Blood and Immunity

Question 1

Explain the threat posed by the many different types of infectious agents, and the requirements of an effective immune system.

Describe the main features of the systemic immune system, the lymphoid system and lymphocyte recirculation.

Answer 1

infectious agents can release toxins and damage cells.

an effective immunne systme contains neutrophils, eosinophils, basophils, mast cells, macrophages and monocytes, natural killer cells, dendrite cells, Th and Tc cells and B cells.

Question 2

List and categorise the main cellular and secreted mediators of immunity.

Answer 2

Antimicrobial secretions are antibodies/immunoglobulins, pentraxins, collections, complement proteins, defensins, lytic enzymes, interferons and cytotoxins.

Regulatory or inflammatory secretions are cytokines, chemokines, prostaglandins, leukotrienes and histamines. The main division are ones that have direct protective effects in the immune response, and others have roles in regulating the immune responses.

Question 3

Explain the requirements for recognition and defensive functions within the immune system.

Answer 3

The body needs to have mechanisms for recognising infections, with interaction with microbes and their counterparts, and defence, which is the elimination of microbes and their products.

Question 4

List the main properties of innate and adaptive immunity.

Answer 4

innate immunity - rapidly activated, same on repeat exposure, moderate efficacy, general response, recognition of ‘pathogen-associated molecular patterns’ (PAMPs) and recognition by ‘pattern recognition receptors’ (PRRs), activity of neutrophils, eosinophils, basophils, mast cells, monocytes and macrophages, dendritic cells and natural killer cells

adaptive immunity - slow, improves with repeated exposure, high efficacy, specific response, recognises antigens, ecognises this by antigen-specific receptors clonally expressed by lymphocytes, T and B cells

Question 5

Outline the stages of primary and secondary immune responses, indicating the contributions of innate and adaptive components.

Answer 5

primary - innate response occurs at site of infection, complement proteins and macrophages introduced, inflammatory response, inflammatory mediators are produced from either complement proteins, macrophages or mast cells, attract leukocytes and serum proteins from the bloodstream

Components of infective microbes (antigens) are carried to a draining lymph node. Some are captured by dendritic cells and carried to the lymphoid tissue. Specific T and B lymphocytes are produced and recirculated to the site of infection.

Following primary infection, memory T and B cells give faster and bigger responses on a second exposure to the same infection.

Question 6

Outline the different strategies of immunity required to combat different categories of infective agents.

Answer 6

For an extracellular infection, complement proteins, phagocytes and antibodies are involved as they can bind to the surface of the microbe.

For an intracellular vesicular infection, where the microbe has been engulfed by a macrophage, helper T cells hyperactivate the macrophage to digestive resistant microbes.

For intracellular cytosolic infections, interferon proteins, natural killer cells and cytotoxic T cells are activated. This applies in particular to viruses. Interferons block the ability of viruses to replicate in cells. Natural killer cells and cytotoxic T cells kill infected cells to limit virus reproduction.

Question 7

Give examples of immunopathological disorders, including immunodeficiency, allergy, autoimmunity, transplant rejection and lymphoproliferative disorders.

Answer 7

immunodeficiency - primary SCIDS, secondary AIDS
allergy - allergic rhinitis (hayfever)
autoimmunity - autoimmune thyroiditis and rheumatoid arthritis.
transplant rejection - kidney
lymphoproliferative disorders - lymphoma, leukemia, myelomas

Question 8

Describe the range of secreted and cell surface pattern recognition receptors of the innate immune system, including Creactive protein, mannan binding lectin, CD14, mannose receptor, scavenger receptor, and Tolllike receptors.

Answer 8

macrophages can express a range of pattern recongition receptors for various microbes: mannose receptor, glucan receptor, scavenger receptor, CD11b/CD18, LPS receptor (CD14)

Toll-like receptors (TLRs) recognise a variety of pathogen-associated molecular patterns (PAMPs). There are a variety of different TRLs present in humans. Some are present on the surface of the cell which they interact with. Others are found in the cytoplasm of the cells and interact with the nucleic acids of the microbes that have invaded the cell.

