Vascular disease

Question 1

Overview of the essential features and components of the immune system. Humoral and cellular immunity: cells involved. Complement and antibodies.

Question 2

what are non specific mechanisms involved in preventing infection

Answer 2

Non-specific mechanisms include the skin barrier, lysozyme in secretions, ciliary motion in the respiratory tract, gut colonisation by harmless bacteria

Question 3

what are innate mechanisms involved in defence against infection

Answer 3

Innate mechanisms lack memory

Question 4

what is specific immunity

Answer 4

Specific immunity is characterised by specificity and memory, and only used when other mechanisms are bypassed

Question 5

what does failure in mechanical barriers (non specific defences) result in

Answer 5

Mechanical barriers: failure results in infection e.g. defects in mucociliary lining in cystic fibrosis

Question 6

what are secretory factors

Answer 6

Secretory factors act as chemical barriers e.g. absence of gastric acid in atrophic gastritis causes overgrowth of gut bacteria

Question 7

what are cellular factors

Answer 7

Cellular factors include neutrophil polymorphs and macrophages: ingest & kill bacteria

Question 8

what are examples of innate immunity (non specific)

Answer 8

Complement: complex series of interacting plasma proteins. A major effector mechanism for antibody mediated reactions, can be activated by some bacteria
Complement system: The complement system is a group of proteins that can recognize and destroy pathogens directly or indirectly through the recruitment of other immune cells.
Designed to remove or destroy antigen by either lysis or opsonisation (enhanced phagocytosis).
2 phases activation
of C3 component and activation of lytic pathway

Question 9

what are the 4 essential features to the immune system

Answer 9

SPECIFIC IMMUNITY (Adaptive)

Specificity: or adaptive, consists of a specific response to an antigen and a non specific augmentation of the effect.

diversity -ability to recognize and respond to all pathogens

memory- second time around a quicker and larger response

recruitment- of other defence mechanisms e.g. innate mechanisms such as complement and macrophage activation

Question 10

what is the role of antigens

Answer 10

Provoke an immune response and react with immune products or cells
Antigenic molecule (antigen) may have many antigenic sites (epitopes)
Each epitope can stimulate a different immune reaction
The immune system can produce humoral (antibody) or cellular (Lysis) immune reactions to antigens

Question 11

where do t lymphocytes and plasma cells originate in

Answer 11

plasma cells and t lymphocytes originate in the bone marrow

Question 12

what is the role of t lymphocytes

Answer 12

produce cellular immune reaction and produce humeral immune reaction (antibodies)

Question 13

what is the role of a T cell membrane receptor

Answer 13

Recognises antigen as part of a complex of
antigenic peptide and MHC Complex (APC)

Question 14

describe a t lymphocyte

Answer 14

cytotoxic - i.e. or helper release cytokines triggering inflammation

Question 15

what do b lymphocytes do

Answer 15

Plasma cells produce immunoglobulin (antibodies) and are derived from B-lymphocytes

Question 16

what do immunoglobulin cells do

Answer 16

antibody molecule - binds to antigen

Question 17

describe the immune response humoral and cellular

Answer 17

Processing and presentation of antigen by APC to lymphocyte (T cells need help for recognition ). Helper T-cell receptor and MHC bind. APC and T-cell interaction influenced by co-stimulators (cell adhesion molecules and cytokines).

Antibody production involves 4 cell types APC, B-lymphocytes and 2 types of T-cells. Antigen contact and release of cytokines by Helper T- cells stimulate B-cell division, differentiation and production of appropriate antibody. Memory cells produced with same Ig.

Cytotoxic T-cells lyse cells expressing antigens or release cytokines which trigger inflammation. Complement is activated by antibody, bacteria or mannose binding lectin, and removes and destroys antigen either by direct lysis or opsonisation.

Question 18

what are the types of immunodeficency

Answer 18

defective immunity can be divided into 2 main categories primary and specific
primary - congenital or acquired

secondary

specific - antibody , cell mediated

non specific - phagocyte, complement

Question 19

what are opportunistic infections

Answer 19

Opportunistic infections are infections caused by microorganisms such as bacteria, viruses, fungi, and parasites that take advantage of a weakened immune system in the body. These infections are called “opportunistic” because they typically do not cause illness in people with healthy immune systems, but can be life-threatening in individuals with compromised immune systems, such as those with HIV/AIDS, cancer, organ transplant recipients, and individuals taking immunosuppressive medications.

