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Immunology Flashcards

1
Q

Immune system Primary Organs

A

bone marrow and thymus

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2
Q

Immune system Secondary Organs

A

spleen lymph nodes, tonsils, peyer patches

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3
Q

Lymph Node

A

has many afferent and efferent. Encapsulated with trabeculae. Nonspecifc filtration by macrophages, circulation of B and T cells and immune response activation.

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4
Q

Follicle

A

Site of B cell localization and proliferation. In outer cortex primary follicles are dense and quiescent. secondary follicles have pale central germinal centers and are active

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5
Q

Medulla

A

medullary sinuses communicate with efferent lymphatics and contain reticular cells and macrophages

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6
Q

Paracortex

A

contains T cells. region of cortex between follicles and medulla. Contains high endothelial venules through with T and B cells enter from blood.
Enlarge in extreme cellular immune response
Not developed in DiGeorge

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7
Q

Cervical, supraclavicular LN

A

Drain head and neck

URI, mononucleosis, Kawasaki

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8
Q

Mediastinal LN

A

Drain Trachea and esophagus

TB, sarcoidosis, lung cancer, granulomatous disease

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9
Q

Hilar LN

A

Drain lungs

TB, sarcoidosis, lung cancer, granulomatous disease

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10
Q

Axillary LN

A

Drain upper limb, breast, skin above umbilicus

Mastitis, metastasis (breast cancer)

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11
Q

Celiac LN

A

Drain liver, stomach, spleen, pancreas, upper duodenum

Mesenteric Lymphadenitis, typhoid, UC, celiac disease

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12
Q

Superior Mesenteric LN

A

Drain lower duodenum, jejunum, ileum, colon to splenic flexure
Mesenteric Lymphadenitis, typhoid, UC, celiac disease

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13
Q

Inferior Mesenteric LN

A

Drain colon from splenic flexure to upper rectum

Mesenteric Lymphadenitis, typhoid, UC, celiac disease

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14
Q

Para-aortic LN

A

Drains testes, ovaries, kidneys, uterus

Metastasis

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15
Q

External Iliac LN

A

Drains Cervix, superior bladder and body of uterus

STI

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16
Q

Internal iliac

A

drains lower rectum to anal canal, bladder, vagina, cervix, prostate
STI

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17
Q

Superficial inguinal LN

A

drains anal canal, skin below umbilicus, scrotum, vulva

STI, medial foot/leg cellulitis

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18
Q

Popliteal LN

A

Dorsolateral foot, posterior calf drainage

Lateral foot/leg cellulitis

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19
Q

Spleen

A

LUQ, anterolateral to left kidney, protected by ribs 9-11
Barrel hoop basement membrane
T cells in periarteriolar lymphatic sheath (white pulp)
B cells in follicles in white pulp
Marginal zone- between red and white pulp, contain macrophages and specialized B cells, APCs
Remove encapsulated bacteria

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20
Q

Splenic dysfunction

A

decrease IgM –> decrease complement –> increased susceptibility to encapsulated bacteria (SCD)

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21
Q

Postsplenectomy blood findings

A

Howell Jolly bodies
Target cells
thrombocytosis
lymphocytosis

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22
Q

Thymus

A

Anteriosuperior mediastinum.
Site of T cell differentiation and maturation.
3RD PHARYNGEAL POUCH
Cortex- dense with immature T cells
Medulla- pale with mature T cells and Hassall corpuscles
Neonates: sail shaped on CXR
Hypoplastic thymus in SCID and DiGeorge
Thymoma- neoplasm, MG, SVC syndrome, pure red cell aplasia, Good syndrome

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23
Q

Innate Immunity

A

Neutrophils, macrophages, monocytes, DC, NK cells, complement
germline encoded
resistance persists through generations- does not change in lifetime
Nonspecific, fast, no memory
TLRs recognize PAMPs –> activate NFkB

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24
Q

Adaptive Immunity

A

T cells, B cells, Ab
VDJ recombination during lymphocyte development
microbial resistance not heritable
Highly specific, refined over time, memory response, fast and robust

