Cell Biology and Immunology 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
2
Q
Hemidesmosome
A
Structure that adheres cell to the basement membrane via keratin interaction
Made of integrins (not calcium-dependent)
Autoantibodies → bullous pemphigoid
3
Q
Gap junctions
A
Made of connexin
4
Q
Describe the steps of base excision repair
A
- 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
5
Q
What is the embryological derivation of the thymus?
A
Endoderm 3rd pharyngeal pouch
6
Q
Where are Peyer’s patches located?
A
In the wall of the ileum
7
Q
What are the primary lymph organs?
A
Bone marrow, thymus
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
9
Q
T cell receptor CD2 (immunoglobulin)
A
LFA-3 T cell adhesion and signaling
10
Q
T cell receptor L-selectin
A
GlyCAM-1 (sulfated sialyl-Lewis)
T cell adhesion to endothelial cells
11
Q
T cell receptor CD28
A
B7-1, B7-2
Second T cell signal after TCR-MHC Class II binding
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
13
Q
T cell receptor (TCR)
A
MHC + peptide
First antigen recognition signal to activate T cell
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
15
Q
T cell receptor VLA-4
A
VCAM-1 on endothelial cells Adhesion to endothelium
16
Q
IL-12
A
Stimulates differentiation of CD4+ T cells into CD4+ Th1 cells
17
Q
IL-4
A
Stimulates differentiation of CD4+ T cells into CD4+ Th2 cells
18
Q
TGF-β + IL-6
A
Stimulates differentiation of CD4+ T cells into CD4+ Th17 cells
19
Q
TGF-β
A
Stimulates differentiation of CD4+ T cells into CD4+ Treg cells
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)
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)
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)
23
Q
IL-10, TGF-β
A
Anti-inflammatory cytokines released by CD25+ Treg cells and macrophages
24
Q
CD14
A
TLR on macrophages that recognizes LPS on gram - bacteria
25
Leukotriene B4
Produced from arachidonic acid by 5-lipooxygenase to activated neutrophils
26
C3a, C5a
Anaphylatoxins trigger mast cell degranulation → histamine-mediated vasodilation of arterioles and increased vasular permeability in venules
27
C3b
Opsonin for phagocytosis
28
C5b
Complexes with C6-C9 to form membrane attack complex (MAC)
29
Sialyl Lewis X
Found on leukocytes
Binds P-selectin (Weibel-Palade bodies) and E-selectin (induced by TNF and IL-1) on endothelial cells to facilitate rolling
30
ICAM, VCAM
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
31
Leukocyte adhesion deficiency
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
32
Neutrophil chemoattractants
Bacterial products
IL-8
C5a
LTB4
33
Chediak-Higashi Syndrome
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
34
IL-8
Produces by macrophages to recruit neutrophils
35
How do CD8+ cells kill?
Perforins → create pores
Granzymes → activates apoptosis via caspases
Expression of FasL → binds Fas on target cell to activate apoptosis
36
Activation of CD4+ T cells
Signal 1: TCR binds MHC class II + antigen on APCs
Signal 2: CD28 on T cells bind B7 on APCs
37
Activation of CD8+ T cells
Signal 1: TCR binds MHC class I + antigen on any nucleated cell
Signal 2: IL-2 from CD4+ Th1 cells
38
Activation of B cells
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
39
Antinuclear antibodies (ANA)
SLE, Sjogren Syndrome
40
Anti-histone
Drug-induced lupus (e.g. procainamide, hydralazine, isoniazid)
41
Anti-SSA/Ro
Anti-SSB/La
Both are anti-ribonucleoprotein antibodies associated with Sjogren Syndrome
42
T cell maturation
Double positive T cells undergo positive selection in thymus cortex
Single positive T cells undergo negative selection in the thymus medulla
43
Anti-mitochondrial
Primary sclerosing cholangitis
44
Anti-topoisomerase I/Anti-Scl-70
Systemic sclerosis
45
Anti-ACh receptor
Myathenia gravis (type II hypersensitivity)
46
Anti-basement membrane (type IV collagen)
Goodpasture syndrome (type II hypersensitivity)
47
Anti-centromere
Limited scleroderma (CREST syndrome)
48
Anti-desmoglein
Pemphigus vulgaris
49
Anti-dsDNA
Anti-Smith
SLE (more specific than ANA)
Smith is snRNP involved in spliceosomes
50
Anti-glutamate decarboxylase
Type 1 diabetes mellitus
51
Anti-hemidesmosome
Bullous pemphigoid
52
Anti-Jo-1
Anti-SRP
Anti-Mi2
Polymyositis
Dermatomyositis
53
Anti-microsomal
Anti-thyroglobulin
Hashimoto thyroiditis
54
Anti-smooth musle
Autoimmune hepatitis
55
Anti-TSH receptor
Graves disease
56
Anti-U1 RNP (ribonucleoprotein)
Mixed connective tissue disease
57
c-ANCA/PR3-ANCA
Granulomatosis with polyangiitis (Wegner)
58
IgA anti-endomysial
IgA anti-tissue transglutaminase
Celiac disease
59
p-ANCA/MPO-ANCA
Microscopic polyangiitis
Churg-Strauss syndrome
60
Rheumatoid factor
Anti-CCP
RF = IgM against Fc region of IgG
Rheumatoid arthritis
61
Cetuximab
Antibody against EGF receptor
62
Trastuzumab (Herceptin)
Inhibitor of HER2 tyrosine kinase receptor (extracellular domain)
63
Bevacizumab
Antibody against VEGF --\> inhibits angiogenesis
64
Rituximab
Anti-CD20 antibody that promotes complement-mediated lysis of malignant B cells May cause reactivation of HBV
65
TNF (Tumor Necrosis Factor)
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
IFN-γ
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
