MCD Flashcards
What is an important risk factor for C.diff infection?
antibiotic tx
What is the most common helminth infection?
Ascariasis
What is anchorage dependence?
Describes that cells need to be attached to ECM in order for survival, protein synthesis and cellular proliferation to occur
What is the most important kind of receptor in mediating anchorage dependence?
integrins - heterodimers of alpha/beta subunits(both span plasma membrane once). Have an extracellular “head” and “tails” which span the plasma membrane. Linked, via actin binding proteins, to actin cytoskeleton of cell.
How do signals generated from integrins interact with signals generated from the binding of growth factors?
Integrin signalling complex and growth factor receptors can each activate identical signalling pathways eg MAPK, but individually the action might be weak. Together can act synergistically for strong and sustained activation.
A 68 year-old man has a Hb concentration slightly higher than the normal range. How is the normal range determined?
A normal range is just a range taken from a healthy population
Give two important factors that can affect the parameters of the normal range of Hb conc.
Ethnicity, size
A 68 yo man has a scan and he has a mass on his left kidney. Considering this, what is the most likely cause for his elevated Hb?
An Erythropoietin secreting renal tumour causing increased erythropoiesis so increased Hb
What are two possible causes of increased Hb and their mechanisms?
Polycythaemia Vera- an intrinsic bone marrow disorder, myeloproliferative neoplasm independent of erythropoietin
Chronic hypoxia due to altitude or COPD leading to increased erythropoietin production
Blood doping (unlikely with old man)
Erythropoietin secreting tumour
What is immunological tolerance? In what kind of immune cells does immunological tolerance occur?
Acquired inability to respond with an immune reaction to an antigenic stimulus which organism normally responds.
“3As”
Acquired - involves cells of the acquired immune system and is ‘learned’
Antigen specific
Active processes in neonates, the effects of which are maintained throughout life
Involves cells of the acquired/adaptive immune system - B and T cells.
What is the difference between central and peripheral tolerance?
Central tolerance occurs during lymphocyte development
Peripheral tolerance - mechanisms to generate tolerance once mature lymphocytes have been developed
What is the mechanism of central tolerance?
occurs during lymphocyte development, involves T cell selection in the thymus (negative selection: high affinity, high abundance of TCR for peptide antigen on MHC`) and B cell selection in the bone marrow (crosslinking of surface Immunoglobulin by polyvalent antigens expressed on bone marrow stromal cells facilitates deletion).
What is the mechanism of peripheral tolerance?
Peripheral tolerance - mechanisms to generate tolerance once mature lymphocytes have been developed - involves anergy, ignorance of antigen at immunologically privileged sites and suppression/regulation.
What is anergy?
The presentation of an antigen in the absence of costimulation under unusual circumstances (no pathogen/inflammation to stimulate PRR on APC) – this makes the lymphocytes enter a refractory state.
what is immunological ignorance?
Occurs when the antigen concentration is too low. It can be due to the absence of antigen presenting molecules, It occurs at immunologically privileged sites where the immune cells don’t normally penetrate - cells in site are MHC Class 2 negative. This is ignorance – the T cells never see their antigen
describe the process of suppression and regulation during peripheral tolerance
Autoreactive T cells may be present that don’t respond to autoantigens.
Tregs are specialised cells that can regulate the activity of other T cells.
What is the main difference between type II and type III hypersensitivity reactions in autoimmune disease?
Type 2 - insoluble antigens (cell surface or matrix bound antigens), antibody mediated cytotoxicity
Type 3 - soluble antigens, immune complex mediated
What are 4 ways in which pathogenic infections can contribute to the onset of autoimmune disease?
Can reduce ignorance through tissue damage- expose immunologically privileged sites (NB Sympathetic Ophthalmia is not pathogenic but example of failure of ignorance)
Immune deviation, shift in type of immune response e.g. Th1 to th2 response
Induction of co-stimulatory molecules or inappropriate MHC class II expression- pro inflammatory
Molecular mimicry of self: If pathogen expresses molecule that is very similar to self molecule then induces immune response against self
Name three physiological inhibitors of the clotting cascade.
Antithrombin, plasminogen activator, protein c (by thrombin)
What is the mechanism of action of warfarin?
Vitamin K epoxide reductase inhibitor
Reduced levels of factors 2,7,9,10
Which plasma protein does heparin act on to have its anticoagulant effects?
Antithrombin
Explain the adenoma-carcinoma sequence in colorectal cancer.
APC gene damage leads to hyperproliferation of the epithelium
K-ras (oncogene) mutation combined with hypomethylation of DNA leads to formation of adenoma
Mutation of p53 leads to development of a carcinoma
Smads and p53, loss of heterozygosity and telomerase activation - cancer
What are the clinical features of colorectal cancer?
PR bleeding unexplained iron deficiency anaemia change in bowel habit abdominal cramps mucus PR constitutional (fatigue, weight loss)
Explain the Dukes staging of colorectal cancer. How does this relate to prognosis?
It is a method of explaining how far the tumour has spread in the body. It is a good measure of prognosis. It also determines what type of treatment can be given to the patient. The worse the stage the worse the prognosis
Dukes’ A - confined within the bowel wall (including the muscle)
Dukes’ B – growth beyond the muscularis propria
Dukes’ C1 - metastasis in lymph nodes, apical LN negative
Dukes‘ C2 – apical LN positive (distant metastatic spread)
What are bacterial exotoxins and bacterial endotoxins?
Endotoxins - LPS by gram negative bacteria
Exotoxins - protein factors produced by the bacteria
What are pyrotoxins?
factors released by bacteria which cause cytokine release therefore producing fever
Name two bacterial pathogens that use pyrotoxins
streptococcus pyogenes staphyloccoccus aures
Name the general term for the type of toxin that binds directly to both MHCII and T cell receptors
superantigen
Name 5 virulence factors and for each one, name a bacterial pathogen that uses them
neurotoxins - botulinum
enterotoxins - vibrio cholerae
Pili - neisseria gonorrhoeae
Secretion systems 3 (samonella) and 4 (legionaires)
capsule - step pneumoniea
