Atypical Immune response

Question 1

what are the 3 possible effects to infection?

Answer 1

sterilising immunity, non sterilising immunity and immune failure

Question 2

how can viruses line Tb evade this strong immune response?

Answer 2

the bacterium basically inhibits the phagosome which prevents it from binding with lysosome and can’t phagocytose cell

Question 3

what characteristics does the HIV virus display?

Answer 3

-has a protein coat
-envelope virus
-GP120 binds to receptors on cell surface
-belongs to a group of viruses called retroviruses

Question 4

what causes the virus to escape the initial immune control?

Answer 4

failure of the main infected cell - CD4 T helper cell, they begin to fail and numbers of them decline rapidly

Question 5

what keeps HIV in check?

Answer 5

cytotoxic T cells CD8+

Question 6

sterilising immunity?

Answer 6

recovery - due to a combo of innate and acquired immune response

Question 7

non sterilising immunity?

Answer 7

chronic infection- dosent fullt clear the infection

Question 8

immune failure?

Answer 8

immune system fails to clear the infection - overwhelms individual leading to death

Question 9

what causes TB?

Answer 9

mycobacterium tuberculosis

Question 10

what characterises mycobacterium TB?

Answer 10

-slow growing
-takes weeks to grow on agar plates so challenging for medical professionals

Question 11

how is TB infected?

Answer 11

-inhalation
-lodges in lungs if not cleared
-gives rise to progressive pulmonary infections
-prodominantly infects lungs

Question 12

which part of lungs does TB affect?

Answer 12

apices, increases higher up the lungs where there is no fluid

Question 13

what happens to lungs in TB?

Answer 13

normal spongy architecture changes to cheesy material

Question 14

what happens when TB is not cleared?

Answer 14

Rarely, 5-10% of infected individuals will go on to develop progressive disease, a progressive pneumonia which is very destructive and produces cavities destroying normal lung parenchyma. These cavities open into the bronchi, allowing spread of the mycobacterium through coughing.

Question 15

what is immunity like to TB?

Answer 15

• Non sterilising, but very vigorous
• Cell mediated immunity crucial - antibodies do form but don’t seem to play a role in protection
• Macrophages remain key controlling cell, as we see in granuloma
• T cell production of interferon gamma, which activates macrophages
• Cytokines involved in this process all key
  For 90-95% of people, this immune response will keep the organism at check and control it, but it wont clear it.

Question 16

what are the triggers for reactivation of TB which has not been cleared?

Answer 16

immunosuppression, coinfection with HIV, smoking, or age, as immunity wanes

Question 17

how does TB evade the immune system?

Answer 17

mycobacterium can survive within a phagocytic cell

Question 18

why can mycobacterium can survive within a phagocytic cell?

Answer 18

Firstly, it subverts the intracellular trafficking that occurs following phagocytosis. Normally a phagosome would fuse with a lysosome. But the bacterium alters the constitutents of the phagosome so that it becomes coated with a host protein called Coronin 1, an actin associated protein that inhibits the ability of the phagosome to fuse with the lysosome, which subverts the ability of phagocytes to mediate killing of the bacteria

Question 19

what does a retrovirus mean?

Answer 19

reverse the normal flow of information from DNA → RNA → protein. They reverse transcribe the genome of the HIV (RNA) into back DNA, which is then translocated in the nucleus and integrated into the host genome.

Question 20

what allows HIV to bind to CD4 cells and CCR5

Answer 20

gp120

Question 21

what is the main cell that the virus HIV attacks?

Answer 21

Cd4+ T helper cells
stops the ability of them being produced

Question 22

what cells keep HIV in check for thr first few months?

Answer 22

CD8 T cells

Question 23

what is the viral set point?

Answer 23

at some point a draw is reached when a fair number of CD8+ cells are able to target the virus, although it has evaded many of the more important responses, but any more mutation would likely result in a ‘lack of fitness’ for the viruses to replicate or do what they are supposed to

Question 24

what happens to most people the first time they get dengue?

Answer 24

recover within a week without any ill effects

Question 25

what is the key pathological feature of dengue?

Answer 25

destruction of the endothelial cell capillary barrier and a variety of inflammatory cytokines produced by virally infected macrophages can lead to this endothelial cell barrier being broken down, and fluid escapes from the capillaries to the tissue.

Question 26

what can the fluid leakage cause in dengue?

Answer 26

This gives rise to oedema, that can fill up the lungs, areas of the brain and have multi-system effects which if unchecked can progress to severe illness, and death.

Question 27

what are the symptoms of febrile dengue?

Answer 27

• High fever and chills
• Typically persistent or unremitting, although a saddleback pattern can be observed
• Children experience a higher fever and vomiting but are usually less symptomatic than adolescents and adults, except that febrile convulsions can occur.
• Fever lasts for 3-7 days from illness onset.
• Systemic symptoms such as headache, malaise, retro-orbital pain, arthralgia, myalgia, bone pain, nausea, vomiting and altered taste sensation.
• Presence of upper respiratory symptoms help to differentiate influenza from dengue.
• Examination findings can include rash, flush, conjunctival or pharyngeal injection, mild bleeding manifestations, generalised lymphadenopathy and a palpable liver.
• A tourniquet test can be positive as it demonstrates impaired capillary function but is a non-specific finding.

Question 28

what are the features of severe dengue?

Answer 28

• Characterised by severe plasma leakage
• Haemorrhage
• Multi-system organ damage

Question 29

what is the rule of thumb for the different types of dengue?

Answer 29

-recovery from one gives you lifelong immunity from that specific type
-a second infection by a different type leads to dengue heamorragic fever