Question 20

what is an example of a fungal opportunistic infection

Answer 20

Aspergillus:

Question 21

what is an example of a fungal opportunistic infection

Answer 21

Aspergillus:

Question 22

is secondary or primary immunodeficiency more common

Answer 22

secondary immunodeficiency is more common than primary forms

Question 23

what are the causes of secondary immunodeficney

Answer 23

decreased production

malunutrition

lymphoproliferative disease

drugs

infections

increased loss or catabolism

nephrotic syndrome

protein losing enteropathy

burns

Question 24

how does exposure to hiv and aidsaffect immune comptence

Answer 24

you can be symptomatic for a whole and have tempers which reduce immune competence and lead to opportunistic infections

Question 25

what are hypersensitivity infections

Answer 25

Damaging immunological reactions:
Type I: immediate hypersensitivity “allergy” due to ↑ IgE on mast cells & basophils
Type II: antibody to cell-bound antigen
Type III: immune complex reactions
Type IV: delayed sensitivity mediated by T cells
Complex reactions: ? > one reaction type

Question 26

what is a type.1 hypersensitivity

Answer 26

immediate hypersensitivity e.g. hayfeveer conjuctivitis

systemic anaphylaxis = potentially fatal

ype 1 hypersensitivity is an allergic reaction that occurs when the immune system overreacts to a harmless substance, called an allergen, that enters the body. This type of hypersensitivity is also known as an immediate hypersensitivity reaction because it usually occurs within minutes to hours after exposure to the allergen.

During a type 1 hypersensitivity reaction, the immune system produces an antibody called Immunoglobulin E (IgE) in response to the allergen. IgE then binds to mast cells and basophils in the body, triggering the release of chemical mediators such as histamine, leukotrienes, and prostaglandins. These chemical mediators cause the symptoms of the allergic reaction, such as itching, hives, swelling, runny nose, and difficulty breathing.

Common allergens that can trigger a type 1 hypersensitivity reaction include pollen, dust mites, animal dander, insect venom, certain foods such as peanuts and shellfish, and certain medications.

Treatment for type 1 hypersensitivity reactions typically involves avoiding the allergen, taking antihistamines or other medications to relieve symptoms, and in severe cases, receiving epinephrine (adrenaline) through an injection to prevent anaphylaxis, a life-threatening allergic reaction. Allergy shots (immunotherapy) may also be used to reduce the severity of allergic reactions over time.

Question 27

what is type 2 hypersensitivity

Answer 27

ystem attacks its own cells or tissues. This occurs when the immune system mistakenly identifies a cell or tissue as foreign or harmful, and produces antibodies that target and destroy it.

There are several mechanisms by which type 2 hypersensitivity can occur, including:

Antibody-dependent cell-mediated cytotoxicity (ADCC): Antibodies bind to a specific antigen on the surface of a target cell, which triggers the destruction of the cell by immune cells such as natural killer cells.
Complement-mediated lysis: Antibodies activate the complement system, which leads to the formation of membrane attack complexes that destroy the target cell.
Antibody-mediated cellular dysfunction: Antibodies bind to cell surface receptors and interfere with their normal function.
Type 2 hypersensitivity can result in a variety of autoimmune and immune-mediated diseases, including autoimmune hemolytic anemia, autoimmune thrombocytopenia, Goodpasture syndrome, and myasthenia gravis.

Treatment for type 2 hypersensitivity depends on the underlying condition and may include immunosuppressive drugs, plasmapheresis (a procedure that removes harmful antibodies from the blood), or intravenous immunoglobulin (IVIG) therapy (a treatment that provides the body with additional antibodies).

often involves reactions to drugs bound to roc or platelet surface

Question 28

what examples of type 2 hypersensitiity

Answer 28

myasthenia gravis

lens induced uveitis
pemphigus

Question 29

what is type 3 hypersensitivity reactions

Answer 29

immune complex reactions
Type 3 hypersensitivity reactions, also known as immune complex-mediated hypersensitivity, occur when an excess of immune complexes (antigen-antibody complexes) accumulate in the body and deposit in tissues, triggering an inflammatory response.

