The immune system Block 4 Week 1 Flashcards

Question

What are innate immune cells and adaptive immune cells ?

Answer 1

Innate immune cells: - Mast cell - Macrophage - Dendric cell Adaptive immune cell: - Natural killer T-cells (debatable) - B lymphocytes - T lymphocytes - plasma cells Most white blood cells circulate in the blood. With the exception of dendric cells and macrophages which are found within tissues

Answer 2

These are the cells of the innate immune system. They all have a much shorter lifespan in comparison with cells from the adaptive immune system. - Neutrophils are the most abundant followed by monocytes

Answer 3

Include Lymphocytes so B- lymphocytes and T-lymphocytes. Remember Leukocyte (WBC) and lymphocyte are different. - There are two types of T-cells; cytotoxic t-cells and t-helper cells

Answer 4

A hematocrit test measures the proportion of red blood cells in your blood. Anaemic Polycythaemia : Polycythaemia, also known as erythrocytosis, means having a high concentration of red blood cells in your blood. This makes the blood thicker and less able to travel through blood vessels and organs. Many of the symptoms of polycythaemia are caused by this sluggish flow of blood.

Answer 5

- This is a test to check the types and numbers of cells in your blood, including red blood cells, white blood cells and platelets. - Blood samples are put into a machine to fins the number of different types of cells in your blood. - You need a specific test tube to test for a specific thing which is they they have different tops

Answer 6

- When oxygen levels decrease the levels of erythropoieten (EPO) increase. When oxygen levels increase EPO goes down. - EPO is produced in the kidneys by special cells called juxta tubular interstitial cells of the renal cortex. They produce 90% of the EPO in blood. - They sense oxygen through oxygen - dependent prolyl hydroxylase that regulates the the stability of the primary transcription factor for EPO, hypoxia-inducible factor 1(alpha) (HIF-1(alpha)). This is a transcription factor that is activated by low oxygen and that drives up the production of EPO in the kidney. - So what you find in the if you have a situation of hypoxia or low oxygen, you have an increase in this transcription factor, that increases the amount of EPO that's been made by the kidney that then passes into circulation. EPO the makes it to the bone marrow where you see an increase in EPO. - Cyclists in the 90s abused EPO drug to allow them to cycle for longer

Answer 7

- Conditions affecting specifically erythropoiesis (red blood cell production) in the bone marrow are described as pure red cell aplasia (PRCA) - Conditions affecting production of other cell types in addition to RBCs (white cells and platelets) is termed pancytopenia - Diamond - Blackfan anemia is the most common PRCA

Answer 8

HSC can differentiate into a progenitor cell, and this will then go down to produce the circulating cells. But what it needs to do here is when it divides, it needs to make an identical daughter cell, so production, you won't exhaust the stem cell pool. Youre maintaining the number of stem cells you. - If you have a genetic or chemical change in the stem cell it will lose its self renewing ability and will only differentiate. This is when you start to lose the stem cell pool. And that can lead to bone marrow failure condition.

Answer 9

HSC can differentiate into a progenitor cell, and this will then go down to produce the circulating cells. But what it needs to do here is when it divides, it needs to make an identical daughter cell, so production, you won't exhaust the stem cell pool. Youre maintaining the number of stem cells you. - If you have a genetic or chemical change in the stem cell it will lose its self renewing ability and will only differentiate. This is when you start to lose the stem cell pool. And that can lead to bone marrow failure condition.

Answer 10

- Hemolytic anemia is a disorder in which red blood cells are destroyed faster than they can be made. - Lifespan of normal red blood cells is 120 days. Haemolytic anemia would significantly reduce that lifespan - Erythrocyte destruction normally happens because: 1. Extrinsic hemolytic anemia: External pathogens destroy the red blood cell e.g. drugs, toxins and antibodies. 2. Intrinsic hemolytic anemia: There is something intrinsically wrong with the erythrocyte e.g. absence of specific enzymes

Answer 11

relating to or denoting any disease or condition which arises spontaneously or for which the cause is unknown. - Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder in which the body cannot properly regulate the number of immune system cells (lymphocytes)

Answer 12

- A trained pathologist can tell a huge amount from a blood film. So if blood film is just a tiny amount of blood tissue, about five microliters of blood on a slide that's then smeared across and then stained with a certain chemicals. - reticulocytes are red blood cells that are still developing - polychramasia - is the presentation of multicolored red blood cells in a blood smear test. suggests an underlying blood disorder.

Answer 13

Haemoglobinopathies are autosomal co-dominant genetic defects resulting in abnormal structure of one of the globin chains of the haemoglobin molecule. - Sickle cell anemia is an one oft he most common haemoglobinopathies.