Question 9

Explain the features of specific antigen recognition by antibodies.

Answer 9

Antibodies are also known as immunoglobulin. They include antigen combining sites, which the antigenic determinant, or epitope, joins to.

The epitope and combining site are held together by noncovalent interactions between their surfaces. These are only effective over short distances.

The combining site has to be complementary to the shape of the epitope.

Question 10

Describe the direct recognition of native antigens by surface immunoglobulins of B lymphocytes, leading to plasma cell formation and antibody production.

Answer 10

When an epitope binds to a surface immunoglobulin, this triggers the activation of the B cell. The B cell then differentiates into a plasma cell.

The plasma cell no longer expresses surface immunoglobulins. Instead, its activity is focused on creating antibodies.

Question 11

Explain clonal selection of antigen specific lymphocytes, and how this ensures the specificity of the adaptive immune response.

Answer 11

Clonal selection occurs by specific lymphocytes being produced due to their antigen recognition. The lymphocytes with the highest affinity will be reproduced.

Question 12

Explain how clonal selection and memory cell formation are utilised in vaccination.

Answer 12

The injection of an inactivated form of a virus can lead to a small amount of antibody production. Then, on infection of an activated form of the virus, a much larger antibody response is generated.

Question 13

Describe the structure of immunoglobulins.

Answer 13

The immunoglobulin has a Y-shaped structure. It is made of four polypeptide chains: two logn heavy chains and two short light chains. The antigen combining sites are formed by the terminal regions of the heavy and light chains.

The light chains have two domains, and the heavy chains have four domains. Each domain is stabilised by a disulfide bond. The disulfide bonds bind covalently to each other, connecting the two heavy chain strands and connecting the light chain to the heavy chain.

Question 14

Outline the molecular features of immunoglobulin class switching and how this determines the quality of the antibody response.

Answer 14

Class switching can change the gene expressed and the constant domain of the heavy chain.

Question 15

Describe the structure and tissue distribution of the immunoglobulin classes.

Answer 15

IgM (pentamers) - blood

IgG (monomers) - blood, tissues, placental transfer

IgA - blood/tissues (monomers), mucosal secretions and milk (dimers)

IgE (monomers) - tissues (bound to mast cells)

IgD - mucosa of upper aerodigestive tract

Question 16

Outline the role of antimicrobial defensins.

Answer 16

Their most common antimicrobial function is the formation of destructive pores in membranes of pathogens including enveloped viruses.

Question 17

Explain how particular isotypes of antibodies interact with defence components by virtue of the properties of their Fc regions.

Answer 17

Antibodies can also act as intermediaries to activate other defensive components that interact with the Fc regions of antibodies. Thus, IgM and IgG antibodies can activate the complement system of proteins; phagocytes have Fc receptors (FcR) that bind IgG or IgA; natural killer cells similarly bind IgG; mast cells have FcR specific for IgE; eosinophils have FcR specific for IgG or IgE.

Question 18

Outline the properties of complement and the pathways of complement activation.

Answer 18

A complement is a collection of proteins found in the circulation and tissues fluids. They complement the effects of antibodies. Complement proteins can act as activation enzymes, immune defence molecules, and control proteins.

The activation of complement proteins is triggered by infection and immune activation, and occurs as a cascade or chain reaction with amplification. The central event of complement activation is the conversion of C3 to C3a and C3b. These are known as C3 convertase enzymes.

Question 19

Describe the structure of the membrane attack complex of complement.

Answer 19

Membrane attack complex of complement refers to the association of the complement proteins C5, C6, C7, C8, and C9 to form a potentially cytolytic complex. When C5 is activated in either the classical or alternative pathway, the resulting C5b molecule contains binding sites for the next components in the pathway.

Question 20

Describe the innate and adaptive mechanisms of opsonization of microbes for phagocytosis.

