The immune system Block 4 Week 3 Flashcards
Betamethasone ?
- inhibit neutrophil apoptosis
- inhibit NF-Kappa B and other inflammatory transcription factors
- inhibit phospholipase A2 leading to decreased formation of arachidonic acid
- steroid medication
Indications:
- topically used to treat inflammatory conditions such as eczema
- as injection to treat rheumatic disorders, gastrointestinal disorders.
contraindications:
- if injected avoid live viruses
- topically: acne, fungal and viral lesions
side effects:
- increased risk of infection, mood altered, psychotic disorder
Prednisolone
- Prednisolone is available only on prescription as tablets and as a liquid you swallow
- It helps by reducing swelling (inflammation) and can also calm down your immune system
- Prednisolone is a steroid or corticosteroid medicine
Indication:
- used to treat endocrine , dermatological, rheumatic
Contraindications:
- avoid live virus
Describe chlorphenamine ?
- antihistamine medication
- over the counter
Describe hydrocortisone ?
- corticosteroid
- The medicine comes in different forms, including skin creams for the body and scalp, injections and tablets. The type of hydrocortisone you use will depend on your health problem.
- Skin: It works by calming down your body’s immune response to reduce pain, itching and swelling (inflammation).
-You may take hydrocortisone tablets if your body does not make enough cortisol – for example if you have Addison’s disease, or if you’ve had your adrenal glands taken out.
The tablets can also be prescribed for hypopituitarism, a rare condition affecting the pituitary gland.
- Hydrocortisone injections are used to treat swollen and painful joints in people with injuries and arthritis. They help to reduce pain and swelling (inflammation).
Describe Adrenaline? epinephrine ?
-inside epipens
- When injected, adrenaline rapidly reverses the effects of anaphylaxis by reducing throat swelling, opening the airways, and maintaining heart function and blood pressure.
Describe the scalp ?
- The scalp consists of the skin and subcutaneous tissue covering the neurocranium.
-It consists of five (5) layers from superficial to deep, namely (SCALP):
-skin
- dense connective tissue
-the epicranial aponeurosis
-loose connective tissue
- pericranium.
The scalp is highly vascular and is supplied by branches of both the internal and external carotid arteries. These branches anastomose freely with each other.
Describe the muscles of facial expression ?
MUSCLES OF FACIAL EXPRESSION:
-The muscles of facial expression are derived embryologically from the second pharyngeal arch (and
therefore supplied by its nerve – facial nerve, the seventh cranial nerve).
-These muscles are functionally
divided into groups that guard/control the main orifices of the face (orbit, nose, mouth).
-Each orifice has a sphincter, an opposing dilator, elevator, and depressor arrangement of muscles.
-The primary function of these muscles is to control the respective orifices, and facial expression is only a secondary effect of this control.
Orbicularis oculi: sphincter
Ocipitofrontalis and levator palpebrae superiors which are dilators/elevators
- Occipitofrontalis is a long and wide muscle of the scalp, spanning from the eyebrows to the superior nuchal lines of occipital bones
Muscles of the nostrils ?
- sphincter – compressor naris
- dilators/elevators – dilator naris, levator labii superioris alaeque nasi (near the eye to the top of the mouth), depressor septi
Muscles of the lips and cheeks ?
-sphincter – orbicularis oris
- dilators – levator labii superioris alaeque nasi, levator labii superioris (goes all the way from the near the eye to the top of the mouth), levator anguli oris,
zygomaticus major and minor, risorius, depressor anguli oris, depressor labii inferioris,
buccinator and mentalis.
Note that buccinator (Latin for trumpeter) is an accessory muscle of mastication as it returns food material
from the vestibule of the mouth (the cheek pouch) to between the teeth for chewing.
The INFRATEMPORAL FOSSA
The infratemporal fossa is an irregularly shaped three-dimensional space lying deep to the ramus of the
mandible. It contains the pterygoid muscles, and nerves to the mandibular teeth and tongue pass through
this clinically important region.
Identify the boundaries of the infratemporal fossa:
-laterally, the mandibular ramus
-medially, the lateral pterygoid plate
-anteriorly, the maxilla
-posteriorly, the tympanic plate, and the mastoid and styloid processes of the temporal bone
Identify the following contents of the infratemporal fossa
-the lateral and medial pterygoid muscles
-the maxillary artery
-the inferior alveolar and lingual nerve
The INFRATEMPORAL FOSSA
The infratemporal fossa is an irregularly shaped three-dimensional space lying deep to the ramus of the
mandible. It contains the pterygoid muscles, and nerves to the mandibular teeth and tongue pass through
this clinically important region.
Identify the boundaries of the infratemporal fossa:
-laterally, the mandibular ramus
-medially, the lateral pterygoid plate
-anteriorly, the maxilla
-posteriorly, the tympanic plate, and the mastoid and styloid processes of the temporal bone
Identify the following contents of the infratemporal fossa
-the lateral and medial pterygoid muscles
-the maxillary artery
-the inferior alveolar and lingual nerve
- The Lingual nerve (LN) is a branch of the mandibular division of the trigeminal nerve (V3) that is responsible for general somatic afferent (sensory) innervation.
The INFRATEMPORAL FOSSA
The infratemporal fossa is an irregularly shaped three-dimensional space lying deep to the ramus of the
mandible. It contains the pterygoid muscles, and nerves to the mandibular teeth and tongue pass through
this clinically important region.
