Immunology

Question 1

Interleukin-1beta (pro-inflammatory cytokine)

Answer 1

• activates vascular endothelium, makes it sticky so it can communicate with leukocytes
• increases access of effector cells
• produces fever
• activates lymphocytes
• local tissue destruction
• leads to production of interleukin-6

Question 2

TNF-alpha (pro-inflammatory cytokine)

Answer 2

• activates vascular endothelium
• increases vascular permeability (leads to increased IgG, complement, and cells to tissues and increased drainage of lymph nodes)
• systemic effcts: fever, moblization of metabolites, shock
• it also activates the macrophages, helps them become better killers, increases vasculature permeability & that means fluids can leave the vasculature and go to the site of infection (that is really important because there are some soluble components of immunity. we have discussed complement but also immunoglobulins can leave vasculature thanks to TFN-a)

Question 3

interleukin-6 (pro-inflammatory cytokine)

Answer 3

• activate lymphocytes (important in the production of inflammatory type of adaptive cells called TH17, increases antibody production, particularly of IgA, leads to fever
• increased antibody production

Question 4

Chemokine (CXCL8)

Answer 4

• chemotactic factor recruits neutrophils, basophils and T cells to site of infection

Question 5

IL-12

Answer 5

• Activates NK cells
• induces the differentiation of CD4 T cells into TH1 cells
• leads to cytotoxic T cell differentiation and is really important for the differentation of CD4 T cells into TH1 cells.

Question 6

what promotes leucocyte recruitment?

Answer 6

Pro-inflammatory cytokines and chemokines

Question 7

Who are the first responders to the site of infection?

what cell takes DAYS to respond?

Answer 7

NEUTROPHILS are the first responders, and arrive at the site of infection within hours
Monocytes takes 2-3 days

Question 8

in response to chemokine production what happens to leukocyte

Answer 8

1. chemokine will bind to receptors as neutrophil (leukocyte) is rolling along the vascular endothelium.
2. binding of chemokine causes the leukocyte (neutrophil, monocyte) to stop and SPREAD OUT, adhering really strongly via integrins.
3. chemokine causes integrins that are normally into a low-affinity state to go into a HIGH-AFFINITY state.

Question 9

what activates the vascular endothelium ?

Answer 9

cytokines

Question 10

What are selectins?

Answer 10

adhesion molecules that allow leucocytes to roll on the vascular endothelium

Question 11

What state are integrins normally in?

what molecule causes them to change state and to what?

Answer 11

integrins are normally in a low-affinity state
CHEMOKINES activate integrins to become high affinity (leukocyte spread out, high-integrins, leaves vasculature, via a chemokine gradient, goes to the site of infection)

Question 12

How do leukocytes leave the vasculature ? and what directs them towards the site of infection?HOW THE HELL DO THEY KNOW WHERE TO GO ?

Answer 12

Leukocytes transmigrate out of the vasculature and follow a chemotactic gradient towards the site of infection.

Question 13

What are type I interferons?

Answer 13

type I interferons are CYTOKINES with potent antiviral activity

Question 14

What cell types can Type I interferons activate?

Answer 14

• NK cells and Dendritic cells

Question 15

How does an NK cell recognise self from non-self?

Answer 15

NK cells have two types of receptors, activating receptors and inhibitory receptors. 
if a cell is stressed/infected, it will express a stress ligand for the NK cell, NK cell will recognise this via its activating receptor. 
If the inhibitory receptor of the NK cell recognise an MHC class I molecule , there is a negative signal occuring, preventing the NK cell from killing the cell.

Question 16

What sort of phagocyte is likely to be involved in combating chronic infections?

Answer 16

Monocytes/macrophages.
macrophages and monocytes are slow responders and they can be activated to become super killers (triggering PRR) to deal with this sort of chronic, slow growing infection.

Question 17

What do TLR 2 and TLR6 (dimer) recognise?

Answer 17

TLR 2,6 recognise components of the gram +ve cell wall.
they recognise diacyl lipopeptides
e.g on Mycobacteria

TLR 2 6 are membrane proteins at the cell surface

Question 18

What do TLR 2 and TLR 1 recognise ?

Answer 18

TLR-2 & TLR-1 recognise triacyl lipopeptides of the gram positive cell wall. for example of S. aureus.

TLR-2 and TLR-1 are membrane proteins at the cell surface

Question 19

What does TLR-5 recognise and where is it?

Answer 19

TLR-5 membrane protein on the cell surface.
recognises FLAGELLA.
e.g V. cholerae

Question 20

What does TLR-4 recognise and where is it?

Answer 20

TLR-4 Membrane protein on the cell surface
recognises LPS, major structure of gram negative cell wall.
e.g E.coli

Question 21

What does TLR-3 recognise and where is it?

Answer 21

TLR-3 recognises dsRNA

located on surface of endosomes.

Question 22

What does TLR-7 recognise and where is it?

Answer 22

TLR-7 recognises ssRNA

located on the surface of endosomes

Question 23

What does TLR-9 recognise and where is it ?

Answer 23

TLR-9 recognises CpG DNA

located on the surface of endosomes

Question 24

What do rig-like helicases recognise and what happens as a result ?

Answer 24

Rig like helicases (Rig-1 and MDA-5 are located in the cytoplasm and recognise viral dsRNA, pattern recognition by RIG like helicases leads to INTERFERON AND INFLAMMATORY CYTOKINE PRODUCTION.

double-stranded viral RNAs can be recognised by TLRs in endosomes and by RIG-I or MDA-5 in the cytosol to induce the expression of interferons.

Question 25

How is the production of interleukin-1beta different to other pro-inflammatory cytokines?

Answer 25

Unlike other pro-inflammaotry cytokines, production of bioactive IL-1Beta rqeuires:
TWO SIGNALS
SIGNAL 1: pattern recognition from a PRR that leads to transcription and translation of Pro-IL-1Beta
SIGNAL 2: cleavage of Pro-IL-1beta by the inflammasome.

thus we end up with the mature form of IL-1beta

Question 26

what is a critical difference between receptors of cells of the innate immune system and cells of the adaptive immune system?

Answer 26

Lymphocytes have their antigen receptors, and will uniquely express their own. Contrast that to a macrophage, a macrophage has dozens of PRR, it will have TLR, NLR, Rig-like helicases.

Question 27

What sort of chains are B cell receptors composed of ?

Answer 27

Two identical heavy chains and two identical light chains

Question 28

What sort of chains are T cell receptors composed of?

Answer 28

an alpha and beta chain