Answer 14

infants and male adults: 1mg Adolescent: 2-3 mg Menstruating adolescent: 3-4mg Menstruating adult: 2-3 mg Pregnancy: 3-4 mg# High iron content foods: - Dark green leafy vegetables - Iron fortified cereals - Whole grains - Beans - Nuts - Meat

Answer 15

- Vitamin B6 and Vitamin B12/ folate deficiency

Answer 16

The two main components of hemoglobin are the globin and heme. - globin is produced in the cystol - heme synthesis happens in both the cystola nd mitochondria of erythrocytes. - It begins with glycine and succinyl coenzyme A and ends with the production of a protoporphyrin IX ring. The binding of the protoporphyrin to a Fe2+ ion forms the final heme molecule.

Answer 17

- mean corpuscle volume - is a measurement of the red blood cell size - mean corpuscular hemoglobin (MCH) - average amount of hemoglobin in each cell - Mean corpuscular hemoglobin concentration (MCHC) is a measurement of the average amount of hemoglobin in a single red blood cell (RBC) as it relates to the volume of the cell. Hematocrit - is a percentage by volume of red blood cell in your blood.

Answer 18

- A special type of immune cell that is found in tissues, such as the skin, and boosts immune responses by showing antigens on its surface to other cells of the immune system. - A dendritic cell is a type of phagocyte and a type of antigen-presenting cell (APC) - Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. They act as messengers between the innate and the adaptive immune systems.

Answer 19

-Macrophages are specialised cells involved in the detection, phagocytosis and destruction of bacteria and other harmful organisms. - In addition, they can also present antigens to T cells and initiate inflammation by releasing molecules (known as cytokines) that activate other cells.

Answer 20

-Macrophages are specialised cells involved in the detection, phagocytosis and destruction of bacteria and other harmful organisms. - In addition, they can also present antigens to T cells and initiate inflammation by releasing molecules (known as cytokines) that activate other cells.

Answer 21

- Mast cells play an important role in how the immune system responds to certain bacteria and parasites and they help control other types of immune responses. They contain chemicals such as histamine, heparin, cytokines, and growth factors. - they can be activated to release a wide variety of inflammatory mediators, by many different antigens including allergens, pathogens and physiological mediators

Answer 22

- Blood groups depend on the presence of different antigens on the surface of red blood cells (RBCs). - Understanding different blood groups is vital in preventing problems during blood transfusions. - Erythrocytes (RBCs) have multiple glycoprotein antigens attached to their cell surface. The most important are ABO antigens, which determine a person’s ABO blood group. - An individual inherits one ABO allele from each parent, with A and B alleles being codominant and producing the A and B antigens respectively.

Answer 23

Blood types: Group A - antigen A Group B - antigen B Group AB - antigen A and B Group O - neither antigen A or B - Each person also has ABO antibodies in their plasma, which will recognise and attack RBCs expressing foreign antigens. -These antibodies develop over the first months and years of life. This is crucial in blood transfusion as giving someone an incompatible blood group can be potentially fatal. Blood types: Group A - B antibodies Group B - A antibodies Group AB - neither antibody Group 0 - both A and B antibodies

Answer 24

Chromosome 9

Answer 25

The patient with the blood type that can receive blood from everyone is type AB (+) The blood type which can donate blood to everyone is type O (-)

Answer 26

The second most important blood grouping system is based on Rhesus (Rh). There are 5 types of Rh antigens but Rh D is the most immunogenic and most likely to precipitate an immune reaction. The presence of Rh D on an erythrocyte cell surface makes them Rh (+) and the absence makes them Rh (-). Rh positive: have the Rh D antigen and can receive both Rh+ and Rh- blood Rh positive: have the Rh D antigen and can receive both Rh+ and Rh- blood

Answer 27

The second most important blood grouping system is based on Rhesus (Rh). There are 5 types of Rh antigens but Rh D is the most immunogenic and most likely to precipitate an immune reaction. The presence of Rh D on an erythrocyte cell surface makes them Rh (+) and the absence makes them Rh (-). Rh positive: have the Rh D antigen and can receive both Rh+ and Rh- blood Rh positive: have the Rh D antigen and can receive both Rh+ and Rh- blood

Answer 28

Rhesus disease: Aka haemolytic disease Is a condition where antibodies in a pregnant woman's blood destroy her baby's blood cells Anti-D antibody is usually absent in Rh- patients (until they have been exposed to Rh+ erythrocytes). Rh- patients should not be transfused with Rh+ blood as this can cause them to develop anti-D antibodies.This may cause transfusion reactions in the future. What symptoms will a baby/foetus have if they have rhesus disease: - but it can cause the baby to become anaemic and develop jaundice. - However HDN is relatively rare because of routine antenatal serology and administration of prophylaxis which is a Anti-D therapy. Anti-D immunoglobulin will bind and neutralise any RhD+ cells preventing the development of maternal antibodies

Answer 29

Rh ( +) : 85% Rh (-) : 15% It is very likely a Rh (-) mother will have a Rh (+) foetus

Answer 30

We prevent transfusion reaction through a process called Cross Matching. If we give bloods which do not complement each other we will see agglutination of the blood in vivo.

Answer 31

Examples are: Sickle cell anaemia Thalassaemia: any of a group of hereditary haemolytic diseases caused by faulty haemoglobin synthesis, widespread in Mediterranean, African, and Asian countries.

