Week 11 - Disease causing immune responses

Question 1

What are two reasons hypersensitivity reactions may arise?

Answer 1

• Dysregulated/uncontrolled immune responses to foreign antigens
• Immune responses directed against self-antigens

Question 2

When do immediate hypersensitivity reactions occur, and what cells/molecules do they involve?

Answer 2

Rapidly, within minutes after exposure

They involves allergens, IgE antibodies and Mast cells

Question 3

IgE production requires Th-cells. How are These regulated?

Answer 3

Regulated by T-cell derived cytokines
Stimulatory: IL-4 & IL-13
Inhibitory: IFN-y

Question 4

Is hypersensitivity evident on first exposure to an allergen?

Answer 4

No, usually appears on repeated contact

Question 5

What leads to mast-cell degranulation and mediator release?

Answer 5

Mast cell’s IgEs cross linking by the antigen

Question 6

What are the four most common allergic disorders?

Answer 6

Atopic eczema, food allergy, allergic rhinitis and asthma

Question 7

How do allergic disease patterns change with age?

Answer 7

Food allergy and atopic dermatitis are the first signs. These move to persistent asthma and allergic rhinitis, which usually persist into later childhood

Question 8

Which antibodies are involved in Antibody mediated hypersensitivity reactions (T2)?

Answer 8

IgM and IgG

Question 9

What are three mechanisms of immune system action involved in Type 2 HS reactions?

Answer 9

Phagocytosis by neutrophils and macrophages
Cytotoxic action by killer cells
Lysis mediated by the complement system

Question 10

What are two diseases manifesting Type 2 HS ?

Answer 10

Myasthenia gravis, rheumatic heart disease, autoimmune haemolytic anaemia

Question 11

What do the antibodies of Type 2 HS reactions, react with?

Answer 11

They react against antigens that are components of the cell membrane, and may deposit on any tissue expressing that antigen. This is why they cause diseases specific for a particular tissue

Question 12

What causes autoimmune haemolysis?

Answer 12

IgG or IgM auto-antibodies against RBC antigens are generated, which either causes agglutination and complement destruction of RBCs, or splenic macrophages binding the IgG coated RBCs, gradually destroying them

Question 13

What is allo-immune haemolysis?

Answer 13

ABO blood group incompatibility leading to complement activation. This causes opsonization and phagocytosis, or RBC lysis

Question 14

What is haemolytic disease of new born caused by?

Answer 14

Second onwards pregnancies where the mother is Rh- but the baby is Rh+

Question 15

What does Immune-complex mediated hypersensitivity (T3) involve?

Answer 15

Immune complexes: usually antigen+IgG or IgM
Complement cascade
Monocytes
Polymorphonuclear cells (PMNs), which cause local tissue damage and inflammation

Question 16

What are the causes of T3 HS diseases, such as polyarteritis nodosa?

Answer 16

Immune complexes are normally broken down by complement components like C3b coating them and allowing them to be phagocytosed by the liver and spleen macophages.
If this fails to happen, immune complexes are deposited on blood vessels, especially in kidneys and synovium.
This leads to systemic disease, which often manifests with vasculitis, arthritis and renal disease

Question 17

What does T-cell mediated Hypersensitivity (Type 4) reactions involve?

Answer 17

T cells, lymphokines, antibodies, antigens and macrophages.

Question 18

What are the two major causes of T-cell mediated hypersensitivity reactions?

Answer 18

T-cell mediated autoimmune diseases - usually limited to a few organs and not systematic
T cell mediated hypersensitivity reactions to environmental antigens - including contact sensitivity to chemicals

Question 19

Which type of hypersensitivity reaction is granuloma formation in an infection with Mycobacterium tuberculosis?

Answer 19

Type 4 - T-cell mediated hypersensitivity.

Question 20

What are the mechanisms of tissue injury in T4 HS reactions?

Answer 20

Inflammation induced by cytokines produced by CD4+ T-cells
Killing of host cells by CD8+ cytotoxic lymphocytes
Th1 production of IFN-y, principal macrophage activator
Th17 cells recruit leukocytes, including neutrophils
— macrophages and neutrophils are a major cause of tissue injury

Question 21

What are the principal antigenic barriers to transplantation?

Answer 21

Major Histocompatibility complex (MHC) and human leukocyte antigen (HLA)

Question 22

Why does transplantation rejection occur?

Answer 22

Inflammatory reactions damage transplanted tissues. This is mediated by the adaptive immune system, and MHC antigens contribute most to the rejection

Question 23

What are the two forms of recognition in transplant rejection?

Answer 23

Direct - T-cells recognise allogeneic MHC molecules in the graft, displayed by donor dendritic cells in the graft
Indirect - graft alloantigens may be processed and presented by the recipients dendritic cells

Question 24

What happens in hyperacute transplant rejection and why does it occur?

Answer 24

Occurs within minutes, there is thrombosis of graft vessels and ischaemic necrosis of transplant
This is due to the presence of preformed antibodies specific for antigens on graft endothelial cells

Question 25

What happens in acute transplant rejection and why does it occur?

Answer 25

This occurs within days or weeks of transplant, as a result of active immune response of recipient, stimulated by alloantigens in the graft. CD8+ cells destroy the graft cells directly

Question 26

How does chronic transplant rejection occur?

Answer 26

Progressive loss of graft function, that may be associated with graft fibrosis, T-cells reacting against graft alloantigens, and some effects from alloantibodies

Question 27

What does chronic inflammation lead to in the tissues?

Answer 27

Tissue remodelling - this is a result of repeated hypersensitivity reactions