Lecture 32 (Autoimmunity)

the body needs to respond to foreign antigens and not to self antigens, so what is the body's solution to that issue?

self-tolerance!!

the anemia and skin lesions associated with SLE are caused by which hypersensitivity?

type II hypersensitivity

what is the most common test used to help in the diagnosis of SLE?

ANA test (antinuclear antibodies)

the glomerulonephritis and arthritis associated with SLE are cause by which hypersensitivity?

type III hypersensitivity

self-tolerance occurs in both __ and ___ cells

B and T-cells

what is self-tolerance?

the lack of immune response to self antigens

what are the two types of self-tolerance?

central tolerance and peripheral tolerance

immature self-reactive lymphocytes die or alter specificity

a) central tolerance
b) peripheral tolerance

a) central tolerance

central tolerance occurs in the ______ and ______ _______

thymus and bone marrow

mature self-reactive lymphocytes die, are turned off, or are suppressed by T-regulatory cells

a) central tolerance
b) peripheral tolerance

b) peripheral tolerance

peripheral tolerance is maintained in ______ _______ and __________

lymph nodes and circulation

___ cells need exposure to self antigens within bone marrow

B-cells

central tolerance occurs via what two mechanisms?

-clonal anergy
-clonal deletion

what is clonal anergy?

soluble self-antigen leads to anergy of cell without cross-linking of lymphoid receptor

what is clonal deletion

cross-linking of lymphoid receptor (sIg) with self-antigen leads to apoptosis (clonal deletion)

where do T cells mature?

thymus

where do B cells mature?

bone marrow

T cells:

clonal deletion: those that react strongly with self-antigens

a) negative selection

b) positive selection

a) negative selection

T cells:

those that react weakly are selected

a) negative selection

b) positive selection

b) positive selection

B cells primarily use __________________ in central tolerance

a) clonal deletion
b) clonal anergy

b) clonal anergy

T cells primarily use ___________________ in central tolerance

a) clonal deletion
b) clonal anergy

a) clonal deletion

what is special about Tregs in regards to their activation by antigen?

1. can be activated without co stimulation
2. can be activated by smaller amounts of antigen

what are the 4 mechanisms of peripheral tolerance?

-immuno-privileged organs
-clonal anergy
-clonal deletion
-suppression

absence of T-cell costimulation = ?

anergy

insufficient antigen exposure can lead to _________

anergy

______ is a "death receptor" expressed by all cells

Fas

Fas/FasL interactions = ?

apoptosis

one way to eliminate T or B cells responding to self peptide is for another responding T cell to engage ______ ligand on the autoreactive cells

Fas

mutations in Fas and/or Fas ligand in humans result in...

Auto-immune Lymphoproliferative Syndrome (ALPS)

what is the phenotype for T regulatory cells

CD4+CD25+Foxp3+

________ is the alpha chain of IL-2 receptor

CD25

do normal B cells or Treg cells recognize self antigens? why?

*Treg cells do recognize self antigens because they have an immuno-suppressive role

B cells do not recognize self antigens because that would be a breakage of self-tolerance

-auto-antibodies are found in normal, healthy patients
-antibodies against proteins in aged RBCs for removal
-may detect auto-antibodies following infections

a) non-pathogenic autoimmunity
b) pathogenic autoimmunity

a) non-pathogenic autoimmunity

associated with either normal or abnormal immune response

a) non-pathogenic autoimmunity
b) pathogenic autoimmunity

b) pathogenic autoimmunity

what is an example of a normal immune response in the context of mechanisms of autoimmunity?

when newly exposed self-antigens are targeted by our immune system

*usually following trauma or illness that exposed the privileged sites' antigens

what are the 4 main types of an abnormal immune response in the context of mechanisms of autoimmunity?

1. cytokine dysregulation
2. loss of suppression activity
3. genetic defect
4. molecular mimicry

-Rheumatic fever
-stimulates antibody that cross reacts with cardiac, joints, and kidney tissue
-can stimulate B cells or T cells
this is a classic example of which abnormal immune response in autoimmunity:

a) Cytokine dysregulation
b) Loss of suppression activity (no Tregs)
c) Genetic defect (missing Fas/FasL)
d) Molecular mimicry

d) Molecular mimicry

what are the 3 predisposing factors to getting autoimmune diseases?

-genetic predisposition (MOST IMPORTANT)
-breed predisposition
-intestinal microflora

in the context of autoimmunity and tissue damage from hypersensitivity reactions, which type is least common?

type I hypersensitivity

Acute Rheumatic fever is an example of which hypersensitivity?

type II hypersensitivity

auto-antibodies bind to self proteins is an example of which type of hypersensitivity?

type II hypersensitivity/type II immune reactions

IMHA is an example of ________ hypersensitivity

type II

auto-antibodies form immune complexes with self antigens and create inflammation and resultant tissue injury is an example of which type of hypersensitivity?

type III hypersensitivity

which of the following is a type IV hypersensitivity issue:

a) SLE
b) Rheumatic Fever
c) Type 1 diabetes
d) Glomerulonephritis

c) Type 1 diabetes

for suspected autoimmune hemolytic anemia which test would be indicated:

a) Coombs test or slide/saline agglutination
b) ANA test

a) Coombs test or slide/saline agglutination

for suspected SLE which would be indicated:

a) Coombs test or slide/saline agglutination
b) ANA test

b) ANA test

in Myasthenia gravis your body makes antibodies against what?

a) Acetylcholine
b) Acetylcholine receptors
c) Myasthenia
d) gravis

b) Acetylcholine receptors