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USMLE Step 1 > Cell Biology and Immunology > Flashcards

Cell Biology and Immunology Flashcards

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USMLE® Step 1 flashcards
1
Q

Desmosome (macula adherens)

A

Adhesion molecules that bind epithelial cells together via keratin interactions

Made of cadherins (calcium-dependent)

Autoantibodies → pemphigus vulgaris

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2
Q

Hemidesmosome

A

Structure that adheres cell to the basement membrane via keratin interaction

Made of integrins (not calcium-dependent)

Autoantibodies → bullous pemphigoid

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3
Q

Gap junctions

A

Made of connexin

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4
Q

Describe the steps of base excision repair

A
  1. Glycosylase cleaves the altered base leaving an empty sugar-phosphate site 2. Endonuclease cleaves the 5’ end 3. Lyase cleaves the 3’ sugar phosphate 4. DNA polymerase fills the gap 5. Ligase seals the nick
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5
Q

What is the embryological derivation of the thymus?

A

Endoderm 3rd pharyngeal pouch

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6
Q

Where are Peyer’s patches located?

A

In the wall of the ileum

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7
Q

What are the primary lymph organs?

A

Bone marrow, thymus

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8
Q

T cell receptor LFA-1 (integrin)

A

ICAM-1, ICAM-2 (immunoglobulin) Integrin activation increases a T cell’s affinity for the ligand allowing adhesion

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9
Q

T cell receptor CD2 (immunoglobulin)

A

LFA-3 T cell adhesion and signaling

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10
Q

T cell receptor L-selectin

A

GlyCAM-1 (sulfated sialyl-Lewis)

T cell adhesion to endothelial cells

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11
Q

T cell receptor CD28

A

B7-1, B7-2

Second T cell signal after TCR-MHC Class II binding

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12
Q

T cell receptor CTLA-4

A

B7-1, B7-2 CTLA-4 is only expressed on activated T cells and binding sends an inhibitory signal

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13
Q

T cell receptor (TCR)

A

MHC + peptide

First antigen recognition signal to activate T cell

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14
Q

T cell receptor CD40 ligand (CD40-L)

A

CD40 on B cells

Expression of CD40-L is induced by T cell activation

Binding induces activation of B cells → class switching, affinity maturation, antibody production

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15
Q

T cell receptor VLA-4

A

VCAM-1 on endothelial cells Adhesion to endothelium

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16
Q

IL-12

A

Stimulates differentiation of CD4+ T cells into CD4+ Th1 cells

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17
Q

IL-4

A

Stimulates differentiation of CD4+ T cells into CD4+ Th2 cells

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18
Q

TGF-β + IL-6

A

Stimulates differentiation of CD4+ T cells into CD4+ Th17 cells

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19
Q

TGF-β

A

Stimulates differentiation of CD4+ T cells into CD4+ Treg cells

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20
Q

What cells are antigen-presenting cells (APC)?

A

B cells

Macrophages

Dendritic cells

Langerhans cells (dendritic cells in the skin and mucous membranes)

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21
Q

Function of CD4+ Th1 cells

A

Secretes IFN-γ → activates macrophages, converts them to epithelioid histiocytes (hallmark of granuloma)

Secretes IL-2 → activation of cytotoxic CD8+ T cells, autocrine proliferation of Th1 cells

Inhibited by IL-4 and IL-10 (from Th2 cells)

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22
Q

Function of CD4+ Th2 cells

A

Secretes IL-4/IL-13 → B cell class switching to IgG and IgE

Secretes IL-5 → recruits eosinophils for parasite defense, B cell maturation into plasma cells, IgA class switching

Secretes IL-10 → inhibits Th1 phenotype

Inhibited by IFN-γ (from Th1 cells)

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23
Q

IL-10, TGF-β

A

Anti-inflammatory cytokines released by CD25+ Treg cells and macrophages

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24
Q

CD14

A

TLR on macrophages that recognizes LPS on gram - bacteria

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25
Q

Leukotriene B4

A

Produced from arachidonic acid by 5-lipooxygenase to activated neutrophils

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26
Q

C3a, C5a

A

Anaphylatoxins trigger mast cell degranulation → histamine-mediated vasodilation of arterioles and increased vasular permeability in venules

