Diseases of the Immune System

Question 1

What is the main function of the immune system?

Answer 1

To prevent or limit infection by microorganisms.

Question 2

What is the body’s first line of defence?

Answer 2

Intact skin and mucous membranes

Question 3

If the microorganisms breach this line and enter the body what is the second line of defence?

Answer 3

The innate arm of the immune system is available to destroy the invaders.

Question 4

What is the the third line of defence?

Answer 4

A highly specific protection is provided by the adaptive (acquired) arm of the immune system, but takes several days for this arm to become fully functional.

Question 5

Innate part of the immune system

Answer 5

• Pre-formed
• Humoral: Complement and neutrophils
• Cell mediated: macrophages and natural killer cells
• No memory

Question 6

Why can the innate arm of the immune system function immediately when a microorganism enters?

Answer 6

The components of the innate arm are performed and fully active.

Question 7

Adaptive part of the immune system

Answer 7

• Highly specific, several days to become active
• Humoral: B-cells and antibodies
• Cell mediated: helper T cells and cytotoxic T cells
• Memory - and response next time will be faster

Question 8

What are the two components of the adaptive arm?

Answer 8

Cell-mediated immunity and antibody mediated (humoral) immunity.

Question 9

What does the cell-mediated arm and antibody medicated arm consist of?

Answer 9

T cells whereas the antibody mediated arm consists of antibodies and B cells.

Question 10

What is the main function of the antibodies?

Answer 10

To neutralise toxins and viruses and to opsonise bacteria (poke holes in them).

Question 11

Both cell-mediated and antibody mediated responses are characterised by 3 important features, what are they?

Answer 11

1. They exhibit remarkable diversity
2. They have long memory and can respond many years after the initial exposure
3. They exhibit exquisite specificity- which is essential or the immune system attacks the host.

Question 12

How do immune cells develop?

Answer 12

From mutipotent stem cells in the bone marrow into either myeloid precursors or lymphoid precursors. These precursors in turn differentiate into end cells that have various immune functions.

Question 13

What are the 5 class of antibodies/ immunoglobulins?

Answer 13

IgG
IgA
IgM
IgE
IgD

Question 14

What do immunoglobulins consist of?

Answer 14

Two heavy chains and two light chains (determined by molecular weight), one heavy and one light chain interact to form an antigen-binding unit. Variable domains of heavy and light chains bind antigens and are different between Igs depending of their target.

Question 15

Immunoglobulin classes

Answer 15

All classes of Igs have variable heavy (Vh) and variable light (Vl) chains that bind antigen. IgG, A, and D have three constant domains.
The heavy chains of IgM and IgE have a fourth constant domain.

Question 16

What does IgE in hypersensitivity: Anaphylaxis do?

Answer 16

Produced in response to an antigen, Binds to mast cells or basophils, causes degranulation of mast cell or basophil and release of reactive substances such as histamine

Question 17

Leukotrienes and prostaglandins=

Answer 17

Swelling, redness, increased mucus secretion, smooth muscle contraction (breathing difficulty).

Question 18

Hypersensitivity: Cytotoxic (II)- Involves what?

Answer 18

Activation of complement by the combination of IgG or IgM antibodies with an antigenic cell. This activation stimulates complement to lyse the affected cell which might be either a foreign cell or a host cell that carries a foreign antigenic determinant such as a drug on its surface.

Question 19

Hypersensitivity: Immune Complex (III) what does it involve?

Answer 19

Involves antibodies against soluble antigens circulating in the serum. The antigen-antibody complexes are deposited in organs and cause inflammatory damage.

Question 20

Hypersensitivity: Immune Complex (III)- how does the antigen-antibody complex activate complement and cause a transient inflammatory reaction how does it reach which location?

Answer 20

These complexes circulate in the blood, pass between endothelial cells of the blood vessels, and become trapped in the basement membrane beneath the cells.

Question 21

What is glomerulonephritis?

Answer 21

An immune complex condition, usually resulting from an infection that causes inflammatory damage to the kidney golmeruli.

Question 22

Hypersensitivity: Delayed (IV)- Why does this take a day or more to manifest?

Answer 22

Because of the time required for the T cells and macrophages to migrate to an accumulate near the foreign antigens.

Question 23

When does sensitisation occur?

Answer 23

When foreign antigens, particularly those that bind to tissue cells are phagocytised by macrophages and presented to receptors on the T cell surface.

Question 24

What happens to the t-cells on contact and what does this mean?

Answer 24

Cause the T-cells to proliferate and mature creating memory. Therefore, on re-exposure inflammation occurs leading to dermatitis etc this type of hypersensitivity reaction is the basis of latex allergies.

Question 25

What is Stevens-Johnson Syndrome?

Answer 25

A rare and potentially fatal immune reaction market by the loss of skin and mucous linings.

Question 26

What type of reaction is stevens-johnson syndrome?

Answer 26

Delayed type cell-mediated hypersensitivity reaction mediated primarily by cytotoxic t-cells attacking keratinocytes in the skin.

Question 27

What does Steven-Johnsons Syndrome cause?

Answer 27

Separation of epidermis from dermis and inflammation, necrolysis.

