

the primary (immediate) response to an antigen. It fixes complement but does not cross the placenta.

112

Antigen receptor for IgM is on...

surface of B cells.

113

Form of IgM

monomer on B cell or pentamer when secreted; the pentamer shape allows it to efficiently trap free Ags out of tissue while the humoral response evolves.

114

IgD is found...

on the surface of many B cells and in the serum.

115

IgE binds...

mast cells and basophils. Has the lowest concentration in serum.

116

When exposed to an allergen, IgE will..

cross-linke mediating immediate (type I) hypersensitivity through the release of inflammatory mediators such as histamine.

117

IgE mediates immunity to...

worms by activating eosinophils.

118

Thymus-independent antigens are...

antigens lacking a peptide component (ex. lipopolysaccharides from gram-negative bacteria).

119

Thymus-independent antigens cannot be...

presented by MHC to T cells. They are weakly or non-immunogenic.

120

Vaccines for thymus-independent antigens often require...

boosters. (ex. pneumococcal polysaccharide vaccine).

121

Thymus-dependent antigens are...

antigens containing a protein component (ex. diphtheria vaccine).

122

As a result of direct contact between B cells with thymus-dependent antigens and Th cells, there is...

class switching and immunologic memory.

123

Acute phase reactants are...

factors whose serum concentrations change significantly in response to inflammation.

124

Acute phase reactants are produced by the...

liver in both acute and chronic inflammatory states.

125

Acute phase reactants are induced by...

IL-6, IL-1, TNF-alpha and IFN-gamma.

126

Positive Acute phase reactants

-serum amyloid A
-C-reactive protein
-ferritin
-fibrinogen
-hepcidin

127

Negative acute phase reactants

-albumin
-transferrin

128

Serum amyloid A

prolonged elevation can lead to amyloidosis

129

C-reactive protein

opsonin; fixes complement and facilitates phagocytosis
(measured clinically as a sign of ongoing inflammation)

130

Ferritin

binds and sequesters iron to inhibit microbial iron scavenging

131

Fibrinogen

coagulation factor; promotes endothelial repair; correlates with ESR

132

Hepcidin

prevents release of iron bound by ferritin leading to anemia of chronic disease

133

Albumin

reduction during acute phase reaction acts to conserve amino acids for positive reactants

134

Transferrin is downregulated in the acute phase to be...

internalized by macrophages to sequester iron.

135

Complement is a system of...

interacting plasma proteins that play a role in innate immunity and inflammation. MAC defends against gram-negative bacteria.

136

Activation of the Complement pathways

Classic pathway - IgG or IgM mediated
Alternative pathway - microbe surface molecules
Lectin pathway - mannose or other sugars on microbe surface

137

Functions of complement

C3b - opsonization
C3a, C4a, C5a - anaphylaxis
C5a - neutrophil chemotaxis
C5b-9 - cytolysis by membrane attack complex

138

The two primary opsonins in bacterial defense are...

C3b and IgG. C3b also helps clear immune complexes.

139

Complement activation on self cells is prevented by...

decay-accelerating factor (DAF aka CD55) and C1 esterase inhibitor.

140

C1 esterase inhibitor deficiency causes...

hereditary angioedema. ACE inhibitors are contraindicated.

141

C3 deficiency increases risk of...

severe, recurrent pyogenic sinus and respiratory tract infections. It increases susceptibility to type III HSRs.

142

C5-C9 deficiencies increase...

susceptibility to recurrent Neisseria bacteremia.

143

DAF deficiency causes...

complement-mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria.

144

Cytokines secreted by macrophages

IL-1
IL-6
IL-8
IL-12
TNF-alpha

145

IL-1 is an...

endogenous pyrogen (aka osteoclast-activating factor).

146

IL-1 causes...

fever and acute inflammation. It activated endothelium to express adhesion molecules and induces chemokine secretion to recruit leukocytes.

147

IL-6 is an...

endogenous pyrogen that causes fever and stimulates production of acute phase reactants.

148

IL-8 is the major...

chemotactic factor for neutrophils.

149

IL-12 induces...

differnetiation of T cells into Th1 cells and activates NK cells.

150

TNF-alpha mediates...

septic shock, activates the endothelium and causes leukocyte recruitment, vascular leak.

151

Cytokines secreted by all T cells

-IL-2
-IL-3

152

IL-2 stimulates...

growth of helper, cytotoxic and regulatory T cells

153

IL-3 supports the...

growth and differentiation of bone marrow stem cells. It functions like GM-CSF.

