Diseases of Immunity 1 Lecture Flashcards
Define autoimmune disease
Illnesses which occur when body’s tissues are attacked by its own immune system
Requirements for autoimmune disease?
Presence of an immune reaction specific for some self-antigen or self-tissue
Evidence that such a reaction is not secondary to tissue damage but is of primary pathogenic significance
Absence of another well-defined cause
Similarity with experimental animal models of proven autoimmunity
Define Type 1 Diabetes
Appears to be the result of an autoimmune attack on the islet cells of the pancreas
Define Good Pasture’s Syndrome
Antibodies to basement membranes of lung and kidney induce lesions in these organs
What are systemic or generalized disease?
Systemic Lupus Erthematosus
What are organ-specific diseases?
Type 1 Diabetes
Multiple Sclerosis
Goodpasture’s Syndrome
Define tolerance
is the phenomenon of unresponsiveness to an antigen as a result of exposure of lymphocytes to that antigen
Define self-tolerance
Refers to lack of responsiveness to an individual’s own antigens, an it underlies our ability to live in harmony with our cells and tissues
Define central tolerance
immature self-reactive T and B lymphocytes clones that recognize self-antigens during their maturation in the lymphoid organs are killed or rendered harmless
Where are T and B cell maturated?
Thymus and bone marrow
What is negative selection or deletion?
Killing my apoptosis or deletion
What is AIRE?
Autoimmune Regulator
Present host antigens to the T cells
What is regulatory T cells?
Self-recognizing T cells that get out before being killed
- Turn down immune responses
- Promote tolerance
What is B cell receptor editing or apoptosis?
B cells that encounter self-antigen but does not die, it is edited to not recognize self-antigen
Define Anergy
Prolonged or irreversible functional inactivation, induced by encounter with antigens under certain conditions
- Lack of second signal
- Inhibitory second signal (CTLA4)
(affects B cells too)
What is suppression by regulatory T cells?
Specific CD4+ T cells (express CD25 and Foxp3)
Require IL2 to surviveSecrete immunosuppressive cytokines as IL10 and TGF-beta
What is deletion by activation-induced cell death?
CD4+ T cells that recognize self-antigens may receive signals promoting their death by apoptosis (cell activation induced cell death)
How does autoimmunity arise from a combination of?
- Inheritance of susceptibility gens (which may contribute to breakdown of self-tolerance)
- Environmental triggers (infections and tissue damage, which promote the activation of self-reactive lymphocytes
With both of these there is imbalance
What does microbes expressing B7 do?
B7 binds to CD28 on self-reactive T cells leading to autoimmunity
What happens when a microbe mimics self-antigens?
Binds self-reactive T cells and causes autoimmunity
What are virtually diagnostic of SLE?
Antibodies to double stranded DNA and the Smith antigen (RNA and associated proteins)
What are antinuclear antibodies?
Against DNA, histones, non-histone proteins bound to RNA, nucleolar antigens
What causes SLE?
Failure of the mechanism to maintain self tolerance (defective elimination of self-reactive B cells in bone marrow or defects in peripheral immune tolerance mechanisms acting on B cells)
What are genetic factors predispose person to SLE?
Specific alleles of HLA-DQ locus
Lack of complement proteins (phagocytes fail to remove immune complexes and thus their deposition occurs –> Type III hypersensitivity)
Failure to remove debris of apoptotic cells
UV: stimulates keratincytes to produce pro-inflammatory IL1 cytokine