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27
Q

C3b

A

Opsonin for phagocytosis

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28
Q

C5b

A

Complexes with C6-C9 to form membrane attack complex (MAC)

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29
Q

Sialyl Lewis X

A

Found on leukocytes

Binds P-selectin (Weibel-Palade bodies) and E-selectin (induced by TNF and IL-1) on endothelial cells to facilitate rolling

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30
Q

ICAM, VCAM

A

Cellular adhesion molecules on endothelial cells upregulated by TNF and IL-1 that bind to integrins on leukocytes to facilitate adhesion to the vessel wall

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31
Q

Leukocyte adhesion deficiency

A

Autosomal recessive defect in leukocyte integrin (CD18) that prevents binding to ICAM-1 preventing leukocyte adhesion to endothelium

Manfested by recurrent bacterial and fungal infections that lack pus formation, delayed separation of umbilical cord, increased circulating neutrophils

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32
Q

Neutrophil chemoattractants

A

Bacterial products

IL-8

C5a

LTB4

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33
Q

Chediak-Higashi Syndrome

A

Autosomal recessive protein trafficking defect that impairs phagolysosome formation

Symptoms include increased risk of pyogenic infections, neutropenia, giant granules in leukocytes, defective primary hemostasis, oculocutaneous albinism, peripheral neuropathy

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34
Q

IL-8

A

Produces by macrophages to recruit neutrophils

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35
Q

How do CD8+ cells kill?

A

Perforins → create pores

Granzymes → activates apoptosis via caspases

Expression of FasL → binds Fas on target cell to activate apoptosis

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36
Q

Activation of CD4+ T cells

A

Signal 1: TCR binds MHC class II + antigen on APCs

Signal 2: CD28 on T cells bind B7 on APCs

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37
Q

Activation of CD8+ T cells

A

Signal 1: TCR binds MHC class I + antigen on any nucleated cell

Signal 2: IL-2 from CD4+ Th1 cells

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38
Q

Activation of B cells

A

Antigen binds to B-cell IgM or IgD → IgM or IgD secreting plasma cell

OR

B cell MHC class II presents antigen to CD4+ T cell → CD40L on T cell binds CD40 on B cell (2nd signal) → T cell produces IL-4 and IL-5 → B cell isotype switching, hypermutation, and maturation into plasma cells

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39
Q

Antinuclear antibodies (ANA)

A

SLE, Sjogren Syndrome

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40
Q

Anti-histone

A

Drug-induced lupus (e.g. procainamide, hydralazine, isoniazid)

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41
Q

Anti-SSA/Ro

Anti-SSB/La

A

Both are anti-ribonucleoprotein antibodies associated with Sjogren Syndrome

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42
Q

T cell maturation

A

Double positive T cells undergo positive selection in thymus cortex

Single positive T cells undergo negative selection in the thymus medulla

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43
Q

Anti-mitochondrial

A

Primary sclerosing cholangitis

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44
Q

Anti-topoisomerase I/Anti-Scl-70

A

Systemic sclerosis

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45
Q

Anti-ACh receptor

A

Myathenia gravis (type II hypersensitivity)

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46
Q

Anti-basement membrane (type IV collagen)

A

Goodpasture syndrome (type II hypersensitivity)

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47
Q

Anti-centromere

A

Limited scleroderma (CREST syndrome)

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48
Q

Anti-desmoglein

A

Pemphigus vulgaris

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49
Q

Anti-dsDNA

Anti-Smith

A

SLE (more specific than ANA)

Smith is snRNP involved in spliceosomes

50
Q

Anti-glutamate decarboxylase

A

Type 1 diabetes mellitus

51
Q

Anti-hemidesmosome

A

Bullous pemphigoid

52
Q

Anti-Jo-1

Anti-SRP

Anti-Mi2

A

Polymyositis

Dermatomyositis

53
Q

Anti-microsomal

Anti-thyroglobulin

A

Hashimoto thyroiditis

54
Q

Anti-smooth musle

A

Autoimmune hepatitis

55
Q

Anti-TSH receptor

A

Graves disease

56
Q

Anti-U1 RNP (ribonucleoprotein)

A

Mixed connective tissue disease

57
Q

c-ANCA/PR3-ANCA

A

Granulomatosis with polyangiitis (Wegner)