Answer 20

Another way for phagocytosis to occur is by coating the microbes with other molecules of the immune system to make the bacteria more attractive to be bound by the phagocyte. The chemicals used to do theis are known as opsonins. Pattern recognition molecules are a form of opsonin.

Question 21

Outline the mechanisms of phagocytosis and intracellular killing.

Answer 21

The macrophage expresses receptors for many bacterial constituents. Bacteria binding to macrophage receptors initiate the release of cytokines and small lipid mediators of inflammation. The macrophage then engulfs and digests the bacteria to which they bind.

Question 22

Outline the extracellular killing of large parasitic organisms by eosinophils.

Answer 22

Phagocytes contain lysosomes and phagolysosomes to digest engulfed microbes. Some microbes are too large to be engulfed, an eosinophil can be bound to the surface of the parasite via complement and C receptors. It releases digestive enzymes onto the outside of the parasite. This is extracellular digestion.

Question 23

Explain how mast cells can be triggered to release inflammatory mediators.

Answer 23

Mast cells are similar to basophils, but unlike them are resident in tissues. Mass cells are covered in specific IgE antibodies, if an antigen binds, this triggers the activation of the mass cell. C3a and C5a can also bind to the mast cells and trigger activation. Mast cell degranulation is where mast cells release their granules, which are inflammatory mediators.

Question 24

Describe the stages of the inflammatory process, and give examples of the main inflammatory mediators.

Answer 24

The purpose of inflammation is to promote the movement of cells and molecules of the immune system from the blood to the tissues and cells where the infection is located. Introducers of inflammation are C3a and C5a which are known as anaphylatoxins.

Many inflammatory mediators are present on the walls of blood vessels. They can cause vasodilation, leukocytes are not moving slower through the infected tissue.

Question 25

Outline the stages of leukocyte endothelial interaction and leukocyte extravasation, and the main adhesion molecules involved in these processes.

Answer 25

Adhesion molecules (eg selectins and itegrins) are expressed for leukocytes to bind to. Vascular permeability increases, facilitating the movement of leukocytes stuck to the blood vessel wall into the infected tissue, and more fluid moves to the infected area, bringing complement proteins and antibodies.

Question 26

Explain the process of chemotaxis.

Answer 26

Chemotaxis involves the directional movement of cells in response to chemical signals (chemoattractants).

Chemotaxis of leukocytes occurs via molecules such as chemokines to localize the site of infection and destroy the infecting pathogen.

Question 27

List the main cytokine mediators of the systemic acute phase response, and the processes involved.

Describe common features of the presentation, investigation and management of a bacterial infection.

Answer 27

This is a body-wide response to infection. This involves the production of inflammatory proteins called cytokines: interleukin (IL-1), interleukin (IL-6) and tumour necrosis factor (TNF). Key features of this response are a fever, leukocytosis, which is the increased release of leukocytes from the bone marrow (mainly neutrophils), and acute phase proteins being released from the liver. The C-reactive protein levels are raised.

Question 28

Describe the characteristic features and outline the functions of the cell types found in circulating blood.

Answer 28

red blood cells (98%)
white blood cells (>2%) - neutrophils, eosinophils and basophils, which make up 40-75%, 5%, and 0.5% of leukocyte percentage, respectfully, lymphocytes, which make up 20-50% of white blood cell concentration, and monocytes, which make up 1-5%.

Question 29

Describe the process of haematopoiesis and the symptoms of bone marrow failure in acute leukaemia

Answer 29

Haematopoiesis requires proliferation and differentiation to produce a variety of mature blood cells with specialised functions from progenitor cells.

leukeima is caused by malignancies of immature haematopoietic cells that are present in the blood and bone marrow and an increased number of circulating leukocytes is usually seen

Clinical features of acute leukaemias are a reduced production of red cells, which leads to anaemia. This causes breathlessness, dizziness, and fatigue. Sufferers can also be pale. Reduced production of mature myeloid cells leads to an increased susceptibility to bacterial or fungal infections. Low platelet count leads to bleeding of the skin, gums, nose, and gut.

