reduced numbers of circulating neutrophils. can be caused by auto-immune antibodies that are against neutrophil surface antigens.
autoimmune hemolytic anemia
IgG and IgM bind to erythrocyte surface, where they activate complement by the classical pathway
5 mechanisms that contribute to self-tolerance
1. Negative selection in bone marrow (B cells) and Thymus (T cells)
2. Expression of tissue-specific proteins in the thymus (possible by AIRE transcription factor)
3. No lymphocyte access to some tissues (brain, eyes, testis, fetus)
4. T reg cells supress autoimmune responses
5. induction of anergy in autoreactive B and T cells
systemic lupus erythmatosus
what causes SLE?
IgG is made against normal self-antigens. Those IgG make complexes with those antigens, and they clog the capillaries of glomerulous in kidney, and this can be deadly if not treated.
an example of a systemic autoimmune disease
SLE! since the disease can affect any/all tissues of body, the course of the disease is highly variable in individuals.
with this disease (80% of patients) produce IgM, IgG, and IgA specific for the Fc region of human IgG
two approaches to rheumatoid arthritis
1. an anti-TNF-alpha monoclonal antibody (infliximab)
2. anti-CD20 monoclonal antibody (rituximab)
CD20 is expressed on...
expressed on the surface of all B-cells beginning
the dominant genetic factor for susceptibility to autoimmune disease
HLA (human leukocyte antigen) complex (=the human MHC)
a major risk factor for several autoimmune diseases esp. Ankylosing Spondylitis (Ankylosing spondylitis is a long-term disease that causes inflammation of the joints between the spinal bones, and the joints between the spine and pelvis. It eventually causes the affected spinal bones to join together.)
the likelihood of developing certain autoimmune diseases in persons who inherit particular HLA alleles than in persons who lack these alleles.
These substitutions change the peptide-binding groove by having ________ charged residues instead of the two __________ charged residues.
How do pathogens trigger autoimmune disease?
1. Molecular mimicry 2. Collateral damage from normal immune responses to the pathogen, 3. Polyclonal activation
1. trauma to 1 eye releases antigens that were sequestered within the eye
2. the antigens are carried to lymph nodes, and activate T cells
3. Effector T cells travel to both eyes and attack the antigen in both eyes
immediate hypersensitivity (IgE mediated)
delayed type hypersensitivity (DTH, T cell mediated)
antibody mediated hypersensitivity
immune complex mediated hypersensitivity
Some autoimmune disorders may start out as localized
disorders, but progress to systemic disorders.
As tissue is damaged, it releases cryptic or sequestered antigens, which in turn provoke the production of new autoantigens.
This leads to further tissue damage and the release of more autoantigens.