Identify the boundaries of the infratemporal fossa:
-laterally, the mandibular ramus
-medially, the lateral pterygoid plate
-anteriorly, the maxilla
-posteriorly, the tympanic plate, and the mastoid and styloid processes of the temporal bone
Identify the following contents of the infratemporal fossa
-the lateral and medial pterygoid muscles
-the maxillary artery
-the inferior alveolar and lingual nerve
The INFRATEMPORAL FOSSA
The infratemporal fossa is an irregularly shaped three-dimensional space lying deep to the ramus of the
mandible. It contains the pterygoid muscles, and nerves to the mandibular teeth and tongue pass through
this clinically important region.
Identify the boundaries of the infratemporal fossa:
-laterally, the mandibular ramus
-medially, the lateral pterygoid plate
-anteriorly, the maxilla
-posteriorly, the tympanic plate, and the mastoid and styloid processes of the temporal bone
Identify the following contents of the infratemporal fossa
-the lateral and medial pterygoid muscles
-the maxillary artery
-the inferior alveolar and lingual nerve
Neurovascularture of the head and neck
-The head and neck are supplied with arterial blood via the common carotid arteries and branches of the
subclavian arteries.
- The cranial cavity and brain receive their blood supply via the internal carotid and
vertebral arteries while the external carotid arteries supply the face and upper neck.
-The veins draining the corresponding areas supplied by the arteries bear similar names to the arteries. All
these veins ultimately drain into the internal jugular vein. The internal jugular vein lies lateral to the
common carotid artery in the neck. The vagus nerve can be found lying posterior to these vascular
structures. All three of these structures (artery, vein, nerve) are enclosed within the carotid sheath.
-The hypoglossal nerve, the 12th cranial nerve, can be seen crossing lateral to the external carotid
artery (just superior to the carotid bifurcation) towards the tongue which it supplies with motor
fibres.
Neurovascularture of the head and neck
Identify the following structures:
-vertebral artery
-common carotid artery
- internal carotid artery
external carotid artery
- maxillary artery
-internal jugular vein
-hypoglossal nerve
- vagus nerve
-superior thyroid artery
-lingual artery
-facial artery
-superficial temporal artery
Neurovascularture of the head and neck
Identify the following structures:
-vertebral artery
-common carotid artery
-internal carotid artery
-external carotid artery
-maxillary artery
- internal jugular vein
-hypoglossal nerve
-vagus nerve
- superior thyroid artery
-lingual artery
- facial artery
-superficial temporal artery
Carotid sheath
The carotid sheath is an important landmark in head and neck anatomy and contains several vital neurovascular structures, including the carotid artery, jugular vein, vagus nerve, and sympathetic plexus. It extends upwards from the arch of the aorta and terminates at the skull base.
The carotid sheath is a condensation of the deep cervical fascia that surrounds the main neurovascular structures of the neck: the common and internal carotid artery, the internal jugular vein, and the vagus nerve (CN X).
Infratemporal fossa ?
Maxillary artery ?
- Branches off the external carotid.
- goes through the infratemporal fossa
- then into the pterygopalatine fossa
External jugular vein
- The external jugular vein crosses superiorly across the sternocleidomastoid
Hypoglossal nerve
- How you know its hypogglossal nerve: crosses internal and external common carotid laterally
Carotid sheath contents
Common carotid, azygous nerve, internal jugular vein
Internal and external carotid
Omohyoid muscle crosses over the structures in the carotid sheath
Facial artery
-Crosses the top of the of the submandibular gland to the masetter
Superficial temporal artery
Another branch of the external carotid
It goes behind the muscles and arises at the top of the zygomatic arch
Zygomatic bone and zygomatic arch
What are Myeloproliferative neoplasms ?
- Myeloproliferative neoplasms are a group of diseases in which the bone marrow makes too many red blood cells, white blood cells, or platelets. ALSO KNOWN AS BLOOD CANCER
There are 6 types of chronic myeloproliferative neoplasms:
1. Chronic myelogenous leukemia.
2. Polycythemia vera.
3. Primary myelofibrosis (also called chronic idiopathic myelofibrosis).
4.Essential thrombocythemia.
5.Chronic neutrophilic leukemia.
6. Chronic eosinophilic leukemia
Infratemporal fossa
The infratemporal fossa is the area behind the ramus which has been cut out so we can see inside the infratemporal fossa.
- The ramus of the mandible makes up the lateral wall of the infratemporal fossa.
- The back wall is the lateral pterygoid plate which is part of the sphenoid bone
- Maxillary artery is heading towards the pterygoid fossa of the skull
- The masseter muscle lies on top of it
Structures in infratemporal fossa
- Maxillary artery
- Medial pterygoid muscle
- Lateral pterygoid muscle
- Lingual nerve
- Inferior alveolar nerve (runs through the mandibular foramen to supply the teeth )
Depressor anguli oris
Branches of the external carotid artery ?
The major ECA branches are:
- the superior thyroid
-ascending pharyngeal
- lingual
- facial
- occipital
- posterior auricular
- superficial temporal
- maxillary arteries
Some Anatomists Like Freaking Out Poor Medical Students
Describe polycythemia vera ?
Also known as erythrocytosis.
Primary polycythemia is too much red blood cell. Its caused by genetic mutation. An example of polycythemia is polycythemia vera which is caused by a mutation in JAK2
- PV is rare. It’s usually caused by a change in the JAK2 gene, which causes the bone marrow cells to produce too many red blood cells.
