Immunological tolerance and Autoimmune disease

Question 1

what is immunological tolerance

Answer 1

failure to repsond to an antigen

Question 2

Is immunological tolerance an active or passive response ?

Answer 2

Active and specfic response to particular epitope

Question 3

what are the 2 broad types of immunological tolerance

Answer 3

• natural “self” tolerance

- induced tolerance

Question 4

why is natural tolerance a good thing ?

Answer 4

This is what tells the immune system to not attack body’s own proteins and self/antigens
if they do attack self-Ag = autoimmune disease

Question 5

what is the most important concept to remember about tolerance

Answer 5

self-tolerance

-prevents body from mounting immune response on its tissues

Question 6

what is the diff. b/w central and peripheral tolerance

Answer 6

central - occurs in the organs where lymphocytes dev. so involves immature lymphocytes
peripheral - occurs at peripheral sites involving mature lymphocytes

Question 7

In what organs do B and T cells develop and mature

Answer 7

B cells - bone marrow

T cells - thymus

Question 8

when a lymphoid progenitor cell encounters a self-Ag in the thymus, it can undergo Positive or Negative selection. What is the difference b/w these

Answer 8

Positive selection of T cell - progenitor cell binds MHC and binds self-Ag w/low avidity
Negative selection - progenitor cell binds MHC BUT binds self-Ag w/high avidity

Question 9

what part of the thymus does positive selection occur

Answer 9

cortex region

Question 10

what part of the thymus does negative selection occur

Answer 10

medulla region

Question 11

the basis of central tolerance follows what strategy

A) negative selection or B) positive selection

Answer 11

A ) negative selection

-b/c if bind to self-Ag then its deleted via apoptosis

Question 12

In certain cases there are some self-reactive ______ t cells that are NOT deleted, but instead differentiate into ______ T cells

Answer 12

CD4 helper t cells

-become regulatory t cells

Question 13

Peripheral tolerance in T cells occurs if an auto-reactive T cell escapes the thymus, and becomes mature. When this mature t cell binds self-Ag what 4 mechanism can occur ?

Answer 13

1 - Deletion
2 - Anergy
3 -Supression
4 - Ignorance

Question 14

what is T cell clonal anergy, a mechanism of peripheral tolerance

Answer 14

cell becomes non active, b/c co-stimulatory molecule activation is down regulated

Question 15

what molecules are neccesary for normal co-stimulatory molecule activation

Answer 15

CD28 binds to B7

Question 16

what molecules cause co-stimulatory activation to be downregulated in anergy, a mechanism of peripheral tolerance

Answer 16

CTLA-4 competes with CD28 ….. thus CTLA-4 binds to B7

CTLA-4 binds w/higher affinity than CD28

Question 17

what is T cell suppression, a mechanism of peripheral tolerance

Answer 17

inhibition of cell activity (can inhibit in various ways)

Question 18

in T cell supression, there are 3 ways in which the t cell activity can be inhibited. What are they ?

Answer 18

1 - inhibit Ag recognition
2 - inhibit proliferation
3 - inhibit effector functions

Question 19

T cell ignorance, a mechanism of peripheral tolerance, is also known as ?

Answer 19

passive tolerance

-simply a RARE nonresponsiveness of t cell

Question 20

what can cause t cell ignorance (mechanism of peripheral tolerance) ?

Answer 20

• sequestered Ag
• Ag not expressed on MHC molecules
• Ag cant get across some sort of barrier

Question 21

Central tolerance in B cells occurs differently than in T cells. If lymphiod progenitor cells bind a self-Ag w/high avidity, what 2 things can happen

Answer 21

1 - deletion (basis of central tolerance)

2 - receptor editing

Question 22

what is receptor editing ?

Answer 22

it is the process of restructuring the gene segments on the B receptor, in an attempt to make them NOT bind to self-Ag w/high avidity

Question 23

what are the 2 outcomes of receptor editing in B cells

Answer 23

• still bind self-Ag w/high avidity = deletion

- bind w/self-Ag w/low avidity = maturation

Question 24

_____ and ______ of the self-Ag determine the fate of B cells survival

Answer 24

nature (multivalent Ag) and concentration

Question 25

High concentrations of self-Ag would induce B cell ______, whereas low concentrations of self-Ag would induce __________.

Answer 25

high = apoptosis
low = anergy

Question 26

T/F Self reactive B cells never escape the bone marrow, so there is no need for B cell peripheral tolerance ?

Answer 26

F, there is B cell peripheral tolerance

Question 27

In order for B cells to become activated, they need the assistance of what cells ?

Answer 27

Helper T cells

Question 28

How do Helper T cells affect the outcome of B cell activation in the periphery ?

Answer 28

Two signal Hypothesis

* B cells need both signals to become activated*

Question 29

what are the signals that Helper T cells provide to B cells in the Two Signal Hypothesis

Answer 29

Signal 1 - Via Ag receptor

Signal 2 - Via CD40 and CD40L

Question 30

what is the result of the B cell only recieves ONE of the signals from the T cell ?

Answer 30

Result in B cell anergy

Question 31

administering foreign Ag can preferentially result in “induced tolerance.” What are 3 of the most common administering routes to get induced tolerance.

Answer 31

• Oral tolerance
• Ag administered subcutaneously
• Ag administered intradermally

Question 32

Usually, a state of immune _____________ follows oral administration of an Ag

Answer 32

hyporesponsiveness

Question 33

in general how do autoimmune diseases result ?

Answer 33

when central and peripheral tolerance is BROKEN

Question 34

there are many factors that can predispose an individual for an autoimmune disease, these vary greatly amongst individuals, what are some of these factors ?

Answer 34

• genetics
• gender
• environment (climate)
• immune regulation (or there of)

Question 35

autoimmune diseases can differ b/w gender, in what two ways ?

Answer 35

• Incidence (women get more typically)

- severity (differs b/w diseases)

Question 36

incomplete deletion of self reactive cells, and/or altered regulation which stimulates previously anergic self-reactive cells are both common ways to do what ?

Answer 36

initiate and autoimmune response

Question 37

what are the 2 theories of what activates autoimmunity

Answer 37

Induction of costimulators on APC (bystander activation)

Molecular mimicry

Question 38

what are the 2 categories of autoimmune disease, and what is a example disease of each

Answer 38

systemic

organ specific

Question 39

Lupus (SLE) and Rheumatoid arthritis R(A) are both examples of what category of autoimmune disease ? What about multiple sclerosis (MS) and Insulin Dep. Diabetes Mellitus (IDDM) ?

Answer 39

Systemic - Lupus and RA

Organ specific - MS and IDDM

Question 40

what are some characterisitics of SLE, a systemic autoimmune disease

Answer 40

• multisystem disorder
• 10:1 female predominance
• onset b/w 15-25
• multiple sympotms making hard to diagnose

Question 41

what are some characteristics of MS, an organ specific autoimmune disease

Answer 41

• most common inflammatory disease of CNS
• 3:2 female predominance
• loss of myelin and depletion of oligodendrocytes which impairs nerve conduction

Question 42

what are the two ends of the spectrum of autoimmune disease, and how do they relate to each other

Answer 42

systemic(non organ specific) vs. organ specific

* ind. may develop more than one autoimmune disease but will NOT be one from opposite sides of spectrum*