Answer 32

Describe sickle cell anaemia cause? Mutation in the HBB (haemoglobin beta chain) Glutamic acid is replaced by valine; this variant is often called HBS Sickle shape changed haemoglobins affinity for oxygen Missense mutation

Answer 33

If an individual inherits 2 A genes, one from each parent they do not have sickle cell disease. Haemoglobin AA If an individual inherits 1 sickle cell gene and one normal gene. They have sickle cell trait. Haemoglobin AS If an individual inherits 2 sickle cell genes. They have sickle cell disease. Haemoglobin SS

Answer 34

Haemolytic Disease of the New-born (HDN) Anti-D antibodies cause the most severe type of HDN. Exposure of a Rh- person to the Rh D antigen causes Rh D sensitisation. For instance, during a first pregnancy if the foetus is Rh+. The presence of Rh D antigens in the maternal circulation stimulates the production of anti-D antibodies. Maternal anti-D antibodies recognise and destroy foetal Rh+ RBCs. Upon first exposure, the antibodies are IgM, which cannot cross the placenta and will not cause issues in the first pregnancy. However, future Rh+ pregnancies will result in the production of large amounts of IgG anti-D which can cross the placenta and cause haemolysis. Thankfully the administration of anti-D Ig prophylaxis to unsensitised Rh- mothers has significantly reduced the incidence of HDN caused by anti-D antibodies. The prophylaxis works by destroying foetal RBCs that leak into the maternal circulation, reducing the chance of Rh D sensitisation. ABO typing tests the patient’s blood for the presence of A/B antigens, and A/B antibodies. This is followed by Rh typing. The lab will also screen the patient’s blood for atypical antibodies. Cross-matching involves mixing the donor’s blood with the recipient’s blood to detect any immune reaction.

Answer 35

*Clinical biochemistry * *Haematology * *Histopathology * *Immunology * *Medical microbiology

Answer 36

Infectious disease –Incidence of polio, measles, mumps, rubella, diphtheria, pertussis (whooping cough), and meningitis caused by haemophilus influenzae type b reduced by 95 to 100% since introduction of vaccination.

Answer 37

Human Papilloma Virus: GSK vaccine against HPV prevents 90 per cent of new infections and all persistent infections

Answer 38

*Immunotherapy –Cytokine targeted therapy for AI diseases: e.g. Rheumatoid arthritis –Checkpoint inhibitors for cancer immunotherapy –CAR T cell therapy

Answer 39

*Transplantation –Approx. 80% of lung, liver and kidney recipients now survive >1yr

Answer 40

Fetal life -yolk sac from week 4 of development -liver until shortly before birth -spleen until cartilagenous bones vascularised What are the sites of haemopoiesis in adults? Adult / infant life - marrow of most bones in children - mainly marrow of pelvis, sternum, vertebrae and cranial bones in adults (due to fat deposition in marrow of long bones)

Answer 41

The neck or cervical region is divided into triangles for descriptive purposes: a) a median anterior triangle (visceral compartment), continuous inferiorly with the superior mediastinum in the thorax, and b) two posterior triangles, one on each side, continuous inferolaterally with the axilla. These triangles are bounded by muscles and bones.

Answer 42

The mastoid process is a pyramidal bony projection from the posterior section of the temporal bone.

Answer 43

The mental foramen is a bilateral opening in the vestibular portion of the mandible through which nerve endings, such as the mental nerve, emerge

Answer 44

The platysma is a superficial muscle found in the neck a broad thin sheet of muscles which is superficial to the other structures we will be examining today. The platysma covers the anterolateral surface of the neck

Answer 45

The anterior triangle is often divided, for descriptive purposes, into two triangles along the mid-line. Clinically, however, it is better to conceive it as a single median visceral compartment of the neck. BOUNDARIES OF THE ANTERIOR TRIANGLE -the anterior border of the sternocleidomastoid muscle -the inferior border of the mandible -the mid-line of the neck

Answer 46

BOUNDARIES OF THE ANTERIOR TRIANGLE -the anterior border of the sternocleidomastoid muscle -the inferior border of the mandible -the mid-line of the neck

Answer 47

THE HYOID BONE AND THE SUPERFICIAL MUSCLES ATTACHED TO IT - the hyoid bone the suprahyoid muscles: -digastric, -stylohyoid, -mylohyoid, -geniohyoid the infrahyoid muscles: -sternohyoid, -omohyoid, -thyrohyoid, -sternothyroid Note that the suprahyoid and infrahyoid muscles form smaller triangles within the bigger anterior triangle.