Question 30

Understand the basic composition of blood and the relevance of blood analysis to the diagnosis of disease

Answer 30

blood is a composition of around 35% cells and 55% plasma. It is a vehicle to transport gases, nutrients, cells, hormones, antibodies and metabolites around the body.

In a full blood count (FBC), a sample of blood is sent to the laboratory and the red blood cells, white blood cells and platelets are counted. This is used to test for, diagnose, and monitor many different conditions.

Question 31

List the components of blood. State the approximate proportions of red and white cells and plasma in normal blood.

Answer 31

RBCS - 42-45%
WBCS and platelets - 1%
Plasma - 55-58%

Question 32

Outline the important haematological parameters and blood counts. State approximate normal values for haemoglobin and haematocrit and define mean corpuscular volume (MCV).

Answer 32

Blood counts are of great clinical value. Cells per volume is counted by machine or manually, usually in cells per litre of blood. Haematocrit is the packed cell volume. The blood is centrifuged down, and the value is the percentage that is red blood cells. In males this is 40-52%, and in females it is 36-48%. Haemoglobin -is measure in grams per litre. In males, the value is 135-175 g/L, and in females it is 115-155 g/L. This value is used to identify anaemia.

Mean corpuscular volume (MCV) is the volume (fl) of individual red blood cells. And is found by dividing the haematocrit by the number of red blood cells per litre. This is useful in identifying certain diseases, such as microcytic anaemia, macrocytic anaemia, and alcohol abuse.

The Hb/RBC gives the mean corpuscular Hb (MCH), which is reduced when cells are small or in iron deficiency. The Hb/PCV gives the mean corpuscular Hb concentration (MCHC), which is lowered when cells are large with impaired haem production (macrocytic anaemia).

Question 33

Describe the basis of blood grouping and identify the major groups. Describe the basis and treatment of Rhesus incompatibility between fetus and mother.

Answer 33

Blood group A has A antigens and b-antibodies. Blood group B has B antigens and a-antibodies. Blood group AB has AB antigens. Blood group O has no A or B antigens but has a and b antibodies. Groups A and O are the most common, and O Rh –ve is a universal donor for emergencies

This is important for pregnancy as it links to haemolytic disease of the newborn. This can be prevented with Anti-D immunisation which is given to the mother after the delivery of her first child, and binds to infant cells that have passed into the mother and prevents the mother raising antibodies.

Question 34

Describe five cardinal symptoms associated with inflammation and tissue damage.

Answer 34

pain, redness, heat, swelling and loss of function

Question 35

Describe the factors that regulate blood flow through a tissue under normal circumstances and describe how acute inflammatory mediators alter local blood flow.

Answer 35

In the normal state, blood flow through tissue depends on systemic arterial pressure local vascular resistance, neuronal constrictor and dilator influences, endocrine and paracrine hormones .

In the acute inflammatory state, physiological influences on arteriolar tone are overridden by inflammatory vasodilators. Histamine released from skin mast cells leads to vasodilation and localised redness.

Bradykinin has a direct vasodilator effect and causes the release of endothelial prostaglandins.

Vasodilator peptides are present in sensory nerves.

Question 36

With the aid of a diagram describe the ‘triple response’ and explain the neurogenic basis of acute inflammation and sensation of pain.

Answer 36

There is an initial ‘flush’ in the area of damage. Histamine is released from mast cells and immediate vasodilation occurs. In the ‘flare’ phase, extensive vasodilatation in the undamaged area surrounding ‘flush’ occurs.

In the ‘wheal’ stage, oedema (swelling) in the damaged area (white area) occurs. A later event associated with the ‘flush’ that happens is direct damage to the endothelium, activation of complement and/or mediator modification of vascular permeability that leads to protein extravasation.

Question 37

Identify three characteristics of post-capillary venules that make them an ideal site for ‘extravasation’.