In a type 3 hypersensitivity reaction, the immune system recognizes a foreign substance, such as a bacterium, virus, or protein, and produces antibodies to neutralize it. However, if too many antibodies are produced, they can form immune complexes that are too large to be cleared by the body’s immune system. These complexes then accumulate in the bloodstream and eventually deposit in tissues, such as joints, skin, and kidneys, triggering inflammation and tissue damage.
Result from the deposition of formation of immune complexes in tissues
Serum sickness (urticaria, arthralgia, + glomerulonephritis). Antisera raised in animals repeatedly injected.
Vasculitis
Arthus reaction – local form in skin at site of injection of antigen, result inflammation.

Question 30

what is type 4 hypersensitivity

Answer 30

delayed hypersensitivity

Sensitised T cells react with antigen
T cells secrete cytokines
Cytokines attract and activate more T cells, macrophages and eosinophilsdel
Activated macrophages form granulomas

Question 31

name examples of delayed hypersensitivity type 4

Answer 31

Examples: TB, leprosy
Corneal and other transplant organ rejection
Sympathetic ophthalmia
Sjogren’s syndrome

Question 32

what are autoimmune diseases

Answer 32

Immune system reacts against “self” antigens
The immune system is usually specifically unreactive (tolerant) to these antigens
Disease may be restricted to one organ (organ-specific autoimmune disease) e.g. myaesthenia gravis, autoimmune thyroiditis…..
or involve antigens distributed throughout the body (non-organ specific autoimmune disease) e.g. rheumatoid disease, systemic lupus erythematosus
Autoimmune diseases are more common in women than in men

Question 33

how is immunity in the eye preserved

Answer 33

Blood retinal barrier
Very similar to the blood brain barrier as both are neural derived tissues
The ocular space is said to be immune privileged
First coined by Peter Medewar in the 1940s

Question 34

what are the components of the retinal blood barrier

Answer 34

Tight Junctions
Increased numbers of Pericytes around retinal blood vessels.
Retinal pigmented epithelium

Question 35

what are the consequences of immune privilege

Answer 35

Two edged sword
Confers protection via barriers
Offers “safe harbour” and chemo-resistance to infectious organisms that breach the barrier
Protection is not absolute
Intervention breaches privilege

Question 36

what is ischaemia

Answer 36

Ischaemia is the result of impaired blood supply to a tissue, with consequent hypoxia (decreased oxygen concentration)
Infarction is death (necrosis) of tissue as a result of ischaemia

Question 37

what vascular lesions can cause iscahemia

Answer 37

thrombosis in arteries and veins

embolism. detached thrombus or other material

spasm - due to smooth muscle contraction in arteries

atheroma - common in arteries

steal - diversion of blood to adjacent areas

hyperviscollqy - increased palsma or white blood viscosity

vasculitis - due to inflammation of vessel walls

compression- common in veins

Question 38

what are clots and thrombi

Answer 38

A blood clot forms outside the body, or in the body after death

Clots are deep red, or (if settled) have lower deep red layer and upper clear layer

A thrombus forms within the vascular system, and only during life

Thrombi are often laminated with variable red/white layers (more red if venous; more white if arterial)

Question 39

what are causes of thrombosi

Answer 39

virchrows triad

abnormal vessel surface , abnormal blood flow and abnormal blood constituents

Question 40

what is haemostasis

Answer 40

Hemostasis is the body’s process of stopping bleeding from a damaged blood vessel. This process involves a series of complex interactions between blood vessels, platelets, and clotting factors in the blood.

When a blood vessel is damaged, the smooth muscle in the vessel wall contracts to reduce blood flow to the site of injury. This is followed by the formation of a platelet plug, in which platelets become activated and aggregate at the site of injury to form a temporary seal to prevent further bleeding.

Next, a series of clotting factors in the blood are activated, leading to the formation of a fibrin clot. The fibrin clot reinforces the platelet plug and stabilizes it to form a more permanent seal to stop the bleeding.

After the bleeding has stopped, the fibrin clot gradually dissolves and the damaged blood vessel repairs itself.

Disorders of hemostasis can lead to bleeding disorders, such as hemophilia and von Willebrand disease, or clotting disorders, such as deep vein thrombosis and pulmonary embolism. The treatment of these disorders depends on the underlying cause and may involve medications to promote clotting or prevent clotting.

