Molecular Medicine Flashcards
What are the phases of the cell cycle?
G0: Resting phase
G1: Gap 1 - cell increase in size
S: Synthesis of DNA, RNA, Histome and centromere duplication
G2: Gap 2 - cells continue to increase in size
Mitosis
G0
What phase of the cell cycle determine the length of the cell cycle?
Gap 1
What governs G1 phase?
p53
What regulatory proteins govern transition from G1 to S phase the cell cycle?
Cyclin D / CDK4
Cyclin D / CDK6
Cyclin E / CDK2:
What regulatory protein governs synthesis phase?
Cyclin A / CDK2: active in S phase
What regulatory protein governs transition from G2 to m phase?
Cyclin B / CDK1: regulates transition from G2 to M phase
What is the shortest phase of the cell cycle?
Mitosis
What are the features of mitosis?
Somatic cells
Genetically identical to parent cell
Results in 2 diploid daughter cells
What are the features of meiosis?
Gamete cells
Contain one homologue - genetically different
4 haploid cells
What are the phases of mitosis?
Interphase: G0, S phase and G2
Mitosis: M phase
Prometaphase
Metaphase
Anaphase
Telophase
Cytokinesis
G0
What occurs in prometaphase?
Nuclear membrane breaks down allowing the microtubules to attach to the chromosomes
What occurs in metaphase?
Chromosomes aligned at middle of cell
What occurs in anaphase?
The paired chromosomes separate at the kinetochores and move to opposite sides of the cell
What occurs in telophase?
Chromatids arrive at opposite poles of cell
What occurs in cytokinesis?
Actin-myosin complex in the centre of the cell contacts resulting in it being ‘pinched’ into two daughter cells
What is the CD of haematopietic stem cells?
CD34
What is the CD of T helper cells?
CD4, TCR, CD3, CD28
What is the CD of cytotoxic T cells?
CD8, TCR, CD3, CD28
What is the CD of regulatory T cells?
CD4, CD25, TCR, CD3, CD28
What are the CD of B cells?
CD19, CD20, CD40, MHC II, B7
What are the CD of macrophages?
CD14, CD40, MHC II, B7
What are the CD of NK cells?
CD16, CD56
What is the function of CD 1?
This is the MHC MHC molecule that presents lipid molecules
What is the function of CD 2?
Found on thymocytes, T cells, and some natural killer cells that acts as a ligand for CD58 and CD59 and is involved in signal transduction and cell adhesion
What is the function of CD 3?
The signalling component of the T cell receptor (TCR) complex
What is the function of CD 4 ?
Found on helper T cells.
Co-receptor for MHC class II
Used by HIV to enter T cells
What is notable about CD 5 ?
Found in the majority of mantle cell lymphomas
What is CD8?
Found on cytotoxic T cells.
Co-receptor for MHC class I
Found on a subset of myeloid dendritic cells
What is the cell surface rector for macrophages?
CD 14
What CDs are expressed on reed steinberg cells?
CD 15 and CD 30
What is the function of CD 16?
Bind to the Fc portion of IgG antibodies
Fc component is the antibody class component
What is CD 21 located on ?
EBV
What is the function of Cd 95?
Acts as the FAS receptor, involved in apoptosis
What is the function of CD 56?
Unique marker for natural killer cells
What is the function of the rough endoplasmic reticulum?
Translation and folding of new proteins
manufacture of lysosomal enzymes
site of N-linked glycosylation
What cells typically have large rough endoplasmic reticulum?
Extensive RER include pancreatic cells, goblet cells, plasma cells
What is the function of the smooth endoplasmic reticulum?
Steroid, lipid synthesis
What cells have large smooth endoplasmic reticulum?
extensive SER include those of the adrenal cortex, hepatocytes, testes, ovaries
What is the function of Golgi apparatus?
Modifies, sorts, and packages these molecules that are destined for cell secretion
What is the function of mitochondria?
Aerobic respiration. Contains mitochondrial genome as circular DNA
What occurs in the nucleus?
DNA maintenance
RNA transcription
RNA splicing
What is the function of the nucleolus?