154

Cytokine secreted by Th1 cells...

IFN-gamma.

155

IFN-gamma has...

antiviral and antitumor properties. IT activates NK cells to kill virus-infected cells. It increases MHC expression and antigen presentation in all cells.

156

Cytokines secreted from Th2 cells

IL-4
IL-5
IL-10

157

IL-4 induces...

differentiation into Th2 cells. It promotes growth of B cells and enhances class switching to IgE and IgM.

158

IL-5 promotes...

differentiation of B cells. It enhances class switching to IgA. Stimulates growth and differentiation of eosinophils.

159

IL-10 modulates...

inflammatory response. It inhibits the actions of activated T cells and Th1.

160

Interferon alpha and beta are a part of the...

innate host defense against both RNA and DNA viruses.

161

Interferons are...

glycoproteins synthesized by viral-infected cells that act locally on uninfected cells "priming" thme for viral defense.

162

When a virus infects a cell "primed" by interferons, the viral dsRNA activates:

1. RNAase L (leading to degradation of viral/host mRNA
2. protein kinase (leading to inhibition of viral/host protein synthesis)

*This essentially results in apoptosis, thereby interrupting viral amplification.

163

T cell surface proteins

1. TCR (binds antigen-MHC complex)
2. CD3 (associated with TCR for signal transduction)
3. CD28 (binds B7 on APC)

164

Helper T cell surface proteins

CD4
CD40 ligand

165

Cytotoxic T cell surface protein

CD8

166

B cells surface proteins

-Ig (binds antigens)
-CD19, CD20, CD21 (receptor for EBV), CD40
-MHC II, B7

167

Macrophage surface proteins

-CD14, CD40
-MHC II, B7
-Fc and C3b receptors (enhanced phagocytosis)

168

NK cell surface proteins

-CD16 (binds Fc of IgG)
-CD56 (unique marker for NK)

169

Anergy is when...

self-reactive T cells become nonreactive without a costimulatory molecule.

170

Superantigens (from S. pyogenes and S. aureus) act to...

cross-link the beta region of the T-cell receptor to the MHC class II on APCs. They can activate any T cell leading to a massive release of cytokines.

171

Endotoxins/lipopolysaccharide (gram-negative bacteria) directly stimulate...

macrophages by binding to endotoxin receptor CD14; Th cells are not involved.

172

Classic examples of Antigenic variation (5)

1. Salmonella (2 flagellar variants)
2. Borrelia (relapsing fever)
3. Neisseria gonorrhae (pilus protein)
4. influenza virus (major shift, minor drift)
5. Trypanosomes (programmed rearrangement)

173

Some mechanisms for variation include...

DNA rearrangement and RNA segment reassortment.

174

Examples of passive immunity

-IgA in breast milk
-maternal IgG crossing placenta
-antitoxin
-humanized monoclonal antibody

175

Examples of active immunity

natural infection
vaccines
toxoid

176

Pts are given preformed antibodies (passive immunity) after exposure to...

tetanus toxin, botulinum toxin, HBV or Rabies.

177

Combined passive and active immunizations can be given for...

hep B or rabies exposure.

178

Live attenuated vaccine

microorganism loses its pathogenicity but retains capacity for transient growth within the inoculated host. Mainly induces a cellular response.

179

Pros of live attenuated vaccine

induces strong, lifelong immunity

180

Cons of live attenuated vaccine

may revert to virulent form, often contraindicated in pregnancy and immune deficiency

181

Examples of live attenuated vaccine

-mumps
-measles
-rubella
-polio (Sabin)
-influenza (intranasal)
-varicella
-yellow fever

182

Inactivated or killed vaccine

pathogen is inactivated by heat or chemicals; maintaining epitope structure on surface Ag is important; humoral immunity is induced.

183

Pros of inactivated/killed vaccine

stable and safer than live vaccines

184

Cons of inactivated/killed vaccine

weaker immune response, boosters usually required

185

Examples of inactivated/killed vaccine

-cholera
-hep A
-polio (salk)
-influenza (injection)
-rabies

186

Type I Hypersensitivity is...

anaphylactic and atopic. Free antigen cross-links IgE on presensitized mast cells and basophils, triggering immediate release of vasoactive amines that act at postcapillary venules.

187

In Type I HSR, the rxn develops...

rapidly after Ag exposure because of preformed Ab. The delayed response follows due to production of arachidonic acid metabolites (leukotrienes).

