AUTOIMMUNITY Flashcards
is a problem of self/non-self discrimination
Autoimmunity
Breakdown of the immune system’s ability to discriminate between self and nonself
Autoimmunity
• A varied group of chronic illnesses that involves almost every human organ system
• Seen when demonstrable immunoglobulins of cytotoxic T cells display specificity for self antigen that contribute to pathogenesis of a cell disorder
Autoimmune disorder
• Characterized by persistent activation of immunologic effector mechanism
Autoimmune disorder
Antigens that do not normally circulate the blood
Altered antigens that arise because of chemical, physical or biological processes.
A foreign Antigen that is shared with self antigen and tissue component
Mutation of immunocompetent cells
Loss of immunoregulatory function of T lymphocyte subset
• The autoimmune response are directed against antigens present only in a particular organ
ORGAN SPECIFIC AUTOIMMUNE DISEASE
• The autoantibodies bind to self antigen to the organ cells and lead to the destruction of cells
ORGAN SPECIFIC AUTOIMMUNE DISEASE
• the autoantibodies bind to self-antigens on cells and lead to either overstimulation of the cell or suppression of the normal functioning of the cells
ORGAN SPECIFIC AUTOIMMUNE DISEASE
• auto antibodies to self- RBCs are formed
AUTOIMMUNE HEMOLYTIC ANEMIA
• The autoantibodies bind to antigens on RBCs and lead to the lysis of RBCs (due to complement activation)
AUTOIMMUNE HEMOLYTIC ANEMIA
• Maybe be caused by drugs (cephalosporins, dapsone)
AUTOIMMUNE HEMOLYTIC ANEMIA
o Acts as haptens (incomplete antigen; needs a carrier RBC)
cephalosporins, dapsone
• The drug-RBC antigen complex induces the immune system to produce antibodies.
AUTOIMMUNE HEMOLYTIC ANEMIA
• Lead to the activation of complement
Other causes of AIHA
• Antibodies reactive to body temperature (37°C)
Warm autoimmune hemolytic anemia
• IgG and complement coats the RBC
Warm autoimmune hemolytic anemia
• Cold reactive IgM reacts with RBC
Cold autoimmune hemolytic anemia
• Room temperature (32°C)
Cold autoimmune hemolytic anemia
• IgG protein reacts with RBC in colder parts of the body producing complement component binding
Paroxysmal cold hemoglobinuria
• a chronic disease resulting from the non-absorption of vitamin B12 (essential for RBC development)
PERNICIOUS ANEMIA
• Results to inability to secrete intrinsic factor (IF)
PERNICIOUS ANEMIA
most common in late adult life
PERNICIOUS ANEMIA
• The basic abnormality of the disease is severe atrophic gastritis
PERNICIOUS ANEMIA
Presence of Intrinsic Factor-blocking antibody is diagnostic of PA
PERNICIOUS ANEMIA
• Autoantibodies to platelets bind to many of the major platelet membrane glycoproteins
IDIOPATHIC THROMBOCYTOPENIC PURPURA
are the major antigens with which the platelet autoantibodies bind
• Platelet GpIIb /IIIa and GPIb/IX
• The antibody coated platelets are destroyed
IDIOPATHIC THROMBOCYTOPENIC PURPURA
• The number of platelets drastically decrease
IDIOPATHIC THROMBOCYTOPENIC PURPURA
• Classic symptoms: petechiae, bruising and bleeding after minor trauma
IDIOPATHIC THROMBOCYTOPENIC PURPURA
• Autoantibodies to certain antigens on the membrane of kidney glomeruli and lung alveoli are formed
GOODPASTEUR SYNDROME
• Complement activation is evident after autoantibody bind membrane antigen
GOODPASTEUR SYNDROME
• This may result in an inflammatory reactions in lungs and kidney
GOODPASTEUR SYNDROME
• The kidneys may be damage or patients may suffer from pulmonary hemorrhage
GOODPASTEUR SYNDROME
• Bleeding in the lungs are seen
GOODPASTEUR SYNDROME
• Chronic autoimmune thyroiditis
HASHIMOTO’S THYROIDITIS
• Autoantibodies against many thyroid proteins and T cells are formed
HASHIMOTO’S THYROIDITIS
• Clinical picture:
o Goiter
o Hypothyroidism
o Thyroid autoantibodies
o Hyperplasia
HASHIMOTO’S THYROIDITIS
Symptoms of hypothyroiditis
Dry skin, decrease sweating, puffy face, edematous eyelids, weight gain (decrease in T3 and T4 slows down metabolism) and brittle hair
• Autoantibodies on thyroid stimulating hormone (TSH) receptors bind to TSH receptors on thyroid
GRAVE’S DISEASE
• Leads to overproduction of thyroid hormones
GRAVE’S DISEASE
• May produce Hyperthyroidism
GRAVE’S DISEASE
GRAVE’S DISEASE
• Causes
Grave ophthalmopathy and Grave’s dermopathy
• A condition caused by autoimmune response against the beta cells in pancreas resulting in destruction of beta cells
INSULIN DEPENDENT DIABETES MELLITUS (IDDM)
• Self-reactive cytotoxic T cells (CLTs) against the beta cells migrate to areas of beta cells in pancreas
INSULIN DEPENDENT DIABETES MELLITUS (IDDM)
• Autoantibodies to beta cells may activate the complement cascade and destroy beta cells.