The affected bone marrow cells can also develop into other cells found in the blood, which means that people with PV may also have abnormally high numbers of both platelets and white bloods cells.
Although caused by a genetic change, PV isn’t usually inherited. Most cases develop later in life. The average age at diagnosis is 60.
- Secondary polycythaemia is where an underlying condition causes more erythropoietin to be produced. This is a hormone produced by the kidneys that stimulates the bone marrow cells to produce red blood cells.
Health conditions that can cause secondary polycythaemia include:
chronic obstructive pulmonary disease (COPD) and sleep apnoea – these can cause an increase in erythropoietin, due to not enough oxygen reaching the body’s tissues
a problem with the kidneys – such as a kidney tumour or narrowing of the arteries supplying blood to the kidneys
-Relative polycythemia is an elevated hematocrit marked with a normal to high normal RBC mass and low normal to decreased plasma volume.[15] In spite of the absence of true erythrocytosis, patients with relative polycythemia are at a higher risk for thromboembolic complications
Describe Essential thrombocythemia ?
Essential thrombocythemia: Is a rare blood disease in which the bone marrow produces too little platelets.
- Primary myelofibrosis (also called chronic idiopathic myelofibrosis).
- Primary myelofibrosis is a condition characterized by the buildup of scar tissue (fibrosis) in the bone marrow, the tissue that produces blood cells. Because of the fibrosis, the bone marrow is unable to make enough normal blood cells. The shortage of blood cells causes many of the signs and symptoms of primary myelofibrosis.
Initially, most people with primary myelofibrosis have no signs or symptoms. Eventually, fibrosis can lead to a reduction in the number of red blood cells, white blood cells, and platelets. A shortage of red blood cells (anemia) often causes extreme tiredness (fatigue) or shortness of breath. A loss of white blood cells can lead to an increased number of infections, and a reduction of platelets can cause easy bleeding or bruising.
Because blood cell formation (hematopoiesis) in the bone marrow is disrupted, other organs such as the spleen or liver may begin to produce blood cells. This process, called extramedullary hematopoiesis, often leads to an enlarged spleen (splenomegaly) or an enlarged liver (hepatomegaly). People with splenomegaly may feel pain or fullness in the abdomen, especially below the ribs on the left side. Other common signs and symptoms of primary myelofibrosis include fever, night sweats, and bone pain.
JAK 2 gene
What are hypersensitivity reactions ?
-Hypersensitivity reactions are an overreaction of the immune system to an antigen which would not normally trigger an immune response. The antigen may be something which would in most people be ignored – peanuts, for example, or it may originate from the body. In either case, the damage and clinical symptoms result from the body’s response to the substance rather than damage caused by the substance itself.
- The vulnerability of an individual to these reactions can have a genetic link. Overreaction to innocuous antigens are linked to changes in the CD regions of T-helper cell membranes, explaining why reactions like peanut allergies can commonly run in families. Overreaction to self-antigens is normally due to a failure in central tolerance, and this failure can also have genetically-inheritable features.
What happens when you are first exposed to a potential allergen ?
- As is the case for many immune reactions, hypersensitivity reactions require two separate interactions of the immune system with the antigen. The first time an antigen enters the body, it is picked up by antigen-presenting cells (such as macrophages or dendritic cells) and taken to the nearest lymph node, where it is presented to naïve T-cells. Cross-linking of the antigen with T-cells, as well as co-stimulatory molecules, can lead to activation of that T-cell and subsequent differentiation into “primed” Th1, Th2, or Th17 cells, which are specific to that antigen and can stimulate further immune responses if they meet the antigen again. It is this second meeting that could result in a hypersensitivity reaction.
What happens when you are first exposed to a potential allergen ?
- As is the case for many immune reactions, hypersensitivity reactions require two separate interactions of the immune system with the antigen. The first time an antigen enters the body, it is picked up by antigen-presenting cells (such as macrophages or dendritic cells) and taken to the nearest lymph node, where it is presented to naïve T-cells. Cross-linking of the antigen with T-cells, as well as co-stimulatory molecules, can lead to activation of that T-cell and subsequent differentiation into “primed” Th1, Th2, or Th17 cells, which are specific to that antigen and can stimulate further immune responses if they meet the antigen again. It is this second meeting that could result in a hypersensitivity reaction.
What are the different types of hypersensitivity reactions ?
- Type 1 (immediate) hypersensitivity
- Type 2 ( cell bound antigens)
- Type 3 ( immune complex disease)
- Type 4 (delayed) hypersensitivity
Describe Type 1 hypersensitivity reactions ?
- In Type 1 hypersensitivity reactions mast-cell activation is induced by secretion of IgE antibodies.
- Initial exposure to the antigen causes the priming of Th2 cells, and their release of IL-4 causes the B cells to switch their production of IgM to IgE antibodies which are antigen-specific. The IgE antibodies bind to mast cells and basophils, sensitising them to the antigen.
- When the antigen enters the body again, it cross links the IgE bound to the sensitised cells, causing the release of preformed mediators including histamine, leukotrienes and prostaglandins. This leads to widespread vasodilation, bronchoconstriction, and increased permeability of vascular endothelium.
- The reaction can be divided into two stages – immediate, in which release of pre-formed mediators causes the immune response, and the late-phase response 8-12 hours later, where cytokines released in the immediate stage activate basophils, eosinophils, and neutrophils even though the antigen is no longer present
- Allergic rhinitis is where an allergy to something like pollen, dust or mould irritates your nose and causes cold-like symptoms.