Answer 37

The capillary bed consists of a monolayer of endothelial cells known as the permeability barrier. Plasma proteins and water stay within the lumen of the vessel.

Question 38

Describe how humoral and cellular factors act in concert to increase venular permeability and fluid extravasation during an acute inflammatory response.

Answer 38

Agents that increase venular permeability contract pore proteins by elevating Ca2+ levels.

Agents that decrease venular permeability relax pore proteins by cyclic AMP.

Question 39

To give a brief description of lymph and the lymphatic system with its interspersed lymph nodes

Answer 39

thymus and bone marrow are primary lymphoid tissue

Lymph is the interstitial fluid from capillary beds that is not picked up by venules. It is returned to the circulatory system via lymphatic vessels. Lymphatics are open-ended tubes ultimately carrying the lymph back to the venous circulation (subclavian veins) via the thoracic duct or right lymphatic duct.

On the way, the lymph goes through one or more lymph nodes, and blocked lymph vessels or nodes prevent drainage causing swelling (lymphoedema) which can be a side effect of radiotherapy.

Question 40

Describe the secondary lymphoid organs: lymph nodes, spleen and mucosa associated lymphoid tissue (MALT)

Answer 40

The secondary lymphoid tissues are the lymph nodes, the spleen, and the mucosa associated lymphoid tissue (MALT). These are the tonsils, adenoids, Peyer’s patches and diffuse cells in the respiratory, genitourinary and gastrointestinal systems.

Question 41

Give an account of the structure of lymph nodes as important sites of antigen presentation and lymphocyte proliferation.

Answer 41

Lymph nodes have an outer cortex and an inner medulla, which are supported by a reticular network and surrounded by a connective tissue capsule. Lymph enters via afferent lymphatics into a network of sinuses (subcapsular, cortical and medullary) which ultimately drain into efferent lymphatics.

Macrophages and dendritic cells enter the node via lymphatics. The superficial cortex contains lymphoid follicles (the deep cortex/paracortex does not). The blood supply enters and leaves at the hilum.

Lymphocytes enter the node from the bloodstream via HEVs (high endothelial venules with cuboidal epithelium). They leave within a few hours if they do not recognise antigen.

Lymphocytes travel constantly between lymph nodes and secondary lymph organs in search of matching antigens. They can travel in the lymph vessels, but 90% travel in the bloodstream.

Question 42

Understand, in principle, location and cells involved in antigen presentation

Answer 42

A macrophage (or dendritic cell) becomes activated after ingesting a microbe, and travels in the lymph to the closest node to present protein fragments. Antigen presentation occurs in the paracortex (T cell area), leading to T cell activation and proliferation.

B cells then pick up the antigen in the follicle, ingest it and move to the B/T cell zone interface. The activated T and B cells meet at the B cell-T cell zone interface. The T helper cell specific for this antigen activates the B cell to proliferate and mature. The activated B cell then moves back to the cortex to proliferate and mature. This results in a germinal centre.

The lighter staining germinal centres characterise the secondary follicles in the cortex. They represent areas of B cell maturation, in which some of the activated B cells die off. The others differentiate a majority into plasma cells, a minority into memory cells. At higher magnification, large, paler nuclei are visible. They represent follicular dendritic cells which hold and present antigen during this maturation process. Germinal centres indicate an active B cell response.

Question 43

Describe basic group processes.

Answer 43

Groups vary according to their structure and function. To function well, groups require several characteristics. These are the establishment of group norms, roles for group members, cohesiveness and sometimes, effective leadership.

Question 44

Apply knowledge of group processes to help change health behaviour.

Answer 44

A cohesive group may influence someone to change their health behaviours as they feel influenced by the others in the group. An effective leader may lead to respect, which can strongly influence recovery. There can be an element of conformity - we may go along with something because everybody else is. A review of the efficacy of NHS smoking cessation programmes found that group interventions worked better than 1 to 1 treatments.

