The immune system Block 4 Week 1 Flashcards
What is Anaemia ?
What are the signs of anaemia?
- Caused by reduced number of red blood cells
- Results in reduced oxygen delivery
Signs:
-Pallor (pale appearance under eyes should be red)
-Tachycardia (too fast heart rate)
-Glossitis (tongue becomes inflamed and swollen, normally de to vit B12 deficiency)
-Koilonychia (spoon nails - soft nails that look scooped out)
-Dark urine (like cola)
Symptoms:
- Lethargy
-Dizziness
-Shortness of breath
-Chronic fatigue
-Poor concentration
Severe symptoms:
- Jaundice
-Splenomegaly ( because of reduced red blood cells being produced in the bone marrow, the spleen overcompensates
-Hepatomegaly
-Angina
-Cardiac failure
-Fever
What are different types of anemia?
- Microcytic anaemia
- Iron deficiency anaemia
- Macrocytic anaemia
- Megaloblastic anaemia
- Pernicious anaemia
- Normocytic anaemia
- Sickle cell anaemia
- Thalassemia
- Congenital pernicious anaemia
Describe microcytic anaemia ?
Microcytic anemia happens when your red blood cells are smaller than usual because they don’t have enough hemoglobin.
- On a blood smear red blood cells appear hypochromic (have less color than normal because there is not enough pigment that carries oxygen.
- The main causes of microcytic anemia is iron deficiency, inflammatory disease and thalassemia. The most common cause is iron deficiency.
- Low MCV indicates microcytic anaemia.
- Thalassaemia carriers
Thalassaemia is the name for a group of inherited conditions that affect a substance in the blood called haemoglobin.
People with thalassaemia produce either no or too little haemoglobin, which is used by red blood cells to carry oxygen around the body.
What is macrocytic anaemia?
- Red blood cells are large than usual. These abnormal blood cells lack nutrients red blood cells need to function normally. Macrocytic anemia isn’t a serious illness but it can cause serious medical issues if left untreated.
- It can result from a vitamin deficiency or an underlying condition like hypothyroidism
- High MCV indicates macrocytic anaemia
What is Pernicious anemia ?
- Pernicious anemia is a decrease in red blood cells that occurs when the small intestines cannot properly absorb vitamin B12.
- Your body needs vitamin B12 to make healthy red blood cells, white blood cells, and platelets. Since your body doesn’t make vitamin B12, you have to get it from the foods you eat or from supplements
- Treatment for pernicious anemia involves vitamin B12 injections to restore levels to an optimal range, followed by continued injections or oral medications to maintain these levels.
- Can be due to an autoimmune condition targeting gastric parietal cells. Which produce HCL and intrinsic factor vitamin B12.
What is Congenital pernicious anemia ?
Results when a person is born with an inability to produce intrinsic factor
This results in malabsorption of vitamin B12 which means the body cannot make enough healthy RBCs causing you to become anaemic
What is normocytic anaemia ?
- occurs when the red blood cells size is normal but the number of red blood cells and hemoglobin has decreased.
- Normocytic normochromic anemia is the type of anemia in which the circulating red blood cells (RBCs) are the same size (normocytic) and have a normal red color (normochromic). However the number of red blood cells have decreased.
- Normocytic normochromic anemia most commonly occurs as a result of miscellaneous chronic infections and systemic diseases
Causes of normocytic anaemia:
-Haemorrhagic anaemia
-Chronic disease
-Aplastic anaemia
-Haemolytic anaemia
Normocytic anemia is a type of anemia and is a common issue that occurs for men and women typically over 85 years old.
A normocytic anemia is when the red blood cells (RBCs) are of normal size. Normocytic anemia is defined when the mean corpuscular volume (MCV) is between 80 and 100 femtolitres (fL), which is within the normal and expected range. However, the hematocrit and hemoglobin are decreased
What is sickle cell anemia ?