188

Type I HSR test

skin test specific for IgE

189

Type II HSR is...

cytotoxic (antibody mediated) - IgM, IgG bind to fixed Ag on "enemy" cell, leading to cellular destruction.

190

3 mechanisms of Type II HSR

1. opsonization leading to phagocytosis or complement activation
2. complement-mediated lysis
3. antibody-dependnet cell-mediated cytotoxicity, usually due to NK cells or macrophages

191

In Type II HSR, antibody and complement lead to...

MAC.

192

Test for Type II HSR

direct and indirect Coombs

193

Direct Coombs

detects antibodies that have adhered to pt's RBCs

(ex. test an Rh+ infant of an Rh- mother)

194

Indirect Coombs

detects antibodies that can adhere to other RBCs

(ex. test an Rh- woman for Rh+ antibodies)

195

Type III HSR is...

immune complex - antigen-antibody (IgG) complexes activate complement which attracts neutrophils; neutrophils release lysosomal enzymes.

196

Serum sickness is...

an immune complex disease (type III) in which antibodies to the foreign proteins are produced (takes 5 days). IMmune complexes forma and are deposited in membranes where they fix complement (leading to tissue damage).

197

Most serum sickness is now caused by...

drugs acting as haptens. Fever, urticaria, arthralgias, proteinuria, lymphaadenopathy 5-10 days after exposure.

198

Arthus rxn is a...

local, subacute antibody-mediated HSR type III. Intradermal injection of antigen induces antibodies, which form antigen-antibody complexes in the skin.

199

Arthus rxn is characterized by...

edema, necrosis, and activation of complement.

200

Test for Arthus rxn (or Type III HSRs)

immunofluorescent staining

201

Type IV HSR is a...

delayed (T cell mediated) type. Sensitized T lymphocytes encoutner antigen and then release lymphokines which leads to macrophase activation.

NO antibody involved.

202

Test of Type IV HSR

patch test, PPD

203

Examples of Type I HSR

1. anaphylaxis (bee sting, food/drug allergy)
2. allergic/atopic disorders (rhinitis, hay fever, eczema, hives, asthma)

204

Presentation of Type I HSR

immediate, anaphylactic, atopic

205

Presentation of Type II HSR (8)

1. autoimmune hemolytic anemia
2. pernicious anemia
3. ITP
4. erythroblastosis fetalis
5. rheumatic fever
6. goodpasture syndrome
7. bullous pemphigoid
8. pemphigus vulgaris

206

Presentation of Type II HSR

disease tends to be specific to tissue or site where antigen is found

207

Type III HSR examples (5)

1. SLE
2. polyarteritis nodosa
3. poststreptococcal glomerulonephritis
4. serum sickness
5. arthus rxn

208

Type III HSR presentation

associated with vasculitits and systemic manifestations

209

Type IV HSR examples (5)

1. MS
2. Guillain-Barre
3. GVHD
4. PPD (test for TB)
5. Contact dermatitis (poison ivy, nickel allergy)

210

Allergic rxn to blood tranfusion pathogenesis

Typer I HSR against plasma proteins in transfused blood.

211

Allergic rxn to blood transfusion presentation

urticaria, pruritis, wheezing, fever. Treat with antihistamines.

212

Anaphylactic rxn to blood transfusion pathogenesis

severe allergic rxn; IgA-deficient individuals must receive blood products that lack IgA

213

Anaphylactic rxn to blood transfusion presentation

dyspnea, bronchospasm, hypotension, respiratory arrest, shock

214

Febrile nonhemolytic transfusion rxn pathogenesis

Type II HSR. Host antibodies agaisnt donor HLA Ags and leukocytes.

215

Febrile nonhemolytic transfusion rxn presentation

fever, HAs, chills, flushing

216

Acute hemolytic transfusion rxn pathogenesis

Type II HSR. Intravascular hemolysis (ABO blood group incompatibility) or extravascular hemolysis (host Ab rxn against foreign antigen on donor RBCs).

217

Acute hemolytic trasnfusion rxn presentation

fever, hypotension, tachypnea, tachycardia, flank pain, hemoglobinemia (intravascular), and jaundice (extravascular hemolysis).