Question 45

Discuss the role of social support in promoting physical and psychological health.

Answer 45

The main findings were that there was small effect size for interventions, those addressing social cognitions were the most effective, and interventions that used CBT can reduce loneliness. Studies with more women showed the greatest reduction in loneliness. However, sometimes selection bias could occur.

Question 46

Place bacteria within the context of other microorganisms.

Answer 46

Bacteria are unicellular microorganisms. They can be free living or host dependent. Some of these relationships are mutualistic, and others can be parasitic with a pathogenic effect.

Question 47

State the structural differences between prokaryotes and eukaryotes.

Answer 47

prokaryotes - unpaired chromosomes and no nuclei

eukaryotes - paired chromosomes and a nuclear structure

Question 48

Outline the principles of the Gram stain and how it is used to recognise the main morphological types of bacteria (eg staphylococci, streptococci, bacilli, etc).

Answer 48

1. stained with crystal violet,
2. flooded with gram’s iodine in order to fix the crystal violet to the peptidoglycan.
3. decolouriser removes the crystal violet
4. add a secondary stain such a safranin red

Question 49

List the structural differences between the two main types of bacteria (eg Gram positive and Gram negative bacteria).

Answer 49

gram negative - thin cell wall, use LPS, sheds lipid A and core polysaccahrides

grame positve - thick cell wall, teichoic and lipoteichoic acids, sheds peptidoglycan fragments, afimbrial adhesins and protein F surface proteins

Question 50

Give examples of common Gram positive and Gram negative bacterial cells.

Answer 50

staphylococci (“staph”), streptococci (“strep”), pneumococci, anthrax

Question 51

List the structure/function of some important molecules of the bacterial cell envelope.

Answer 51

flagella - made of flagellin, used for motility, polar or peritrichous, coiled

pili - made of pilin, used for adhesion, peritrichous

Question 52

Compare and contrast the antigen receptors of T cells and B cells.

Answer 52

T-cell - alpha and beta chain, both with variable and constant domains

B-cell - heavy and light chain, variable and constant domains

Question 53

Define the functional roles of helper and cytotoxic T cells.

Answer 53

helper T-cells - assist in phagocytosis and activate B-cells to produce antibodies

cytotoxic T-cells - destroy infected virulent cells

Question 54

Explain the nature of antigen peptide recognition by T cells and the role of antigen presenting cells (APCs).

Answer 54

APC presents antigen, which is modified before binding with the peptide-binding groove of the T-cell receptor

Question 55

Describe HLA class I and HLA class II molecules as peptide binding and presenting proteins.

Answer 55

An MHC class I molecule is made up of an alpha chain, with 3 domains, and a beta-2 microglobulin. The peptide-binding groove is made up of the alpha-1 and alpha-2 domains. CD8 binds to the alpha-3 domain.

The MHC class II molecule is made up of an alpha and a btea chain. The beta-1 domain and the alpha-1 domain make up the peptide-binding groove. CD4 binds to the beta-2 domain.

Question 56

Outline the different antigen processing pathways that generate peptides that are presented by either HLA class I or HLA class II proteins.

Answer 56

HLA class I - endogenous antigen is degraded by proteasome, peptide fragments transport to ER, loads to MHC class I and is expressed on cell surface.

HLA class II - exogenous antigen is degraded by proteasome into peptide fragments at low pH. HLA class II with invariant chain travels in vesicle, invariant chain is degraded and binds with peptide fragment before being expressed on cell surface.

Question 57

Describe the role of dendritic cells in capturing and processing antigens, and stimulating T cell activation.

Answer 57

CD4 and CD8 are present in order to make sure the correct T-cell presentation is switched on. The CD3 complex has the capacity to send signal 1 to the T-cell so that it can become activated. The interaction of B7.1 or B7.2 with CD28 produces signal 2, to activate the T-cell. Signal 3 is produced by cytokine receptors. This determines the type of CD4 T-helper cell produced.

Question 58

Outline the main types of cytokines and their properties.