58
Q

IgA anti-endomysial

IgA anti-tissue transglutaminase

A

Celiac disease

59
Q

p-ANCA/MPO-ANCA

A

Microscopic polyangiitis

Churg-Strauss syndrome

60
Q

Rheumatoid factor

Anti-CCP

A

RF = IgM against Fc region of IgG

Rheumatoid arthritis

61
Q

Cetuximab

A

Antibody against EGF receptor

62
Q

Trastuzumab (Herceptin)

A

Inhibitor of HER2 tyrosine kinase receptor (extracellular domain)

63
Q

Bevacizumab

A

Antibody against VEGF –> inhibits angiogenesis

64
Q

Rituximab

A

Anti-CD20 antibody that promotes complement-mediated lysis of malignant B cells May cause reactivation of HBV

65
Q

TNF (Tumor Necrosis Factor)

A

Produced by: macrophages

Actions: leukocyte activation, produces fever, increases acute phase proteins, stimulates hematopoiesis, decreases cardiac output, increases thrombogenicity, hypoglycemia Increases vascular permeability, mediates septic shock

66
Q

IFN-γ

A

Produced by: Th1 CD4+ T cells, NK cells Actions: macrophages - activates macrophages (increased expression of MHC, inflammatory cytokines, chemokines, and toxic oxygen radicals, increase phagocytic activity) Th1 CD4+ T cells - autocrine signal to promote differentiation to Th1; inhibits differentiation of Th2

67
Q

IL-10

A

Produced by: CD4+ Th2 cells Act on: macrophages Actions: deactivates macrophages (decreased expression of MHC, inflammatory cytokines, chemokines, and toxic oxygen radicals, decreased phagocytic activity) Inhibits differentiation of Th1 cells

68
Q

IL-2

A

Produced by: T cells

Actions: proliferation and differentiation of T cells

69
Q

IL-12

A

Produced by: T cells, macrophages

Actions: drives differentiation of CD4+ cells into Th1 cells

70
Q

TGF-β

A

Produced by: CD4+ Th2 cells Actions: Stimulates differentiation of Th2 cells Inhibits differentiation of Th1 cells

71
Q

IL-6

A

Produces by: macrophages

Induces the liver to produce acute phase proteins

72
Q

IL-8

A

Produced by: macrophages

Recruits neutrophils

73
Q

IL-1β

A

Produced by: macrophages Activated endothelium

74
Q

IL-1

A

Produced by: neutrophils Activates marophages

75
Q

IL-4 IL-5

A

Produced by: Th2 CD4+ T cells

Stimulated proliferation and differentiation of B cells (isotype switching and affinity maturation)

76
Q

Systemic Lupus Erythematosus (SLE)

A

Antibodies: anti-dsDNA, anti-sm Symptoms: fever, weight loss, fatigue, lymphadenopathy, Raynaud phenomenon, malar “butterfly” rash, causes false positive syphilis test Complications: pericarditis, glomerulonerphritis, vasculitis

77
Q

Dermatomyositis

A

Antibodies: anti-Jo-1 Symptoms: lilac or heliotrope rash of upper eyelids, periorbital edema, Grotton’s lesions on elbows, knees, knuckles Complications: muscle pain

78
Q

Rheumatoid Arthritis

A

Antibodies: rheumatoid factor Symptoms: Complications: joint deformities

79
Q

Mixed Connective Tissue Disease

A

Antibodies: anti-U1-ribonucleoprotein Symptoms: mixed features of SLE, systemic sclerosis, and polymyositis

80
Q

Drug-Induced SLE

A

Antibodies: anti-histone Symptoms: Complications:

81
Q

Systemic Sclerosis

A

Antibodies: anti-Scl-70/anti-DNA topoisomerase I Symptoms: swelling of the fingers and hands, facial skin fibrosis, Raynaud’s phenomenon, calcinosis Complications: malignant hypertension, pericarditis, pulmonary fibrosis

82
Q

Polymyositis

A

Antibodies: anti-Jo-1 Symptoms: Complications: myocarditis

83
Q

Ankylosing Spondylitis

A

Antibodies: HLA-B27 Symptoms: Complications:

84
Q

Limited Scleroderma (CREST)