218

Anti-Ach receptor

myasthenia gravis

219

Anti-basement membrane

goodpasture syndrome

220

anti-cardiolipin, lupus antigocagulant

SLE, antiphospholipid syndrome

221

anticentromere

limited sclerosderma (CREST syndrome)

222

anti-desmoglein

pemphigus vulgaris

223

Anti-dsDNA, anti-Smith

SLE

224

anti-glutamate decarboxylase

T1DM

225

anti-hemidesmosome

bullous pemphigoid

226

antihistone

drug-induced lupus

227

anti-Jo-1, anti-SRP, anti-Mi-2

polymyositis, dermatomyositis

228

antimicrosomal, antithyroglobulin

Hashimoto thyroiditis

229

antimitochondrial

primary biliary cirrhosis

230

antinuclear antibodies

SLE (nonspecific)

231

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

scleroderma (diffuse)

232

anti-smooth muscle

autoimmune hepatitis

233

anti-SSA, anti-SSB (anti-Ro, anti-La)

Sjogren syndrome

234

Anti-TSH receptor

graves

235

Anti-U1 RNP (ribonucleoprotein)

mixed CT disease

236

c-ANCA (PR3-ANCA)

granulomatosis with polyangiitis (Wegener)

237

IgA antiendomysial, IgA anti-tissue transglutaminase

celiac disease

238

p-ANCA (MPO-ANCA)

microscopic polyangiitis, Churg-Strauss

239

Rheumatoid factor (antibody, most commonly IgM, specific to IgG Fc region), anti-CCP

Rheumatoid arthritis

240

Patients with no T cells are susceptible to bacterial...

sepsis.

241

Pts with no T cells viral susceptibility

CMV
EBV
JCV
VZV
chronic infx with respiratory/GI viruses

242

PTs with no T cells fungal/parasitic susceptibility

Candida, PCP

243

Pts with No B cells bacterial susceptibility

Encapsulated bacteria

244

Pts with No B cells viral susceptibility

Enteroviral encephalitis, poliovirus (live vaccine contraindicated)

245

Pts with No B cells fungal/parasitic susceptibility

Giardia (no IgA)

246

Pts w/ no granulocytes bacterial susceptibilty

Staph
Burkholderia cepacia
Serratia
Nocardia

247

Pts with no granulocytes fungal/parasitic susceptibility

Candida
Aspergillus

248

Pts with no complement bacterial susceptibility

Neisseria (no MAC)

249

B-cell deficiencies are tend to produce...

recurrent bacteiral infxns while T-cell deficiencies tend to produce more fungal and viral infections.

250

X-linked (Bruton) agammaglobulinemia defect

Defect in BTK, a tyrosine kinase gene leading to no B cell maturation.

251

X-linked agammaglobulinemia presentation

recurrent bacterial and enteroviral infxns after 6 months (decreased maternal IgG).

252

Findings of X-linked agammaglobulinemia

-normal CD19+ B cell count
-decreased pro-B
-decreased Ig of all classes
-absent LNs and tonsils

253

Selective IgA deficiency presentaiton

-usually asymptomatic
-can see airway and GI infections
-autoimmune disease
-atopy
-anaphylaxis to IgA-containing products

254

Findings of IgA deficiency

-IgA

255

Common variable immunodeficiency defect

defect in B-cell differentiation

256

Common variable immunodeficiency presentation

-can be acquired in 20-30s; increased risk of autoimmune disease, bronchiechtasis, lymphoma, sinopulmonary infxns

257

Findings of common variable immunodeficieincy

-decreased plasma cells
-decreased immunoglobulins

258

DiGeorge syndrome (Thymic aplasia) defect

-22q11 deletion
-failure to develop 3rd and 4th pharyngeal pouches (leading to an absent thymus and parathyroids)

259

Digeorge Syndrome presentation

-tetany (hypocalcemia)
-recurrent viral/fungal infxns (T-cell deficiency)
-conotruncal abnormalities (tetralogy of fallot and truncus arteriorsus)

260

Findings of DiGeorge

-decreased T cells
-decreased PTH
-decreased calcium
-absent thymic shadow on CXR
-22q11 deletion detected by FISH

261

IL-12 recptor deficiency defect

decreased Th1 response; autosomal recessive

262

IL-12 receptor deficiency presentation

disseminated mycobacteiral and fungal infxns; may present after administration of BCG vaccine

263

Findings of IL-12 receptor deficiency

decreased IFN-gamma

264

Autosomal dominant hyper-IgE syndrome (Job syndrome) defect

-deficiency of Th17 cells due to STAT3 mutation leading to impaired recrutiment of neutrophils to the site of infxn

265

Autosomal dominant hyper-IgE syndrome presentation

-coarse Facies
-cold staphylococcal abscesses
-retained primary teeth
-dermatolgic problems (eczema)