-Anemia. Sickle cells break apart easily and die. Red blood cells usually live for about 120 days before they need to be replaced. But sickle cells typically die in 10 to 20 days, leaving a shortage of red blood cells (anemia). Without enough red blood cells, the body can’t get enough oxygen and this causes fatigue.
-There’s no cure for most people with sickle cell anemia. Treatments can relieve pain and help prevent complications associated with the disease.
What is Thalassemia ?
Thalassaemia is the name for a group of inherited conditions that affect haemoglobin.
Occurs when your body is unable to produce enough haemoglobin which functions to carry oxygen throughout the body
This condition is caused by faulty genes
What is Hereditary spherocytosis ?
- Hereditary spherocytosis is an inherited blood disorder. It happens because of a problem with the red blood cells (RBCs). Instead of being shaped like a disk, the cells are round like a sphere. These red blood cells (called spherocytes) are more fragile than disk-shaped RBCs.
- They break down faster and more easily than normal RBCs
- As such they stay in the spleen longer than usual and as such are destroyed
This causes anaemia
Often mild but the stresses on the body due to infection can often lead to jaundice
Mean corpuscular volume flow chart ?
Why are the functions of blood ?
- Transportation – supply of oxygen to tissues, supply of nutrients such as glucose, amino acids, fatty acids; the removal of waste products incl CO2, urea and lactic acid; messenger functions- transport of hormones, signalling of tissue damage
-Regulation: regulation of body temperature; maintain pH (7.35-7.45); hydraulic functions – colloidal osmotic pressure
What is blood composed of ?
- Liquid content - plasma - 55%
- Red blood cells - 45%
- White blood cells and platelets - <1%
What is plasma made up of ?
- yellow
- This can be considered the extracellular matrix (ECM) of blood with a function to keep cells in suspension
- Plasma is
92% water
7% plasma proteins (albumin, globulins, fibrinogen, prothrombin)
1% other substances – electrolytes, nutrients, hormones, gases, waste products
What is Haematopoiesis ?
Haematopoiesis: Production of all blood cells
- The location of haematopoiesis changes during development and throughout an individual’s lifetime.
- The bone marrow is the major site post birth:
All cellular blood components are derived from haematopoietic stem cells.
Haematopoietic stem cells (HSCs) reside in the medulla of the bone (bone marrow) and have the unique ability to give rise to all of the different mature blood cell types and tissues.[4] HSCs are self-renewing cells: when they differentiate, at least some of their daughter cells remain as HSCs so the pool of stem cells is not depleted
- RBC migrate into the blood
- WBC migrate to peripheral tissues and lymphoid organs
Describe the process of haematopoiesis ?
Haematopoietic stem cells (HSCs) reside in the medulla of the bone (bone marrow) and have the unique ability to give rise to all of the different mature blood cell types and tissues.
HSCs are self-renewing cells: when they differentiate, at least some of their daughter cells remain as HSCs so the pool of stem cells is not depleted. This phenomenon is called asymmetric division.
The other daughters of HSCs (myeloid and lymphoid progenitor cells) can follow any of the other differentiation pathways that lead to the production of one or more specific types of blood cell, but cannot renew themselves. The pool of progenitors is different and can be divided into two groups; long-term self-renewing HSC and only transiently self-renewing HSC, also called short-terms. This is one of the main vital processes in the body.
What is derived from myeloid progenitor. This is known as myelopoiesis:
- Megakaryocyte
- Erythrocyte
- Granulated (granulocyte) white blood cells:
- Basophil
- Neutrophil
- Eosinophil
- Macrophage cell: Monocyte
What is derived from lymphoid progenitor. This is known as lymphopoiesis.:
- Natural killer cell
- B lymphocyte - plasma cell
- T lymphocyte
What is thrombopoiesis ?
Thrombopoiesis is haematopoiesis of thrombocytes (platelets)
Describe the regulation of Hematopoiesis ?
The production of blood and immune cells is tightly controlled by cytokines and growth factors:
- Erythrocytes are influenced by a growth factor called EPO (erythropoietin).
