topic 1 steve and cris

Question 1

describe necrosis vs apoptosis

Question 2

define inflammation, the triggers and stages (one sentence per stage describing what it actually means)

Answer 2

aa

Question 3

describe acute inflammation from sophies notes

Answer 3

inflammation is triggered as endothelial cells are activated, these produce cytokinds and prostaglandins which cause vasodilation and increased permability of blood vells in the injured tissue. This leads to hyperameia, exudation, stasis and margination.
Selectins are expressed on the cell surfacing with integrin drawin gthe neutrophils in to attack the cell using oxygen dependent and oxygen indepedent methods. (increased cell adhesion molecules)

Either this works and the inflammation subsides or more leukocytes move into the cell and the inflammation becomes chronic

Question 4

how do neutrophils work in inflammation, what activates them?

Question 5

draw out the resolution repair and regeneration diagram

Question 6

describe chronic inflammation

Question 7

what are the local effects vs systemic effects

Question 8

describe granuloma formation type

Question 9

il-1 tnf-a

Answer 9

learn this please i beg you learn this

Question 10

describe the healing flow chart

Question 11

definition of virus

Answer 11

A virus is a nucleic acid that is wrapped in a protein shell formed from viral proteins. They cannot self replicate, synthesise proteins, derive energy or replicate their own nucleic acid, therefore they need a host cell. Some viruses have an envelope which is a host cell membrane that the virus takes with it as it leaves the cell and certain proteins are embedded in this host cell membrane. An example of an enveloped virus is HIV.

Question 12

describe virus cycle

Answer 12

The viral cell cycle: A virus in order to cause infection has to bind to a human cell, enter the human cell, take the protein shell off (uncoating), replicate proteins and nucleic acid, reassemble and then leave the cell. (maybe just draw the cycle).

Question 13

describe virulence factors

Answer 13

Question 14

is strep pneum gram negative or gram positive. explain

Answer 14

Gram negative bacteria have a single, and thus relatively thinner, peptidoglycan cell wall layer than gram positive bacteria that have many, and thus thicker, peptidoglycan cell wall layers. Furthermore, gram negative bacteria have an outer membrane, whilst the gram positive bacteria lack this structure. Streptococcus pneumoniae is a gram positive bacteria.

Question 15

what antibiotics can we use to treat strep pneum

Answer 15

^The bacteria have developed resistance not the patients
In response to a - penicillin does not inhibit transpeptidase formation, it inhibits transpeptidase activity, which is formation of the bacterial cell wall by crosslinking sugars in the peptidoglycan cell wall, affecting cell wall integrity and ultimately leading to cell lysis.

Question 16

describe outcomes of immune system activation and how we can prevent spread of bacteria

Answer 16

Hand hygiene
Patient placement
Environmental cleaning
PPE
Waste management
Safe disposal of sharps
Reprocessing of reusable equipment

Question 17

describe direct transmission vs indrect trasnmission

Answer 17

Question 18

describe innate vs adaptive

Answer 18

can divide into two

Question 19

humoral vs cell mediated

Question 20

heplper vs cytotoxic

Question 21

HLA 1 vs HLA 2

Question 22

basic definition of antigenic drig vs antigenic shift

Question 23

explain cris’s journey to HIv

Answer 23

as the virus is repliaced for the HIV infected CD4 bearing T cells, components are presented on the HLA class 1 cells. CD8 cells then recognises this and it leads the killing of the cell, resulting in a depletion of CD4 T cells.

Question 24

explain steves journey to HIV

Answer 24

HIv is an enveloped virus to which a protein GP 120 is found on the envelope. GP 120 binds to CD4 helper T ells and a confromation change occurs allowing the virus envelope to fuse with the lymphocyte, and the virus enteres the cell. Reverse transcriptase makes a DNA copy of RNA inside the lymphocyte the capside is digested. Viral DNA is removed from RNA and enterse the cell. Integrase intergrates vrial DNA onto the host genome. This viral DNA is transcribed the viral RNA is transloated into viral proteins. This virus destroys the t cells and after the virus assembles and buds off from the T cells.

protease then organises other enzymes, ready for the cycle to start agin. The result of this viral infection is that it leads to a decrease in CD4 T cells.

Question 25

what is innate immunity comprised of? what are the external vs internal factors of innate immuniyt

Answer 25

how

Question 26

is the lymphatic system related to innate immunity

Answer 26

s the

Question 27

how is the complement system related to innate immunity

Question 28

describe neutrophils, vs macrophages vs nk cells

Answer 28

h

Question 29

ow do the cells of the innate immune system recongise pathogens?