266

Findings of autosomal dominant hyper-IgE syndrome

-increased IgE
-decreased IFN-gamma

267

Chronic mucocutaneous candidiasis defect

T-cell dysfunction

268

Chronic mucocutaneous candidiasis presnetation

noninvasive candida infections of the skin and mucous membranes

269

Findings of chronic mucocutaneous candidiasis

-absent invitro T-cell proliferation in response to candida
-absent cutaneous rxn to candida antigens

270

Severe combined immunodeficiency (SCID) defect

several types including defective IL-2R gamma chain (most common, X-linked), adenosine deaminase deficiency (autosomal recessive)

271

SCID presentation

-FTT
-diarrhea
-thrush
-recurrent viral, bacterial, fungal and protzoal infxns

272

SCID treatment

bone marrow transplant

273

Findings of SCID

-decreased T cell receptor excision circles (TRECs)
-absense of thymic shadow
-absence of germinal centers (LN biopsy)
-absence of T cells (flow cytometry)

274

Ataxia-telangiectasia defect

defects in ATM gene leading to DNA double strand breaks leading to cell cycle arrest

275

Ataxia-telangiectasia presentation

cerebellar defects (ataxia)
spider angiomas (telangiectasia)
IgA deficiency

276

Ataxia-telangiectasia findings

-increased AFP
-decreased IgA, IgG, IgE
-lymphopenia
-cerebellar atrophy

277

Hyper-IgM syndrome defect

most commonly due to defective CD40L on Th cells (class switching defect); X-linked

278

Presentation of Hyper-IgM syndrome

severe pyogenic infections early in life; opportunistic infxn with Pneumocystis, Cryptosporidium, CMV.

279

Findings of Hyper-IgM syndrome

-increased IgM
-decreased IgG, IgA, IgE

280

Wiskott-Aldrich syndrome defect

-mutation in WAS gene (x-linked recessive)
-T cells unable to reorganize actin skeleton

281

Presentation of Wiskott-Aldrich

-Thrombocytopeic purpura
-eczema (esp. trunk)
-recurrent infections
-increased risk of atuoimmune disease and malignancy

282

Findings of Wiskott-Alrdrich

-decreased/normal IgG, IgM
-increased IgE, IgA
-fewre and smaller platelets

283

Leukocyte adhesion deficiency (LAD) type I Defect

defect in LFA-1 integrin (CD18) protein on phagocytes; impaired migration and chemotaxis; AR

284

LAD type I presentation

recurrent bacterial skin and mucosal infections, absent pus formation, impaired wound healing, delayed separation of umbilical cord

285

LAD type I findings

-increased neutrophils
-absence of neutrophils at infection sites

286

Chediak-Higashi syndrome defect

defect in lysosomal trafficking regulator gene (LYST). Microtubule dysfunction in phagosome-lysosome fusion; AR

287

Chekiak-Higashi syndrome presentation

recurrent pyogenic infxns by staph and strep, partial albinism, peripheral neuropathy, progressive neurodegeneration, infiltrative lymphohistiocytosis

288

Chediak-higashi findings

-giant granules in neutrophils and platelets
-pancytopenia
-mild coagulation defects

289

Chronic granulomatous disease defect

defect of NADPH oxidase leading to decreased ROS and absent respiratory burst in neutrophils; X-linked

290

Chronic granulomatous disease presentation

increased susceptiblity to catalase positive organisms

291

Findings of chronic granulomatous disease

-abnormal dihydrorhodamine test
-nitroblue tetrazolium dye reduction test is negative

292

Hyperacute (w/i minutes) transplant rejection pathogenesis

pre-existing recipient antibodies react to donor antigen (type II HSR) and activate complement

293

Hyper acute rejection features

widespread thrombosis of graft vessesl leading to ischemia/necrosis.

(graft must be removed)

294

Acute rejection (wks to months) pathogenesis

Cellular: CTLs activated against donor MHCs

Humoral: similar to hyperacute, excpt antibodies develop after transplant

295

Acute rejection features

-vasculitis of graft vessels with dense interstitial lymphocytic infiltrate
-prevent/reverse with immunosuppressants

296

Chronic (months to years) rejection pathogenesis

recipient T cells perceive donor MHC as recipient MHC and react against donor antigens presented; both cellular and humoral components

297

Chronic rejection features

-irreversible; t-cell and antibody mediated damage
-Heart: atherosclerosis
-Lungs: bronchiolitis obliterans
-Liver: vanishing bile ducts
-Kidney: vascular fibrosis, glomerulopathy

298

GVHD pathogenesis

grafted immunocompetent T cells proliferate in the immunocompromised host and reject host cells with "foreign" proteins leading to severe organ dysfunction