Symptoms of allergic rhinitis include sneezing, itchiness and a blocked or runny nose.
Examples of type 1 hypersensitivity reactions ?
- Allergic rhinitis
- Asthma
- systemic anaphylaxis
Consequences of type 1 hypersensitivity reactions ?
What are allergens ?
Atopy refers to the genetic tendency to develop allergic diseases such as allergic rhinitis, asthma and atopic dermatitis (eczema).
- Atopic eczema is a common skin condition that causes patches of skin that are itchy, cracked and sore.
IgE and mast cells
Immediate and late reaction ?
Effects of mass cell degranulation ?
Describe allergic rhinitis ? Type 1
Perennial rhinitis may be defined clinically as an inflammatory condition of the nose characterised by nasal obstruction, sneezing, itching, or rhinorrhoea, occurring for an hour or more on most days throughout the year.
Describe Asthma ?
Describe Allergic Eczema ? Type 1
Environmental, genetic, and immunologic factors, among others, contribute to an impaired skin barrier and dysregulated immune system.
The pathophysiology of atopic dermatitis is not fully understood. One proposed cause is a mutation of the FLG gene which encodes the protein filaggrin. Filaggrin makes up part of the stratum corneum of the epidermal barrier.2 This barrier is crucial in restricting water loss, and preventing the unwanted entry of irritants, allergens, and skin pathogens.
Therefore, impairment of the epidermis can allow: 2
Environmental allergen penetration through the skin, causing hyper-reactivity and systemic IgE sensitisation (type 1 hypersensitivity reaction).
Entry of pathogens.
Water loss, resulting in dryness.
It is also suggested that those with more T-helper 2 cells (rather than T-helper 1), have a higher production of IgE and increased mast cell hyper-reactivity. This contributes to increased inflammation and pruritus.2
Describe Urticaria ? Type 1
Describe anaphylaxis ? Type 1
Describe HDFN/Rhesus disease ? Type 2
Describe Type 2 hypersensitivity reactions ?
Type 2 hypersensitivity reactions are mediated by antibodies targeting antigens on cell surfaces. When cell surface antigens are presented to T cells, an immune response is started, targeting the cells to which the antigens are attached.
Antibodies binding to cells can activate the complement system, leading to degranulation of neutrophils, a release of oxygen radicals, and eventual formation of membrane attack complex – all of which lead to destruction of the cell. Parts of the complement activation can also opsonise the target cell, marking it for phagocytosis.
The destruction of host cells in this way can lead to tissue-specific damage. Type 2 hypersensitivity reactions may occur in response to host cells (i.e. autoimmune) or to non-self cells, as occurs in blood transfusion reactions.
Type 2 is distinguished from Type 3 by the location of the antigens – in Type 2, the antigens are cell bound, whereas in Type 3 the antigens are soluble.
Drug induced hemolytic anemia ? type 2
Describe Goodpasture syndrome ? type 2
Goodpasture syndrome is a rare disorder in which your body mistakenly makes antibodies that attack the lungs and kidneys.
Treatments include medications and a procedure called plasmapheresis. This procedure removes plasma that contains these harmful antibodies and replaces it with healthy plasma. Untreated, Goodpasture syndrome can cause inflammation of the kidneys (glomerulonephritis) and can lead to permanent kidney failure
Describe myasthenia gravis ?
Describe graves disease ?
- About 3 in every 4 people with an overactive thyroid gland have a condition called Graves’ disease.
Graves’ disease is an autoimmune condition where your immune system mistakenly attacks your thyroid which causes it to become overactive.
The cause of Graves’ disease is unknown, but it mostly affects young or middle-aged women and often runs in families. Smoking can also increase your risk of getting it.
Symptoms:
Anxiety and irritability
A fine tremor of the hands or fingers
Heat sensitivity and an increase in perspiration or warm, moist skin
Weight loss, despite normal eating habits
Enlargement of the thyroid gland (goiter)
Change in menstrual cycles
Erectile dysfunction or reduced libido
Frequent bowel movements
Bulging eyes (Graves’ ophthalmopathy)
Fatigue
Thick, red skin usually on the shins or tops of the feet (Graves’ dermopathy)
Rapid or irregular heartbeat (palpitations)
Sleep disturbance
Mechanism of type 2 hypersensitivity reactions ?
Describe Type 3 hypersensitivity reactions ?
-Type 3 hypersensitivity reactions are mediated by antigen-antibody complexes in the circulation that may be deposited in and damage tissues.
-The complexes may become lodged in the basement membranes of tissues which have particularly high rates of blood filtration. For example, the kidney and synovial joints being common targets.
-Once lodged, the immune complexes rapidly and significantly activate the complement chain, causing local inflammation and attraction of leucocytes.
-Activation of complement results in increased vasopermeability, the attraction and degranulation of neutrophils, and the release of oxygen free radicals which can severely damage surrounding cells.
- Perivascular spaces (PVSs), also known as Virchow-Robin spaces, are pial-lined, fluid-filled structures found in characteristic locations throughout the brain
Type 3 hypersensitivity reactions ?
Immune complexes type3 hypersensitivity
Describe systemic lupus erythematosus ?
- Systemic lupus erythematosus (SLE), is the most common type of lupus. SLE is an autoimmune disease in which the immune system attacks its own tissues, causing widespread inflammation and tissue damage in the affected organs. It can affect the joints, skin, brain, lungs, kidneys, and blood vessels. There is no cure for lupus, but medical interventions and lifestyle changes can help control it.