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25
Q

MHC I

A 
HLA A,B,C
bind TCR and CD8
present endogenous antigens
all nucleated cells, APCs, platelets (NOT RBC)
Antigen loaded in RER
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26
Q

MHC II

A 
HLA (DP, DQ, DR)
Bind TCR and CD4
APC's
Present exogenous antigens
antigen loaded after release of invariant chain in endosome
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27
Q

HLA A3

A

Hemachromatosis

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28
Q

HLA B8

A

Addison disease, MG, Graves

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29
Q

HLA B27

A

psoriatic arthritis, ankylosing spondylitis, IBD associated arthritis, reactive arthritis

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30
Q

HLA C

A

psoriasis

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31
Q

HLA DQ2/DQ8

A

Celiac disease

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32
Q

HLA DR2

A

multiple sclerosis, hay fever, SLE, Goodpasture

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33
Q

HLA DR3

A

DM Type 1, SLE, Graves, Hashimoto, addisons

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34
Q

HLA DR4

A

Rheumatoid arthritis, DM Type 1, addison

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35
Q

HLA DR5

A

Hashimoto

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36
Q

NK cells

A

Innate immune system
use perforin and granzymes –> apoptosis of viral infection
enhanced by IL 2, 12, IFN alpha and beta

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37
Q

B cells

A

Humoral immunity
recognize and present antigen
somatic hypermutation
produce Ab (differentiate into plasma cells or memory cells)

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38
Q

T cells

A

Cell mediated immunity
CD4- help B cells make Ab and produce cytokines
CD8- directly kill virus infected and tumor cells via perforin and granzymes

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39
Q

Differentiation of T cells Positive selection

A

Thymic cortex

T cells expressing TCR capable of binding to self MHC on cortical epithelial cells survive

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40
Q

Differentiation of T cells Negative Selection

A

Thymic medulla

T cells expressing TCRs with high affinity for self antigens undergo apoptosis or become Treg cells.

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41
Q

AIRE deficiency

A

Tissue restricted self antigens are expressed in the thymus duet to AIRE
deficiency: autoimmune polyendocrine syndrome I (candidiasis, hypoparathyroidism, adrenal insufficiency, recurrent candida infection)

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42
Q

Macrophage- lymphocyte interaction

A

Th1 cells secrete IFNy –> enhance ability of monocytes and macrophages to kill microbes they ingest. Also, interaction of T cell CD40L with macrophage CD40.

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43
Q

Cytotoxic T cells

A

Kill virus infected, neoplastic and donor graft cells via apoptosis. Release cytotoxic granules
CD8

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44
Q

Treg cells

A

Maintain specific immune tolerance by suppressing CD4 and CD8.
Express CD3, CD4, CD25 and FOXP3
Produce anti inflammatory cytokines (IL 10, TGF B)

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45
Q

IPEX

A

deficiency of FOXP3 –> autoimmunity
Enteropathy, endocrinopath, nail dystrophy, dermatitis
Associated with DM in male infants
X linked

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46
Q

T cell activation

A
  1. DC samples and processes Ag then migrates to LN
  2. T cell activation- exogenous Ag present on MHC II and recognized by TCR on CD4 cell. Endogenous Ag presented on MHC I to CD8
  3. Proliferation and survival- DC CD80/86 and naive T cell CD28 interaction
  4. Activated Th cell produce cytokines and kill virus infected cell
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47
Q

B cell activation

A
  1. Th cell activation
  2. B cell receptor mediated endocytosis
  3. Exogenous antigen presented on MHC II and recognized by TCR on Th cell
  4. CD40 on B cells bind CD40L on Th cell
  5. Th cell secrete cytokines that determine Ig class switching
  6. B cells are activated and undergo class switching and affinity maturation –> produce Ab
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48
Q

Fab Ab structure

A

Fragment antigen binding.

Variable/hypervariable regions containing light and heavy chains.