A

Antibodies: anti-centromere Symptoms: Complications: gastrointestinal fibrosis

85
Q

Sjogren Syndrome

A

Antibodies: anti-SSA (Ro), anti-SSB (La) Symptoms: dry eyes, inflamed cornea, dry mouth, fissured tongue, dental caries, nose dryness and crusting, parotid gland enlargement Complications: B cell lymphoma

86
Q

Rheumatic Rever

A

Labs: increased antistreptolysin O titer Symptoms: Complications: myocarditis, congestive heart failure

87
Q

Vasculitis

A

Antibodies: C-ANCA, P-ANCA

88
Q

Graves Disease (hypertheyroidism)

A

Antibodies: anti-TSH receptor

89
Q

DiGeorge Syndrome

A

Microdeletion of 22q11 results in developmental failure of the third and fourth pharyngeal pouches –> T cell deficiency (no thymus), hypocalcemia, abnormalities of the heart, great vessels, and face

90
Q

Severe Combined Immunodeficiency Disease (SCID)

A

Cytokine receptor defects of adenosine deaminase deficiency (autosomal recessive) or defective IL-2R gamma chain (X-linked) –> defective cell-mediated and humoral immunity

Characterized by failure to thrive, chronic diarrhea, trush, recurrent viral, bacterial, fungal, and protozoal infections

Tx: sterile isolation, bone marrow transplant

91
Q

X-linked gammaglobulinemia

A

Mutation in the X-linked Bruton tyrosine kinase that results in an inability of B cells to mature; individual has recurrent bacterial, enterovirus, and Giardia infections

92
Q

Common Variable Immunodeficiency (CVD)

A

Low immunoglobulin due to B cell or helper T cell defects; increased risk for autoimmune disease and lymphoma

93
Q

IgA deficiency

A

Low serum concentration of IgA; increased risk for mucosal infection, especially viral

Associated with celiac disease

Can develop anaphylaxis when transfused with blood products with IgA

94
Q

Hyper-IgM Syndrome

A

Characterized by elevated IgM; mutation in CD40L prevents T cell from activating B cell isotype switching

Characterized by recurrent sinopulmonary, gastrointestinal and opportunistic infections

95
Q

Wiskott-Aldrich Syndrome

A

Mutation in WASP gene (X-linked) causes thrombocytopenia, eczema, and recurrent infection.

96
Q

Complement deficiencies

A

C5-C9 deficiencies increase the risk of Neisseria infection

C1 inhibitor deficiency causes symptoms of acute infection (angioedema, especially periorbital) and increased bradykinin → ACEIs are contraindicated

97
Q

Type I Hypersensitivity

A

Immediate hypersensitivity caused by mast cell degranulation following binding to antigen/allergen/IgE (FcεRI - very high affinity); occurs when individual produces a strong Th2 response to produce IgE against allergen

98
Q

Type II Hypersensitivity

A

Antibody-Mediated: (1) Normal cells can be opsonized with autoantibodies with or without complement proteins and are phagocytized by neutrophils and macrophages (2)Antibodies bound to cellular or tissue antigens activate the complement system (classical); inflammation is triggered (3)Antibodies directed against cell surface receptors impair or dysregulate cellular function without causing cell injury or inflammation

99
Q

Type III Hypersensitivity

A

Antigen-antibody immune complexes that are formed in the circulation may deposit in vessels and organs, leading to complement activation and acute inflammation

100
Q

Type IV Hypersensitivity (Delayed Type Hypersensitivity)

A

Cytokine-mediated inflammation caused by CD4+ T cells (Th1 and Th17) → recruit macrophages and direct cell toxicity mediated by CD8+ cells

PPD test takes advantage of this process

101
Q

Describe the process cells use to break down protein antigens

A

Proteins are internalized → ubiquitin ligase tags the protein with ubiquitin → tagged proteins are trafficked to the proteosome and broken down into oligopeptides → oligopeptide is couples to MHC class I in the ER → complex presented on the cell surface for recognition by CD8+ T cells

102
Q

How does opsonization work?

