Immuno exam 1 - Dr. Powell

Question 1

What is the difference between peripheral and central tolerance?

Answer 1

Central tolerance: occurs in generative lymphoid organs (BM, thymus) involving mature self reactive lymphocytes recognizing self antigens.

Peripheral tolerance: in peripheral sites involving mature self-reactive lymphocytes encountering self antigen
• is the mechanism by which mature T cells that recognize self antigens in peripheral tissues become incapable of responding to these antigens
• Clonal deletion/apoptosis- Actual elimination from the cellular repertoire by activation induced cell death
• Clonal anergy- mature cell is present but is functionally inactivated (can be reversed)
• Suppression- inhibition of cellular activity through interaction with other cells
• T regs (CD4+/CD25+ T cells, TGF-b or IL-10 secreting reg T cells)
• Ignorance- co-existence of self-reactive clones and antigen; cells do not respond to antigen

Question 2

How is tolerance achieved? What are the mechanisms leading to peripheral and central tolerance in T and B cells?
CENTRAL

Answer 2

Central:
Choice between lymphocyte activation and tolerance is determined by:
• The properties of the antigens
• State of maturation of the antigen-specific lymphocytes
• Types of stimuli received when these
• lymphocytes encounter self antigens

Question 3

How is tolerance achieved? What are the mechanisms leading to peripheral and central tolerance in T and B cells?
PERIPHERAL

Answer 3

Peripheral:
Factors determining which mechanism(s) are operative:
• Concentration of self antigen in generative lymphoid organs
• Affinity of antigen receptor for antigen
• Nature of antigen
• Concentration and availability of co-stimulatory molecules
• Suppression vua T cell mediation (T regulatory cells)
• Apoptosis if…
o Activation in the absence of IL-2 can lead to death
o Persistent Ag
o Activation-induced cell death

Question 4

Can tolerance be induced? What would be an advantage of induced tolerance?

Answer 4

Yes;
• Foreign antigens may be administered in ways that preferentially induce tolerance rather than immune responses
o Protein antigens administered subcutaneously or intradermally with adjuvants favor immunity
o High doses of antigens administered systemically without adjuvants tend to induce tolerance

Question 5

Oral tolerance:

Answer 5

• Oral administration of Ag favors tolerance induction
• A state of immune hyporesponsiveness follows oral administration of an antigen
• Responsible for maintenance of homeostasis
o No immune response to food antigenslack of toxicity, ease of administration over time, and antigen-specific mechanisms of actiono MS (glatiramer acetate/cop1 - resembles human myelin (4 a.a)
o Uveitis (peptide B27PD – resembles retinal autoantigen protein)
o Type 1 Diabetes (Human insulin)

Question 6

What are some of the factors that contribute to the development of autoimmune disease?

Answer 6

•	Occurs when the immune system becomes dysregulated and attacks the organs it is designedto protect
•	Results when central and peripheral tolerance is broken 
Some factors that can predispose an individual to various autoimmune diseases
•	MHC associations
•	Familial concordance
•	Gender
o	Women>men
o	RA worse in women
o	MS worse in men
•	Climate
•	Chemical Agents
•	Infectious Agents
•	Immune Dysregulation

Question 7

What initiates an autoimmune response?

Answer 7

• Incomplete deletion of self reactive cells
• Aberrant stimulation of “normally” anergic self reactive cells
• Altered regulation of anergic self reactive cells

Question 8

How does central and peripheral tolerance relate to the development of autoimmunity?

Answer 8

Need to have regulatory functions to counteract autoimmune responses.