Immunology

Question	Answer
What are the two primary lymphoid organs?	The bone marrow and the thymus.
What does Waldeyer's ring of lymphoid tissue consist of?	The tonsils and adenoids.
List three tissues responsible for the maturation of leukocytes.	The lymph nodes, bone marrow and spleen.
Where in the thorax is there lymphoid tissue?	The bronchus-related lymphoid tissue.
Where in the gastrointestinal system is there lymphoid tissue?	Lymphoid nodules in the colon, mesenteric lymph nodes, and Peyer's patches in the ileum.
Where in the pelvic region is there lymphoid tissue?	Urogenital lymphoid tissue and iliac lymphoid tissue.
Why can the bone marrow ultimately give rise to the constituents of the immune system?	As it is the source of precursor cells, part of haematopoiesis.
Which stem cell is capable of giving rise to all blood cell lineages?	The pluripotent haematopoietic stem cell.
Where does the majority of haematopoiesis occur? Can it occur in any bone marrow?	Most haematopoiesis occurs in the femurs but it is possible for bone marrow throughout the skeleton to be 'activated' when needed (e.g. in severe infection or anaemia).
Which leukocytes are derived from granulocyte precursor cells?	Granulocytes: neutrophils, basophils and eosinophils.
Which leukocytes are derived from monoblasts?	Monocytes.
What do basophils contain that mast cells also do?	Histamine-containing granules and high-affinity receptors for IgE (resulting in a high affinity for IgE).
What are basophils activated by?	IgE antibodies and anaphylatoxins (C3a, C4a and C5a).
What are the primary products of basophils and what do they do?	Histamine (for vasodilation, increased vascular permeability, and smooth muscle contraction in airways), protease enzymes (e.g. to digest basement membrane for vascular permeability), proteoglycans (e.g. anticoagulant heparin), and chemotactic factors for neutrophils and eosinophils.
Describe the erythema, wheal and flare inflammatory response.	At the site of histamine release there is initial reddening (erythema) as arterioles dilate and post-capillary venules contract. This is followed by increased vascular permeability with leakage of plasma fluid into the tissues causing swelling (wheal). Finally histamine (and other chemicals) act directly on local axons to induce more distant and widespread changes (flare).
What may follow widespread activation of basophils and mast cells with release of mediators into the circulation?	ANAPHYLAXIS. A syndrome of circulatory shock and collapse with low blood pressure and chest tightness leading to arrested breathing and death unless treated.
Roughly what percentage of circulating granulocytes do eosinophils constitute? Roughly how many times higher is their concentration in the tissues?	~3-5% of circulating granulocytes are eosinophils, though they are several hundred times more abundant in the tissues, where they collect preferentially at epithelial surfaces and may survive for several weeks.
What is the granule content of eosinophils?	Their granule contents is most basic proteins which have an affinity for acidic aniline dyes such as eosin, which is the best method for their identification.
What are the main roles of eosinophils?	Protection against multicellular parasites such as worms, which they do by releasing toxic, basic proteins, and they also contribute to allergic disease, including asthma.
Eosinophil granules are divided into specific and primary types. What are the four types of specific granule and what do they do?	Major basic protein (MBP) which is the most cationic/basic protein, eosinophil cationic protein which has bactericidal properties, eosinophil neurotoxin which is toxic to worm parasites (as are the others), and eosinophil peroxidase which catalyses the production of toxic peroxides.
What is the contents of the primarily granules of eosinophils?	The primary granule content is vaguely characterised but may produce changes in airway smooth muscle and vasculature, important in allergic reactions.
Eosinophils are activated by a variety of mediators for which they have receptors. Which two antibodies predominately activate eosinophils?	IgE (which has a role in allergy) and IgA (which has a role in the protection of mucosal surfaces).
How do eosinophils migrate? Name a specific receptor.	Eosinophils use surface molecules to migrate, like neutrophils, but they possess very late antigen 1 (VLA1) which binds vascular cell adhesion molecule-1 (VCAM-1) on the endothelium.
Eosinophils are capable of phagocytosis and intracellular degranulation, but what is their immune mechanism in response to worms and other large parasites?	They employ antibody-guided local release of toxic, basic proteins onto the surface of parasitic worms.
In what way do eosinophils also have properties of the acquired immune response?	They can synthesis and express antibodies on their surface, they can secrete cytokines, and they can maintain and perpetuate a state of cell activation for a longer life.