People with SLE may experience a variety of symptoms that include fatigue, skin rashes, fevers, and pain or swelling in the joints. Among some adults, having a period of SLE symptoms—called flares—may happen every so often, sometimes even years apart, and go away at other times—called remission. However, other adults may experience SLE flares more frequently throughout their life.
Rheumatoid artheritis ?
The most specific autoimmunity known for rheumatoid arthritis (RA) is reflected by generation of anti-citrullinated protein antibodies (ACPA). Presence of ACPA in established RA is associated with disease severity, while generation of ACPA at early developmental phases of RA can have a strong predictive value for progressing to the full-blown disease. Hence, development of ACPA may be of crucial importance to the pathogenesis of RA
Arthus reaction ?
- An Arthus reaction refers to an acute, localized inflammatory response that typically occurs after vaccination. It is classified as a type III hypersensitivity reaction, which is when antigen-antibody clusters, also known as immune complexes, are formed due to an abnormal immune system response.
-An Arthus reaction is the result of a localized inflammation of the small vessels (i.e., vasculitis) near the injection or bite site. This response occurs due to the interaction between the injected antigens and the circulating antibodies (e.g., IgG), which are created after repeated exposure to a specific antigen. As a result, immune complexes are formed around and within the blood vessels of the skin. Subsequently, activation of the complement cascade, which is part of the innate immune system, enhances the local inflammation.
Serum sickness ?
- Serum sickness is a reaction that is similar to an allergy. The immune system reacts to medicines that contain proteins used to treat immune conditions. It can also react to antiserum, the liquid part of blood that contains antibodies given to a person to help protect them against germs or poisonous substances.
Causes
Plasma is the clear fluid portion of blood. It does not contain blood cells. But it does contain many proteins, including antibodies, which are formed as part of the immune response to protect against infection.
Antiserum is produced from the plasma of a person or animal that has immunity against an infection or poisonous substance. Antiserum may be used to protect a person who has been exposed to a germ or toxin. For example, you may receive a certain type of antiserum injection:
If you have been exposed to tetanus or rabies and have never been vaccinated against these germs. This is called passive immunization.
If you have been bitten by a snake that produces a dangerous toxin.
During serum sickness, the immune system falsely identifies a protein in antiserum as a harmful substance (antigen). The result is an immune system response that attacks the antiserum. Immune system elements and the antiserum combine to form immune complexes, which cause the symptoms of serum sickness.
Certain medicines (such as penicillin, cefaclor, and sulfa) can cause a similar reaction.
Injected proteins such as antithymocyte globulin (used to treat organ transplant rejection) and rituximab (used to treat immune disorders and cancers) can cause serum sickness reactions.
Blood products may also cause serum sickness.
- What is the difference between an Arthus reaction and serum sickness?
The primary difference between an Arthus reaction and serum sickness is that serum sickness refers to a systemic reaction, whereas an Arthus reaction is only localized. Additionally, serum sickness usually presents after 6 to 15 days of being exposed to the antigen, however, an Arthus reaction is expected to appear within 24 hours of the exposure. An Arthus reaction occurs more quickly than serum sickness because the individual has already been repeatedly exposed to the antigen and has pre-existing antibodies in the circulation, whereas with serum sickness new antibodies are yet to be formed. Both an Arthus reaction and serum sickness are classified as type III hypersensitivity reactions.
Describe type 4 hypersensitivity ?
-Type 4 hypersensitivity reactions are mediated by antigen-specific activated T-cells. When the antigen enters the body, it is processed by antigen-presenting cells and presented together with the MHC II to a Th1 cell.
-If the T-helper cell has already been primed to that specific antigen, it will become activated. Subsequently, it releases chemokines to recruit macrophages and cytokines such as interferon-γ to activate them.
-Activated macrophages release pro-inflammatory factors, leading to local swelling, oedema, warmth, and redness. They also secrete lysosomal elements and reactive oxygen species, again leading to local tissue damage.
- CD8+ T cells may be involved in type 4 reactions where a foreign antigen is detected on a cell, such as in organ rejection. This is known as cell mediated cytotoxicity, and also results in recruitment and activation of macrophages.
This reaction is also known as delayed-type hypersensitivity due to its characteristic longer time period to appear following antigen exposure. The reaction takes longer than all other types because of the length of time required to recruit cells to the site of exposure – around 24 to 72 hours.
Describe type 4 hypersensitivity reactions ?
Multiple sclerosis ?
Describe DHT response/ contact ?
Describe T cell mediated ?
Contact sensitization ?
Contact sensitization is the initial process involved in the development of an allergic reaction to xenobiotic environmental substances.
-
Organic specific and non organic specific autoimmune diseases
Contact dermatitis ?
Summary of hypersensitive reactions ?
Granulomatous inflammation
Granulomas form when immune cells clump together and create tiny nodules at the site of the infection or inflammation. A granuloma is the body’s way: to contain an area of bacterial, viral or fungal infection so it can try to keep it from spreading; or. to isolate irritants or foreign objects.
Granulomas most frequently form in the lungs, but can also be found in the liver, the eye or under the skin. They can be felt as a lump or can show up on x-rays and during other investigations.
sarcoidosis — a non-infectious disease that can cause multiple granulomas in different parts of the body, but especially in the lungs
What is immunodeficiency ?
Immunodeficiency describes the failure of the immune system to protect the body from infection, due to a either a defect in immune function or a deficiency in a component of the immune system.
Types of Immunodeficiency ?