Question 30

desribe the process of healing if the lung patient survives/

Answer 30

Organisation of lung tissue occurs - macrophages secrete growth factors e.g fibroblast growth factor (for increased proliferation of fibroblasts), endothelial growth factor (for angiogenesis). Once the tissue has many active fibroblasts and blood vessels it is called granulation tissue. Reorganisation of the collagen fibres and regression of blood vessels (wound contraction) turns granulation tissue into a fibrous scar in the lungs. Regeneration might occur in tissues with high turnover (e.g epithelium in the lungs) via the proliferation of stem cells.

Question 31

discuss the effects of cell injury/stress on individual lung cells

Answer 31

The two major factors in cell injury are loss of ATP and disruption of plasma membranes. Loss of ATP can be caused by decreased O2, loss of mitochondrial enzymes, or loss of the mitochondria themselves. The consequences of this are the inability of enzymes to function, especially repairing enzymes, and the failure of ATP dependent membrane pumps. Failure of membrane pumps can cause the cell to lyse via osmosis (necrosis) (also called oncosis), it can also increase intracellular Ca2+. Increased intracellular Ca2+ acts as a 2nd messenger to activate digestive enzymes which cause autolysis and necrosis. Other consequences of disruption to plasma membranes include direct lysis (damage to the cell membrane) and damage to lysosomes releasing digestive enzymes and acidic contents leading to autolysis and necrosis via autodigestion. The plasma membranes of mitochondria can also burst. This releases Cytochrome C into the cytosol which activates caspases triggering apoptosis. If the stress to lung cells is not too severe there may also be metaplastic change from type 1 pneumocytes to a cell type that can better resist the bacterial insult.

Question 32

describe adaptive immunity from sophies notes

Question 33

Describe the mechanism resulting in his symptoms of tiredness, fever and weight loss.

Answer 33

Cytokines released from injured/necrotic cells (and white blood cells) enter “the circulation then act on cells in the hypothalamus to stimulate symptoms such as tiredness, fever and loss of appetite which would contribute to weight loss.

Question 34

Describe the process of healing in the lung if the patient survives.

Answer 34

Organisation of lung tissue occurs - macrophages secrete growth factors e.g fibroblast growth factor (for increased proliferation of fibroblasts), endothelial growth factor (for angiogenesis). Once the tissue has many active fibroblasts and blood vessels it is called granulation tissue. Reorganisation of the collagen fibres and regression of blood vessels (wound contraction) turns granulation tissue into a fibrous scar in the lungs. Regeneration might occur in tissues with high turnover (e.g epithelium in the lungs) via the proliferation of stem cells.

Question 35

Discuss the effects of cell injury and stress on the individual lung cells.

Answer 35

The two major factors in cell injury are loss of ATP and disruption of plasma membranes. Loss of ATP can be caused by decreased O2, loss of mitochondrial enzymes, or loss of the mitochondria themselves. The consequences of this are the inability of enzymes to function, especially repairing enzymes, and the failure of ATP dependent membrane pumps. Failure of membrane pumps can cause the cell to lyse via osmosis (necrosis) (also called oncosis), it can also increase intracellular Ca2+. Increased intracellular Ca2+ acts as a 2nd messenger to activate digestive enzymes which cause autolysis and necrosis. Other consequences of disruption to plasma membranes include direct lysis (damage to the cell membrane) and damage to lysosomes releasing digestive enzymes and acidic contents leading to autolysis and necrosis via autodigestion. The plasma membranes of mitochondria can also burst. This releases Cytochrome C into the cytosol which activates caspases triggering apoptosis. If the stress to lung cells is not too severe there may also be metaplastic change from type 1 pneumocytes to a cell type that can better resist the bacterial insult.

Question 36

What histological findings would indicate signs of necrosis?

Answer 36

Loss of nuclear structure, cell swelling, pale cytoplasm (‘ghost cells’). There may also be lots of neutrophils present, indicating acute inflammation is occurring. Vascular permeability.

Question 37

Explain the difference between a CD8 and CD4 T-cell response, and which is more likely to be relevant in this scenario?

