Robbins 7th ed - Chapter 6 - Diseases of Immunity (2)

Question 1

Name some of the cells and other components involved in innate immunity.

Answer 1

Epithelial cells (forming barriers), Phagocytes, NK cells, complement proteins, C-reactive protein.

Question 2

Name two cells involved in adaptive immunity.

Answer 2

B-cells, T-cells.

Question 3

What are MHC molecules, and on which cell surface are they found?

Answer 3

Major Histocompatibility Complex molecules. MHC I molecules are found on all nucleated cells and platelets. MHC II molecules are found on the surface of Antigen Presenting Cells such as B-cells, Dendritic Cells and Phagocytes. MHC molecules “tag” the cell as being “self”. Only MHC II molecules display antigens on the cell surface.

Question 4

Complete these sentences about T-cells:  
CD4 molecules are found on \_\_\_\_\_\_\_ cells, and bind to class \_\_\_ MHC molecules on antigen-presenting cells.  CD8 molecules are found on \_\_\_\_\_\_\_\_ cells, and bind to class \_\_\_ MHC molecules.  Together with CD4 or CD8 binding to MHC molecules, there is costimulation by the binding of \_\_\_\_\_\_ from T-cells to \_\_\_\_\_\_ on antigen-presenting cells.

Answer 4

CD4 molecules are found on T-helper cells, and bind to class II MHC molecules on antigen-presenting cells. CD8 molecules are found on T-cytotoxic cells, and bind to class I MHC molecules. Together with CD4 or CD8 binding to MHC molecules, there is costimulation by the binding of CD28 from T-cells to the costimulatory molecules CD80 or CD86 on antigen-presenting cells.

Question 5

Name two mechanisms by which Helper-T-cells can activate B-cells.

Answer 5

• By engaging CD40 on the surface of B-cells

- By secreting cytokines

Question 6

What are Langerhans cells?

Answer 6

Immature dendritic cells within the epidermis.

Question 7

What is an important molecule expressed on the surface of all healthy, normal cells, and how does it affect the action of NK cells?

Answer 7

MHC class I molecules effectively “tag” a cell as being “self”, and if NK-cell surface receptors bind to this, their destructive processes are inhibited. If a cell becomes virally infected or cancerous, there is reduced expression of MHC class I, and this allows NK-cells to destroy the cell.

Question 8

What are the four types of hypersensitivity reactions?

Answer 8

• Type 1: Immediate hypersensitivity, where there is release of vasoactive substances and inflammatory cytokines, from IgE-mediated triggering of mast cells
• Type 2: Antibody-mediated disorders, directed at antigens on self-cells.
• Type 3: Immune-complex-mediated disorders, whereby antibodies bind antigens, and this complex activates inflammation.
• Type 4: Cell-mediated immune disorders, whereby sensitized T-cells cause injury.

Question 9

Give an example (or two) for each of the four types of hypersensitivity reactions.

Answer 9

• Type 1: Anaphylaxis, Allergies, Bronchial asthma
• Type 2: Autoimmune haemolytic anaemia, Grave’s disease, Myasthenia Gravis
• Type 3: SLE, Poststreptococcal glomerulonephritis
• Type 4: Contact dermatitis, MS, T1DM, Transplant rejection, TB, RA

Question 10

What cell types are involved in Type I Hypersensitivity?

Answer 10

Mast cells

Question 11

What is the importance of an individual’s prior exposure to an antigen in Type I Hypersensitivity?

Answer 11

Type I Hypersensitivity occurs in individuals who have been previously sensitized to the antigen.

Question 12

In Type I Hypersensitivity, there are two phases of the reaction. What happens in the “initial response” ?

Answer 12

Antigen binds to mast cell’s IgE, Mast cells release granular contents, Vasodilation, Increased vascular permeability/leakage, Leukocytes are recruited, Smooth muscle spasms/contracts.

Question 13

What are the granular contents of mast cells?

Answer 13

Histamine, Proteases, Chemotactic factors (ECF, NCF)

Question 14

In Type I Hypersensitivity, there are two phases of the reaction. What happens in the “late-phase response” and when does this start?

Answer 14

This starts a few hours after the contact with the allergen. This phase is characterized by leukocyte infiltration and tissue injury.

Question 15

What cell types are involved in Type II Hypersensitivity?

Answer 15

Phagocytes and Neutrophils. Note that in Myasthenia Gravis, there is no inflammation or cell destruction, so these cells are not involved.