INSULIN DEPENDENT DIABETES MELLITUS (IDDM)
INSULIN DEPENDENT DIABETES MELLITUS (IDDM) HLA
• HLA DR3, DR4, DQ2, and DQ8
• Occurs in the neuromuscular junctions (site where the muscle and the nerve connects)
MYASTHENIA GRAVIS
• Binding of autoantibodies to acetylcholine receptors on the muscle cells
MYASTHENIA GRAVIS
• Leads to breakdown in the normal communication between nerves and muscles
MYASTHENIA GRAVIS
• Causes breakdown and fatigue of any muscle
MYASTHENIA GRAVIS
• The autoimmune responses are directed against self antigens present in many organs and tissues of the body resulting in widespread tissue damage to the host.
ORGAN NONSPECIFIC AUTOIMMUNE DISEASE
• Most prevalent autoimmune disease in developed countries.
SYSTEMATIC LUPUS ERYTHEMATOSUS
• Patients develop autoantibodies to a number of self-antigens
SYSTEMATIC LUPUS ERYTHEMATOSUS
• The most common autoantibody found in the serum of SLE patients is the
autoantibody to double stranded DNA (dsDNA)
• Multiorgan system disease
SYSTEMATIC LUPUS ERYTHEMATOSUS
• Anilbodies may belong to lgG or IgM
SYSTEMATIC LUPUS ERYTHEMATOSUS
• Immune complex deposition and subsequent complement activation leads to the tissue destruction.
SYSTEMATIC LUPUS ERYTHEMATOSUS
• Serum level of C3 and C4 are reported/increased
SYSTEMATIC LUPUS ERYTHEMATOSUS
• Malar rash (butterfly rush)
SYSTEMATIC LUPUS ERYTHEMATOSUS
• Seen in 46-65 of SLE patients
Malar rash (butterfly rush)
• Red or purplish and mild and scaly
SYSTEMATIC LUPUS ERYTHEMATOSUS
SYSTEMATIC LUPUS ERYTHEMATOSUS HLA
• HLA-DR3
INTERACTION OF AUTOANTIBODIES WITH SPECIFIC SELF-ANTIGEN
• A chronic systematic inflammatory disease primarily involving the joints
RHEUMATOID ARTHRITIS
• The serum and synovial fluid contain
rheumatoid factor
• Rheumatoid factors are synthesized within
lymphoid infiltrates
activates the complement
• Rheumatoid factor-immunoglobulin complex
• Pain occurs in small joint and later in large joints
RHEUMATOID ARTHRITIS
• Advance cases –
joint deformities
• Invasive pannus (inflammation) consists of macrophages, mast cells and fibroblasts
RHEUMATOID ARTHRITIS
• Synovial fluid contains organized lymphoid tissues (CD4+ T Cell, B cells and macrophages) – same w/ formation of tumor
RHEUMATOID ARTHRITIS
• Increase neutrophil count in synovial fluid - Differential count
RHEUMATOID ARTHRITIS
• An autoimmune disease of central nervous system
MULTIPLE SCLEROSIS
• involves auto reactive T cells
MULTIPLE SCLEROSIS
• Self-reactive T cells are present in the periphery of the host
MULTIPLE SCLEROSIS
• Injuries may lead the brain exposed to self-reactive T cells
MULTIPLE SCLEROSIS
• Self reactive T cells become activated and attack the brain tissues
MULTIPLE SCLEROSIS
• Infiltrates of T cells may cause destruction of myelin sheath
MULTIPLE SCLEROSIS
• Destruction of myelin sheath leads to numerous neurological dysfunctions
MULTIPLE SCLEROSIS
• a chronic, progressive, inflammatory disease of unknown etiology.
ANKYLOSING SPONDYLITIS
• The disease primarily affects the sacroiliac joints, vertebral joints, and large peripheral
ANKYLOSING SPONDYLITIS
• Can cause some of the vertebrae in the spine to fuse
ANKYLOSING SPONDYLITIS
• Affects men more often than women
ANKYLOSING SPONDYLITIS
ANKYLOSING SPONDYLITIS
• Early signs and symptoms
o stiffness in vour lower back and hips
o neck pain and fatigue
ANKYLOSING SPONDYLITIS
• The areas most commonly affected are:
o Sacroiliac joint
o The vertebrae in your lower back
o Entheses
o The cartilage
o between your breastbone and ribs
ANKYLOSING SPONDYLITIS HLA
• HLA-B27
HLA DR3, DR4, DQ2, and DQ8
IDDM
HLA-DR3
SLE
HLA-B27
ANKYLOSING SPONDYLITIS
• vertebral joints
ANKYLOSING SPONDYLITIS
• neuromuscular junctions
MYASTHENIA GRAVIS
• Brain tissue • Myelin sheath
MULTIPLE SCLEROSIS
refers to undesirable immune reactions produced by the normal immune system.
• Hypersensitivity (Immunological reaction)
: four types; based on the mechanisms involved and time taken for the reaction
• Hypersensitivity reactions
Classification or Immumologic Reactions (Gell and Coombs)
IgE (Rarely IgG4)
I
Immediate
I
IgG, IgM (Cell-Ag)
II
Cytotoxic
II
Ag-Ab complexes
III
Immune complex
III
T cells
IV
Cell-mediated
IV
Commonly called Allergy
TYPE 1 (IMMEDIATE) HYPERSENSITIVITY
Mediated by IgE antibodies produced by plasma cells in response to stimulation of Th2 cells by an Antigens
TYPE 1 (IMMEDIATE) HYPERSENSITIVITY
Exposure maybe ingested, inhalation, injection, or direct contact
TYPE 1 (IMMEDIATE) HYPERSENSITIVITY
Can be systemic or localized to a specific target tissue or organ
TYPE 1 (IMMEDIATE) HYPERSENSITIVITY