Hypersensitivity and autoimmunity

Question 1

Autoimmune disease

Answer 1

Failure or breakdown of immune system that maintains tolerance to self tissues- body thinks own cells organs are foreign and starts attacking them

Question 2

What is loss of tolerance probably due to?

Answer 2

Abnormal positive/negative selection or lack of control of self-reactive lymphocytes (B and T-cells)

Question 3

Hypersensitivity responses can be defined as?

Answer 3

damaging responses produced during normal immune responses ie allergies, autoimmunity

Question 4

What Types of hyper responses are there?

Answer 4

I II III and IV

Question 5

Which Types are antibody mediated? (humoral)

Answer 5

Type I, II and III

Question 6

Which type is cell- mediated? (WBC’s rather than antibodies)

Answer 6

IV

Question 7

What ‘Type’ do autoimmune diseases usually fall into?

Answer 7

Type II, III and IV depending on the type of damage associated with the disease

Question 8

Type I hypersensitivity

Answer 8

rely on (IgE) antibody- can also be called IgE- mediated sensitivities
reaction within minutes- most allergic reactions are type I sensitivity reactions
body recognises an environmental antigen as a pathogen and releases IgE and triggers mast cell responses- turns into allergen
apc (antigen presenting cell) presents allergen to T helper cell. Causes B cells to differentiate to produce IgE against the antigen- makes IgE antibodies think it's foreign

cytokines released- allergic response occurs- itching/inflammation, tissue damage

Question 9

What are antigens that cause allergic reactions called?

Answer 9

Allergens

Question 10

Two steps of an allergic reaction?

Answer 10

Step 1: first exposure- sensitisation

Step 2: subsequent exposure- more serious

Question 11

Why do some people have allergies?

Answer 11

these people have certain genes that cause their T- helper cells to be more hypersensitive to certain antigens

Question 12

Allergies: genetic link?

Answer 12

Production of T-helper cells is genetically linked, allergies tend to run in families

Question 13

Where do you tend to find IgE and where don’t you?

Answer 13

Tend not to find free IgE in the bloodstream but find IgE bound to cells ( particularly mast cells, basophils, eosinophils). Have a v. high affinity for Fc (antibody receptors that antigens bind to) receptors on these cells.

Question 14

Type II

Answer 14

All about specificity, antiobody-mediated
IgG, bind to specific antigens on its own cell surface
antibodies are produced in response to the antigens on the cell surfaces- trigger the complement system causing cell lysis
blood disorders:- types of anemia

Question 15

Type III

Answer 15

immune complex-mediated:-
IgG clump together
immune complexes are clumps of antibodies that have stuck together
low conc of antibody + high conc. antigen makes small complexes form (localised)
these then become deposited in tissue (systemic)- recruitment of inflammatory cells- tissue damage
could result in Lupus- attacks healthy tissue by mistake - Rheumatoid arthritis.

Question 16

Define atopy

Answer 16

Atopy refers to the genetic tendency to develop allergic diseases

Question 17

Type IV

Answer 17

cell-mediated- The body’s CD4 helper T cells (Th1 and Th2) and CD8 Tcells recognise the foreign antigen. Then CD8 cells start to produce cytokines which leads to apoptosis and furthermore, an inflammatory response
e.g Type 1 diabetes, MS

Question 18

Early phase response

Answer 18

• occurs within minutes

- pre-formed mast cell mediators (histamine, heparin, chemotactic factors)

Question 19

Late phase response

Answer 19

newly synthesised mediators
Th2 cytokines
eosinophil mediators

Question 20

immune complex formation in localised Type III hypersensitivity

Answer 20

causes localised inflammation and can be cleared away by macrophages

Question 21

Immune complex formation in systemic Type III hypersensitivity

Answer 21

Complexes are deposited in tissues and organs such as the skin, joints, kidneys and blood vessels

Question 22

Aetiologies (causes) of autoimmune disease

Answer 22

• Genetic Factors- allergies can be hereditary due to T cells
• Immune Regulatory Factors- defective tolerance induction
• Hormonal Factors - particularly female hormones
• Environmental Factors- infectious agents, sunlight, drugs, chemicals etc
• other factors- trauma, malignant disease

Question 23

what are the pathogenic mechanisms involved in autoimmune disease

Answer 23

cell-mediated- T cell activity
antibody-mediated B cell activity
antibody + complement (auto) antibody activation of complement-mediated inflammation
immune complex-mediated Type III hypersensitivity
recruitment of innate compounds- phagocytes, cytokine, NK cells

Question 24

Organ specific autoimmune disease:- Thyroid

Answer 24

Graves’ disease
hyperthyroidism
excess of thyroid hormone in the body
over activity of thyroid gland

Question 25

Organ specific autoimmune disease:- Stomach

Answer 25

pernicious Anaemia- causes your immune system to attack the cells in your stomach that produce the intrinsic factor, which means your body is unable to absorb vitamin B12.

Question 26

Organ specific autoimmune disease:- Adrenal

Answer 26

Addison’s disease- insufficient amount of certain hormones produced by adrenal glands- causes postural hypotension in back (arched forward), weight loss, weakness

Question 27

Non-organ specific autoimmune disease:- Muscles

Answer 27

dermatomyositis- distinctive skin rash, muscle weakness, inflamed muscles

Question 28

Non-organ specific autoimmune disease:- Skin

Answer 28

scleroderma- rare but results in hard, thickened areas of skin

Question 29

Non-organ specific autoimmune disease:- Joints

Answer 29

Rheumatoid arthritis- pain, swelling and stiffness in the joints

Question 30

Systemic autoimmune disease example?

Answer 30

Lupus which attacks your own tissues and organs. Inflammation caused by lupus can affect many different body systems- including your joints, skin, kidneys, blood cells, brain, heart and lungs

Question 31

What is an Fc receptor?

Answer 31

antibody receptor involved in antigen recognition which is located at the membrane of certain immune cells including B lymphocytes, natural killer cells, macrophages, neutrophils, and mast cells

Question 32

what is a mediator?

Answer 32

mediators are released from the mast cell through de-granulation following the activation of cell surface receptors on mast cells. They can be performed (e.g histamine, heparin, tryptase, chymase) or newly synthesised (e.g prostaglandins, leukotrienes)

Question 33

Cytokines

Answer 33

a broad category of proteins that are important in cell signalling. They are released during late-phase reactions

Question 34

Mast cells

Answer 34

a type of WBC
In type 1 hypersensitivity, mast cells remain inactive until an allergen binds to IgE already attached to the mast cell. This leads to de-granulation of the mast cell.

Question 35

Complement

Answer 35

The complement system is part of the immune system that enhances (complement) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from the organism, and also to attack the pathogen’s plasma membrane.

Question 36

Which cell types can mediate ADCC (antibody-dependent cell-mediated cytotoxicity?

Answer 36

typically Natural killer cells but macrophages, neutrophils and eisonophils can too

Question 37

Central tolerance?

Answer 37

Deletion of auto reactive (attacking itself) T and B cells during cell maturation

Question 38

Peripheral tolerance?

Answer 38

Inhibiting the activity of auto-reactive cells which escape the central tolerance process.

Question 39

organ specific means

Answer 39

when the specific auto-antigens are present only in a specific organ or tissue, and therefore affects a single organ or tissue

Question 40

immune tolerance meaning

Answer 40

prevention of an immune response against a particular antigen
e.g usually tolerant to self antigens