Autoimmune Disease

Question 1

Cells involved in innate immunity

Answer 1

Macrophages
Dendritic cells
Mast cells
Neutrophils
Complement

Question 2

Cells involved in adaptive immunity

Answer 2

T cells

B cells

Question 3

Overview of innate immunity

Answer 3

Pattern recognition against broad classes of antigen
No memory
No amplification
Little regulation
Fast réponse (hours-days)
Short duration

Question 4

Overview of adaptive immunity

Answer 4

Highly specific
Strong memory and amplification
Many regulatory mechanisms
Slow response (days to weeks for initial infection)
Responses may last months-years

Question 5

Interactions between innate and adaptive immunity

Answer 5

Dendritic cells present antigens to T cells
T cells activate monocytes and macrophages
B cell antibodies activate complement

Question 6

Phagocytic cells

Answer 6

Neutrophils: eat and destroy pathogens
Macrophages: also produce chemokine to attract other immune cells
Dendritic cells: also present antigen to adaptive immune system

Question 7

Histamine producing cells

Answer 7

Mast cells, basophils, eosinophils: produce histamine and other chemokine and cytokines
Vasodilation
Immune cell attraction
Defence against parasites
Help wound healing
Also cause allergy and anaphylaxis

Question 8

Complement

Answer 8

Directly attacks pathogens via alternative and lectin pathways
May be activated by adaptive immune system via antibodies

Question 9

Cytokines

Answer 9

Signals between different immune cells

Question 10

Chemokines

Answer 10

Attract other immune cells to sites of inflammation

Question 11

Definition of autoimmunity

Answer 11

Adaptive immune system recognises and targets the body’s own molecules, cells and tissues

Question 12

Main characteristics of autoimmunity

Answer 12

T cells that recognise self-antigens
B cells and plasma cells that make autoantibodies
Inflammation in target cells, tissues and and organs is secondary to actions of T cells, B cells and autoantibodies

Question 13

Autoinflammation

Answer 13

Seemingly spontaneous attack so system inflammation
No demonstrable source of infection as precipitating cause
Absence of high-titre autoantibodies and antigen-specific auto reactive T cells
No evidence of auto-antigenic exposure
Caused by innate immunity

Question 14

Autoimmunity

Answer 14

Theoretical concept rather than autoimmune disease which has distinct clinical entities
Some people have autoantibodies without any symptoms
Overlap with normal immune functions such as anti-tumour immunity

Question 15

Failure of central tolerance

Answer 15

Mechanism of autoimmunity
T cell selection in the thymus
B cell selection in the bone marrow

Question 16

Genetic predisposition

Answer 16

Mechanism of autoimmunity
Certain HLA (MHC) types select for certain self-antigens
Other genes that regulate immune functions

Question 17

Antigenic factors

Answer 17

Mechanism of autoimmunity
Infections that trigger autoimmune responses
Environmental triggers such as UV light and smoking
Alteration in self-proteins that increase their immunogenicity

Question 18

Triad of autoimmune disease

Answer 18

Genetic predisposition
Immune regulation
Environmental triggers

Question 19

Organ specific autoimmunity

Answer 19

Affect a single organ
Autoimmunity limited to autoantigens of that organ
Overlap with other organ specific diseases
Autoimmune thyroid disease is typical

Question 20

Systemic autoimmunity

Answer 20

Affect several organs simultaneously
Autoimmunity associated with auto antigens found in most cells of body
Overlap with other non-organ specific diseases
Connective tissue diseases are typical

Question 21

General clinical features of autoimmune disease

Answer 21

More than 100 different diseases
Can affect any organ of the body
Onset in middle age, old age
More common in the elderly and women
Leads to loss of organ function
Lifelong chronic conditions
Characteristic exacerbation and remission
Traditionally divided into organ specific or systemic
Common for diseases to overlap

Question 22

Hashimoto’s thyroiditis

Answer 22

Destruction of thyroid follicles by autoimmune process
Associated with autoantibodies to thyroglobulin and thyroid peroxidase
Leads to hypothyroidism

Question 23

Grave’s disease

Answer 23

Inappropriate stimulation of thyroid gland by anti-TSH-autoantibody
Leads to hyperthyroidism

Question 24

Myasthenia gravis

Answer 24

Autoantibodies block acetylcholine receptor
Causes problems with keeping eyes open, speaking, swallowing and smiling
Find that problems are worse as the day progresses

Question 25

Pernicious anaemia

Answer 25

Autoantibodies against intrinsic factor production

Reduces ability to absorb B12 resulting in anaemia

Question 26

SLE

Answer 26

Systemic Lupus Erythematosus
Systemic autoimmune disease
Typical symptoms are photosensitive malar rash, multiple mouth ulcers, arthralgia, alopecia
Autoantibodies form against many different molecules in the cell nucleus including ddDNA, dsDNA, ribosomes and histones

Question 27

Lupus nephritis

Answer 27

1) Immune complex deposition - antibodies against antigens in the nucleus combine with their targets to form immune complexes in the circulation which can deposit in any organ (typically kidneys) and cause inflammation
2) Inflammation
3) Leaky glomerulus
4) Loss of renal function
5) Scarring
6) Irreversible renal failure

Question 28

Examples of connective tissue disease

Answer 28

SLE
Scleroderma
Polymyositis
Sjogrens syndrome
Ubiquitous antigens cause multi system inflammation