Question 41

what is thrombosis

Answer 41

when a blood clot forms in the blood vessels

Question 42

what s systemic thrombotic emboli

Answer 42

Systemic thrombotic emboli refer to blood clots that form in one part of the body and then travel through the bloodstream to other parts of the body, where they can cause blockages and tissue damage.

These clots can arise from various sources, such as from the heart in the case of atrial fibrillation or heart valve disease, or from other locations such as the deep veins of the legs (deep vein thrombosis), arteries in the legs or pelvis, or from tumors.

When a clot travels through the bloodstream and lodges in a blood vessel, it can block blood flow to the affected tissue or organ

An embolus or emboli (plural) is a small, detached object that travels through the bloodstream and lodges in a blood vessel, obstructing blood flow to that particular area.

Question 43

how can systemic thrombotic emboli affect the eye

Answer 43

embolus to the retina - e..g cholesterol crystals from the atheromatous plaque in the aorta

Question 44

what are types of emboli

Answer 44

Atheromatous (cholesterol)
Platelet (cause TIAs if in brain; amaurosis fujax in retina)
Infective
Fat
Gas (e.g. “the bends”)
Amniotic fluid
Tumour
Foreign material (e.g. IV drug abuse)

Question 45

what is infarction

Answer 45

Ischaemic death (necrosis) of tissue eg heart (myocardial infarction); brain (cerebral infarction)
Infarcts elicit an inflammatory response
Gangrene is infarction of mixed tissues in bulk (e.g. gut wall, part of limb)

In some tissues, ischaemic necrosis may result from impaired vascular flow short of total cessation (e.g. central retinal vein occlusion; CRVO)

Question 46

what are examples of vascular disease in the eye

Answer 46

Central retinal vein occlusion (CRVO)
Atherosclerosis
Central retinal artery occlusion
Hypertension
Diabetes
Diabetic retinopathy
Arteritis
Diseases with secondary vascular consequen

Question 47

what causes central retinal artery occlusion : haemorragic infarction

Answer 47

causes - glaucoma , changes in iop , hypertension diabetes mellitus

flame shaped haemorrhages and oedema

Question 48

what is atherosclerosis (atheroma)

Answer 48

ATHEROSCLEROSIS (ATHEROMA)

Disease of large and medium-sized arteries
Lesions: fatty streaks, fibrolipid plaques and complicated lesions
Risk factors ↑age, males, hypertension, smoking and diabetes mellitis
Associated high Low Density Lipoprotein; low HDL blood
Major cause of organ ischaemia

Question 49

what are complications of atherosclerosis

Answer 49

In the eye:
Central retinal
artery occlusion

Question 50

what is atherosclerosis and what is its complications

Answer 50

Atherosclerosis is a condition in which plaque builds up inside arteries, which can lead to a range of cardiovascular diseases. Here’s how atherosclerosis is related to myocardial infarction, angina, and heart failure:

Myocardial infarction: Atherosclerosis can lead to the development of coronary artery disease (CAD), which occurs when plaque builds up in the coronary arteries that supply blood to the heart muscle. Over time, the plaque can cause the artery to narrow or become completely blocked, reducing blood flow to the heart. This can lead to a heart attack or myocardial infarction, which occurs when the heart muscle is damaged due to a lack of oxygen-rich blood.
Angina: Atherosclerosis in the coronary arteries can also cause chest pain or discomfort, known as angina. This occurs when the heart muscle is not receiving enough oxygen due to reduced blood flow from narrowed or blocked arteries. Angina is often triggered by physical activity or emotional stress and typically subsides with rest or medication.
Heart failure: Atherosclerosis can also contribute to heart failure, which occurs when the heart is unable to pump blood effectively to meet the body’s needs. Over time, atherosclerosis can cause damage to the heart muscle, leading to reduced cardiac function and an increased risk of heart failure.

Question 51

what are the physical characteristics of atheroma

Answer 51

mild atheroma - small fatty streaks and clot like lesions

Question 52

how is central retinal artery occlusion caused by atherosclerosis

Answer 52

The inner two thirds of the retina are atrophic, with loss of ganglia and bipolar cells, changes are irreversible and occur quickly, after 2hrs following complete occlusion through atherosclerosis

Question 53

what can hypertension be classified into

Answer 53

primary (essential) hypertension and secondary hypertension

Question 54

what is secondary hypertension caused by

Answer 54

Classified into essential (primary) hypertension and secondary hypertension
Secondary hypertension is due to renal disease, adrenal tumours, aortic coarctation and steroid therapy
Further classified into benign hypertension (gradual organ damage; accelerates atheroma)
and malignant hypertension (severe & often acute renal, retinal and cerebral damage

Question 55

what can accelerate retinal artery artesclerosis

Answer 55

Accelerated retinal artery atherosclerosis in benign hypertension

Question 56

how is the light reflex reduced in focal haemorrhages

Answer 56

Note focal haemorrhages, and the very narrow blood vessels: the wall of the arteriole is narrowed and consequently the lumen, and the light reflex is reduced.

