Exam 4: Dr. Thomason Autoimmunity

Question 1

What do immune mediated diseases develop from?

Answer 1

An inappropriate immune system response against cells and tissues normally present in the body

Question 2

What can inappropriate immune responses to self-antigens lead to?

Answer 2

Many and varied types of diseases

Question 3

What can disorders involve with immune-mediated diseases?

Answer 3

Specific organs or multiple body systems

Question 4

What do immune mediated diseases require?

Answer 4

A variety of diagnostic tests and treatment options

Question 5

What is the key to autoimmunity?

Answer 5

The loss of self-tolerance

Question 6

What is immunological self-tolerance?

Answer 6

Ability to tolerate self-antigens that encompass the tissues of the body
Potentially auto-reactive T and B lymphocytes met be brought under control

Question 7

Describe central tolerance

Answer 7

Immature T cells
Must pass 2 tests before exiting the thymus and enter the periphery
Additional safe guards in the periphery

Question 8

What are the two tests in central tolerance?

Answer 8

Positive selection

Negative selection

Question 9

Where does positive selection occur?

Answer 9

In the thymic cortex

Question 10

What is positive selection?

Answer 10

Immature T cell must prove that it has created a TCR capable of interacting with a peptide antigen presented to that T cell by an MHC molecule

Question 11

What happens with a T cell with a functional TCR?

Answer 11

It passes the test of positive selection and progresses to negative selection

Question 12

What happens if a T cell does not pass positive selection?

Answer 12

It dies by apoptosis

Question 13

Where does negative selection occur?

Answer 13

In the thymic medulla

Question 14

What is negative selection?

Answer 14

Immature T cell must prove that it’s TCR is not capable of responding to these self-antigens with high affinity

Question 15

What do cells interact with in negative selection?

Answer 15

Thymic DCs that contain self proteins

Question 16

What happens to TCRs on cells without a high affinity for self-proteins in negative selection?

Answer 16

They pass the test

Question 17

What happens to TCRs on cells with a high affinity for self-proteins in negative selection?

Answer 17

They fail the test

Question 18

What happens to T cells that fail negative selection?

Answer 18

They may potentially have auto reactive TCRs and undergo apoptosis

Question 19

What do positive and negative selection lead to?

Answer 19

Marked loss of cells during intrathymic maturation

Question 20

What do immature B cells undergo?

Answer 20

A process similar to negative selection

Question 21

Where do B cells derive?

Answer 21

Bone marrow

Question 22

Where do the final stages of B cell maturation occur?

Answer 22

Extramedullary locations (Peyer’s patches)

Question 23

What can interaction of the BCR with self-antigens lead to in receptor editing during B cell maturation?

Answer 23

Deletion or gene rearrangements and expression of a new BCR

Question 24

In receptor editing, what will happen if the new BCR is not self-reactive?

Answer 24

Cell maturation will continue

Question 25

In receptor editing, what will happen if the new BCR is self-reactive?

Answer 25

Cell will die

Question 26

Is immunological self-tolerance 100% effective?

Answer 26

No, some auto-reactive T cells escape clonal deletion and enter peripheral circulation

Question 27

What are cell that escape the central censorship controlled by?

Answer 27

Apoptosis | Suppression by regulatory T cells

Question 28

What are regulatory T cells?

Answer 28

Regulatory cells that suppress immune responses of other cells

Question 29

How are excessive reactions prevented?

Answer 29

By a "self-check" system built into immunity

Question 30

What is autoimmunity?

Answer 30

Failure of self-tolerance to eliminate self-reactive T and B lymphocytes into circulation Presentation of an auto-antigen by APC allowing excessive activation of T cells

Question 31

What is involved in T cell activation?

Answer 31

Tc: Destruction of target cell (NK cells and cytotoxic T cells) Th1: IL-2 and IFN-γ Th2: IL-4, 5, 9, 14

Question 32

What is involved in B cell activation?

Answer 32

Plasma cells that have antibody secretion

Question 33

How does the activation of Th2 cells contribute to B cell activation and plasma cells?

Answer 33

The ILs that come from it can activate plasma cells

Question 34

Describe the spectrum of autoimmune diseases

Answer 34

Many and varied immune-mediated diseases May involve a specific organ or multiple body systems Both humoral and cellular mechanisms of tissue damage

Question 35

What are organ specific autoimmune diseases?

Answer 35

Immune reactions to a specific tissue antigen

Question 36

What are non-organ specific autoimmune diseases?

Answer 36

Immune response to dispersed antigens which leads to systemic deposition of immune complexes

Question 37

What are examples of organ specific immune-mediated diseases?

Answer 37

``` Immune-mediated neutropenia, thrombocytopenia, and hemolytic anemia Myasthenia gravis Non-erosive polyarthritis rheumatoid arthritis Discoid lupus erythematosus ```

Question 38

What is an example of non-organ specific immune-mediated diseases?

Answer 38

Systemic lupus erythematosus

Question 39

What are causes of autoimmunity?

Answer 39

``` Genetic predisposition Infectious diseases Predisposing factors (age, gender, lifestyle, diet) Drugs and vaccines Environmental Hormonal influences Cancer ```

Question 40

Describe primary immune-mediated diseases

Answer 40

Absence of any identifiable trigger factor True immune mediated disease Diagnosis of exclusion

Question 41

Describe secondary immune-mediated diseases

Answer 41

Underlying trigger factor

Question 42

How are normal canine erythrocytes removed?

Answer 42

Via the mononuclear phagocyte system (MPS)

Question 43

What does the MPS identify?

Answer 43

Antibodies against membrane bound antigens

Question 44

What is immune-mediated hemolytic anemia?

Answer 44

Premature destruction of erythrocytes Immune response directly/indirectly targets RBCs Anti-RBC antibodies bind to RBC membrane

Question 45

Describe primary IMHA

Answer 45

Idiopathic No identifiable cause Predominant form of IMHA

Question 46

Describe microorganisms as infectious triggers

Answer 46

Infects or attach to the membrane of a host cell Cell surface expression of the microbial antigen Appropriate immune response Nonspecifically destroys the host cell

Question 47

What are causes of secondary immune-mediated diseases?

Answer 47

``` Inflammation Infection Neoplasia Drugs Tick borne infection Post-vaccination Bee-sting envenomation ```

Question 48

What is the most significant trigger for autoimmunity?

Answer 48

Secondary immune-mediate diseases

Question 49

What is an infectious trigger for secondary immune mediated diseases?

Answer 49

Viral infection

Question 50

How does a viral infection trigger secondary-immune disease?

Answer 50

Activation of numerous clones of B lymphocytes | Nonspecifically activate B cells and autoantibodies

Question 51

What do drugs and vaccines do to caue a secondary immune mediated diseases?

Answer 51

Acts as a happen, binds to the membrane of a cell to form a target of an immune response May modify the structure of a protein

Question 52

Describe genetic predisposition in primary immune mediated diseases

Answer 52

Genetic etiology is perpetuated in a population | Gene most strongly linked to autoimmunity (MHC and presenting self antigens to auto-reactive T cells)