Describe the participation of eosinophils in allergic reactions.	Their participation in allergic reactions is predominately through inflammation and tissue damage by releasing toxic enzymes, oxidative substances and eosinophil-derived neurotoxin.
What is characteristic about the nucleus of a neutrophil?	They have a polymorphic/multi-lobed nucleus.
What is the range of concentrations of neutrophils in the circulation?	~2x10^9 - 7x10^9 /L
What is the main role of neutrophils?	The killing and removal of bacteria and fungi.
Which type of granule appears during neutrophil development in the bone marrow?	Primary/azurophilic.
What is the most common granule in the neutrophil cytoplasm?	The secondary/specific granules which develop later than primary/azurophilic granules but are 3x more prevalent.
Both primary and secondary neutrophilic granules may be released intracellularly or extracellularly following fusion with...what?	The plasma membrane.
List stimuli that are capable of mobilising neutrophilic granules.	Products of bacterial cell walls; complement proteins; the leukotriene group of lipid mediators; and small bioactive peptides called cytokines.
Give an example of a product of a bacterial cell wall that may bind with a neutrophilic surface receptor and mobilise its granules?	N-formyl-methionyl-leucylphenyl-alanine (FMLP).
Give an example of a complement product that can bind to a neutrophilic surface receptor to mobilise its granules.	iC3b.
What are leukotrienes?	Biologically active products of the lipoxygenase pathway of arachidonate metabolism (conversion of a phospholipid called arachidonic acid from the cell membrane to a lipid mediator from a macrophage to another granulocyte to have a chemotactic effect on the neutrophil).
Give three examples of cytokines that can mobilise neutrophilic granules.	Neutrophil activation protein-1, tumour necrosis factor-α, and granulocyte-monocyte colony stimulating factor.
Which antibacterial effector molecules are present in the primary granules of neutrophils?	Collagenase and elastase to break down fibrous structures in the extracellular matrix to facilitate the progress of neutrophils through the tissues, and cathepsin G which is toxic to a range of gram-positive and gram-negative organisms.
What do secondary neutrophilic granules have which enhance their directional response and are involved in chemotaxis?	Receptors for the molecules that activate them.
What do secondary neutrophilic granules contain?	Lactoferrin, which decreases the cell surface charge and enhances cell adhesion, and may help generate hydroxyl free radicals, which are microbial toxins.
Where are compounds which activate neutrophils and mobilise their granules (such as FMLP) likely to come from?	Sites of inflammation and infection.
What do neutrophils do under normal healthy conditions?	Neutrophils continuously roll along the endothelial linings of blood vessels, tethered by weak cell-cell interactions mediated by specific cell receptors, until specialised adhesion molecules are activated to stop this and facilitate their entry into the tissues.
Where is blood flow slowest? This is the same area that emits a tissue response to make the endothelial lining of vessels 'stickier' to attract neutrophils.	At the post-capillary venules.
What prompts the endothelial cells of the post-capillary venules to emit a tissue signal to attract neutrophils?	Tissue damage products such as cytokines.
Name a mediator that has a dilative effect on vessel walls.	Histamine.
How do cytokines and dilative mediators work together on a blood vessel to get neutrophils to the necessary site?	Cytokines bind to endothelial cells in the blood vessel lining to elicit them to produce a tissue response signal. This forms a chemotactic gradient for neutrophils to follow, by 'rolling' and using pseudopodia. This tissue response signal is produced by increased expression of antigens on the endothelial cells for which neutrophils have a matching receptor. At the site of inflammation/infection dilative mediators such as histamine will have been released which make the blood vessels 'leakier' so that once a neutrophil reaches the appropriate site, it can extend its pseudopodia through the endothelial wall and pull itself through into the tissue.
Define chemotaxis.	Chemotaxis is the directed movement of a cell along a gradient of increasing concentration of the attracting molecule (the chemoattractant).
What are pseudopodia and how do they work?	Pseudopodia are thin, foot-like extensions of cell membrane and cytoplasm that extend to a surface it can bind to (which has complementary antigens to its ligands), anchors itself, then draws the rest of the cytoplasm up and repeats - a migratory mechanism. The pseudopodia are rich in microtubules, actin, myosin, and actin-binding protein which forms the actin into a strong lattice structure.
How is phagocytosis achieved in neutrophils?	Neutrophils extend pseudopodia around an organism/particle and these eventually meet to form a vacuole called a phagosome. This can now be fused with granules, releasing their digestive and toxic contents to attack the foreign body.
Can neutrophils ingest more than one bacterium or fungus at once?	Yes!