Question 57

how does malignant hypertension effect the eyes

Answer 57

Malignant hypertension is a severe and rapidly progressive form of hypertension that can cause damage to various organs, including the eyes. Retinal hemorrhages are a common complication of malignant hypertension and occur when small blood vessels in the retina rupture and leak blood into the surrounding tissues.

The exact mechanisms by which malignant hypertension causes retinal hemorrhages are not fully understood, but it is thought to be related to the high pressure within the blood vessels. As blood pressure increases, the small blood vessels in the retina become less elastic and more prone to rupture. The force of the blood flowing through these fragile vessels can cause them to break, leading to retinal hemorrhages.

In addition, malignant hypertension can also damage the larger blood vessels that supply the retina, causing ischemia (lack of oxygen) and further weakening the smaller vessels. This can lead to a vicious cycle of damage, with the retinal vessels becoming increasingly fragile and prone to rupture.

Retinal hemorrhages caused by malignant hypertension can vary in severity, ranging from small, scattered spots to large, extensive bleeds that can affect vision.

Question 58

how can malignant hypertension cause microinfarcts and papillodema

Answer 58

micro infarcts are the cotton wool spots

Micro infarcts: Malignant hypertension can cause damage to small blood vessels throughout the body, including those in the brain. The high blood pressure can cause these vessels to become narrowed or completely blocked, leading to ischemia (lack of oxygen) and tissue damage. Micro infarcts are small areas of tissue damage in the brain that can result from these blockages. They can cause a range of symptoms depending on their location and size, including headaches, dizziness, weakness, and cognitive impairment.
Papilledema: Malignant hypertension can also cause swelling of the optic disc, which is the part of the eye where the optic nerve enters the retina. This condition is known as papilledema and can cause vision changes, such as blurring or loss of vision. The exact mechanism by which malignant hypertension causes papilledema is not fully understood, but it is thought to be related to increased pressure within the blood vessels supplying the optic disc.

Question 59

what can diabetes mellitus cause

Answer 59

Causes premature atheroma
Microangiopathy (damage to small blood vessels), leading to damage to kidneys, nerves and the retina
Complications include gangrene, renal failure and blindness
Effective control of diabetes reduces the incidence of renal and retinal disease
can cause retinal miscroaneurysms

Question 60

what is diabetic retinopathy

Answer 60

retinopathy may progress and lead to blindness (there are small for like capillary microanyerusms) that may become visible

diabetes mellitus also causes cataracts

Question 61

what is arteritis

Answer 61

inflammation of arterial wall

Giant cell (temporal, or cranial) arteritis can affect the ophthalmic and retinal arteries

leading to retinal ischaemia and infarction 

and/or anterior ischaemic optic neuropathy

giant cells are red dots on a staining picture

the arterial wall is thickened and its lumen is reduced to a thin channel

Question 62

what are examples of retinal degenerations

Answer 62

Retinitus Pigmentosa - RPE comes into contact and binds to retinal veins
Wet AMD

can cause retinal hameorrahes due to occlusion or weakening of vessel walls

Question 63

what are examples of retinal cancers

Answer 63

ocular cancers

retinoblastoma

uveal melanoma

can cause retinal hamorrahes due to occlusion or weakening of vessel walls

Question 64

what are diseases with secondary vascular consequences

Answer 64

central retinal vein occlusion CRVO- atherosclerosis

central retinal artery occlusion - hypertension

diabetes - diabetic retinopathy

arteriris

Question 65

what are vascular diseases of the eye

Answer 65

Major cause of visual impairment from middle age onwards.
Retinal ischaemia, by atheroma, vasculitis, thrombosis, or embolism
Retinal haemorrhages, associated with trauma and infection, but most common in diabetic and hypertensive retinopathy