- Platelets are influenced by a growth factor called Thrombopoieten
- Interleukins are a group of cytokines that are expressed and secreted by white blood cells .
Describe Erythropoiesis ?
- Is the production of red blood cells.
- It is stimulated by decreased O2 in circulation, which is detected by the kidneys, which then secrete the hormone erythropoietin.
- Erythropoiesis occurs in the bone marrow
Steps to produce erythrocytes:
-Multipotential haematopoietic stem cell
-Common myeloid progenitor
-Proerythroblast
-Basophilic erythroblast
-Polychromatic erythroblast
-Orthochromatic erythroblast
-Polychromatic erythrocyte (reticulocyte)
-Erythrocyte
Describe Hemoglobin ?
How do we get rid of old red blood cells ?
- RBC have a lifespan of 120 days
- RBCs do not have repair processes. Aged cells are removed by macrophages of the spleen
- Haemoglobin is separated into Iron and porphyrin ring:
Iron transported to BM via transferrin for new RBC production
Porphyrin ring excreted via digestive or urinary tract
Bilirubin –urine
Biliverdin - faeces
What is the function of plantlets aka thrombocytes ?
Describe thrombopoiesis ?
- Thrombopoiesis is the formation of thrombocytes (blood platelets) in the bone marrow
- Thrombopoietin (TPO) is the main regulator of thrombopoiesis. TPO is produced by the liver and kidney.
- The process of Thrombopoiesis is caused by the breakdown of proplatelets (mature megakaryocyte membrane pseudopodial projections). Platelets are formed by megakaryocytes.
What are the 5 cardinal signs of inflammation ?
Five cardinal signs of inflammation – pain, heat, redness, swelling and loss of function.
Describe Leukocytes ?
- Leukocytes are also known as white blood cells.
- Made in the bone marrow
- Leukocytes are part of the body’s immune system. They help the body fight infection and other diseases.
- Types of leukocytes are granulocytes (neutrophils, eosinophils, and basophils), monocytes, and lymphocytes (T cells and B cells).
What are innate immune cells and adaptive immune cells ?
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
Different innate immune cells ?
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
Adaptive immune cells?
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
What is the hematocrit test?
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.
What is a Full Blood Count ?
- 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
Describe the regulation of erythropoiesis ?
- 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
What is pure red aplasia ( PRCA) ?
What is pancytopenia ?
- 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
Anameia can be caused by changes in the bone marrow some things which can cause this are
Panytopenia is a complete drop in all cells in the bone marrow
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.
Panytopenia is a complete drop in all cells in the bone marrow
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.
What is Haemolytic anaemia ?
- 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:
- Extrinsic hemolytic anemia: External pathogens destroy the red blood cell e.g. drugs, toxins and antibodies.
- Intrinsic hemolytic anemia: There is something intrinsically wrong with the erythrocyte e.g. absence of specific enzymes
Describe autoimmune hemolytic anemia ? (AIHA)
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)
You can diagnose hemolytic anemia from blood films.
- 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.
What is Haemoglobinopathy ?
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.
Describe hemoglobin ?
Describe iron - deficiency anemia ?
Describe the histology of iron deficiency anemia ?
How much iron do we need daily ?
What are sources of iron ?
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
What is Sideroblastic anemia ?
Anaemia can arise from a lack of vitamins tell me a bit more about this ?
- Vitamin B6 and Vitamin B12/ folate deficiency
Describe the formation of Haemoglobin ?
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.
Full blood count and anemia ?
- 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.
Describe the histology of different types of anemia ?
What do dendric cells do ?
- 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.
What do macrophage cells do ?
-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.
What do macrophage cells do ?
-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.
What do mast cells do ?
- 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
There are 30 ways to categorize blood groups. One of them is the the ABO blood group system . Tell me a bit more about this
- 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.
Describe ABO blood types ?
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
On which chromosome is the gene which encodes for ABO blood groups found?
Chromosome 9
Which blood type can recieve and donate from anyone ?
