Autoimmunity and Hypersensitivity

Question 1

What is an autoimmune disease

Answer 1

A failure or breakdown of immune system that maintains tolerance to self tissues, loss of tolerance is probably due to abnormal selection or lack of control of self-reactive lymphocytes (B and T-cells)

Question 2

How may damage in different autoimmune diseases result

Answer 2

from different effector mechanisms

Question 3

2 risk factors

Answer 3

environmental and genetic (normaly both cause it)

Question 4

treating autoimmune disease

Answer 4

• blanket immunosuppression (stops immune system)= side effects e.g. infection
• targeted selective approach= target the aberrant immune activation while leaving the rest of the immune system intact

Question 5

hypersensitivity responses

Answer 5

*Hyper response from the immune system causes autoimmunity
*Harmful immune responses that may produce tissue injury and cause serious disease
*4 categories: Type I, II, III, IV (V)
*Type I, II (V), and III, are antibody mediated while type IV is T cell mediated
*Autoimmune diseases usually fall into Type II, III, and IV categories depending on the type of damage associated with the disease
*Type 1 associated with allergy

Question 6

type I hypersensitivity

Answer 6

IgE mediated
1. first exposure to allergen
2. activation of TFH cells and stimulation of IgE class switching in B cells
3. production of IgE
4. binding of IgE to FcęRI on mast cells
5. repeated exposure to allergen
6. activation of mast cells: release of mediators- can be immediate or late-phase reaction

Important in allergy but also give rise to autoimmunity

Question 7

immediate immune response in allergy

Answer 7

*Immediate reaction
*IgE mediated effects
*Vasodilation, oedema and vascular congestion
Is type 1

Question 8

late-phase immune response in allergy

Answer 8

*Late reaction
*Eosinophil, neutrophil and T cell infiltrates

Question 9

Type 1 effects

Answer 9

Mast cell:
* Vasodilation
* Vascular leak
* Broncho-constriction
* Intestinal hypermobility
* Inflammation
* Tissue damage

Eosinophil:
* Killing of parasites and host cells
* Tissue damage

Question 10

atopy

Definition + clinical consequence

Answer 10

Aa predisposition to an immune response against diverse antigens and allergens (allergy)
Clinical consequence= increased propensity to hypersensitivity reactions

Question 11

type II hypersensitivity

Answer 11

labeled cytotoxic/ cytolytic & involve IgM or IgG interacting with foreign cells to cause their destruction (cell lysis), such as when donor blood is rejected or Rh mother forms antibodies against Rh+ fetus

Injury caused by anti-tissue antibody

Question 12

type III hypersensitivity

Answer 12

labeled immune complex; antigens combine with antibodies and deposit in tissues & blood vessels, causing inflammation & tissue destruction

Immune complex-mediated tissue injury

Question 13

type IV hypersensitivity

Answer 13

T cell (cytokine) mediated-> cell killing and tissue injury

Question 14

T-cell mediated immunologic disease

Answer 14

• type 1 diabetes; [T cell specificity= islet cell antigens (GAD65, insulin)]
• rheumatoid arthritis; [T cell specificity= Joint synovial antigen (Type 2 collagen)]
• multiple sclerosis; [T cell specificity= Myelin basic protein (MOG PLP)]

Question 15

genetic risk factors

Answer 15

• Genetic background of an individual may pre-dispose them to an autoimmune disease
• Complex, multi-factorial, and by no means the whole story - there are risk factors that are independent of genetic background

Question 16

environmental risk factors

Answer 16

• most likely by far is prior infection
• Other factors may include drugs, trauma, food

Question 17

immunological tolerance

Answer 17

State of unresponsiveness to specific antigen:
* Antigens can be self or foreign
* Prevents adaptive responses that are damaging (immune pathology)= B cells and T cells
* Can be exploited by microbes and tumours
* Pregnancy, transplantation, autoimmune disease and cancer

Question 18

Challenge of immunological tolerance

Answer 18

T cell pool: autoimmunity OR productive immunity (want this but need to control only self-recognising mechanisms)

Question 19

examples of autoimmune disease

2 types

Answer 19

• systemic
• organ specific

Question 20

systemic autoimmune disease

Answer 20

• Autoimmune process is diffuse is spread throughout the body
• Affects more than one organ - not necessarily the same ones in different individuals
• Mozaics of disease

Question 21

organ specific autoimmune disease

Answer 21

• Autoimmune process directed against one organ
• Type 1 Diabetes - pancreas
• Autoimmune Thyroiditis
• Clear certain organ is being targeted

Question 22

what are hypersensitivity responses

Answer 22

damaging responses produced during normal immune responses

Question 23

what can chronic activation lead to

Answer 23

autoimmune disease - different effector mechanisms influence the disease phenotype

Question 24

Autoimmune disease

Answer 24

Failure or breakdown of immune system that maintains tolerance of self tissues
Loss of tolerance is probs due to abnormal selcetion or lack of control of self-reactive lymphocytes (B and T-cells)

Question 25

relationship between igE and igG and fc receptors

Answer 25

Yeah not sure, but is learning outcome… google? :)

Question 26

differences between type II and III antibody mediated hypersensitivity

Answer 26

type 2 and type 3 hypersensitivity both result from the same class of antibody, called IgG. The difference between them lies in the form of antigens that generate a response. Additionally, type 2 can also involve IgM antibodies.

Question 27

type 1 results from which class of antibody

Answer 27

IgE

Question 28

Define immune tolerance

(brief)

Answer 28

state of unresponsiveness to specific antigens