Lecture #12

Question 1

What are B1 cells?

Answer 1

Subclass of B lymphocytes belong to the humoral immunity, have IgM BCR that shows polyspecificity with low affinity to many different antigens 
Ex: ant HSP, anti actin, anti dsDNA, anti albumin...

Question 2

Idiotype/ anti idiotype network explain

Answer 2

A network of antibodies produced against antibodies that are potentially autoreactive, many generations of these antibodies will eventually lead to attanuation of the autoimmunity. 
the classes are named: Ab1 - idiotype
Ab2 - anti idiotype
Ab3 - Anti anti idiotype 
etc...

Question 3

Cental tolerance takes placr in the _________ explain

Answer 3

Thymus
Elimination of T cells that recognize MHC molecule + self peptide with high avidity
Negative selection

Low or intermediate avidity T cells are not eliinated in the thymus

Question 4

AIRE

Answer 4

Transcription factor activating all the somatic genes in the mTEC in order for them to be presented to the developing T cells

Question 5

What are the 6 mechanisms of peripheral tolerane?

Answer 5

1. Anergy
2. Ignorance
3. Antigen segregation
4. Cytokine deviation
5. Treg
6. Clonal exhustion

Question 6

Anergy

Answer 6

Without co stimulation from the innate immunity the lymphocye won’t be able to react to the primary signal

Question 7

Igonrance

Answer 7

Low avidity TCR binding won’t evoke a signal

Question 8

Antigen segregation

Answer 8

Potentially self reactive T cells are not activated in immunoprivilaged sites (brain, eye, thyroid, testis, placenta) due to:

1. physical barrier with tight junctions and no lymphatic drainage
2. secretion of anti inflammatory cytokines IL10, TGF beta
3. Induction of apoptosis of the lymphocyte by expression of FasL

Question 9

Cytokine deviation

Answer 9

The activation of Th1 will inhibit Th2 and vise versa
Th1 by secreting IFN gamma
Th2 by secreting IL4, IL10, TGF beta

Question 10

Treg

Answer 10

1. Native Treg (Foxp3+ induced in the thymus in response to self antigens)
2. Induced Treg (Foxp3+ induced by tolerogenic DC upon secretion of TFG beta)
3. Tr1 (Foxp3- present in intestinal tissue and responsible on the production of IL10 to suppress self reactive T cells)

Question 11

Clonal exhaustion

Answer 11

High amoubt of antigen will cause T cell death by Fas- FasL interaction

Question 12

Properties of autoimmune diseases

Answer 12

1. Multifactorial
2. B cell, T cell and immune complex mediated
3. Approx 5% of adult population mainly women
4. Characterized by worsening periods and remissions

Question 13

Genes determining autoimmune suseptibility

Answer 13

HLA
AIRE
C1q, C3, C4
Fas 
Fc gamma RIIB
Genes influencing cytokine exp. 
Genes influencing the exp. of costimulatory molecules (PD1, PD1L, CTLA4)
CD22 (regulatory molecule in mature B cells that limits BCR signal transduction in case of DNA damage)

Question 14

Microbes that may induce autoimmunity

Answer 14

S.pyogenes - RF
Poliovirus - Myasthenia gravis
HIV - RFactor production
Measles virus - anti myelin basic protein