Answer 48

THE SMALLER TRIANGLES AND THEIR BOUNDARIES - the carotid triangle: Bounded by the sternocleidomastoid, posterior belly of digastric and superior belly of omohyoid - the digastric (submandibular) triangle: Bounded by the mandible and the anterior and posterior bellies of the digastric muscle - the submental triangle: Bounded by the anterior bellies of the digastric and the body of the hyoid bone - the muscular triangle: Bounded by the sternocleidomastoid, superior belly of omohyoid and the midline

Answer 49

MAJOR CONTENTS OF THE ANTERIOR TRIANGLE Now that you are familiar with the boundaries of the anterior triangle and muscles forming smaller triangles within the anterior triangle, explore the contents of the anterior triangle. - the larynx - the pharynx - the oesophagus the carotid sheaths and their neurovascular contents: -the common carotid artery -the internal jugular vein -the vagus nerve -the thyroid and parathyroid glands - the mylohyoid muscle - the recurrent laryngeal nerve - the superior laryngeal nerve -the hypoglossal nerve -branches of the external carotid artery - the submandibular salivary gland

Answer 50

MAJOR CONTENTS OF THE ANTERIOR TRIANGLE Now that you are familiar with the boundaries of the anterior triangle and muscles forming smaller triangles within the anterior triangle, explore the contents of the anterior triangle. - the larynx - the pharynx - the oesophagus the carotid sheaths and their neurovascular contents: -the common carotid artery -the internal jugular vein -the vagus nerve -the thyroid and parathyroid glands - the mylohyoid muscle - the recurrent laryngeal nerve - the superior laryngeal nerve -the hypoglossal nerve -branches of the external carotid artery - the submandibular salivary gland - there is no internal carotid vein just an internal jugular vein

Answer 51

The posterior triangle is bounded anteriorly by the posterior border of the sternocleidomastoid, posteriorly by the anterior border of the trapezius, and inferiorly by the middle third of the clavicle. The roof (most superficial boundary) of the posterior triangle is formed by cervical investing fascia.

Answer 52

The posterior triangle is bounded anteriorly by the posterior border of the sternocleidomastoid, posteriorly by the anterior border of the trapezius, and inferiorly by the middle third of the clavicle. The roof (most superficial boundary) of the posterior triangle is formed by cervical investing fascia. BOUNDARIES OF THE POSTERIOR TRIANGLE -the posterior border of the sternocleidomastoid muscle -the anterior border of the trapezius muscle - the middle third of the clavicle

Answer 53

This layer of the deep cervical fascia is a collar of fascia surrounding the whole neck and contains the trapezius and sternocleidomastoid muscles.

Answer 54

MAJOR CONTENTS OF THE POSTERIOR TRIANGLE Muscles forming the floor of the triangle: -splenius capitis -levator scapulae -scalene muscles: scalenus posterior, medius, anterior -the inferior belly of the omohyoid muscle -the spinal accessory nerve - the branches of the cervical plexus

Answer 55

MAJOR CONTENTS OF THE POSTERIOR TRIANGLE Muscles forming the floor of the triangle: -splenius capitis -levator scapulae -scalene muscles: scalenus posterior, medius, anterior -the inferior belly of the omohyoid muscle -the spinal accessory nerve - the branches of the cervical plexus

Answer 56

S: superior thyroid artery. A: ascending pharyngeal artery. L: lingual artery. F: facial artery. O: occipital artery. P: posterior auricular artery. M: maxillary artery. S: superficial temporal artery.

Answer 57

The stylohyoid muscle connects the hyoid bone to the base of the skull, and it pulls the hyoid bone upward and backward, resulting in elevation of the base of the tongue and elongation of the floor of the mouth

Answer 58

The stylohyoid muscle connects the hyoid bone to the base of the skull, and it pulls the hyoid bone upward and backward, resulting in elevation of the base of the tongue and elongation of the floor of the mouth

Answer 59

major components of carotid triangle: - Internal jugular vein - vagus nerve - External carotid artery

Answer 60

- The cervical plexus is a network of nerve fibres that supplies innervation to some of the structures in the neck and trunk. - It is located in the posterior triangle of the neck, halfway up the sternocleidomastoid muscle, and within the prevertebral layer of cervical fascia. - The spinal nerves C1 – C4 form the basis of the cervical plexus. -Each nerve then divides into anterior and posterior nerve fibres - The cervical plexus begins as the anterior fibres of the spinal nerves C1, C2, C3 and C4.

Answer 61

The branches of the cervical plexus can be split into muscular and sensory branches. Muscular branches: - The muscular branches of the cervical plexus are located deep to the sensory branches. They supply some of the muscles of the neck, back and the diaphragm. Phrenic nerve arises from c3- c5 and provides innervation to the diaphragm. Nerves to the geniohyoid and thyrohyoid: - The C1 spinal nerve gives rise to nerves to the geniohyoid (moves the hyoid bone anteriorly and upwards, expanding the airway) and the thyrohyoid (which depresses the hyoid bone and elevates the larynx). -These nerves travel with the hypoglossal nerve to reach their respective muscles. Ansa Cervicalis: -The ansa cervicalis is a loop of nerves, formed by nerve roots C1-C3. It gives off four muscular branches. - Superior belly of the omohyoid muscle -Inferior belly of omohyoid muscle -Sternohyoid -Sternothyroid These muscles (the infrahyoids) act to depress the hyoid bone; an important function for swallowing and speech.

