Chapter 15: Autoimmunity and Transplantation

Question 1

What is autoimmunity? What is xenoimmunity and alloimmunity?

Answer 1

• Immune system targets self antigens
• Xenoimmunity: immune system targets microbiota
• Alloimmunity: immune system targets transplanted tissue

Question 2

What are some examples of autoimmune diseases and what is their prevalence?

Answer 2

Question 3

What are the layers of self-tolerance?

Answer 3

Question 4

What is negative selection?

Answer 4

• Medullary epithelial cells express tissue specific proteins that are found outside the thymus to present to the T cells
• Controlled by the gene AIRE (autoimmune regulator)

Question 5

What is immunological ignorance?

Answer 5

• Lymphocytes that bind self antigens with relatively low affinity usually ignore them
• But some circumstances become activated when the threshold for lymphocyte activation is sufficiently reduced

Question 6

How is the costimulatory signal sent out using B cell receptors and DNA?

Answer 6

• B cells have low affinity for DNA can escape deletion in the bone marrow and persist in the periphery bit are not normally activated
• When extensive cell death occurs under conditions of inadequate clearance of apoptotic fragments, these B cells can bind and internalize the DNA
• TLR-9 recognizes unmethylated CpG sequences in DNA found in the mitochondria
  
  • Provides the Costimulatory signal for B cell activation

Question 7

How would the body respond to trauma to the eyes?

Answer 7

• Release of intraocular protein antigens carried to a lymph node and activates T cells. Effector T cells return via bloodstream and encounter antigen in both eyes

Question 8

What are immunologically privileged sites?

Answer 8

• certain sites in the body that do not mount an immune response against tissue allografts
• Can be due to both physical barrier to cell and antigen migration and the presence of immunosuppressive cytokines
• Damage to an immunologically privileged site can induce an autoimmune response

Question 9

What is molecular mimicry?

Answer 9

• Pathogens express antigens that are similar but not identical to host molecules which can result in antibodies that cross react with those host molecules

Question 10

How can autoimmune reactions be regulated?

Answer 10

• Controlled by various stages by regulatory T cells
• Regulatory cells can suppress auto reactive lymphocytes that recognize a variety of different self antigens, as long as antigens are from the same tissue or are presented by the same APC

Question 11

What are the two classifications of autoimmune diseases? What are some examples?

Answer 11

• Organ specific or systemic disease

Question 12

How are some common autoimmune diseases classified by immunopathogenic mechanisms?

Answer 12

• Antibody against cell-surface or matrix antigens
• Immune complex diseases
• T cell mediated diseases

Question 13

What are 4 autoimmune diseases involved in aspects of the immune response?

Answer 13

• Systemic lupus, T1 diabetes, Myasthenia, and multiple sclerosis

Question 14

What is autoimmune hemolytic anemia?

Answer 14

• Antibodies target red blood cells
• Can occur at warm temperatures above the body’s natural temperature or when exposed to cold temperatures
• Causes are not well understood, occurs after infections, cancers or along other autoimmune disorders

Question 15

What is multiple sclerosis?

Answer 15

• Immune system destroys myelin sheaths structure
• TH1 and TH17 cells are primarily associated with pathogenesis
  Symptoms:
• Blurred/ double vision
• Red green color distortion
• Pain and loss of vision due to swelling of optic nerve
• Trouble walking and difficulty with balance
• Numbness, prickling, or pins and needles
  Causes:
• Unknown possible various factors contribute to development of MS

Question 16

What are the survival rates for organ transplantations?

Answer 16

Question 17

How does transplantation rejection occur?

Answer 17

• Mediated by T response to MHC molecules
• To increase success rate, MHC molecules must match between donor and recipient
• Very difficult to find a perfect MHC match, the greater the MHC match the less sever the reaction is
• Medication that induces immunosuppresive state helps
• Acute rejection - the rejection of tissue after 10-13 days cannot be prevented unless immunosuppressive treatment is done

Question 18

What results in identical MHC grafts being rejected?

Answer 18

• Peptides from other alloantigens bound to graft MHC molecules
• Self-proteins that are presented on MHC molecules are different between donor and recipient
• Minor histocompatability antigens
• Rejection is not as rapid but immunosuppressive drugs are still required to prevent organ damage

Question 19

What is direct allorecognition?

Answer 19

• Host T cell recognition of donor APCs directly without antigen processing
• Occurs in the graft itself or upon the migration of donor APCs from the graft regional lymph node

Question 20

What is indirect allorecognition?

Answer 20

• Recipient’s APC process and present the alloantigens to T cells
• Antigens presented include peptides derived from the minor H antigens and from allogeneic HLA class I and class II allotypes

Question 21

What is hyperacute rejection?

Answer 21

• Preformed antibodies react with endothelium
• Immediate reaction
• Activates complement and blood clotting cascade leads to damage
• Preformed antibodies include those that target blood group antigens and polymorphic MHC molecules

Question 22

What is late failure of a transplanted organ?

Answer 22

• Caused by chronic injury to graft
• Chronic allograft vasculopathy
• Arteriosclerosis of graft blood vessels, which leads to hypoperfusion of the graft and its eventual fibrosis and atrophy

Question 23

What are the targets of immunosuppressive drugs that are used in organ transplantation?

Answer 23