L4&5 Lymphoid Organs & Cell Migration

Question 1

What do Th cells produce?

Answer 1

Cytokines

Question 2

How many antigen binding domains do B cells have?

Answer 2

2 - heavy chain & light chain

Question 3

Is the immunity to viruses/cancer different to the immunity to bacteria/fungi?

Answer 3

Yes - viruses are intracellular parasites - need that extra level (T cell immunity)

Question 4

What are the primary lymphoid organs, and what are they sites of?

Answer 4

Bone marrow & thymus

Sites of haemopoiesis

Question 5

What are the secondary lymphoid organs, and what are they home to?

Answer 5

Lymph nodes, spleen, GALT

Home to most non-circulating immune cells

Question 6

Where do neutrophils originate?

Answer 6

Bone marrow

Question 7

Do neutrophils circulate?

Answer 7

No - one way journey to an infection, phagocytose, then die

Question 8

Where do DCs travel?

Answer 8

From bone marrow to spleen and tissues

Question 9

What is the function of the spleen?

Answer 9

To protect against septicaemia

Question 10

What do cytokines act as?

Answer 10

Intercellular communication molecules

Question 11

What are the features of cytokines?

Answer 11

Pleiotropic - many functions
Redundant - some can mediate a similar function
Extremely potent mediators - interact with high affinity receptors

Question 12

To what does IL-2 bind?

Answer 12

High affinity IL-2 receptor aka CD25

Question 13

What is the IL-2R composed of?

Answer 13

IL-2Rα chain, IL-2Rβ chain, IL-2Rγ chain

Question 14

What is required for full activation of the IL-2R?

Answer 14

Phosphorylation of residues on IL-2Rβ by JAKs phosphorylate tyrosine kinase. Signal transduction is then delivered to the nucleus via Ras-MAPK & PI3K-Akt pathways. IL-2Rα chain has no signal transducing activity itself

Question 15

How many different subclasses of Th cells are there?

Answer 15

4

Question 16

Patients with severe COVID-19 have higher serum levels of what, compared with individuals with mild disease?

Answer 16

Proinflammatory cytokines (TNFα, IL-1β, IL-2, IL-6) and chemokines (IL-8)

Question 17

How many faces does IL-6 have?

Answer 17

2 faces - Th1 and Th2 cytokine

Question 18

What happens to cells with a functional BCR/TCR?

Answer 18

They are then selected for tolerance to self-antigens and recognition of non-self-antigens (pathogens)

Question 19

What is Leucomax?

Answer 19

A recombinant GM-CSF (used in chemotherapy to target rapidly dividing cells in bone marrow, usually mid week between cycles, results in neutropenia)

Question 20

What is Neulasta (Amgen)?

Answer 20

A recombinant G-CSF

Question 21

Do most B cells reach circulation?

Answer 21

No

Question 22

Why do most B cells never reach circulation?

Answer 22

They fail to make a BCR or are autoreactive

Question 23

What happens if B cells recognise the body’s own self-antigens?

Answer 23

They are killed by apoptosis

Question 24

Where does T cell education take place?

Answer 24

Thymus

Question 25

What happens to the thymus as we get older?

Answer 25

It shrinks

Question 26

What is found in the outer cortex of the thymus?

Answer 26

Immature proliferating thymocytes

Question 27

What is found in the inner medulla of the thymus?

Answer 27

More mature thymocytes

Question 28

What does the spleen monitor?

Answer 28

Blood-borne infections

Question 29

What does the white pulp of the spleen contain?

Answer 29

T cells and B cells, arranged around PALS (periarteriolar lymphoid sheath)

Question 30

What does the red pulp of the spleen do?

Answer 30

Removes aging RBCs & platelets, then they are phagocytosed by macrophages

Question 31

What happens to a naive lymphocyte when it is activated by recognising its antigen?

Answer 31

It is retained and undergoes clonal expansion, it then differentiates into effector cells (days later), and exits lymph node

Question 32

What is the B cell area of the lymph node?

Answer 32

Cortex

Question 33

What are the T cell areas of the lymph node?

Answer 33

Paracortex and medulla

Question 34

Where does homing of immune cells from circulation occur?

Answer 34

HEV (high endothelial venule) sites

Question 35

What does the primary follicle of the lymph node contain?

Answer 35

Mainly mature naive B cells

Question 36

What is the site of B cell proliferation after antigen recognition?

Answer 36

Germinal centre of secondary follicle

Question 37

Where is MALT (mucosal-associated lymphoid tissue) found?

Answer 37

GI, respiratory & genitourinary tracts GALT(GI-associated) in gut and BALT (bronchus-associated) in lungs Intestine: mesenteric LNs, Peyer's patches (mainly lower ileum)

Question 38

5 classic symptoms of inflammation:

Answer 38

redness (rubor), heat (calor), pain (dolar), swelling (tumor), altered function

Question 39

What is inflammation characterised by?

Answer 39

Immune cell migration, serum protein & cellular leakage into inflammatory site (oedema)

Question 40

Where can cell migration take place?

Answer 40

1. to sites of infection and inflammation 2. from blood to lymph and vice versa 3. from primary to secondary lymphoid organs 4. between secondary lymphoid organs

Question 41

What is the significance of 1-2% of cells circulating per day?

Answer 41

There is a better chance of encounter with a foreign pathogen

Question 42

What are the 3 components of the inflammatory response?

Answer 42

1. blood supply is increased to the area 2. capillary permeability increases, allowing exudation of serum proteins in surrounding tissue (Abs & complement, acute-phase proteins) 3. leukocyte migration to site: phased appearance

Question 43

What is chemotaxis?

Answer 43

Directional migration of cells up a concentration gradient of chemotactic molecules

Question 44

What is chemokinesis?

Answer 44

Non-directional movement

Question 45

What is a chemotactic source?

Answer 45

Site of inflammation, tissue damage, parasitic infection, complement C5a, or immune reactions

Question 46

What are the 2 binding sites of chemokines?

Answer 46

1. to proteoglycans on blood side of blood vessels | 2. to chemokine receptors on leukocytes

Question 47

What produces IL-8 (CXCL7), and what does IL-8 do?

Answer 47

IL-8 is produced by macrophages and it attracts neutrophils to the site of infection/inflammation

Question 48

What chemokines are abbreviated by CXC?

Answer 48

α chemokines

Question 49

What chemokines are abbreviated by CC?

Answer 49

β chemokines

Question 50

What does C5a do, besides act as a complement protein?

Answer 50

It is a chemoattractant for neutrophils & macrophages

Question 51

What happens during the Acute Phase Response?

Answer 51

Increase in the appearance of various proteins in circulation i.e. cytokines & anti-microbial proteins. Activated macrophages & DCs following recognition of PAMPs

Question 52

Are CRP levels increased or decreased in severe COVID-19 cases?

Answer 52

Increased

Question 53

In response to what cytokines does CRP synthesis in the liver increase 1000-fold during infection?

Answer 53

IL-1 and IL-6 | IL-6 is also elevated in severe COVID-19 cases