Answer 62

The branches of the cervical plexus can be split into muscular and sensory branches. The cutaneous branches of the cervical plexus supply the skin of the neck, upper thorax, scalp and ear. Sensory branches: Greater auricle nerve: - formed by fibred from c2 and c3 - It provides sensation to the external ear and the skin over the parotid gland. It is the largest ascending branch of the plexus. Transverse cervical plexus: - The transverse cervical nerve is also formed by fibres from C2 and C3 - supplies sensation to the anterior neck. Lesser Occipital nerve: - The lesser occipital nerve is derived from the C2 root - It supplies cutaneous sensation to the posterosuperior scalp Supraclavicular nerve: - The supraclavicular nerves are a group of nerves formed from the C3 and C4 roots. They arise from the behind the posterior border of sternocleidomastoid, and provide sensation to the skin overlying the supraclavicular fossa and upper thoracic region and sternoclavicular joint.

Answer 63

- Vitamin B12 supplement - injection

Answer 64

- also known as iron (II) sulfate - used to treat iron deficiency

Answer 65

- also known as vitamin B9 - converted into folate in the body dietary supplement - It is recommended you take folic acid as soon as you start trying for a baby and during the first 12 weeks of pregnancy.

Answer 66

lymphoid tissue, cells and organs that make up the lymphatic system, such as white blood cells (leukocytes), bone marrow, and the thymus, spleen, and lymph nodes.

Answer 67

Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. Serum and plasma both come from the liquid portion of the blood that remains once the cells are removed, but that's where the similarities end. Serum is the liquid that remains after the blood has clotted. Plasma is the liquid that remains when clotting is prevented with the addition of an anticoagulant

Answer 68

Interleukin 7

Answer 69

The innate immune is continuous and does not stop when the adaptive immune response begins.

Answer 70

- opsonizing: making (a foreign cell) more susceptible to phagocytosis. - Complement cascade, forms a part of the innate immune system. Complement components are generally made in the liver and circulate in their inactive form until they are needed. - The overall aim of the complement system is to support other parts of the immune response by opsonizing pathogens and triggering inflammation. - There are three ways to activate the complement system, involving different molecules initially but converging to produce the same effector molecules. Each involves activation of enzymes that cleave their substrates to form a cascade, so that the complement response is amplified. The three pathways are: - The Classical Pathway - The Mannose-Binding Lectin Pathway - The Alternative Pathway All three pathways produce C3 convertase, an enzyme which triggers further effects downstream

Answer 71

The Classical Pathway: - The classical pathway is activated when a complement protein called C1q binds either directly to a pathogen, or onto an antigen-antibody complex. - This will then trigger cleavage of the subsequent complement proteins in the cascade, resulting in production of C3 convertase and it’s downstream effects. Its involvement in antigen-antibody complexes means it has a role in the adaptive immune response as well as the innate. The Mannose-Binding Lectin (MBL) Pathway: -Mannose-Binding Lectin (MBL) is a protein produced in the liver. Its role is to detect carbohydrates containing mannose on the surface of pathogens, activating a protease called MASP. -MASP is responsible for cleaving complement components, which activates a similar cascade to the classical pathway, eventually producing C3 convertase. The Alternative Pathway: - The alternative pathway is usually activated by bacterial endotoxin, a lipopolysaccharide present on the outer membrane of gram negative bacteria. This results in spontaneous hydrolysis of C3 into small amounts of factor C3b, which combines with other factors to produce C3 convertase.

Answer 72

-Opsonisation (c3b) -Lysis of pathogens (c5b, MAC) -Chemotaxis (c3a, c5a) -Inflammation (c3a, c4a, c5a) Opsonisation: -C3 convertase converts factor C3 into C3a and C3b. -C3b binds to antigens on the pathogen, which stimulates neutrophils and macrophages to phagocytose pathogens – this is called opsonisation. Lysis: - involves the formation of MAC ( membrane attack complex) - C3 convertase generated C3a and C3b - These combine with other factors to produce C5 convertase - C5 convertase converts c5a and c5b - C5b combines with several factors to produce MAC The MAC ruptures the bacterial cell membrane, allowing fluid to enter the bacteria and causing cell lysis. However, because they possess a cell wall, gram positive bacteria and fungi do not swell and hence cannot be lysed by the complement system. Chemotaxis: - C5 convertase produces C5a. - C5a attracts neutrophils and macrophages to the site of infection and stimulates the movement of cells from capillaries to tissues. - C3a is another complement component that acts as a chemotaxin. Inflammation: - C3a, C4a and C5a are the complement components responsible for causing inflammation. - They bind to mast cells and basophils to cause degranulation. -The histamine and serotonin released increase vascular permeability. -C3a, C4a and C5a also promote synthesis of pro-inflammatory cytokines.