Question 16

What cell types are involved in Type III Hypersensitivity?

Answer 16

Neutrophils, Platelets aggregating, Phagocytes

Question 17

In Type III Hypersensitivity, where are the immune complexes usually deposited?

Answer 17

They are deposited in areas that receive a good blood supply, such as the kidneys (nephritis), the blood vessels (vasculitis), the joints (arthritis) and the skin.

Question 18

In Transplant/Graft Rejection, what is involved in the Direct Pathway?

Answer 18

Antigen-Presenting Cells of the graft itself activate the host’s CD8+ T-cells, which destroy graft tissue, as well as CD4+ T-cells, which secrete cytokines and activate macrophages.

Question 19

In Transplant/Graft Rejection, what is involved in the Indirect Pathway?

Answer 19

The host’s antigen-presenting cells display antigens taken from the graft cells. This activates CD4+ T-cells, which secrete cytokines, activate macrophages, and activate B-cells to produce antibodies.

Question 20

Which type of hypersensitivity reaction is involved in T2DM? And which one for T1DM? Name the antigens involved in each case.

Answer 20

T2DM: Type II (antibodies bind to insulin receptors, leading to insulin resistance).
T1DM: Type IV (T-cells are activated by antigens of the pancreatic islet β-cells).

Question 21

What are epithelioid cells?

Answer 21

These form in Type IV hypersensitivities. Macrophages accumulate at the site, and then undergo morphologic transformation into epithelium-like cells and are then referred to as epithelioid cells. Epithelioid cells are clumped together, usually surrounded by a collar of lymphocytes, and this complex is called a granuloma, which may also contain giant cells.

Question 22

Which cell type can only recognize membrane-bound antigens: T-cells or B-cells?

Answer 22

T-cells

Question 23

What are HLA-A, HLA-B and HLA-C?

Answer 23

These are loci on chromosome 6, encoding the subunits that form the MHC-I molecule.

Question 24

What are HLA-DP, HLA-DQ and HLA-DR?

Answer 24

These are loci on chromosome 6, encoding the subunits that form the MHC-II molecule.

Question 25

What is β2-microglobulin?

Answer 25

It is a small polypeptide that completes the structure of the MHC-I molecule, after its other subunits have been transcribed from HLA-A, HLA-B and HLA-C.

Question 26

What is the significance of various HLA-alleles and autoimmune diseases?

Answer 26

HLA alleles such as B27 and DR3 in individuals are associated with increased rates of autoimmune diseases such as ankylosing spondylitis and Sjӧgren syndrome.

Question 27

What is Goodpasture syndrome? What is the antigen, which tissue does it affect, and what class of hypersensitivity is it?

Answer 27

Goodpasture syndrome is a Type II Hypersensitivity disease, whereby antibodies bind to antigens on the basement membrane of lung alveoli and kidney glomeruli, inducing complement- and Fc receptor-mediated inflammation.

Question 28

What is an Fc-receptor?

Answer 28

The Fc-receptor is found on the cell surface of B-cells, Dendritic cells, Macrophages, Mast Cells, Neutrophils and other leukocytes. The Fc-receptor binds antibodies.

Question 29

Give a definition for Central Immunologic Tolerance.

Answer 29

Central tolerance refers to the death (deletion) of self-reactive T- and B-lymphocyte clones during their maturation in the central lymphoid organs (thymus and bone marrow).

Question 30

Give a definition for Peripheral Immunologic Tolerance.

Answer 30

Peripheral tolerance refers to the processes that occur outside of the thymus and bone marrow in order to silence autoreactive T-cells and B-cells that have escaped central tolerance during their maturation.

Question 31

What are the four different processes that make up Peripheral Tolerance?

Answer 31

Anergy, Suppression by regulatory T-cells, Clonal deletion, Antigen sequestration.

Question 32

What is anergy?

Answer 32

Anergy is a part of Peripheral Tolerance. Autoreactive T-cells that bind to self-antigens in the periphery do not have the costimulatory signals as in normal immune responses, and so these T-cells are irreversibly inactivated.

Question 33

What are regulatory T-cells, with regard to peripheral tolerance?

Answer 33

Regulatory T-cells are a specific type of CD4+ cell that can suppress autoreactive T-cells in the periphery, by mechanisms poorly understood.

Question 34

How does clonal deletion occur in peripheral tolerance?