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49
Q

Fc Ab Structure

A 
Constant
Carboxy terminal
Complement binding
Carb side chain
Determine isotype
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50
Q

Generation of Ab Diversity

A
  1. random recombination of light chain or heavy chain
  2. Random addition of nucleotides to DNA during recombination by TdT
  3. Random combination of heavy chains with light chains
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51
Q

Generation of Ab specificity

A 
Somatic hypermutation and affinity maturation (variable region)
Isotype switching  (constant region)
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52
Q

IgG

A

Main Ab in secondary response to Ag
Most abundant
Fix complement, opsonize bacteria, neutralize toxins
CROSS PLACENTA

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53
Q

IgA

A

prevent attachment of bacteria and viruses to mucus membranes
Cross epithelial by transcytosis
Most produced Ab overall
Produced in GI tract

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54
Q

IgM

A

Immediate response to Ag.
Fixes complement
Ag receptor on surface of B cell
Pentamer –> avid binding to Ag while humoral response evolves

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55
Q

IgE

A

bind to mast cells and basophils
cross links when exposed to allergen –> histamine release
TYPE 1 HYPERSENSITIVITY
Parasites

56
Q

Thymus independent Ag

A

Lack peptide component
cannot be presented to MHC to T cells
weakly immunogenic
booster vaccines

57
Q

Thymus dependent Ag

A

contain peptide component. Class switching and immunologic memory occur as a result of direct contact of B cells with Th cells

58
Q

Complement

A 
Innate immunity and inflammation
Synthesized in liver
MAC - defend against Gram (-)
Classic- IgG IgM
Alternative- microbial surface molecules
Lectin- mannose
59
Q

Complement opsonization

60
Q

Complement Anaphylaxis

A

C3a, C4a, C5a

61
Q

Complement Neutrophil chemotaxis

62
Q

Complement cytolysis

A

C5b-9 = MAC

63
Q

Opsonins

A

C3b and IgG in bacterial defense

enhance phagocytosis

64
Q

Inhibitors

A

DAF (CD55) and C1 esterase help prevent complement activation on self cells

65
Q

Early Complement Deficiencies

A

C1-4

Increased risk of severe, recurrent pyogenic sinus and URI. Increased risk of SLE

66
Q

Terminal Complement deficiencies

A

C5-9

Increased susceptibility to recurrent Neisseria bacteremia

67
Q

C1 esterase inhibitor deficiency

A

Causes hereditary angioedema due to unregulated activation of kalikrein –> increase braykinin
low C4
ACEi contraindicated

68
Q

Paroxysmal Nocturnal Hemoglobinuria

A

defect in PIGA gene –> prevent formation of GPI anchors for complement inhibitors (DAF or MIRL)
Intravascular hemolysis –> low haptoglobin, dark urine

69
Q

IL1

A

cause fever, acute inflammation,
activates endothelium to express adhesion molecules.
induce chemokine secretion to recruit WBCs
osteoclast activator
Secreted by macrophages

70
Q

IL6

A

cause fever and stimulate production of acute phase protiens

secreted by macrophages

71
Q

TNFa

A 
activates endothelium
Cause WBC recruitment
vascular leak
causes cachexia in malignancy
maintains granulomas in TB
mediate fever and sepsis
Secreted by macrophages
72
Q

IL8

A

Major chemotactic factor for neutrophils

Secreted by macrophages

73
Q

!L12

A

Induce differentiation of T cells into Th1
activate NK cells
secreted by macrophages

74
Q

IL2

A

stimulate growth of helper, cytotoxic, regulatory T cells and NK cells
secreted by T cells

75
Q

IL3

A

Supports growth and differentiation of bone marrow stem cells
like GM CSF
secreted by T cells

76
Q

IFNy

A

secreted by NK ells and T cells in response to Ag or IL12 from macrophages
stimulates macrophages to kill pathogens
inhibit Th2 differentiation

77
Q

IL4

A

induce differentiation of T cells into Th2 cells.
Promote growth of B cells
Enhance class switching to IgE and IgG
Secreted by Th2

78
Q

IL5

A

promote growth and differentiation of B cells
Enhance class switching of IgA
stimulate growth and differentiation of eosinophils
Secreted by Th2

79
Q

IL10

A

Attenuate inflammatory response
Decrease MHC class II and Th1 cytokines
Inhibit activated macrophages and DC
Secreted by Treg and Th2 cells

80
Q

Respiratory burst

A

activate NADPH oxidase complex –> rapid release of ROS.