Answer 73

There is coupling between receptors and function

Answer 74

- After a pathogen has entered the body, it is vital for cells of the immune system to identify the pathogen as foreign and destroy it. - In the innate immune system, this involves interaction between Pathogen Associated Molecular Patterns (PAMPs) and Pattern Recognition Receptors (PRRs). - Pattern recognition receptors identify pathogens by recognizing “pathogen associated molecular patterns” (PAMPs) which are signatures produced by the pathogens. - The innate immune system is rapid and non-specific, quickly phagocytosing foreign cells. It uses Pattern Recognition Receptors (PRRs) to recognise pathogens. - Pattern Recognition Receptors are infection recognition receptors located on immune cells such as macrophages and dendritic cells. They bind to Pathogen Associated Molecular Patterns (PAMPs). A PAMP is a specific arrangement of carbohydrates, lipids and nucleic acids on the surface of a pathogen that signals to a phagocyte that a cell is foreign. Many different molecules can act as PAMPs, including peptidoglycans, endotoxin and flagellin.

Answer 75

PRRs can be located on the cell surface, for extracellular infection recognition, or in the cytoplasm, to target intracellular pathogens such as viruses The main type of PRR on the cell surface is a Toll-like receptor (TLR), of which there are 11 types in humans, all recognising different PAMPs. - There are multiple other types of PRR, including mannose receptors, but these exist in fewer numbers. -Unlike components of the adaptive immune system, PRRs are not specific to individual pathogens, but to groups of pathogens. Thus, they do not possess cellular memory.

Answer 76

- Phagocytosis is a major mechanism for detecting and removing potentially pathogenic material. Phagocytes also have lysosomes which are membrane-bound organelles containing hydrolytic enzymes. These fuse with phagosomes and release their cargo into the phagosome, degrading any internalised particle. -

Answer 77

Many cells are capable of phagocytosis, but some immune cells are specialised for this role: Neutrophils: - are abundant in the blood and essential in acute inflammation, as they are the first immune cells to arrive at the infection site. Macrophages: - are tissue-resident cells that act as an initial defence mechanism and serve to activate the adaptive immune response. Dendritic cells: - antigen presenting cells – these cycle through the bloodstream, tissues and lymphoid organs, sampling potential pathogens and acting as a major link between the innate and adaptive immune systems.

Answer 78

Pathogen killing can occur in one of two ways: The oxygen-dependent pathway (oxidative burst): - involves the generation of reactive oxygen species (ROS) such as superoxide radicals and hydrogen peroxide. These highly reactive radical molecules react with proteins, lipids and other biological molecules to kill the pathogen. -Superoxide radicals form via the enzyme NADPH oxidase. After that, another enzyme- superoxide dismutase- converts these species to hydrogen peroxide. -The oxygen-independent pathway involves the destruction of the pathogen via lysosomal enzymes such as proteases, phospholipases, nucleases and lysozymes. These enzymes help to kill pathogens, primarily by breaking down their cell membrane. However, this a less effective mechanism when compared to the oxygen-dependent pathway.

Answer 79

- neutrophils most abundant - monocytes second most abundant - dendric cells least abundant

Answer 80

Production is stimulated in the bone marrow by the growth factor granulocyte-macrophage colony-stimulating factor. GM- CSF - Another way neutrophils can catch bacteria is using "neutrophil extracellular traps" aka NETs. This is when they extrude their DNA to trap bacteria so they become motile so they can catch up with the bacteria and eat them. https://www.histology.leeds.ac.uk/blood/blood_wbc.php

Answer 81

- monocytes can differentiate into macrophages which are more longer lived. - macrophages are more long lived than neutrophils - Over the last few years as well, accumulating evidence that some tissue macrophages can arise independently of haematopoietic stem cells and populate the tissues from birth from embryonic precursors. - macrophages look different depending on where they are found. So in the liver for example they are Kupffer cells. - Kupffer cells are liver resident macrophages that localize within the lumen of the liver sinusoids and are adherent to the endothelial cells that compose the blood vessel walls.

Answer 82

The major function of dendritic cells is as a link between the innate and the adaptive immune systems. As immature dendritic cells they travel in the bloodstream and migrate through tissues and continually sample the pathogens they find via macropinocytosis. Following phagocytosis, the cell becomes mature and migrates to a peripheral lymphoid organ such as a lymph node, the spleen, or gut-associated lymphoid tissue to present the antigen to a T cell. This then activates the T cell to initiate an adaptive immune response. Dendritic cells can be recognised by the presence of multiple cytoplasmic projections from their surface, giving them a large surface area to volume ratio that aids close contact with multiple cells. These processes look similar to the dendrites of neurons, which gave dendritic cells their name.

Answer 83

Granulocytes and monocytes, collectively called myeloid cells, are differentiated descendants from common progenitors derived from hematopoietic stem cells in the bone marrow.

Answer 84

Monocytes are a type of phagocyte found in the bloodstream. They circulate around the body, and when a tissue is infected or inflamed they may leave the bloodstream and enter the tissue. In the tissue they differentiate into macrophages, which form the major resident population of phagocytes in normal tissues. Monocytes are phagocytic but since most infections occur in tissues, it is the ability of monocytes to differentiate that is particularly key. If a particular set of signals are present, it is also possible for monocytes to differentiate into dendritic cells in the tissues. Monocytes are the largest type of phagocyte, with a kidney bean shaped nucleus when seen under a microscope.