When large numbers of neutrophils are involved in the phagocytosis of an invading body, what do the dead/dying neutrophils form if the lesion is infective?	Pus!
When large numbers of neutrophils are involved in the phagocytosis of an invading body, what do the dead/dying neutrophils form if the lesion is inflammatory?	A sterile abscess.
What are opsonins?	Antigens which coat microorganisms and which are used to activate neutrophils and enhance engulfment by them.
Name two oxygen-independent mechanisms of killing bacteria and fungi that neutrophils carry out.	Lysozyme and cathepsin use.
Name two oxygen-dependent mechanisms that neutrophils use to kill bacteria and fungi.	The respiratory burst and the hydrogen-peroxide-myeloperoxidase-halide system, in which chemical processes involving O2 produce toxic metabolites such as Cl2 and OH- free radicals.
What percentage range of circulating leukocytes do monocytes constitute?	5-10%
What are monocytes termed when they enter the extravascular pool and tissues?	Macrophages.
How do monocytes/macropages compare in size to neutrophils and lymphocytes?	They are larger, and they also have a single nucleus and abundant granular cytoplasm.
List some specialised forms of the mature monocyte.	Alveolar macrophages in the lung, Kupffer cells in the liver, mesangial cells in the kidney, microglial cells in the brain, osteoclasts in the bone, and others lining channels in the spleen and lymph nodes.
Describe some of the changes in a monocyte when it transforms into a phagocytic macrophage in the tissues.	The cell enlarges and forms numerous lysosomes and mitochondria.
List 4 functions of monocytes/macrophages.	They are synthetically active and produce a variety of factors that control cellular proliferation and maturation; mononuclear macrophages phagocytose foreign antigens and process them, and their class 1 and class 2 human leukocyte antigen (HLA) surface proteins present antigenic fragments for lymphocytic activation; mononuclear macrophages remove abnormal or senescent erythrocytes and salvage iron for reutilisation by erythroid precursor cells; and mononuclear macrophages clear the blood and tissues of neoplastic or foreign cells by phagocytosis.
What are the 3 ways in which monocytes migrate?	Randomly; into sites of inflammation; or in a tissue-directed way to become specialised cells.
Mononuclear phagocyte system (MNPS) secretions include...	...lysozyme to cleave bacterial cell walls; acid hydrolases to allow cell mobility and are also bactericidal; plasminogen activators and superoxides (H2O2) are microbicidal; and cytokines such as IL-1 to activate T cell and TNF-α which is cytotoxic.
List 3 chemicals that activate monocytes and state where they are released from.	Interferon-γ - secreted by T cells, granulocyte-monocyte colony stimulating factor - secreted by T cells, and tumour necrosis factor-α which they secrete themselves to act in a positive autocrine feedback loop.
What structural changes does a mononuclear phagocyte system (MNPS) undergo, and what processes does it increase/carry out, once activated?	The MNPS increases in size, as well as in adherence due to increased surface expression of antigens including major histocompatibility complex molecules. They also increase their secretions both to activate themselves further and increase their cytotoxicity against invading organisms; and there is an increase in the numbers of cytoplasmic pinocytic vesicles, and an increased phagocytic and secretory capacity. Lastly, there is also pseudopod formation for both migration and phagocytosis.
What are the two main immune functions of monocytes?	The ingestion and killing of intracellular parasites, such as Mycobacterium tuberculosis, and they also play a critical role in activating T lymphocytes by antigen presentation in specific immune responses.
Which properties do monocytes have in common with neutrophils?	Many bactericidal, phagocytic, chemotactic, opsonic and cytotoxic properties.
What is antigen presentation in monocytes?	After a macrophage ingests and digests molecular or cellular antigens, it can inject fragments of processed antigen into its membrane so that the antigen fragment becomes a part of surface protein complexes. This presentation is to activate T cells.
Where do lymphocytes derive their name from?	From a close association with the lymphatic system.
What is the ratio of B lymphocytes to T lymphocytes?	1:5
Where did B lymphocytes get their name from?	They were first isolated from the lymphoid organ of a chick known as the Bursa of Fabricius.
How are B lymphocytes differentiated from T lymphocytes using an electron micrograph?	B lymphocytes have a 'hairy' appearance compared to T lymphocytes as they are covered in highly specialised glycoprotein molecules on their surfaces.
Where do B lymphocytes differentiate before being released, fully mature, into the circulation?	The bone marrow.
What is the primary role of B lymphocytes?	The recognition of antigens by antibodies on their surfaces.

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