A

IgG and C3b are potent opsonizers

Both bind to the cell surface of a foreign cell

The Fc region of IgG and C3b receptors bind to phagocytes to aid in phagocytosis

IgM can trigger the complement cascade but it’s Fc region is not recognized by phagocytes

103
Q

PD-1

A

PD-1 is expressed on CD4+ T cells; when it binds to PD-1L, often expressed on tumor cells → downregulation of immune response against tumor cells by CD8+ T cells

Antibody against PD-1 blocks T cell inhibition restoring cytotoxic response and promoting apoptosis of tumor cells

104
Q

Omalizumab

A

IgG1 monoclonal antibody that binds to IgE

Indicated as an add-on therapy for severe allergic asthma

105
Q

Wiskott-Aldrich Syndrome

A

X-linked mutation in WASP gene

Thrombocytopenia, eczema, recurrent infections due to defective humoral and cellular immunity (defective B and T cells)

106
Q

IFN-α and IFN-β

A

Produced by most human cells in response to viral infection

IFNs bind to receptors on infected and neighboring cells that results in transcription of antiviral enzymes capable of halting protein synthesis (only active in the presence of dsRNA)

IFNs also induce MHC class I expressin on all cells and stimulate the activity of NK and cytotoxic T cells causing infected cells to undergo apoptosis

107
Q

Ataxia-telangiectasia

A

Mutation in ATM gene → DNA double strand breaks → cell cycle arrest

Characterized by ataxia, telangiectasias, and sinopulmonary infections (IgA deficiency)

108
Q

Chronic granulomatous disease

A

X-linked or autosomal recessive defect in NADPH peroxidase preventing production of HOCl preventing O2 dependent killing in phagolysosomes

Characterized by recurrent infections by catalase + organisms (Pseudomonas, Listeria, Aspergillus, Candida, E. coli, S. aureus, Serratia)

Dx: abnormal dihydrorhodamine (flow cytometry) test, nitroblue tetrazolium dye (would turn blue in the present of working enzyme)

Tx: IFN-gamma

109
Q

IL-3

A

Produced by: all T cells

Actions: supports the growth and differentiation of bone marrow stem cells

110
Q

Modes of exocrine and endocrine secretion

A
111
Q

Tight junctions (zona occludens)

A

Composed of claudins and occludins

Prevents paracellular movement of solutes

112
Q

Adherens junction (zonula adherens)

A

Forms “belt” connecting actin cytoskeletons of adjacent cells with cadherins (calcium-dependent)

113
Q

What causes increased ESR?

A

IL-1, IL-6, and TNF-α mediate systemic inflammatory response and stimulates hepatic secretion of acute-phase proteins

High levels of circulating fibrnogen increase the ESR

114
Q

Transcriptional changes associated with epigenetics

A

DNA methylation → inhibits gene transcription

Histone methylation → inhibits gene transcription (mostly)

Histone acetylation → increases gene transcription

M = Mute

A = Active

115
Q

Proteins and their functions in prokaryotic DNA replication

A

Helicase: unwinds double helix

Topoisomerase II (gyrase): removal of supercoils (target of fluoroquinolones)

Primase (RNA polymerase): synthesis of RNA primer

DNA polymerase III (5’ to 3’ DNA synthesis and 3’ to 5’ exonuclease/proofreading)

DNA polymerase I: same as DNA polymerase III but also removes RNA primer and replaces it with DNA

DNA ligase: joining of Okazaki fragments in lagging strand

116
Q

What is the function of the nucleolus?

A

Primary site of rRNA transcription by RNA polymerase I, maturatio and assembly of ribosomal subunits

RNA polymerase II makes mRNA (inhibited by amanita muschroom poison → hepatotoxicity)

RNA polymerase III makes tRNA

117
Q

What are the mRNA stop codons?

A

UAA, UAG, UGA

U Go Away

U Are Away

U Are Goe

118
Q

Apoptosis

A
  1. Intrinsic pathway: withdrawal of regulation factors (e.g. IL-2) or exposrure to injurious stimuli –> increased proportion of pro-apoptotic (BAX, BAK) and anti-apoptotic (Bcl-2) proteins –> increased mitochondrial permeability –> release of cytochrome c –> activation of caspases
  2. Extrinsic pathway: CD8+ release of perforins and granzymes, Fas-FasL activation signal (required for T cell negative selection; defect basis for autoimmunity) –> activation of caspases
119
Q

Start codon

A

AUG (codes for methionine in eukaryotes)

120
Q

What code is at the 3’ end of tRNA?

A

CAA

Can Carry Amino Acids

USMLE Step 1 (20 decks)

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