Organisation of the Immune System Flashcards

Barriers: recall the physical and chemical barriers used by the immune system in host defense Cell types: list the different cell types of the immune system, explain how they may be distinguished, and briefly summarise their functions Lymphoid organs: recall the primary and secondary lymphoid organs, summarise their structure, and differentiate between their functions Lymphocyte recirculation: summarise the re-circulation of lymphocytes, and explain its importance

1
Q

What are primary lymphoid organs?

A

Where lymphocytes are produced by lymphopoiesis (lymphoid stem cells differentiate to mature functional lymphocytes).

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2
Q

List examples of primary lymphoid organs. (x2)

A

Thymus and bone marrow.

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3
Q

What are secondary lymphoid organs?

A

Where lymphocytes interact with antigens and each other to generate an immune response.

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4
Q

List examples of secondary lymphoid organs. (x3)

A

Spleen, lymph nodes and mucosal associated lymphoid tissues (MALT).

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5
Q

What are alternative names for primary and secondary lymphoid organs?

A

PRIMARY: generative lymphoid organs. SECONDARY: peripheral lymphoid organs.

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6
Q

What are ALL lymphocytes derived from?

A

From precursor bone marrow stem cells. By the way, all the next cards about lymphocytes relates to the ADAPTIVE IMMUNE system.

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7
Q

What is the anatomical position of the thymus?

A

Found below the thyroid in the thoracic cavity.

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8
Q

What is the structure of the thymus?

A

Has two lobes. Septum divides lobes into lobules. Dark-staining regions around the outside of the lobule = cortex. Light-staining region in the middle = medulla (medulla means middle).

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9
Q

What is the function of the Hassall’s corpuscles?

A

Have fibroblast cells, so involved in the formation of regulatory T-cells.

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10
Q

What is the function of the thymus?

A

Performs an immune function. Packed with MATURING and PROLIFERATING T-lymphocytes.

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11
Q

What is the function of the bone marrow?

A

Site of haematopoiesis – the process of differentiation and maturation of ALL blood cells.

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12
Q

What happens visibly to the thymus and bone marrow during infection?

A

Thymus – no obvious change during infection. Bone marrow – visible change during infection where there is increased white cell production.

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13
Q

What is the difference between a foetus and adult in relation to sites of haematopoiesis?

A

Foetus: bone marrow very cellular, and liver and spleen involved. Adults: large, flat bones are involved. Not the liver or spleen.

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14
Q

How many litres are returned to the blood from the lymphatic system each day?

A

2-3 litres per day.

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15
Q

What is the function of lymph nodes – how is this exercised?

A

Nodes filter antigens in the lymph – see if immune system recognises any of those antigens. Afferent lymphatic vessels bring lymph fluid into the node, while efferent leaves the node. Fluid collected is filtered through lymphocytes so can react if antigens are present.

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16
Q

What is the structure of the lymph node?

A

Refer to photo. Artery and vein lead in and out. Note the afferent and efferent lymphatic vessels.

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17
Q

Where are immune cells found in the lymph node? (x3) What does enlargement of the lymph node denote?

A

Lymphoid cells on the OUTSIDE tend to be B cell aggregates in the follicles. If ONGOING immune response, B cells will proliferate and produce antibodies in germinal centres [yellow circles]. Germinal centres are distinct spheres of proliferating B-cells. T-cells are closer to the medullary sinus than the B cells, and macrophages are present to engulf pathogens. Enlargement demonstrates ONGOING immune response and hence proliferation of immune responses.

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18
Q

What do germinal centres indicate?

A

Germinal centres show ongoing immune response. [This is basically emphasising the previous flashcard.]

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19
Q

What is a high endothelial venule? Organ where there are no HEVs?

A

Specialised area of ARTERY with much thicker endothelium that causes T/B-cells to leave circulation and ENTER the lymph node following chemical signals from chemokines. SPLEEN does NOT have high endothelial venules.

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20
Q

What is the function of the spleen?

A

Filters antigens in the blood (while lymph nodes do the same but for LYMPH).

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21
Q

What is the anatomical position of the spleen?

A

Look at photo.

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22
Q

What is the structure of the spleen? Histologically?