Answer 37

CD4 helper T cells are the cells most relevant in this scenario. CD4 along with CD3 and TCR are able to identify bacterial fragments presented on HLA II by antigen presenting cells such as macrophages and neutrophils. In contrast, CD8 cytotoxic T cells have a CD8 which recognises intracellular antigens such as proteins produced by a virus or cancer mutation within the context of an MHC/HLA I protein.

Question 38

Explain what is causing the mans shortness of breath

Answer 38

The activation of endothelium near the site of injury during acute inflammation triggers the release of cytokines which cause vasodilation and increased permeability of blood vessels. This causes blood flow changes and the loss of a fibrinous exudate into the tissue which contains fluids and proteins, causing tissue oedema. The exudate contains fibrinogen which is converted into fibrin to help seal damaged blood vessels and stabilise damaged tissue. The fibrin can accumulate onto the pleura and become compacted by organ movement creating a dense fibrinous exudate (pleural effusion). This buildup of dense exudate and oedema causes shortness of breath.
The release of inflammatory cytokines such as TNFa act on the endothelial cells near the site of injury to cause upregulation of selectin molecules and a decrease in cytoskeleton stabilisers that make the blood vessels more leaky and increase blood flow to the area. The leakiness of the vessels enables fibrin and fibronectin to move into the tissue and form an extracellular matrix for neutrophils to move along. The fibrinous exudate also means that this part of the lung fills up with fluid, decreasing the ability of the lung to efficiently exchange oxygen and carbon dioxide at the alveoli. This reduced gas exchange can be felt as a shortness of breath as less air can fill the lungs.

Question 39

If these symptoms were consistent with a viral infection, outline the immune factors that will have become active in this man’s body to assist him to deal with the infection

Answer 39

CD8+ cytotoxic t cells will kill infected cells by recognising the viral antigens presented on HLA I on infected cells.
B cells will proliferate and differentiate into plasma cells that produce neutralising antibodies, which bind viral proteins to prevent viral entry into cells.
Infected cells will produce IFN in response to detecting viral genome within the cells

Question 40

What aspects of his response to the infection might account for his fever, sweating and loss of interest in food?

Answer 40

Chronic inflammation: high levels of circulating pro-inflammatory cytokines such as IFN-alpha, IL-1, IL-6 and TNF-alpha act on the hypothalamus to induce fever, sweating and to reduce appetite.
Inflammatory response: local effects - vasodilation (calor - heat), systemic effects - pyrexia (caused by cytokines and acute phase reactions which can also impact appetite).

Question 41

What aspects of his response to the infection might account for his mildly enlarged tonsils, widespread cervical, axillary and inguinal lymphadenopathy?

Answer 41

Tonsils: first line defence against inhaled or ingested pathogens involved in innate immune response. Proliferation of immune cells in tonsils causing enlargement
Lymphadenopathy: secondary lymphoid organs where mature lymphocytes encounter antigens and undergo proliferation, therefore causing swollen lymph nodes during a response to infection.

Question 42

If you suspect that the virus involved is HIV, what would you expect to find in the man’s blood at this time that might confirm such a diagnosis?

Answer 42

Reduced CD4+ T cell count, antibodies against HIV viral proteins (gp120 spike protein) and detectable viral RNA.
Seroconversion illness (could also mention that his symptoms are indicative that he is likely in this phase) - if measured at this point would be able to notice detectable levels of antibodies in blood.

Question 43

Explain 3 mechanisms which antibodies use to contribute to the immune response

Answer 43

Neutralisation - block entry of pathogen into cells by binding receptors
Opsonization - tagging cells for phagocytosis
Complement Activation (classical pathway)

Question 44

If the symptoms were confirmed to be associated with HIV infection, outline the course you would expect the illness to take. Describe the changes in concentrations of viral and immune factors that would be measurable in the man’s blood as the illness progresses. Describe what you would expect to see in these factors after the man starts treatment for HIV.

Answer 44

At the start of infection the virus level/load will increase quickly.
Seroconversion illness (flu-like) - occurs around 4-6 weeks, immune system reacts, CD4 count and viral load decrease.
Asymptomatic HIV: Can last many years. Viral load can reach around 50,000 copies per ml of blood. Checkpoints - CD4<500 (risk of illness - treatment?), CD4<200 (risk of illness increases).
Late stage HIV: CD4<50 usually very sick. Lack of CD4+ T cells means that opportunistic infections arise such as toxoplasmosis, Candida albicans infections.
With treatment:
Notice that the viral load will begin decreasing (to a point where it is undetectable) and CD4 count will begin to increase again.