Ribosome production
What is the function of the function of a ribosome?
Translation
What is the function of the proteasome?
Along with the lysosome pathway involved in degradation of protein molecules that have been tagged with ubiquitin
What is the function of complement proteins?
Circulating plasma proteins involved in inflammatory and immune reaction of the body.
Complement proteins are involved in chemotaxis, cell lysis and opsonisation
What disease is associated with deficiency of C1 inhibitor deficiency?
Hereditary angiodema
Probable mechanism is uncontrolled release of bradykinin resulting in oedema of tissues
What disease is associated with classical pathway complement protein deficiency?
Immune complex diseases
HSP and SLE
What are the complement proteins in the classical pathway?
C1q, C1rs, C2, C4 deficiency (classical pathway components)
What is associated with a C3 deficiency?
Bacterial infections
What is associated with C5 deficiency?
Leiner disease
- recurrent diarrhoea, wasting and seborrhoeic dermatitis
What is associated with C5-C9 deficiency?
encodes the membrane attack complex (MAC)
particularly prone to Neisseria meningitidis infectio
What complement proteins encode MAC?
C5-C9
What is the function of IL-1?
Produced by macrophages
Induces fever
Acute inflammation
What is the function of IL-2?
Produced by Th-1 cells
Stimulates growth and differentiation of T cell response
What is the function of IL-3?
Produced by activated T helper cells
Stimulates differentiation and proliferation of myeloid progenitor cells
What is the function of IL-4?
Produced by Th2 cells
Stimulates proliferation and differentiation of B cells
What is the function of Il-5?
Produced by Th2 cells
Stimulate production of eosinophils
What is the function of IL -6?
Produced by Macrophages, Th2 cells
Stimulates differentiation of B cells
Induces fever
What is the function of IL - 8?
” Eight - brings a mate”
Produced by Macrophages
Neutrophil chemotaxis
What is the function of IL - 10?
Produced by Th2 cells
Inhibits Th1 cytokine production
Also known as human cytokine synthesis inhibitory factor and is an ‘anti-inflammatory’ cytokine
What is the function of IL -12?
Dendritic cells, macrophages, B cells
Activates NK cells and stimulates differentiation of naive T cells into Th1 cells
Function of TNF alpha?
Produced by macrophages
Induces fever
Neutrophil chemotaxis
What is the function of Interferon-γ?
Activates macrophages
What is the function of endothelin?
potent, long-acting vasoconstrictor and bronchoconstrictor
Thought to be behind primary pulmonary hypertension (endothelin antagonists are now used), cardiac failure, hepatorenal syndrome and Raynaud’s.
What is the mechanism by which endothelin works? What promotes release and inhibits release?
G-protein linked to phospholipase C leading to calcium release
Promotes release: angiotensin II, ADH, hypoxia, mechanical shearing forces
Inhibits release: Nitric oxide. prostacyclin
What diseases are associated with HLA-A3?
Haemochromatosis
What encodes the HLA antigen?
Chromosome 6
A,B,C - class one antigens
DP, DQ, DR - class two antigens
What diseases are associated with HLA-B51?
Behçet’s disease
What diseases are associated with HLA-B27?
ankylosing spondylitis
reactive arthritis
acute anterior uveitis
Ulcerative colitis
What diseases are associated with HLA-DQ2 or HLA-DA8?
Coeliac disease
What disease are associated with HLA-DR2?
narcolepsy
Goodpasture’s
What disease are associated with HLA-DR3?
dermatitis herpetiformis
Sjogren’s syndrome
primary biliary cirrhosis
What disease are associated with HLA-DR4?
type 1 diabetes mellitus*
rheumatoid arthritis - in particular the DRB1 gene (DRB104:01 and DRB104:04 hence the association with DR4)
What is the mechanism of type 1 hypersensitivity reaction?
Antigen reacts with IgE bound to mast cells
What is the mechanism of type 2 hypersensitivity reaction?
IgG or IgM binds to antigen on cell surface
What is the mechanism of type 3 hypersensitivity reaction?
Free antigen and antibody (IgG, IgA) combine