A

White pulp is where lymphocytes reside, and red pulp is where erythrocytes present. Periarterial lymphatic sheath (PALS): immediately surrounds the arteries (in white pulp), with predominantly T-cells. Primary follicles possess primarily B-cells. Phagocytes also present and scavenge for dead cells/pathogens. Histologically, white pulp stains dark purple, and red stains lighter.

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23
Q

What are mucosal associated lymphoid tissues?

A

These describe the PHYSICAL BARRIES that prevent against invasion from pathogens in the first place. Most of MALT has a high surface area. Because they are the physical barriers, they are heavily defended by the immune system. Include the epithelium of the skin and the surface of the gut.

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24
Q

Describe the lymphatic system in relation to the gut.

A

Epithelium of the gut is an example of MALT.

□ Intraepithelial lymphocytes reisde on villus. These villi have lymphatic drains to mesenteric lymph nodes.

□ Peyer’s patches (found only in the gut) are large aggregates of lymphocytes and follicles especially B-cells, that drain to lymph nodes.

□ Specialised mucosal epithelium over peyer’s pathces contain microfold cells which sample antigens in gut and present to lymphocytes in peyer’s patches.

25
Q

Describe the skin in relation to the lymphatic system.

A

□ Lymphatic vessels drain from skin and intraepidermal lymphocytes. □ Epidermal langerhans (specialised dendritic cells) [look at Tissues: Specialised Tissues module] capture and present antigens migrating through those lymphatic vessels in the epidermis.

26
Q

What is lymphocyte recirculation?

A

Primary lymphoid tissues produce naïve lymphocytes that enter the blood and circulate BETWEEN blood and secondary lymphoid tissues until they react or die. Move into lymphoid organs where immune cells may be holding out antigens etc.

27
Q

What does extravasation of naïve T-cells into lymph nodes mean?

A

This is the mechanism that allows lymphocytes to circulate BETWEEN blood and secondary lymphoid tissues. The process where lymphocytes roll along the cell surface and bind. This causes them to leave the circulation and enter the lymph node. They get back into the blood from the lymph through the subclavian duct. Extravasation denotes something that leaves the bloodstream.

28
Q

What is the process of extravasation of naïve T-cells into lymph nodes?

A
  1. Naïve T-cells roll along the endothelium until they reach the HEV (high endothelial venule). 2. Selectin (on the T cell) binds weakly to endothelial CD34 (on the lymph node endothelium in the HEV). This allows rolling interaction. 3. Chemokines present on surface of HEV changes the conformation of integrin on T-cells, which means that the T-cell has a high affinity binding to the endothelium. 4. T-cells move over endothelium into lymphoid tissue. Called transendothelial migration.
29
Q

Why is lymphocyte recirculation important? (x4)

A

There are a large number of T cells with different specificities (meaning specific things that they bind to). There are a large number of B cells with different specificities. There may only be limited amounts of antigen. Secondary lymphoid organs may contain cells that are presenting antigens for detection.

30
Q

What do lymphocytes look like? (x2 points about histological appearance)

A

Small cells with agranular (lacking granules) cytoplasm and large nucleus.

31
Q

How do we differentiate between B and T lymphocytes?

A

It is done by a process called CLUSTER OF DIFFERENTIATION which discriminates between cells of the haematopoietic system. The process works because all cells contain markers which are recognised by antibodies – one cell type may contain a marker that another does not have. By using antibodies which bind to these cell markers, we can identify the presence of these cells.

32
Q

What is the proportion of the T-lymphocytes found in different regions of the body? (x2)

A

2% are found in the blood. The rest are found in lymph. Remember, T cells are involved in cell-mediated immunity; they use the blood to travel to certain locations/recirculate.

33
Q

What CD (cluster of differentiation) markers do T-lymphocytes express?

A

They ALL express CD3. There are two main types of T-lymphocytes: those with an alpha-beta TCR (T-cell receptor) (90% of all T-cells), and those with a gamma-delta TCR (10% of T-lymphocytes). abTCR: 2/3 have CD4; 1/3 have CD8. CD4 and CD8 are CO-RECEPTORS.

Don’t worry about the others.

34
Q

What CD markers do B-lymphocytes express?

A

They express CD19 and CD20 (not CD3/4/8).

35
Q

What do the CD4 and CD8 lymphocyte sub-types do?

