Exam 4: Dr. Thomason Autoimmunity Flashcards
What do immune mediated diseases develop from?
An inappropriate immune system response against cells and tissues normally present in the body
What can inappropriate immune responses to self-antigens lead to?
Many and varied types of diseases
What can disorders involve with immune-mediated diseases?
Specific organs or multiple body systems
What do immune mediated diseases require?
A variety of diagnostic tests and treatment options
What is the key to autoimmunity?
The loss of self-tolerance
What is immunological self-tolerance?
Ability to tolerate self-antigens that encompass the tissues of the body
Potentially auto-reactive T and B lymphocytes met be brought under control
Describe central tolerance
Immature T cells
Must pass 2 tests before exiting the thymus and enter the periphery
Additional safe guards in the periphery
What are the two tests in central tolerance?
Positive selection
Negative selection
Where does positive selection occur?
In the thymic cortex
What is positive selection?
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
What happens with a T cell with a functional TCR?
It passes the test of positive selection and progresses to negative selection
What happens if a T cell does not pass positive selection?
It dies by apoptosis
Where does negative selection occur?
In the thymic medulla
What is negative selection?
Immature T cell must prove that it’s TCR is not capable of responding to these self-antigens with high affinity
What do cells interact with in negative selection?
Thymic DCs that contain self proteins
What happens to TCRs on cells without a high affinity for self-proteins in negative selection?
They pass the test
What happens to TCRs on cells with a high affinity for self-proteins in negative selection?
They fail the test
What happens to T cells that fail negative selection?
They may potentially have auto reactive TCRs and undergo apoptosis
What do positive and negative selection lead to?
Marked loss of cells during intrathymic maturation
What do immature B cells undergo?
A process similar to negative selection
Where do B cells derive?
Bone marrow
Where do the final stages of B cell maturation occur?
Extramedullary locations (Peyer’s patches)
What can interaction of the BCR with self-antigens lead to in receptor editing during B cell maturation?
Deletion or gene rearrangements and expression of a new BCR
In receptor editing, what will happen if the new BCR is not self-reactive?
Cell maturation will continue
In receptor editing, what will happen if the new BCR is self-reactive?
Cell will die
Is immunological self-tolerance 100% effective?
No, some auto-reactive T cells escape clonal deletion and enter peripheral circulation
What are cell that escape the central censorship controlled by?
Apoptosis
Suppression by regulatory T cells
What are regulatory T cells?
Regulatory cells that suppress immune responses of other cells
How are excessive reactions prevented?
By a “self-check” system built into immunity
What is autoimmunity?
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
What is involved in T cell activation?
Tc: Destruction of target cell (NK cells and cytotoxic T cells)
Th1: IL-2 and IFN-γ
Th2: IL-4, 5, 9, 14
What is involved in B cell activation?
Plasma cells that have antibody secretion
How does the activation of Th2 cells contribute to B cell activation and plasma cells?
The ILs that come from it can activate plasma cells
Describe the spectrum of autoimmune diseases
Many and varied immune-mediated diseases
May involve a specific organ or multiple body systems
Both humoral and cellular mechanisms of tissue damage
What are organ specific autoimmune diseases?
Immune reactions to a specific tissue antigen
What are non-organ specific autoimmune diseases?
Immune response to dispersed antigens which leads to systemic deposition of immune complexes
What are examples of organ specific immune-mediated diseases?
Immune-mediated neutropenia, thrombocytopenia, and hemolytic anemia Myasthenia gravis Non-erosive polyarthritis rheumatoid arthritis Discoid lupus erythematosus
What is an example of non-organ specific immune-mediated diseases?
Systemic lupus erythematosus
What are causes of autoimmunity?
Genetic predisposition Infectious diseases Predisposing factors (age, gender, lifestyle, diet) Drugs and vaccines Environmental Hormonal influences Cancer
Describe primary immune-mediated diseases
Absence of any identifiable trigger factor
True immune mediated disease
Diagnosis of exclusion
Describe secondary immune-mediated diseases
Underlying trigger factor
How are normal canine erythrocytes removed?
Via the mononuclear phagocyte system (MPS)
What does the MPS identify?
Antibodies against membrane bound antigens
What is immune-mediated hemolytic anemia?
Premature destruction of erythrocytes
Immune response directly/indirectly targets RBCs
Anti-RBC antibodies bind to RBC membrane
Describe primary IMHA
Idiopathic
No identifiable cause
Predominant form of IMHA
Describe microorganisms as infectious triggers
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
What are causes of secondary immune-mediated diseases?
Inflammation Infection Neoplasia Drugs Tick borne infection Post-vaccination Bee-sting envenomation
What is the most significant trigger for autoimmunity?
Secondary immune-mediate diseases
What is an infectious trigger for secondary immune mediated diseases?
Viral infection
How does a viral infection trigger secondary-immune disease?
Activation of numerous clones of B lymphocytes
Nonspecifically activate B cells and autoantibodies
What do drugs and vaccines do to caue a secondary immune mediated diseases?
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
Describe genetic predisposition in primary immune mediated diseases
Genetic etiology is perpetuated in a population
Gene most strongly linked to autoimmunity (MHC and presenting self antigens to auto-reactive T cells)