Answer 85

Granulocytes are a group of phagocytes with dense granules in their cytoplasm, and include neutrophils, eosinophils, and basophils. Neutrophils are the most phagocytic of these cells: they are the most abundant white blood cell, and can be identified by their granular cytoplasm and lobulated nuclei (usually 2-5 lobules). They are formed from myeloid stem cells found within bone marrow. They are normally found within the bloodstream, but during the acute phase of infection they are among the first inflammatory cells to reach the site of infection. They are particularly specialised at killing intracellular pathogens due to cytoplasmic granules with toxic substances such as antimicrobial peptides, enzymes, and reactive oxygen species. Neutrophils are short-lived cells and normally die following phagocytosis and use of their granules – dying or dead neutrophils are a major part of the pus seen with infection. Neutrophils are also important for inducing inflammation and recruiting inflammatory cells through release of cytokines and other inflammatory factors.

Answer 86

- Resting blood vessel contains lots of RBCs, lymphocytes, phagocytes. - When we have a tissue site that causes local infection it activates the complement cascade - The macrophage produces cytokines and histamines - All of these tings affect the endothelial cell wall locally. - Leukocytes stick to the wall of the blood vessel Extravasation: migration between endothelial cells to get out of the lumen and into the tissue space.

Answer 87

HSP90 (Heat shock protein 90)

Answer 88

Phagocytic macrophages can be influenced in different directions by different types of engagement with cytokines. - The classical activation is stimulating one type of immune response - The alternate activation is stimulating another type of immune response - Cytokines can act in cascades. So one cytokine can trigger another cytokine and so on. Where you intervene in a cascade can have different clinical outcomes. We have to understand how these cascades work to develop effective interventions. - Tumor necrosis factor (TNF) is a cytokine which is considered one of the main mediators of joint inflammation in Rheumatoid arthritis. We use specific antibodies to target TNF to treat RA.

Answer 89

- Tumor necrosis factor (TNF) is a cytokine which is considered one of the main mediators of joint inflammation in Rheumatoid arthritis. We use specific antibodies to target TNF to treat RA. - However blocking TNF affects another pathway which has an adverse effect. It causes tuberculosis reactivation. - so of you have TNF blockade you are much more prone to latent TB reactivation.

Answer 90

- The spleen is an organ located in the upper left abdomen, and is roughly the size of a clenched fist. - In the adult, the spleen functions mainly as a blood filter, removing old red blood cells. It also plays a role in both cell-mediated and humoral immune responses. - The spleen is connected to the stomach and kidney by parts of the greater omentum – a double fold of peritoneum that originates from the stomach: - Gastrosplenic ligament – anterior to the splenic hilum, connects the spleen to the greater curvature of the stomach. - Splenorenal ligament – posterior to the splenic hilum, connects the hilum of the spleen to the left kidney. The splenic vessels and tail of the pancreas lie within this ligamen

Answer 91

- The spleen is a highly vascular organ. It receives most of its arterial supply from the splenic artery. This vessel arises from the coeliac trunk. As the artery reaches the spleen, it branches into five vessels - Venous drainage occurs through the splenic vein. It combines with the superior mesenteric vein to form the hepatic portal vein. The blood then goes to the liver. - Nerve supply to the spleen is the cervical plexus

Answer 92

The lymphatic vessels of the spleen follow the splenic vessels mentioned above and drain into the pancreaticosplenic lymph nodes, and ultimately the coeliac nodes.

Answer 93

- The spleen filters the blood The spleen contains two types of tissues with different functions: white pulp and red pulp. White pulp (25%) : - comprises lymph-related nodules called malpighian corpuscles which contain: -Periarteriolar lymphoid sheaths rich in T-lymphocytes and macrophages. - A marginal zone, rich in macrophages -Lymphoid follicles, rich in naive B-lymphocytes - Because of this, the white pulp of the spleen has a very important role in the normal immune response to infection. Antigen presenting cells may enter the white pulp, resulting in activation of the T-lymphocytes stored there. These in turn, activate the B-lymphocytes in the follicles, converting them to plasma cells which then produce of IgM antibodies initially and eventually IgG antibodies. Red pulp: - The red pulp makes up roughly 80% of the spleen parenchyma. It is separated from the white pulp by the marginal zone. The red pulp is primarily made up of tissue known as the cords, which is rich in macrophages, and the venous sinus. Functions of the red pulp: - Removal of old, damaged and dead red blood cells along with antigens and microorganisms – the venous sinuses have gaps in the endothelial lining which allows normal cells to pass through, abnormal cells remain in the cords and are phagocytosed by macrophages -Phagocytosis of opsonised bacteria by macrophages -Sequestration of platelets. -Storage of red blood cells in case of hypovolaemia (lose red blood cells) , these can then be released following an injury resulting in blood loss -Prenatally, it is haematopoietic until about the fifth month of gestation when bone marrow becomes the main site for haematopoiesis.

