Autoimmunity Flashcards
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
The key to autoimmunity is the ______
Loss of self tolerance
Immunological self tolerance
Ability to tolerate self-antigens that encompass the tissues of the body
Central tolerance
Immature T cells
- must pass positive and negative selection in the thymus before entering the periphery
Positive selection
Occurs in the thymic cortex
- immature T cell must prove that it has a TCR capable of interacting with a peptide antigen presented by MHC
- T cells that do not pass die by apoptosis
Negative selection
Occurs in the thymic medulla
- immature T cell must prove that it’s TCR is not capable of responding to self-antigens with high affinity
- cells interact with thymic DC that contain self-proteins
TCRs ____ a high affinity for self-proteins pass the test
Without!
Maturation of B cells
Immature B cells undergo similar process to negative selection
- derive in the bone marrow, final stages occur in extramedullary locations (ex: Peyer’s patches)
Receptor editing
Interaction of BCR with self-antigens may lead to deletion or gene rearrangements and expression of a new BCR
- if new BCR is NOT self reactive, cell maturation will continue
Peripheral tolerance
Occurs in peripheral lymphoid organs
- cells that escape central censorship are controlled by apoptosis and Tregs
Tregs
Regulatory cells that suppress immune responses of other cells
T cell activation
- Tc: destruction of target cell (NK and cytotoxic T cells)
- Th1: IL-2, IFN-gamma
- Thj2: IL-4, IL-5, IL-9, IL-14
B cell activation
Plasma cells –> antibody secretion
Autoimmune diseases may involve
Specific organs or multiple body systems and both humoral and cellular mechanisms of tissue damage
Organ specific
Immune reactions to a specific tissue antigen
Non-organ specific
Immune response to dispersed antigens which leads to systemic deposition of immune complexes
Autoimmune diseases are more common in ____
Dogs
- less common in cats/horses
- sporadic in production animals
Autoimmunity causes
- genetic predisposition
- infectious diseases
- predisposing factors (age, gender, etc)
- drugs, vaccines
- environmental
- hormonal influences
- cancer
Primary
Absence of any identifiable trigger factor
- idiopathic
- true immune mediated disease
- diagnosis of exclusion
Secondary
Underlying trigger factor
- need to get rid of secondary cause to treat
Mononuclear phagocyte system
Removes old erythrocytes in the liver and spleen
- identifies antibodies against membrane bound antigens
IMHA
Premature destruction of erythrocytes
- immune response directly/indirectly targets RBCs
- anti-RBC antibodies bind to RBC membrane
Primary IMHA
Predominant form
- idiopathic
- immune response to self-antigens –> antibodies cover RBC –> gets destroyed by macrophages
Extravascular hemolysis
Secondary
- antibodies are directed against foreign antigens located inside RBC
- end product is the same as primary = RBC destruction
MIcroorganisms
Infects or attaches to membrane of host cell
- cell surface expression of microbial antigen
- appropriate immune response
- non specifically destroys the host cell
Secondary immune-mediated disease causes
- inflammation
- infection
- neoplasia
- drugs
- tick borne infection
- post vaccination
- bee sting
Infectious triggers
Most significant trigger for autoimmunity
- immediately after infection or lag time
- viral infection: activation of numerous clones of B cells, or non specifically activate B cells and autoantibodies
Drugs and vaccines
Act as a hapten, binds to membrane of a cell to form a target of an immune response
- may modify the structure of a self-protein
Secondary immune mediated treatment
Treat underlying condition
- supportive care
- immunosuppressive therapy
Genetic predisposition
Genetic etiology is perpetuated in a population
- gene most strongly linked to autoimmunity - MHC, presenting self-antigens to auto-reactive T cells
Intravascular hemolysis
Antibodies AND complement coats the RBC = osmotic cell lysis