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 (-)
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
Describe the Rhesus blood grouping system ?
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
Describe Rhesus disease ?
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
How much of the population id Rh (+) or Rh (-) ?
Rh ( +) : 85%
Rh (-) : 15%
It is very likely a Rh (-) mother will have a Rh (+) foetus
What is cross matching ?
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.
What is Haemoglobinopathies?
Genetic anaemia
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.
Describe sickle cell anaemia cause?
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
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
Where is sickle cell disease most prevelant ?
Where is sickle cell disease most prevelant ?
What is the benefit of having sickle cell carrier (hetrozygous) ?
4What are the sites of haemopoiesis in fetuses ?
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)
Mastoid processs ?
The mastoid process is a pyramidal bony projection from the posterior section of the temporal bone.
the body, angle, ramus and mental protuberance of the mandible
The mental foramen is a bilateral opening in the vestibular portion of the mandible through which nerve endings, such as the mental nerve, emerge
the suprasternal (jugular) notch
the clavicle
the clavicle
the trapezius muscle
the sternocleidomastoid muscle
platysma
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
Describe the anterior triangle ?
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
BOUNDARIES OF THE ANTERIOR TRIANGLE
-the anterior border of the sternocleidomastoid muscle
-the inferior border of the mandible
-the mid-line of the neck
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.
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
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
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
Posterior triangle
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
cervical investing fascia
This layer of the deep cervical fascia is a collar of fascia surrounding the whole neck and contains the trapezius and sternocleidomastoid muscles.
Posterior triangle
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
Posterior triangle
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
Branches of the external carotid artery ?
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.
Anterior and posterior belly of the diagastric muscle
Stylohyoid muscle
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
Stylohyoid muscle
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
carotid triangle
major components of carotid triangle:
- Internal jugular vein
- vagus nerve
- External carotid artery
Muscular triangle
omohyoid muscle
Describe the cervical plexus ?
- 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.
Branches of the cervical plexus ?
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.
Branches of the cervical plexus ?
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.
Lymphoid tissues
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.
What is coagulation ?
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
antibody structre
antibody structure
Non- immunological barriers to infection
The innate immune is continuous and does not stop when the adaptive immune response begins.
Examples of non-immunological innate responses
Describe the complement cascade / complement system ?
- 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
Summarise the three classical pathways ?
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.
Once activated the complement system has several effects
-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.
There is coupling between receptors and function
Describe the Pathogen Associated Molecular Patterns (PAMPs) and Pathogen Recognition Receptors ?
- 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.
What are Toll like receptors ?
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.
Principles of phagocytosis ?
- 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.
-
How to phagocytes kill pathogens ?
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.
Describe neutrophils ?
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
Describe monocytes ?
- 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.
Describe dendric cells?
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.
What are myeloid cells ?
Granulocytes and monocytes, collectively called myeloid cells, are differentiated descendants from common progenitors derived from hematopoietic stem cells in the bone marrow.
monocytes to macrophages
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.
Granulocytes
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.
- 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.
Describe cytokines ?
Steroids block cytokine release
HSP90 (Heat shock protein 90)
We can recognize viruses or bacterium through specific receptors and depending on which a specific cytokine is produced.
We can recognize viruses or bacterium through specific receptors and depending on which a specific cytokine is produced.
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.
What can happen if you block cytokines
- 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.
Describe the spleen?
- 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
Functions of the spleen ?
- 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.
What is splenomegaly ?
-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
What is secondary lymphoid tissue and what occurs there?
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.
Describe the structure of a lymph node ?
- 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
What is lymphocyte recirculation >?
- 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
What is the lymphatic system ?
- 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.
There are 2 main systems of lymphatic vessels which are superficial and deep
-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.
Describe the drainage of lymph ?
-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.
Describe superficial lymphatic drainage ?
- 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
Hyposplenism ?
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
Describe the anatomy and function of the thymus ?
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.
Describe the anatomy and function of the thymus ?
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.