Answer 94

-Splenomegaly common in chronic disease (malaria, leishmaniasis, Hodgkin’s disease) - people who have spleen removed have lower amounts of antibodies in the blood. People without spleen are at an increased risk of infection. - individual with no spleen have an increased number of abnormal red blood cells

Answer 95

Primary lymphatic organs are where lymphocytes are formed and mature. They provide an environment for stem cells to divide and mature into B- and T- cells: There are two primary lymphatic organs: -Thymus (T lymphocytes) -Bone marrow (B lymphocytes)

Answer 96

Secondary lymphoid organs: These organs include the lymph nodes, the spleen, the tonsils and certain tissue in various mucous membrane layers in the body (for instance in the bowel). It is in these organs where the cells of the immune system do their actual job of fighting off germs and foreign substances The sites where naive lymphocytes are kept for activation. Maturation, activation occurs here. Acquired immune system turned on here: -Tonsils/Appendix/Peyer’s patch/Spleen/Lymph nodes -Mucosal associated lymph tissue (MALT) -Gut associated lymph tissue (GALT) -Nasal associated lymph tissue (NALT) Mucosal associated lymph tissue: - M cells are highly specialised cells present within the epithelium overlying organised lymphoid follicles of the small and large intestine. - They play a central role in the initiation of mucosal immune responses by transporting antigens and microorganisms to the underlying lymphoid tissue. In this way the mucosal immune system encounters the limitless variety of antigens that enter the body through the gut mucosa and reacts by mounting specific mucosal and systemic immune responses.

Answer 97

- Each node contains T lymphocytes, B lymphocytes, and other immune cells. They are exposed to the fluid as it passes through the node, and can mount an immune response if they detect the presence of a pathogen. This immune response often recruits more inflammatory cells into the node – which is why lymph nodes are palpable during infection. - Lymph fluid enters the node through afferent lymphatic channels and leaves the node via efferent channels. Macrophages located within the sinuses of the lymph node act to filter foreign particles out of the fluid as it travels through. - Within the germinal center we have B cells (the outer most portion) - T cells are within the innermost portion

Answer 98

- Lymphocyte recirculation refers to the continuous transport of large numbers of naïve lymphocytes between the blood and lymphatic systems. - After naïve lymphocytes are produced in the thymus or bone marrow, they enter the blood, where they spend about 30 min, before migrating to the lymphoid and nonlymphoid organs. - For the most part their are not many lymphocytes in the veins

Answer 99

- The lymphatic system is a series of vessels and nodes that collect and filter excess tissue fluid (lymph) about 3 litres/24hrs, before returning it to the venous circulation. It forms a vital part of the body’s immune defence. - Lymph capillaries are found between cells (in the interstitial space). These capillaries are in the tissues of every organ in your body, except for your: - cartilage - the cornea and lens of your eye - epithelial (outermost) layer of your skin which is called the epidermis - The central nervous system, including your brain and spinal cord.

Answer 100

-Superficial vessels – arise in the subcutaneous tissue, and tends to accompany venous flow. They eventually drain into deep vessels. -Deep vessels – drain the deeper structures of the body, such as the internal organs. They tend to accompany deep arteries.

Answer 101

-The drainage of lymph begins in lymph channels, which start as blind ended capillaries and gradually develop into vessels. These vessels travel proximally, draining through several lymph nodes. -Eventually the vessels empty into lymphatic trunks (also known as collecting vessels) – and these eventually converge to form the right lymphatic duct and the thoracic duct. -The right lymphatic duct is responsible for draining the lymph from the upper right quadrant of the body. This includes the right side of the head and neck, the right side of the thorax and the right upper limb. -The thoracic duct is much larger and drains lymph from the rest of the body. These two ducts then empty into the venous circulation at the subclavian veins, via the right and left venous angles.

Answer 102

- Everything from the bottom of the feet upwards drains into the inguinal lymph nodes. The medial lymph vessels follow the great saphenous vein. The lateral lymph vessels follow the small saphenous vein. - Everything from the head downwards drains into the cervical lymph nodes. - Everything from the arms, thorax and abdomen drain into the axillary lymph nodes

Answer 103

The integrity and proper function of the spleen are considered important for the protection against infectious diseases in the adult. The reduction of splenic function encountered in various pathological conditions is called functional hyposplenism (FH) - If you have Howell- Jolly bodies in your blood it can indicate hyposplenism/asplenia. - Asplenia is the absence of a spleen

Answer 104

The thymus gland is a small organ that lies in the upper chest under the breastbone. It makes white blood cells, called lymphocytes, which protect the body against infections. Embryologically, the thymus gland is derived from the third pharyngeal pouch.

Answer 105

The thymus gland is a small organ that lies in the upper chest under the breastbone. It makes white blood cells, called lymphocytes, which protect the body against infections. Embryologically, the thymus gland is derived from the third pharyngeal pouch.