- Primary immunodeficiencies are rare and inherited. They present early in life with severe, frequent or opportunistic infections. They can be due to impaired production of components of the immune system or due to a defect within existing parts of the immune system.
- Secondary immunodeficiencies are more common than primary. They may occur as a consequence of infection (e.g. HIV), immunosuppression (e.g. chemotherapy) or malignancy. They can also be secondary to disease states including diabetes. These factors put stress on the body and weaken the immune system. The signs and symptoms are the similar to primary immunodeficiencies, with frequent, recurrent, and unusual infections.
4 types of primary immunodeficiencies ?
- Primary immunodeficiencies - B cell
- Primary immunodeficiencies - T cell
- Primary immunodeficiencies -Neutrophils
- Primary immunodeficiencies - Complement
What is primary immunodeficiency - B cell ?
- B cell immunodeficiencies can be due to a failure in B cell production, a failure to produce high affinity memory cells in germinal centres, or failure to produce the usual spectrum of antibodies.
They rarely cause illness until levels of maternal IgG fall at 4-6 months. It typically presents with recurrent respiratory tract infections, particularly with encapsulated pyogenic bacteria such as Streptococcus pneumoniae and Haemophilus influenza B. Examples include:
- Chronic granulomatous disease
Describe primary immunodeficiency - T - cell ?
T cell deficiency can be due to reduced T cell counts, or impaired activity (Figure 2). This predisposes the sufferer to severe infections by intracellular parasites, bacteria and viruses. This can present with failure to thrive and/or diarrhoea in early life.
It is also associated with mucosal infection by yeasts such as candida (the organism that causes thrush).
Describe primary immunodeficiencies: Neutrophils ?
- Neutrophil defects can be due to a deficiency in neutrophil counts, or an impairment of neutrophil function. Affected individuals present with severe extracellular and gram negative bacterial infections that can be fatal, as they respond very poorly to antibiotics. These patients are especially prone to skin infections and sepsis.
- Chronic granulomatous disease is a neutrophil disorder
What is primary immunodeficiencies - complement
Defects in each of the complement pathways have different implications for the immune system. Deficiency in the classical pathway causes a build up of immune complexes in tissues and an associated inflammatory response. This causes diseases such as systemic lupus erythematosus and an increase in infection by encapsulated bacteria. Deficiency in the alternative pathway can cause severe bacterial infections and renal disease.
C1 esterase inhibitor deficiency (hereditary angioedema) is an autosomal dominant inherited disorder which leads to sudden uncontrolled activation of complement and bradykinin pathways. This leads to recurrent spontaneous attacks of non-itchy angioedema, which can be life-threatening if affecting the airway.
Terminal complement deficiency affects the production of C5-C9 complexes. It is autosomal recessive and causes an inability to produce antigen-antibody complexes, leading to defective opsonisation and phagocytosis. There is an increased risk of infection, particularly by Neisseria meningitidis and Neisseria gonorrhoeae.
C3 deficiency causes impaired opsonisation due to reduced levels of the opsonin C3b. This results in recurrent severe childhood infections, particularly by encapsulated bacteria such as Neisseria meningitidis and Haemophilus influenzae. C3 deficiency is also associated with autoimmune diseases and type III hypersensitivity reactions.
Secondary immunodeficiencies ?
-Secondary immunodeficiencies are more common than primary. They may occur as a consequence of infection (e.g. HIV), immunosuppression (e.g. chemotherapy) or malignancy. They can also be secondary to disease states including diabetes.
-These factors put stress on the body and weaken the immune system. The signs and symptoms are the similar to primary immunodeficiencies, with frequent, recurrent, and unusual infections.
Describe HIV ?
- Human immunodeficiency virus (HIV) is a blood-borne virus typically transmitted via sexual intercourse, shared intravenous drug paraphernalia, and mother-to-child transmission. HIV is a retrovirus that attacks the immune system and weakens the ability to fight infections and disease. AIDS (acquired immunodeficiency syndrome) is the final stage of HIV infection, when the body can no longer fight life-threatening infections. With early diagnosis and effective treatment, most people with HIV will not go on to develop AIDS.
- Transmission is via infected body fluids:
Blood, Serous effusions, Cerebrospinal fluid, Semen, Vaginal fluid, Breast milk
Or other body fluids containing infected blood such as saliva, vomit, and urine.
How can HIV be detected immunologically ?
HIV is a retrovirus, an RNA virus that inserts a DNA copy of its genome into the host cell in order to replicate. There are two different types:
HIV-1 - global pandemic
HIV-2 - mostly western africa
HIV-1 is more transmissible and associated with a faster rate of CD4 decline than HIV-2. Both types of HIV contain the 3 retroviral genes:
Gag - encodes for inner structure proteins
Pol - encodes for enzymes polymerase, integrase, and protease
Env - encodes for the viral envelope, on which is glycoprotein 120 (attaches to CD4 of host)
Immunology
After the virus has infected the body, it attaches to cells bearing the CD4 protein (T-helper lymphocytes, macrophages, monocytes, neural cells).
Uncoating - The viral envelope fuses to the host cell membrane and the viral nucleus is released from its capsid into the hosts cytoplasm.
Reverse transcription - The enzyme reverse transcriptase is used to convert its RNA genomes into DNA that can be integrated into the hosts DNA.
Circularisation - This pro-viral DNA becomes circular (increases efficiency) and migrates to the host cell’s nucleus.