Answer 58

Cytokines are secreted proteins that regulate the amplitude and duration of immune and inflammatory responses. They are simple and have a low molecular mass. They are usually produced transiently and locally and are extremely potent. They bind to specific cell-surface receptors and trigger intracellular processes.

Cytokines include interleukins, tumour necrosis factors, interferons, colony-stimulating factors, or chemokines.

Question 59

Distinguish the derivation and properties of Th1 and Th2 cells.

Answer 59

A dendritic cell deliberately takes up the antigens of a pathogen and expresses it on its surface. This interacts with a T-cell receptor on a CD4 helper 2 cell, with cytokine involvement, which sends signal 3 so that the T-cell will become a T-helper 2 cell. At the same time, the antigen is being recognised directly by a B-cell and presents an MHC class II receptor. The T-cell provides cytokines to the B-cell to produce antibodies.

Question 60

Describe the interactions between antigen presenting cells and helper T cells, and between helper T cells and antigen specific B cells, that lead to antibody production. Outline the anatomical locations of these interactions, and the processes of B cell maturation that occur in germinal centres.

Answer 60

In the paracortex, the activation of specific T and B-cells takes place. Antigen-specific T-cells are activated by dendritic cells, and antigen-specific B-cells are activated by T-cells.

In the germinal centre, the maturation of the activated B-cells occurs. Division increases the size of response, somatic mutation increases the affinity of the response. This is where there is a random mutation of the B-cell receptor on the surface of the B-cell. Class switching increases the defende effector functions, and the formation of plasma cells and memory cells takes place.

Tissue homing of activated lymphocytes is determined by their expression of particular adhesion molecules (eg. integrins) and chemokine receptors.
In the paracortex, the activation of specific T and B-cells takes place. Antigen-specific T-cells are activated by dendritic cells, and antigen-specific B-cells are activated by T-cells.

In the germinal centre, the maturation of the activated B-cells occurs. Division increases the size of response, somatic mutation increases the affinity of the response. This is where there is a random mutation of the B-cell receptor on the surface of the B-cell. Class switching increases the defende effector functions, and the formation of plasma cells and memory cells takes place.

Tissue homing of activated lymphocytes is determined by their expression of particular adhesion molecules (eg. integrins) and chemokine receptors.

Question 61

Explain how Th2 cells can promote mast cell and eosinophil activation.

Answer 61

A T-helper 2 cell can produce interleukin-4, which can lead to a B-cell class switch to produce IgE antibodies and directly activate mast cell production. The T-helper 2 cell can also produce interleukin-5 which can lead to eosinophil production.

Question 62

Explain how Th1 cells promote macrophage activation, and how this can lead to granulomatous inflammation in chronic mycobacterial infections, for example.

Answer 62

T-helper 1 cells can promote granulomatous inflammation when the pathogen cannot be cleared. Chronic stimulation of an immature macrophage can lead to the production of an epithelioid cell. Further chronic stimulation causes a fusion of cells which leads to a multinucleated giant cell.

Question 63

Outline the main immunological features of tuberculosis and leprosy, and how the nature of the T cell response determines the clinical spectrum of leprosy.

Answer 63

Tuberculoid leprosy is a T-helper 1 cytokine-driven disease. The organisms are present at undetectable levels, with low infectivity. Granulomas, local inflammation and peripheral nerve damage occurs. There are normal serum immunoglobulin levels and normal T-cell responsiveness. By interferon gamma, macrophages are activated for intracellular digestion, with some inflammation but the destruction of mycobacteria

Lepromatous leprosy is a T-helper 2 cytokine-driven disease. The organisms show florid growth in macrophages, high infectivity and disseminated infection. There is diffuse nerve damage and hypergammaglobulinemia. There is low or absent T-cell responsiveness. Interleukin-4 is produced, and B-cells are activated. The antibodies have no access to intracellular mycobacteria, leading to the growth of the mycobacteria and severe tissue damage.