Answer 34

Fas-ligand is expressed on autoreactive T-cells after they have repeated stimulation by abundant self-antigens in the periphery. When Fas-ligand binds to Fas on the surface of other T-lymphocytes, apoptosis of both T-cells is induced. Self-reactive B-cells can also be deleted in this way.

Question 35

What is antigen sequestration (in peripheral tolerance)?

Answer 35

Some tissues are described as “immune privileged”, because they do not communicate with blood and lymph (there is a blood-tissue barrier). Examples are testes, eye and brain. The self-antigens of these tissues are hidden from the immune system, and if they become exposed, there can be an autoimmune reaction (e.g. post-traumatic orchitis).

Question 36

Explain the circumstances under which Graft Versus Host disease occurs.

Answer 36

GVH disease occurs in any situation in which immunologically competent cells or their precursors are transplanted into immunologically crippled recipients, and the transferred cells recognize alloantigens in the host.

Question 37

What is the most common transplant that induces Graft Versus Host disease?

Answer 37

Allogeneic Bone marrow transplant.

Question 38

What are two less common transplants that can induce Graft Versus Host disease?

Answer 38

Liver transplant (liver is rich in lymphoid cells that are immunocompetent), or PRBC transfusion of un-irradiated blood.

Question 39

Which cell type mediates Graft Versus Host disease?

Answer 39

T-lymphocytes. Immunocompetent T-cells of the graft recognize HLA antigens of the host as being foreign, and attack them, using both CD4+ and CD8+ T-cells.

Question 40

What types of antibodies are the mediators of disease in Systemic Lupus Erythematosus?

Answer 40

There are a countless number of different IgG antibodies, directed towards different antigens, involved in SLE. These include Anti-Nuclear Antibodies (ANA), antibodies against cytoplasmic components, and antibodies against cell-surface antigens of blood cells.

Question 41

Name some of the tissues that can be affected in SLE.

Answer 41

Skin: malar rash, discoid rash, photosensitivity.
Mouth: oral ulcers
Joints: arthritis
Serous membranes: Pleural effusion / pleuritis, Pericardial effusion / pericarditis
Kidney: glomerulonephritis
CNS: Seizures, psychosis
Haematologic: pancytopaenia

Question 42

What are the three viral enzymes contained in the HIV virus?

Answer 42

Reverse transcriptase, Protease, Integrase

Question 43

What does reverse transcriptase do?

Answer 43

It creates cDNA from retroviral RNA.

Question 44

What is meant by the term “provirus”?

Answer 44

This is a section of dsDNA representing a viral genome that is integrated into the host’s own chromosomes. The provirus comes from reverse transcription of the virus’s dsRNA.

Question 45

What is the basic pathophysiology of drug-induced lupus erythematosus?

Answer 45

Drugs such as hydralazine, procainamide, and isoniazid can induce a positive ANA, and less often a lupus erythemtosus-like syndrome. The effects usually remit after removal of the offending agent.

Question 46

What does the HIV virus do during the latency period of the infection? What triggers the latency period to end?

Answer 46

The HIV genome rests silently as a provirus integrated into the host’s genome in the T-cells, until the T-cell is activated by some new offending antigen, which leads to transcription of T-cell genes such as that for the cytokine IL-2. The proviral DNA is concurrently transcribed, due to having similar promoter regions. This leads to viral reproduction and progression of disease.

Question 47

Name four tissues where amyloid protein deposits accumulate in amyloidosis.

Answer 47

Kidney, Spleen, Liver, Heart.

Question 48

Give a few examples of Type I hypersensitivity disorders.

Answer 48

Asthma, Anaphylaxis, Penicillin Allergy, Allergic Rhinitis (hayfever)

Question 49

Give a few examples of Type II hypersensitivity disorders

Answer 49

T2DM, Goodpasture’s syndrome, Grave’s disease, Myasthenia Gravis, Haemolytic disease of the newborn, Autoimmune haemolytic anaemia, Acute rheumatic fever.

Question 50

Give a few examples of Type III hypersensitivity disorders

Answer 50

Arthus reaction, Serum sickness, SLE, Post-streptococcal glomerulonephritis, Reactive arthritis.

Question 51

Give a few examples of Type IV hypersensitivity disorders

Answer 51

Rheumatoid Arthritis, T1DM, Multiple Sclerosis, TB, Contact dermatitis, Transplant rejection.