A

CD4 lymphocytes are T-helper cells and regulatory cells which secrete cytokines. CD8 lymphocytes are cytotoxic T cells which lyse infected cells and secrete cytokines.

36
Q

How does T-cell and B-cell antigen recognition differ?

A

T-cells only recognise processed antigens presented at the surface of another cell – presented by a major histocompatibility complex (on an antigen presenting cell (APC)). They use their T-cell-receptor. B-cells inly recognise intact antigens found in body fluids and cell surfaces. They do not recognise processed antigens – so, those presented by another molecule (e.g. MHC).

37
Q

What are antigen presenting cells? (x3)

A

Present processed antigen to T lymphocytes with an MHC to initiate an adaptive (acquired) immune response. These cells include dendritic cells, B cells, and activated macrophages.

38
Q

What are the functions of the B lymphocytes? (x2)

A

Express MHC Class II so can present antigen to T-helper cells. They produce antibodies.

39
Q

What is innate immunity?

A

Rapid cellular/soluble component immune response present from birth using PAMPs/DAMPs to detect microbial structures and damage, as well as ‘missing self’ (done by Natural Killer cells). It is not very SPECIFIC. [This is recap from Immunology: Principles of immune responses.]

40
Q

What are the four defensive barriers of the innate system?

A

ANATOMICAL: skin (mechanical barrier, acidic environment) and mucous membranes (secretions trap microbes and cilia expel). PHYSIOLOGICAL: fever (doesn’t favour replication by microbes), low pH in stomach (kills many ingested microorganisms), chemical mediators (lysozymes, interferons, complement). PHAGOCYTIC: cells that ingest material!!! (will be discussed a lot in the next flashcards) INFLAMMATORY: local increased vascular permeability to allow cell escape among other mechanisms.

41
Q

What are the major types of PHAGOCYTES? (x7) NEB MMmmmm DNa

A

NEUTROPHILS: EOSINOPHILS: BASOPHILS: MONOCYTES/MACROPHAGES: MAST CELLS: DENDRITIC CELLS: NATURAL KILLER CELLS: SO, these are all cells involved in the INNATE immune response!!!

42
Q

What do neutrophils look like?

A

Phagocytes with multi-lobed nucleus (polymorphonuclear granulocytes).

43
Q

What are eosinophils – how do they work? (x4)

A

Phagocytic, release granules, and particularly important in defending against parasitic infection. Help with B cell responses by producing IgA.

44
Q

What are basophils – how do they work? (x2)

A

Release granules and may act as antigen-presenting cells for ‘type 2’ immunity (refers to antibody mediated immunity).

45
Q

What do dendritic cells do? (x2) Where are they found?

A

Capture antigens and present these to T-cells. Also secrete cytokines when they recognise microbial patterns. They are networks of cells located at likely sites of infection; when they capture pathogens, they migrate to local lymph node to present antigens to adaptive immune system.

46
Q

How do neutrophils work? (x3 points)

A

Relatively short-lived cells that circulate in blood then migrate to tissues where they bind to pathogens, phagocytose them, and kill them. First cells to be recruited to the site of infection.

47
Q

How do neutrophils exit the circulation and enter tissues to perform their function?

A
  1. Neutrophil rolls along surface of blood vessels, and SELECTIN weakly binds to lining. 2. When it encounters endothelium that’s received signals indicating damage/infection (mediated by chemokines - macrophages release chemokines when they ingest microorganisms), there is a change in the affinity of its INTEGRINS, which means that integrins can now bind tightly to the endothelium. Neutrophil stops rolling. 3. Neutrophil migrates through endothelium – process is called diapedesis 4. More chemokine molecules near site of infection, so moves along gradient toward site of infection – process of chemotaxis. [Principle is the same as with leukocytes but the molecules are different.]
48
Q

What is chemotaxis?

A

Movement along the gradient of a chemokine i.e. neutrophil moves along the chemokine gradient: there will be more chemokines NEARER the site of infection, so by following the chemokine gradient (and travelling towards chemokines of greater concentration), neutrophils are able to travel to the site of infection.