Create and neutralize ROS

81
Q

Chronic Granulomatous Disorder

A

can utilize H2O2 –> ROS –> decrease oxidative burst. increased risk of infection by catalase (+) species
Defect in NADPH oxidase
abnormal dihydrorhodamine test

82
Q

Interferons

A

interfere with RNA and DNA viruses
downregulate protein synthesis to resist potential viral replication and upregulate MHC expression
Activate anti-tumor immunity
Adverse: flu-like symptoms, depression, neutropenia, myopathy, autoimmunity

83
Q

Anergy

A

state when cell cannot be activated by exposure to Ag.

When B or T cells exposed to their Ag without costimulatory signal

84
Q

Passive immunity

A

receive performed Ab
Rapid onset
short span of Ab
breast milk, maternal IgG

85
Q

Active immunity

A

exposure to exogenous antigens
slow onset
long lasting protection
natural infection, vaccines, toxoid

86
Q

Live attenuated vaccines

A

microorganism loses its pathogenicity but retains capacity for transient growth within inoculated host. Induce cellular and humoral responses
Contra in pregnancy and immunodeficiency

87
Q

Killed or inactivated vaccine

A

pathogen is inactivated by heat or chemicals. Maintain epitope structure on surface Ag. Induce humoral response
BOOSTER SHOTS NEEDED

88
Q

Subunit vaccine

A

induce only the Ag that best stimulate the immune system

89
Q

Toxoid Vaccine

A

Denatured bacterial toxin with an intact receptor binding site. stimulates the immune system to make Ab without potential for causing disease

90
Q

Type 1 Hypersensitivity

A

Anaphylactic
Immediate phase: antigen crosslinks preformed IgE on presensitized mast cells –> immediate degranulation –> release of histamine and tryptase
Late phase: chemokines and other mediators from mast cells –> inflammation and tissue damage

91
Q

Type 2 Hypersensitivity

A

Antibodies bind to cell surface antigens –> cellular destruction, inflammation and cellular dysfunction
cell is opsonized by Ab –> phagocytosis or NK kill
binding of Ab to cell surface –> complement and inflammation
Ab bind to cell surface receptor –> abnormal blockade or activate downstream process
Autoimmune hemolytic anemia, transfusion reaction, goodpastures, rheumatic fever, MG, graves, pemphigus vulgaris

92
Q

Type 3 Hypersensitivity

A

Immune complex activate complement which attracts neutrophils –> release lysosomal enzymes
SLE, PAN, poststrep glomerulonephritis
Serum sickness (Ab produced 1-2 weeks later and deposit in tissue)
Arthus reaction (injection of Ag –> immune complex formation in skin)

93
Q

Type 4 Hypersensitivity

A
  1. Direct cell cytotoxicity (CD8) kill target cells
  2. inflammatory reaction- CD4 recognize Ag and release inflammation inducing cytokines
    contact dermatitis, Graft vs host
94
Q

Blood Transfusion reaction: allergic

A

Type 1 hypersensitivity against plasma proteins in transfused blood. IgA deficient individuals should not receive blood products without IgA
Within minutes to 2-3 hours
urticaria, anaphylaxis

95
Q

Blood Transfusion reaction: acute hemolytic

A

Type 2 hypersensitivity
causes intravascular hemolysis ABO
during transfusion or within 24 hours
fever, hypotension, tachy, flank pain

96
Q

Blood Transfusion reaction: febrile hemolytic

A

Cytokines created by donor WBCs accumulate suring stoarge of blood. reaction prevented by leukoreduction
within 1-6 hours
fever, HA, chills, flushing
Children