Question 28

There are 4 etiological categories, what are they?

Answer 28

• Infectious
• Drug-induced
• Malignancy-related
• Idiopathic (unknown)

Question 29

What are the causes of autoimmunity?

Answer 29

• Molecular mimicry
• Release of sequestered antigens
• epitope spreading
• failure of regulatory t-cells

Question 30

Molecular mimicry?

Answer 30

As a result of foreign antigens resembling a component of the body.

Question 31

Sequestered antigens?

Answer 31

Come from immunological privileged sites such as the CNS, eye, sperm and if they enter the circulation accidentally they elicit damaging immune responses.

Question 32

Epitope spreading?

Answer 32

New exposure of sequestered autoantigens as a result of damage to cells caused by viral infection. eg. MS

Question 33

Multiple Sclerosis

Answer 33

Immune cells cause demyelination of the white matter of the brain. Trigger thought to be viral.
Symptoms: Wax and wane and include sensory and motor impairment.
Treatment: Immunosuppressive drugs

Question 34

Chronic Thyroiditis

Answer 34

Hashimoto’s chronic thyroiditis have antibodies to thyroglobulin which cause fibrosis of the thyroid gland.

Question 35

Haemolytic anaemias

Answer 35

Caused by attachment of autoantibodies to cell surfaces and subsequent cell destruction. Pernicious anaemia caused by depleted vitamin B12 caused by antibodies to intrinsic factor, a protein secreted by gastric parietal cells which facilitates absorption of vitamin B12

Question 36

Diabetes Mellitus (type 1, insulin dependent)

Answer 36

Autoreactive T-cells destroy the islet cells of the pancreas.

Question 37

Guillain-Barre Syndrome- Most common cause of acute paralysis in the USA.

Answer 37

Follows a variety of infectious diseases caused by campylobacter jejuni. Antibodies to myelin are formed resulting in ascending paralysis.

Question 38

Coeliac disease (gluten free)

Answer 38

Characterised by diarrhoea, painful abdo, fatty stools and failure to thrive in children. Caused by intolerance to gliadin, an antigen found in gluten that stimulates a cytotoxic T-cell attack on enterocytes.

Question 39

Psoriasis

Answer 39

Chronic autoimmune skin disease characterised by raised red plaques with silvery scales, often on elbows and knees. Genetic predisposition with unknown environmental trigger.
Treatment: Topical corticosteroids, UV phototherapy or systemic immune suppressants.

Question 40

X-linked (Bruton’s agammaglobulinemia) (almost exclusively affects boys)

Answer 40

Specific Deficiency: absence of B cells- very low of undetectable immunoglobulin levels
Defect: Mutant tyrosine kinase and failure of heavy chain gene switching
Clinical Features: Recurrent bacterial infections
Treated: IV IgG and frequent antibiotic therapy

Question 41

Common Variable Immunodeficiency (CVID)

Answer 41

Specific Deficiency: B cells fail to mature into antibody secreting plasma cells. Increased helper t-cell death and decreased t-cell function
Clinical Features: Recurrent UTRIs. Increased risk of gastric cancer and lymphoma.
Treatment: IV IgG

Question 42

Thymic aplasia (DiGeorge Syndrome)

Answer 42

Specific Deficiency: Absence of T cells
Defect: Partial or complete failure of thymus development
Clinical Features: viral, fungal, protozoal infection; tetany due to hypoparathyroidism

Question 43

Severe Combined immunodeficiency (SCID)

Answer 43

Specific Deficiency: Deficiency of both B-cell and T-cell function. Low Ig levels.
Defect: Either defective IL-2 receptor, defective enzymes, absence of class II MHC.
Clinical Features: bacterial, viral, fungal, and protozoal infections

Question 44

Hereditary Angiodema

Answer 44

Specific Deficiency: Deficiency of C1 protease inhibitor and too much C3a, C4a, and C5a generated.
Defect: Rare autosomal dominant disease caused by deficiency of C1 inhibitor
Clinical Features: Edema (esp. laryngeal-can be fatal)
Treatment: Steriod drugs

Question 45

What is selective antibody deficiency (SAD)?

Answer 45

An inadequate antibody response to polysaccharide antigens in an individual with normal response to protein antigens, normal serum levels of immunoglobulins (IgG, IgA, and IgM), and normal IgG subclass concentrations. Polysaccharide nonresponse is the ONLY identifiable abnormality.

Question 46

Which vaccines are polysccharide vaccines?

Answer 46

Prevenar 23- Pneumococcal vaccine

Salmonella enterica serotype typhi vaccine.

Question 47

What does it mean to have SAD?

Answer 47

The body produces antibodies to fight infection, but doesn’t remember some infections from the past.

Question 48

How is SAD managed?

Answer 48

using a blood product called intragram P, blood product is pumped through veins every 4 weeks

Question 49

What causes acquired immunodeficiency?

Answer 49

• Severe malnutrition - reduces supply of amino acids thereby reduces the synthesis of IgG
• Cancers and chemotherapy
• Radiotherapy
• Immunosuppressive therapy in transplant patients
• Corticosteroid drugs for anti-inflammatory treatment in autoimmunity
• Viral infections, e.g. HIV