Integration - The enzyme Integrase integrates the pro-viral DNA into the cellular DNA
Transcription - Pro-viral mRNA is transcribed by the cell’s ribosomes to make viral proteins
Core particle assembly - The viral proteins are transported to the cell membrane, the forming virion begins to bud from the host cell. The polypeptide precursors (for the matrix, capsid and nucleocapsid proteins) is processed by viral protease. The various structural components then assemble to produce a mature HIV virion.
Budding - Release of mature virions, only mature virions are able to infect another cell.
These new replications of HIV infect further CD4 cells. This process has essentially two effects:
To increase the viral load of HIV
To decrease the number of functional CD4 cells
Discuss the possible consequences to a patient’s normal defences against infection of acquired immune deficiency (reduction in CD4 cells) ?
Without treatment, HIV advances in stages, overwhelming the immune system and getting worse over time. The three stages of HIV infection are: acute HIV infection, clinical latency, and AIDS. However the progression of HIV can be prevented by using ART (antiretroviral therapy).
Describe primary HIV infection ?
What is autoinflammation ?
What is autoimmunity ?
Features of Autoimmunity
Autoimmune diseases/autoimmunity affect around 5% of the population and include a diverse range of more than 80 conditions, from rheumatoid arthritis to pernicious anaemia. While there are notable exceptions, autoimmune diseases tend to have certain features in common. These include:
HLA genetic association
Higher incidence among females
Onset in young adulthood or middle age
Detectable autoantibody levels
Positive response to immunosuppressive treatments
Fluctuations in symptom severity, with flare-ups and remissions
The spectrum of autoimmune diseases ranges from organ specific to non-organ specific conditions, based on whether the self-antigen that the immune system is attacking is only present in specific tissues or widely distributed throughout the body.
For example, Hashimoto’s thyroiditis is a classic organ specific condition, with the autoimmune response limited to the thyroid gland. In this condition, there are anti-TPO antibodies. On the other end of the spectrum is systemic lupus erythematosus (SLE).
Systemic lupus erythematosus (SLE) is a systemic condition caused by autoantibodies. These target structures found in nearly all cell types, such as double stranded DNA. For this reason, SLE can cause an array of seemingly unrelated and non-specific symptoms, which can make it difficult to diagnose.
Therapeutic interventions in Autoinflammatory and Autoimmune diseases ?
Describe Essential thrombocythemia ?
Effects of mass cell degranulation ?
Describe anaphylaxis ?
Drug induced hemolytic anemia ?
Inflammation
Describe acute inflammation ?
- Inflammation describes the tissue response to injury and is a series of processes initiated to limit tissue damage
- Acute inflammation occurs in response to a variety of situations where there may be tissue damage. Common causes include infection, hypersensitivity reactions, physical or chemical agents and tissue necrosis.
- Acute inflammation has five main features:
Rubor (redness), Tumour (swelling), Calor (heat), Dolor (pain)
and Loss of function
Tissue changes in acute inflammation ?
Blood flow changes:
-In the first few seconds following injury, there is transient arteriolar vasoconstriction to control any blood loss followed by arteriolar vasodilation to enhance blood flow in nearby capillaries and tissues. This provides blood components for managing the primary injury and initiating repair. The higher blood flow causes the signs of rubor and calor.
-Mast cells, basophils and platelets at the injury site release histamine. This leads to the blood vessels becoming more permeable and the formation of an exudate (protein-rich fluid) within the tissues. The circulation is also slowed which, in combination with fluid exudation, increases the concentration of red blood cells within circulation near the injury site. These two changes lead to the sign of tumour.
Exudation of fluid:
-Exudation of fluid occurs due to Starling’s Law. Vasodilation of arterioles leads to increased hydrostatic pressure and, as a result, higher fluid movement out of vessels. In addition to this, increased vessel permeability allows proteins to move into the interstitium, leading to increased colloid pressure and further increasing fluid movement out of vessels.
-This increase in tissue fluid also leads to increased lymphatic drainage, which can help remove damaging substances and causative microbes.
Exudation occurs as a result of several mechanisms:
-Endothelial contraction, mediated by histamine and leukotrienes
-Cytoskeletal reorganisation, mediated by cytokines, IL-1 and TNF-α.
-Direct injury, from toxic burns or chemicals.
-Leukocyte-dependent injury, due to toxic oxygen species or enzymes from leukocytes.
-Increased transcytosis (channels across endothelial cytoplasm), mediated by VEGF. Vascular endothelial growth factor, originally known as vascular permeability factor, is a signal protein produced by many cells that stimulates the formation of blood vessels
-This fluid allows plasma proteins, such as fibrin, to be delivered directly to the injury site.
Cellular phase of acute inflammation ?
-The main immune cells involved in acute inflammation are neutrophils. The stasis of circulation allows neutrophils to line up along the endothelium near the injury site, known as margination. Next, they roll along the endothelium, sticking intermittently.
-Following rolling, they attach more avidly to the endothelium, known as adhesion. Finally, the neutrophils migrate through the blood vessel walls. Neutrophils can leave blood vessels through relaxation of inter-endothelial cell junctions and digestion of the vascular basement membrane.
-Neutrophils move to areas of damage via chemotaxis. This is often following a concentration gradient of chemotaxins, including C5a, LTB4 and bacterial peptides.
-Neutrophils are necessary as they can phagocytose pathogens and cellular debris to remove them, facilitated by opsonins. Further detail on the process of phagocytosis can be found here.
How does acute inflammation help ?