97
Q

Transfusion related acute lung injury

A

Neutrophils are sequestered and primed in pulmonary vasculature and neutrophils are activated by a product in the transfused blood and release inflammatory mediators –> pulm edema
within minutes to 6 hr
Resp distress, pulm edema

98
Q

Blood Transfusion reaction: Delayed hemolytic

A

Anamnestic response to a foreign Ag on donor RBC. Cause extravascular hemolysis
Onset >24hrs
self limited, mild fever, hyperbilirubinemia

99
Q

X linked agammaglobulinemia

A 
defect in BTK --> no B cell maturation
X linked recessive
recurrent bacterial and enteroviral infections after 6 months
(-) B cell, decreased Ig
absent LN and tonsils
Contra- live vaccines
100
Q

Selective IgA deficiency

A

Asymptomatic
can see airway and GI infections, autoimmune, atopy, anaphylaxis to IgA products
decrease in IgA only, increased susceptibility to giardia
False (+) B-hCG test

101
Q

Common variable immunodeficiency

A

Defect in B cell differentiation
may present in childhood
increase risk of autoimmune disease, bronchiectasis, lymphoma, sinopulm infections
decrease plasma cells and Ig

102
Q

Thymic Aplasia

A

22q11 microdeletion, failure to develop 3rd and 4th pharyngeal pouches –> absent thymus and parathyroid
DiGeorge: thymic, parathyroid, cardiac defect
Velovardiofacial syndroms: palate, facial, cardiac disease
CATCH-22
decrease T cells, PTH and Calcium
Thymic shadow absent on CXR

103
Q

IL12 deficiency

A

decreased th1 response AR
Disseminated mycobacterial and fungal infections
decreased IFNy

104
Q

AD hyper-IgE syndrome

A

Deficiency of Th17 cells due to STAT3 mutation –> impaired recruitment of neutrophils to sites of infection
Cold staph abscesses, retained baby teeth, coarse facies, eczema, increased IgE, bone fractures
increased IgE, eosinophils

105
Q

Chronic mucocutaneous candidiasis

A

T cell dysfunction, impaired cell mediated immunity against Candida via defect in AIRE
persistent Candida albicans infection
absent T cell proliferation

106
Q

Severe combined immunodeficiency

A

IL2R gamma chain defect (X linked), adenosine deaminase deficiency (AR) or RAG mutation –> VDJ recombination defect.
Failure to thrive, chronic diarrhea, thrush, recurrent viral, bacterial, fungal and protozoal infection
decrease TCRECs, absent thymic shadow

107
Q

Ataxia Telangiectasia

A

Defect in ATM gene –> failure to detect DNA damage AR
Ataxia, Angiomas, IgA deficiency
increased sensitivity to radiation
increased AFP, decreased IgA, IgG, and IgE, lymphopenia, cerebellar atrophy, increased risk of lymphoma and leukemia

108
Q

Hyper IgM

A

defective CD40L on Th cells –> class switching defect XR
Severe pyogenic infection, Pneumocystis, CMV, Cryptosporidium
normal or high IgM
low IgG, IgA, IgE

109
Q

Wiskott Aldrich

A

Mutation in WAS gene, leukocytes and platelets unable to recognize actin cytoskeleton –>defective antigen presentation XR
Thrombocytopenia, eczema, recurrent infections
increase risk of autoimmune disease and malignancy
low to normal IgG and IgM
increased IgE and IgA

110
Q

Leukocyte Adhesion Deficiency

A

Defect in LFA 1 integrin protein on phagocytes–> impaired migration and chemotaxis AR
late separation of umbilical cord, absent pus, dysfunctional neutrophils
increased neutrophils in blood but not in infection site

111
Q

Chediak Higashi

A

Defective lysosomal trafficking regulator gene. Microtubule dysfunction in phagosome-lysosome fusion AR
progressice neurodegeneration, lymphohistiocytosis, albinism, recurrent infections, peripheral neuropathy
giant granules, pancytopenia, mild coagulation defects

112
Q

Hyperacute Transplant Rejection

A

within minutes
Pre-existing recipient Ab react to donor Ag (Type 2) –> activate complement
Thrombosis of graft vessels –> ischemia, necrosis
GRAFT MUST BE REMOVED

