MCD

Question 1

What is an important risk factor for C.diff infection?

Answer 1

antibiotic tx

Question 2

What is the most common helminth infection?

Answer 2

Ascariasis

Question 3

What is anchorage dependence?

Answer 3

Describes that cells need to be attached to ECM in order for survival, protein synthesis and cellular proliferation to occur

Question 4

What is the most important kind of receptor in mediating anchorage dependence?

Answer 4

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.

Question 5

How do signals generated from integrins interact with signals generated from the binding of growth factors?

Answer 5

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.

Question 6

A 68 year-old man has a Hb concentration slightly higher than the normal range. How is the normal range determined?

Answer 6

A normal range is just a range taken from a healthy population

Question 7

Give two important factors that can affect the parameters of the normal range of Hb conc.

Answer 7

Ethnicity, size

Question 8

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?

Answer 8

An Erythropoietin secreting renal tumour causing increased erythropoiesis so increased Hb

Question 9

What are two possible causes of increased Hb and their mechanisms?

Answer 9

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

Question 10

What is immunological tolerance? In what kind of immune cells does immunological tolerance occur?

Answer 10

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.

Question 11

What is the difference between central and peripheral tolerance?

Answer 11

Central tolerance occurs during lymphocyte development

Peripheral tolerance - mechanisms to generate tolerance once mature lymphocytes have been developed

Question 12

What is the mechanism of central tolerance?

Answer 12

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).

Question 13

What is the mechanism of peripheral tolerance?

Answer 13

Peripheral tolerance - mechanisms to generate tolerance once mature lymphocytes have been developed - involves anergy, ignorance of antigen at immunologically privileged sites and suppression/regulation.

Question 14

What is anergy?

Answer 14

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.

Question 15

what is immunological ignorance?

Answer 15

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

Question 16

describe the process of suppression and regulation during peripheral tolerance

Answer 16

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.

Question 17

What is the main difference between type II and type III hypersensitivity reactions in autoimmune disease?

Answer 17

Type 2 - insoluble antigens (cell surface or matrix bound antigens), antibody mediated cytotoxicity

Type 3 - soluble antigens, immune complex mediated

Question 18

What are 4 ways in which pathogenic infections can contribute to the onset of autoimmune disease?

Answer 18

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

Question 19

Name three physiological inhibitors of the clotting cascade.

Answer 19

Antithrombin, plasminogen activator, protein c (by thrombin)

Question 20

What is the mechanism of action of warfarin?

Answer 20

Vitamin K epoxide reductase inhibitor

Reduced levels of factors 2,7,9,10

Question 21

Which plasma protein does heparin act on to have its anticoagulant effects?

Answer 21

Antithrombin

Question 22

Explain the adenoma-carcinoma sequence in colorectal cancer.

Answer 22

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

Question 23

What are the clinical features of colorectal cancer?

Answer 23

PR bleeding
unexplained iron deficiency anaemia
change in bowel habit 
abdominal cramps
mucus PR
constitutional (fatigue, weight loss)

Question 24

Explain the Dukes staging of colorectal cancer. How does this relate to prognosis?

Answer 24

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)

Question 25

What are bacterial exotoxins and bacterial endotoxins?

Answer 25

Endotoxins - LPS by gram negative bacteria

Exotoxins - protein factors produced by the bacteria

Question 26

What are pyrotoxins?

Answer 26

factors released by bacteria which cause cytokine release therefore producing fever

Question 27

Name two bacterial pathogens that use pyrotoxins

Answer 27

streptococcus pyogenes staphyloccoccus aures

Question 28

Name the general term for the type of toxin that binds directly to both MHCII and T cell receptors

Answer 28

superantigen

Question 29

Name 5 virulence factors and for each one, name a bacterial pathogen that uses them

Answer 29

neurotoxins - botulinum

enterotoxins - vibrio cholerae

Pili - neisseria gonorrhoeae

Secretion systems 3 (samonella) and 4 (legionaires)

capsule - step pneumoniea