Diseases of Immunity 1 Lecture

Question 1

Define autoimmune disease

Answer 1

Illnesses which occur when body’s tissues are attacked by its own immune system

Question 2

Requirements for autoimmune disease?

Answer 2

Presence of an immune reaction specific for some self-antigen or self-tissue
Evidence that such a reaction is not secondary to tissue damage but is of primary pathogenic significance
Absence of another well-defined cause
Similarity with experimental animal models of proven autoimmunity

Question 3

Define Type 1 Diabetes

Answer 3

Appears to be the result of an autoimmune attack on the islet cells of the pancreas

Question 4

Define Good Pasture’s Syndrome

Answer 4

Antibodies to basement membranes of lung and kidney induce lesions in these organs

Question 5

What are systemic or generalized disease?

Answer 5

Systemic Lupus Erthematosus

Question 6

What are organ-specific diseases?

Answer 6

Type 1 Diabetes
Multiple Sclerosis
Goodpasture’s Syndrome

Question 7

Define tolerance

Answer 7

is the phenomenon of unresponsiveness to an antigen as a result of exposure of lymphocytes to that antigen

Question 8

Define self-tolerance

Answer 8

Refers to lack of responsiveness to an individual’s own antigens, an it underlies our ability to live in harmony with our cells and tissues

Question 9

Define central tolerance

Answer 9

immature self-reactive T and B lymphocytes clones that recognize self-antigens during their maturation in the lymphoid organs are killed or rendered harmless

Question 10

Where are T and B cell maturated?

Answer 10

Thymus and bone marrow

Question 11

What is negative selection or deletion?

Answer 11

Killing my apoptosis or deletion

Question 12

What is AIRE?

Answer 12

Autoimmune Regulator

Present host antigens to the T cells

Question 13

What is regulatory T cells?

Answer 13

Self-recognizing T cells that get out before being killed

• Turn down immune responses
• Promote tolerance

Question 14

What is B cell receptor editing or apoptosis?

Answer 14

B cells that encounter self-antigen but does not die, it is edited to not recognize self-antigen

Question 15

Define Anergy

Answer 15

Prolonged or irreversible functional inactivation, induced by encounter with antigens under certain conditions
- Lack of second signal
- Inhibitory second signal (CTLA4)
(affects B cells too)

Question 16

What is suppression by regulatory T cells?

Answer 16

Specific CD4+ T cells (express CD25 and Foxp3)

Require IL2 to surviveSecrete immunosuppressive cytokines as IL10 and TGF-beta

Question 17

What is deletion by activation-induced cell death?

Answer 17

CD4+ T cells that recognize self-antigens may receive signals promoting their death by apoptosis (cell activation induced cell death)

Question 18

How does autoimmunity arise from a combination of?

Answer 18

• Inheritance of susceptibility gens (which may contribute to breakdown of self-tolerance)
• Environmental triggers (infections and tissue damage, which promote the activation of self-reactive lymphocytes

With both of these there is imbalance

Question 19

What does microbes expressing B7 do?

Answer 19

B7 binds to CD28 on self-reactive T cells leading to autoimmunity

Question 20

What happens when a microbe mimics self-antigens?

Answer 20

Binds self-reactive T cells and causes autoimmunity

Question 21

What are virtually diagnostic of SLE?

Answer 21

Antibodies to double stranded DNA and the Smith antigen (RNA and associated proteins)

Question 22

What are antinuclear antibodies?

Answer 22

Against DNA, histones, non-histone proteins bound to RNA, nucleolar antigens

Question 23

What causes SLE?

Answer 23

Failure of the mechanism to maintain self tolerance (defective elimination of self-reactive B cells in bone marrow or defects in peripheral immune tolerance mechanisms acting on B cells)

Question 24

What are genetic factors predispose person to SLE?

Answer 24

Specific alleles of HLA-DQ locus
Lack of complement proteins (phagocytes fail to remove immune complexes and thus their deposition occurs –> Type III hypersensitivity)
Failure to remove debris of apoptotic cells
UV: stimulates keratincytes to produce pro-inflammatory IL1 cytokine

Question 25

Define Rheumatoid Arthritis

Answer 25

Autoimmune disease that mainly causes chronic inflammation of the joints
Systemic disorder that affects the skin, blood vessels, heart, lungs, and muscles
Slow jiont destruction

Question 26

What are characteristics of rheumatoid arthritis?

Answer 26

Progressive illness that potentially can cause joint destruction and functional disability
Joint inflammation causes swelling, pain, stiffness and redness
Affect tissue surrounding joints (tendons, ligaments, muscles
Cause joint destruction and deformity

Question 27

Infectious agents might trigger what?

Answer 27

the immune system to produce antibodies that attack the synovium, leading to inflammation of joints

Question 28

Treatments of Rheumatoid arthritis?

Answer 28

Anti-TNF therapies

Immunosuppressive agents as corticosteroids

Question 29

How is Rheumatoid arthritis detected?

Answer 29

Rhematoid factors (autoantibodies to autologous IgG) and antibodies to citrulline modified peptides (anti CCP antibodies) are markers

Question 30

Define multiple sclerosis

Answer 30

Demyelinating diseases — CNS nerves degenerate since re-myelination processes not very effective
Decrease nerve function due to myelin loss and secondary axonal damage

Question 31

What is the pathogenesis of multiple sclerosis?

Answer 31

Immune response against myelin sheath

Involves both genetic and environmental factors

Question 32

Chronic inflammatory response causes?

Answer 32

Responsible for demyelination

Inititaed by CD4+ Th1 and TH17 cells that react against self myelin and secrete cytokines

Question 33

Define psoriasis

Answer 33

Inflammatory skin disorder – scaling and shedding of the skin
Genetic and environmental factors

Question 34

What accumulates in the epidermis?

Answer 34

Sensitized populations of CD4+ TH1 and TH17 cells and activated CD8+ T cells