113
Q

Acute Transplant Rejection

A

weeks to months
CD8 and CD4 cells activated against donor MHC (Type 4)
Vasculitis of graft vessel with dense interstitial lymphocytic infiltrate
reverse with immunosuppressants

114
Q

Chronic Transplant Rejection

A

months to years
CD4 respond to recipient APCs on donor (Type 2 and 4)
proliferation of vascular smooth muscle, parenchymal atrophy, interstitial fibrosis

115
Q

Graft vs. Host

A

grafted immunocompetent T cells proliferate in the immunocompromised host and reject host cells with foreign proteins –> organ dysfunction
Type 4
Maculopapular rash, jaundice, diarrhea, hepatosplenomegaly
Bone marrow and liver transplants

116
Q

Cyclosporin

A

Calcineurin inhibitor; bind cyclophilin –> block T cell activation by preventing IL2 transcription
Used in psoriasis, Rheumatoid arthritis
Tox: nephrotoxicity

117
Q

Tacrolimus

A

Calcineurin inhibitor binds FK506 binding protein –> block T cell activation by preventing IL 2 transcription
Used in psoriasis, Rheumatoid arthritis
Tox: nephrotoxicity, increased risk of diabetes

118
Q

Sirolimus

A

mTOR inhibitor binds FKBP –> block T cell activation by preventing IL2 transcription
Used in kidney transplant rejection prophylaxis
Tox: pancytopenia, insulin reisstance, hyperlipidemia

119
Q

Basiliximab

A

Monoclonal Ab blocks IL 2R
Used in kidney transplant rejection prophylaxis
Tox: edema, HTN, tremor

120
Q

Azathioprine

A

anti 6-mercaptopurine –> block nucleotide synthesis
Used in Rheumatoid arthritis, crohns, glomerulonephritis
Tox: pancytopenia

121
Q

Mycophenylate Mofetil

A

Reversibly inhibit IMP dehydrogenase –> no purine synthesis in B and T cells
Use in lupus nephritis
Tox: GI, pancytopenia, HTN, hyperglycemia

122
Q

glucocorticoids

A

inhibit NFkB –> suppress B and T cells
Used in autoimmune diseases, inflammatory disorders, adrenal insufficiency, asthma, CLL, NHL
Tox: cushings, oseoporosis, hyperglycemia, DM, amenorrhea, adrenocortical atrophy, peptic ulcers, avascular necrosis, cataracts

123
Q

Alemtuzumab

A

Anti CD52

Use in CLL, multiple sclerosis

124
Q

Bevacizuman

A

Anti VEGF

used in colorectal cancer, RCC, non small cell lung cancer

125
Q

Rituximab

A

anti CD 20
used in B cell NHL, CLL, rheumatoid arthritis, ITP, multiple sclerosis
Risk of PML in patients with JC virus

126
Q

Trastuzumab

A

anti HER2

used in breast cancer, gastric cancer

127
Q

adalimumab, infliximab

A

anti TNFa

used in IBD, rheumatoid arthritis, ankylosing spondylitis, psoriasis

128
Q

Eculizumab

A

anti C5

used in paroxysmal nocturnal hemoglobinuria

129
Q

Ixekizumab, seclukinumab

A

anti IL17A

used in psoriasis, psoriatic arthritis

130
Q

Natalizumab

A

anti a4-integrin

used in multiple sclerosis, crohns

131
Q

Ustekinumab

A

anti IL12 and IL23

used in psoriasis and psoriatic arthritis

132
Q

abciximab

A

anti platelet gp IIb/IIIa

used in prevention of ischemic complication in patients undergoing percutaneous coronary intervention

133
Q

Denosumab

A

anti RANKL

used in osetoporosis, inhibit osteoclast maturation

134
Q

Omalizumab

A

anti IgE

used in refractory allergic asthma

135
Q

Palivizumab

A

anti RSV F protein

used in RSV prophylaxis for high risk infants.

Step 1 (17 decks)

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