L4&5 Lymphoid Organs & Cell Migration Flashcards
What do Th cells produce?
Cytokines
How many antigen binding domains do B cells have?
2 - heavy chain & light chain
Is the immunity to viruses/cancer different to the immunity to bacteria/fungi?
Yes - viruses are intracellular parasites - need that extra level (T cell immunity)
What are the primary lymphoid organs, and what are they sites of?
Bone marrow & thymus
Sites of haemopoiesis
What are the secondary lymphoid organs, and what are they home to?
Lymph nodes, spleen, GALT
Home to most non-circulating immune cells
Where do neutrophils originate?
Bone marrow
Do neutrophils circulate?
No - one way journey to an infection, phagocytose, then die
Where do DCs travel?
From bone marrow to spleen and tissues
What is the function of the spleen?
To protect against septicaemia
What do cytokines act as?
Intercellular communication molecules
What are the features of cytokines?
Pleiotropic - many functions
Redundant - some can mediate a similar function
Extremely potent mediators - interact with high affinity receptors
To what does IL-2 bind?
High affinity IL-2 receptor aka CD25
What is the IL-2R composed of?
IL-2Rα chain, IL-2Rβ chain, IL-2Rγ chain
What is required for full activation of the IL-2R?
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
How many different subclasses of Th cells are there?
4
Patients with severe COVID-19 have higher serum levels of what, compared with individuals with mild disease?
Proinflammatory cytokines (TNFα, IL-1β, IL-2, IL-6) and chemokines (IL-8)
How many faces does IL-6 have?
2 faces - Th1 and Th2 cytokine
What happens to cells with a functional BCR/TCR?
They are then selected for tolerance to self-antigens and recognition of non-self-antigens (pathogens)
What is Leucomax?
A recombinant GM-CSF (used in chemotherapy to target rapidly dividing cells in bone marrow, usually mid week between cycles, results in neutropenia)
What is Neulasta (Amgen)?
A recombinant G-CSF
Do most B cells reach circulation?
No
Why do most B cells never reach circulation?
They fail to make a BCR or are autoreactive
What happens if B cells recognise the body’s own self-antigens?
They are killed by apoptosis
Where does T cell education take place?
Thymus
What happens to the thymus as we get older?
It shrinks
What is found in the outer cortex of the thymus?
Immature proliferating thymocytes
What is found in the inner medulla of the thymus?
More mature thymocytes
What does the spleen monitor?
Blood-borne infections
What does the white pulp of the spleen contain?
T cells and B cells, arranged around PALS (periarteriolar lymphoid sheath)
What does the red pulp of the spleen do?
Removes aging RBCs & platelets, then they are phagocytosed by macrophages
What happens to a naive lymphocyte when it is activated by recognising its antigen?
It is retained and undergoes clonal expansion, it then differentiates into effector cells (days later), and exits lymph node
What is the B cell area of the lymph node?
Cortex
What are the T cell areas of the lymph node?
Paracortex and medulla
Where does homing of immune cells from circulation occur?
HEV (high endothelial venule) sites
What does the primary follicle of the lymph node contain?
Mainly mature naive B cells
What is the site of B cell proliferation after antigen recognition?
Germinal centre of secondary follicle
Where is MALT (mucosal-associated lymphoid tissue) found?
GI, respiratory & genitourinary tracts
GALT(GI-associated) in gut and BALT (bronchus-associated) in lungs
Intestine: mesenteric LNs, Peyer’s patches (mainly lower ileum)
5 classic symptoms of inflammation:
redness (rubor), heat (calor), pain (dolar), swelling (tumor), altered function
What is inflammation characterised by?
Immune cell migration, serum protein & cellular leakage into inflammatory site (oedema)
Where can cell migration take place?
- to sites of infection and inflammation
- from blood to lymph and vice versa
- from primary to secondary lymphoid organs
- between secondary lymphoid organs
What is the significance of 1-2% of cells circulating per day?
There is a better chance of encounter with a foreign pathogen
What are the 3 components of the inflammatory response?
- blood supply is increased to the area
- capillary permeability increases, allowing exudation of serum proteins in surrounding tissue (Abs & complement, acute-phase proteins)
- leukocyte migration to site: phased appearance
What is chemotaxis?
Directional migration of cells up a concentration gradient of chemotactic molecules
What is chemokinesis?
Non-directional movement
What is a chemotactic source?
Site of inflammation, tissue damage, parasitic infection, complement C5a, or immune reactions
What are the 2 binding sites of chemokines?
- to proteoglycans on blood side of blood vessels
2. to chemokine receptors on leukocytes
What produces IL-8 (CXCL7), and what does IL-8 do?
IL-8 is produced by macrophages and it attracts neutrophils to the site of infection/inflammation
What chemokines are abbreviated by CXC?
α chemokines
What chemokines are abbreviated by CC?
β chemokines
What does C5a do, besides act as a complement protein?
It is a chemoattractant for neutrophils & macrophages
What happens during the Acute Phase Response?
Increase in the appearance of various proteins in circulation i.e. cytokines & anti-microbial proteins. Activated macrophages & DCs following recognition of PAMPs
Are CRP levels increased or decreased in severe COVID-19 cases?
Increased
In response to what cytokines does CRP synthesis in the liver increase 1000-fold during infection?
IL-1 and IL-6
IL-6 is also elevated in severe COVID-19 cases