The changes that occur in acute inflammation help with controlling the infection and restoring tissues to their normal state:
-Exudation of fluid helps deliver plasma proteins to injury sites. It, furthermore, dilutes toxins and increases lymphatic drainage.
Infiltration of neutrophils leads to the removal of pathogens and cellular debris.
-Vasodilation, much like exudation, helps to increase the delivery of necessary proteins and cells and to increase tissue temperature.
Pain and loss of function help to enforce rest and lower the risk of further tissue damage.
How does acute inflammation help ?
The changes that occur in acute inflammation help with controlling the infection and restoring tissues to their normal state:
-Exudation of fluid helps deliver plasma proteins to injury sites. It, furthermore, dilutes toxins and increases lymphatic drainage.
Infiltration of neutrophils leads to the removal of pathogens and cellular debris.
-Vasodilation, much like exudation, helps to increase the delivery of necessary proteins and cells and to increase tissue temperature.
Pain and loss of function help to enforce rest and lower the risk of further tissue damage.
Describe chronic inflammation ?
- Inflammation is the tissue’s response to injury. It describes a series of processes initiated to limit damage to tissue. Chronic inflammation also arises as a response to injury but takes place over a longer period of time than acute inflammation.
How can chronic inflammation arise :
- Chronic inflammation is a combination of inflammation, tissue injury and repair.
There are a number of situations in which chronic inflammation may arise:
-Chronic inflammation may ‘take over’ from acute inflammation if the damage does not resolve or the immune system fails to eradicate the causative agent.
-It may arise de novo, e.g. in autoimmune conditions such as rheumatoid arthritis. This leads to excessive or inappropriate immune system activation.
-It may develop alongside acute inflammation in severe and persistent irritation. This can happen due to recurrent episodes of acute inflammation.
Effects of chronic inflammation ?
-Chronic inflammation can have several complications depending on the area and underlying disease process. These include:
-Fibrosis, e.g. chronic cholecystitis can lead to fibrosis of the gall bladder wall.
-Impaired function, e.g. inflammatory bowel disease.
-Atrophy, e.g. atrophy of gastric mucosa in gastritis.
-Stimulation of immune response, e.g. local and systemic immune effects of rheumatoid arthritis.
Hallmarks of chronic inflammation ?
-Infiltration with mononuclear cells – Macrophages, lymphocytes and monocyte replace neutrophils. These cells have longer life-spans than neutrophils and so persist in the tissue.
-Tissue destruction- This can be a result of prolonged exposure to pathogens, toxins or immune cell activation.
-Healing – Damaged tissue attempts to heal through fibrosis and angiogenesis.
What are granulomas ?
Link between acute and chronic inflammation ?
Inflammation
So, inflammation is the body’s protective response to tissue injury, which can be caused by internal triggers, like cellular injury, and external triggers, such as infectious pathogens, physical trauma, and exposure to allergens or toxins.
During the inflammatory response, the body releases proinflammatory mediators, like cytokines and prostaglandins, that send signals to cells to stop the cause of tissue injury, rid the body of dead cells, and begin tissue repair. The inflammatory process leads to the five cardinal clinical manifestations of erythema, edema, pain, heat, and loss of function.
Describe NSAID action ?
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Describe NSAID action ?
Nonsteroidal anti-inflammatory drugs, or NSAIDs for short, are one type of anti-inflammatory medication that are used for their anti-inflammatory, analgesic, and antipyretic properties. Commonly prescribed NSAIDs include aspirin and aspirin-like drugs, such as ibuprofen and celecoxib.
How do NSAIDs work ?
-Now, NSAIDs treat the symptoms of inflammation by inhibiting proinflammatory mediators, which helps to limit the impact of the inflammatory response. Specifically, NSAIDs inhibit the enzyme cyclooxygenase, or COX, both in the central nervous system, and peripheral tissues. There are two forms of COX: COX-1 and COX-2.
First, COX-1 is known as “good” COX since it’s involved in protective activities such as platelet aggregation, production of protective mucus in the stomach, and maintenance of renal function.
On the other hand, COX-2, or “bad” COX, is only active in inflammatory cells and the vascular endothelium during inflammation and is involved in the production of small pro-inflammatory compounds like prostaglandins. When COX-2 is activated, those five cardinal inflammatory clinical manifestations result.
Alright, it’s important to note that the majority of NSAIDs inhibit both COX-1 and COX-2 to some degree. Inhibition of COX-1 results in undesirable side effects like gastric irritation and decreased renal blood-flow, whereas inhibition of COX-2 results in desirable effects by blocking the enzyme’s activation of inflammatory symptoms, like pain and swelling.
Due to the inhibition of COX-1 and COX-2, common side effects include gastrointestinal problems, such as gastritis, gastric ulcers, and even bleeding; cardiovascular problems, like tachycardia and edema; renal problems like renal impairment and an increased risk of hyperkalemia; as well as central nervous system symptoms, like dizziness.
Other side effects include severe hypersensitivity reactions, such as anaphylaxis and Stevens-Johnson syndrome. Importantly, all NSAIDs, except aspirin, have a Black box warning for an increased risk for adverse cardiovascular thrombotic effects, including fatal myocardial infarction and stroke; and for an increased risk of serious gastrointestinal events such as gastric ulceration, bleeding, and perforation.
Examples of NSAIDs ?
Describe Aspirin ?
Aspirin vs Ibrpuofen
Inhibition of COX by Aspirin and ibruprofen ?
Aspirin side effects ?
Maxillary artery ?
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