4. Autoimmune diseases and immunodeficient states.

AUTOIMMUNE DISEASES AND IMMUNODEFICIENT STATES

Autoimmune diseases

• ★ Autoimmune diseases represent a group of disorders that are caused by a breakdown in the ability of the immune system to differentiate between self- and nonself antigens
• This results in the generation of an immune response against self-antigens
• Normally, there is a high degree of immunologic tolerance to self-antigens, which prevents the immune system from destroying the host cells

Immunologic tolerance

• The ability of the immune system to differentiate self from nonself is called self-tolerance
• It is the HLA antigens encoded by MHC genes that serve as recognition markers of self and nonself for the immune system
• To elicit an immune response, an APC presents the antigen along with an MHC II molecule to a CD4+ helper T cell for binding to its TCR → dual recognition of the MHC-antigen complex which acts as a security check
• The two types of MHC molecules are:

1. a) MHC-I

• Present on every nucleated cell
• Ag binding to MHC-I → activation of cytotoxic T-cell → destruction by CD8+ (cellular reaction)

1. b) MHC-II

• Present on the surface of APC, B-memory cells
• Ag binding to MHC-II → activation of T-helper cells → CD4+ leads to differentiation of B-cells to plasma cells → Ab secretion (humoral reaction)
• Several mechanisms have been postulated to explain the tolerant state:

1. a) Central tolerance

• The elimination of self-reactive T cells in the thymus and B cells in the bone marrow

1. b) Peripheral tolerance

• Deletion or inactivation of autoreactive T cells or B cells that escaped elimination in the central lymphoid organs
• Autoreactive B cells are deleted in the spleen and lymph nodes
• Autoreactive T cells may undergo activation-induced cell death

Etiology of autoimmune diseases

• Not clearly known
• However some factors may be responsible:
• Chronic viral infections
• Radiation
• Genetic factors

Pathogenesis of autoimmune diseases

• The two mechanisms can be split into 2 groups:

1. Group 1 - organ specific
2. Group 2 - organ nonspecific

1) Group 1 → Organ specific

• Disturbances of physiological isolations of organs + tissues due to absence of immune tolerance
• Lymphohistocytotoxic infiltrate occurs in tissues = infiltration of lymphocytes and activated macrophages
• Examples:
• Endocrine glands
• Hashimoto’s thyroiditis - Ab’s against follicular cells of the thyroid gland
• Diabetes type I - absolute insulin deficiency
• Idiopathic Addison’s disease
• Alimentary tract
• Ulcerative colitis - idiopathic activation of T-cells in GI wall
• Blood cells
• Autoimmune hemolytic anemia
• Thrombocytopenia
• Others
• Myasthenia gravis
• Primary biliary cirrhosis

2) Group 2 → Organ nonspecific