299

Features of GVHD

-maculopapular rash, jaundie, diarrhea, hepatosplenomegaly
-usually in bone marrow and liver transplants (rich in lymphocytes)
-potentially beneficial in BMT for leukemia (graft vs. tumor)

300

Cyclosporine MOA

calcineurin inhibitor; binds cyclphilin; blocks T-cell activation by preventing IL-2 transcription

301

Use of cyclosporine

transplant rejection prophylaxis
psoriasis
RA

302

Toxicity of Cyclosporine

-Nephrotoxicity**
-HTN
-hyperlipidemia
-hyperglycemia
-tremor
-hirsutism
-gingival hyperplasia

303

Tacrolimus MOA

calcineurin inhibitor; binds FK506 binding protein; blocks T cell activation by preventing IL-2 transcription

304

Use of Tacrolimus

transplant rejection prophylaxis

305

Toxicity of Tacrolimus

-increased risk of diabetes and neurotoxicity
-nephrotoxic**

306

Sirolimus MOA

mTOR inhibitor; binds FKBP
blocks T cell activation and B cell differentiation by preventing IL-2 signal transduction

307

Use of Sirolimus

kidney transplant rejection prophylaxis

308

Toxicity of Sirolimus

-anemia
-thrombocytopenia
-leukiopenia
-insulin resistance
-hyperlipidemia
-NON-nephrotoxic

309

Basiliximab MOA

monoclonal antibody; blocks IL-2R

310

Basiliximab Use

kidney transplant rejection prophylaxis

311

Basiliximab Toxicity

edema
HTN
tremor

312

Azathioprine MOA

antimetabolite precursor of 6-MP; inhibits lymphocyte proliferation by blocking nucleotide synthesis

313

Azathioprine use

-transplant rejection prophylaxis
-RA
-Crohn disease
-glomerulonephritis

314

Azathioprine toxicity

-leukopenia
-anemia
-thrombocytopenia

315

Glucocorticoids MOA

inhibit NF-kappaB; suppress both B and T cell fxn by decreasing transcription of many cytokines

316

Use of Glucocorticoids

-transplant rejection prophylaxis (immune suppression)
-inflammation

317

Toxicity of Glucocorticoid

-hyperglycemia
-osteoporosis
-central obesity
-muscle breakdown
-psychosis
-acne
-HTN
-cataracts
-peptic ulcers

318

Glucocorticoids can cause iatrogenic...

Cushing Syndrome.

319

Epoeitin alfa (erythropoietin) is used for...

anemias esp. in renal failure.

320

Thrombopoietin is used in...

thrombocytopenia.

321

Oprelvekin (IL-11) is used in...

thrombocytopenia.

322

Filgrastim (granulocyte colony-stimulating-factor) is used in...

recovery of bone marrow.

323

Sagramostim (granulocyte-macrophage colongy-stimulating factor) is used in...

recovery of bone marrow.

324

Aldesleukin (IL-2) is used in...

renal cell carcinoma and metastatic melanoma.

325

IFN-alpha is used in...

Hep B/C, Kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, RCC, and malignant melanoma

326

IFN-beta is used in..

MS.

327

IFN-gamma is used in...

chronic granulomatous disease

328

Alemtuzumab targets...

CD52 and is used for CLL.

329

Bevacizumab targets...

VEGF and is used in colorectal cancer and RCC.

330

Cetuximab targets...

EGFR and is used in Stage IV colorectal cancer and head/neck cancer.

331

Rituximab targets...

CD20 and is used in B-cell non-hodgkin lymphoma, RA, and ITP

332

Trastuzumab targets...

HER2/neu and is used in breast cancer and gastric cancer.

333

Infliximab and adalimumab target...

TNF-alpha and are used in IBD, RA, ankylosing spondyliits and psoriasis.

334

Natalizumab targets...

alpha4-integrin and is used in MS and Crohn disease.

335

Abciximab targets...

glycoprotein IIb/IIIa and is used as an anti-platelet agent for prevention of ischemic complications in pts undergoing percutaneous coronary intervention.

336

Denosumab targets...

RANKL and is used in osteoporosis to inhibit osteoclast maturation.

337

Digoxin immune Fab targets...

digoxin and is used for digoxin toxicity.

338

Omalizumab targets...

IgE and is used for allergic asthma; it prevents IgE binding to FcepsilonRI.

339

Palvizumab targets...

RSV F protein and is used for RSV prophylaxis for high-risk infants.