IL-10
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
IL-2
Produced by: T cells
Actions: proliferation and differentiation of T cells
69
IL-12
Produced by: T cells, macrophages
Actions: drives differentiation of CD4+ cells into Th1 cells
70
TGF-β
Produced by: CD4+ Th2 cells Actions: Stimulates differentiation of Th2 cells Inhibits differentiation of Th1 cells
71
IL-6
Produces by: macrophages
Induces the liver to produce acute phase proteins
72
IL-8
Produced by: macrophages
Recruits neutrophils
73
IL-1β
Produced by: macrophages Activated endothelium
74
IL-1
Produced by: neutrophils Activates marophages
75
IL-4 IL-5
Produced by: Th2 CD4+ T cells
Stimulated proliferation and differentiation of B cells (isotype switching and affinity maturation)
76
Systemic Lupus Erythematosus (SLE)
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
Dermatomyositis
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
Rheumatoid Arthritis
Antibodies: rheumatoid factor Symptoms: Complications: joint deformities
79
Mixed Connective Tissue Disease
Antibodies: anti-U1-ribonucleoprotein Symptoms: mixed features of SLE, systemic sclerosis, and polymyositis
80
Drug-Induced SLE
Antibodies: anti-histone Symptoms: Complications:
81
Systemic Sclerosis
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
Polymyositis
Antibodies: anti-Jo-1 Symptoms: Complications: myocarditis
83
Ankylosing Spondylitis
Antibodies: HLA-B27 Symptoms: Complications:
84
Limited Scleroderma (CREST)
Antibodies: anti-centromere Symptoms: Complications: gastrointestinal fibrosis
85
Sjogren Syndrome
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
Rheumatic Rever
Labs: increased antistreptolysin O titer Symptoms: Complications: myocarditis, congestive heart failure
87
Vasculitis
Antibodies: C-ANCA, P-ANCA
88
Graves Disease (hypertheyroidism)
Antibodies: anti-TSH receptor
89
DiGeorge Syndrome
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
Severe Combined Immunodeficiency Disease (SCID)
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
X-linked gammaglobulinemia
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
Common Variable Immunodeficiency (CVD)
Low immunoglobulin due to B cell or helper T cell defects; increased risk for autoimmune disease and lymphoma
93
IgA deficiency
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
Hyper-IgM Syndrome
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
Wiskott-Aldrich Syndrome
Mutation in WASP gene (X-linked) causes thrombocytopenia, eczema, and recurrent infection.
96
Complement deficiencies
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
Type I Hypersensitivity
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
Type II Hypersensitivity
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
Type III Hypersensitivity
Antigen-antibody immune complexes that are formed in the circulation may deposit in vessels and organs, leading to complement activation and acute inflammation
100
Type IV Hypersensitivity (Delayed Type Hypersensitivity)
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
Describe the process cells use to break down protein antigens
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
How does opsonization work?
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
PD-1
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
Omalizumab
IgG1 monoclonal antibody that binds to IgE
Indicated as an add-on therapy for severe allergic asthma
105
Wiskott-Aldrich Syndrome
X-linked mutation in WASP gene
Thrombocytopenia, eczema, recurrent infections due to defective humoral and cellular immunity (defective B and T cells)
106
IFN-α and IFN-β
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
Ataxia-telangiectasia
Mutation in ATM gene → DNA double strand breaks → cell cycle arrest
Characterized by ataxia, telangiectasias, and sinopulmonary infections (IgA deficiency)
108
Chronic granulomatous disease
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
IL-3
Produced by: all T cells
Actions: supports the growth and differentiation of bone marrow stem cells
110
Modes of exocrine and endocrine secretion
111
Tight junctions (zona occludens)
Composed of claudins and occludins
Prevents paracellular movement of solutes
112
Adherens junction (zonula adherens)
Forms "belt" connecting actin cytoskeletons of adjacent cells with cadherins (calcium-dependent)
113
What causes increased ESR?
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
Transcriptional changes associated with epigenetics
DNA methylation → inhibits gene transcription
Histone methylation → inhibits gene transcription (mostly)
Histone acetylation → increases gene transcription
M = Mute
A = Active
115
Proteins and their functions in prokaryotic DNA replication
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
What is the function of the nucleolus?
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
What are the mRNA stop codons?
UAA, UAG, UGA
U Go Away
U Are Away
U Are Goe
118
Apoptosis
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
Start codon
AUG (codes for methionine in eukaryotes)
120
What code is at the 3' end of tRNA?
CAA
Can Carry Amino Acids