49
Q

What is opsonisation? What can function as opsonins? (x2)

A

Coating of microorganisms with proteins that makes the pathogen more easily recognisable to the phagocyte – this FACILITATES PHAGOCYTOSIS (opsonins are molecules that bind to antigens AND to phagocytes). Antibodies and complements both function as opsonins.

50
Q

What does a complement refer to in immunology?

A

Complements describe the complement system which ENHANCES and AMPLIFIES the ability of specific antibodies in lysing bacteria, and phagocytic cells. It is part of the innate immune system.

51
Q

What is the complement system composed of?

A

The complement system involves ~30 small proteins and glycoproteins, synthesised in the liver and found in the blood as inactive ENZYME precursors and found in high concentrations in the blood.

52
Q

What happens in the complement system?

A

When stimulated, the glycoprotein enzyme precursors are cleaved into an active enzyme. The substrate of each enzyme is the next enzyme in the pathway (i.e. enzyme 1 cleaves precursor 2 into enzyme 2). Let’s say that each enzyme cleaves 10 precursors: This means that each step of the complement system, the enzyme cascade is amplified. The complement pathway leads to the activation of the C3b protein, which opsonises pathogens (by binding to its antigen) – opsonisation enhances phagocytosis remember, hence the functions of the complement system. FINAL COMMON PATHWAY: when C3b activated, there is a final common pathway – formation of a membrane attack complex that’s inserted into the cell membranes of all pathogens. Creates holes in bacterial cell membrane and causes loss of integrity – so bacteria lyses (another function of the complement system). ALSO NOTE: the molecules that are cleaved off the precursors are pro-inflammatory. Can bind to mast cells, causing them to degranulate, releasing histamines = pro-inflammatory.

53
Q

What are the THREE types of mechanism by which neutrophils kill pathogens? (one of these is indirect)

A

OXYGEN INDEPENDENT: enzymes and antimicrobial peptides. OXGEN DEPENDENT (occurs as respiratory burst, meaning rapid release of reactive oxygen species): free radicals, NO, nitrogen intermediates, singlet oxygen (O), hydroxyl radicals, H2O2… NEUTROPHIL EXTRACELLULAR TRAPS: activated neutrophils release granule net-like materials that form extracellular fibres to TRAP microbes, in turn killing the neutrophils but allowing phagocytosis.

54
Q

What are monocytes/macrophages (differentiation)? Functions? (x3)

A

Monocytes in the blood; macrophages in tissue. PHAGOCYTOSIS: Granules containing enzymes fuse with phagosomes, which digest ingested material. MEDIATOR: MACROPHAGE has receptors for microbes, and upon binding and ingesting, release soluble cytokine mediators to recruit further cells. ANTIGEN PRESENTATION: macrophages present fragments of antigen on surface to T-cells.

55
Q

What do mast cells do? (x2)

A

Release granules containing histamine and other mediators including cytokines = pro-inflammatory. Can recognise (by pattern recognition receptors), phagocytose and kill bacteria also.

56
Q

What type of cell are natural killer cells?

A

They are LYMPHOCYTES, but they do not have an antigen-specific receptor – that’s why we don’t put them in the adaptive immunity response – they are part of the innate response.

57
Q

What is the mechanism by which Natural Killer cells lyse other cells? What two ways can a virus affect a cell in relation to this mechanism?

A

Have activating and inhibitory receptors which BALANCE signals and dictate whether target cell is lysed or left alone.

Normal, unaffected cell contains MHC Class I molecules (they are a marker of normal self). However, in a virus infected cell, the virus can downregulate these molecules, so cell no longer gives an inhibitory signal to the NK cell. Stress-induced molecules are also expressed on the cell. So, there is a loss of inhibition, and activation receptors are stimulated – so NK cell lyses the cell as it detects that the cell is ‘missing self’ and there’s a problem.

58
Q

What does ‘missing self’ refer to?

A

Only labelled to ‘self’ cells. Missing self refers to lack of MHC Class I.

59
Q

What is the general function of NK cells? (x2) What are the precise functions? (x3)

A

GENERAL FUNCTIONS: They lyse infected cells and secrete interferon-y (gamma). PRECISE FUNCTIONS: Have receptors that bind to antibody-coated cells – and may kill that cell = Antibody Dependent Cell-mediated Cytotoxicity (ADCC). Important in defence against tumour cells and some viral infections.