Autoimmune Flashcards
IgG
Most abundant of ABs
Activates complement proteins
IgA
Attached to epithelial cells
Prevents microbes from crossing mucus membrane
IgM
Activates complement proteins
Makes bacteria cells clump together
IgD
Never exposed to antigens
When they are exposed, they will create a mold of the antigen that can be used to make antibodies
IgE
Immediate allergic rxns & parasites
T-cells
Responsible for cell-mediated immunity where they kill targets directly or stimulate activity of other leukocytes
Adaptive immunity can be
Active or passive
Lymphoid organs contain
Large quantities of immune cells
Lymphoid organs
Lymph nodes, spleen, tonsils, appendix, bone marrow, thymus
Primary immune response
Latent period of 7-14 days following exposure before antibodies can be produced.
Dominated by IgM with some IgG
Secondary immune response
Occurs upon subsequent exposure to an antigen. Antibodies appear faster because memory cells recognize antigen and can make a faster immune response.
Autoimmunity
Immune reaction to self-antigens
Alloimmunity
Immune reaction to tissues of another individual
In hypersensitivity, what is the body injured by?
The immune response NOT the antigen/allergen
Immediate hypersensitivity rxn
Minutes to hours after exposure
Delayed hypersensitivity rxn
Hours to appear, at severity days after re-exposure to antigen
Anaphylaxis
Most rapid and severe rxn
Type 1 rxn
IgE mediated
Hay fever, allergies
Immediate rxn
Type 2 rxn
AB mediated
Tissue-specific
Immediate
Type 3 rxn
Complement-mediated immune disorders
Ag-AB complex deposited in tissues
Immediate
Type 4 rxn
T-cell mediated rxn
Delayed rxn
Type 1 rxn allergen
Contained within particle too large to be phagocytosed or protected by a nonallergenic coat.
Type 1 Pathogenesis
T-helper cells differentiate B cells into specific IgE-producing cells
IgE antibodies attach to receptors on mast cells or basophils
Allergen binds to cell-associated IgE
Binding triggers degranulation of mast cells/basophils to release histamine
Type 1 primary response
-Occurs 5-30 minutes after exposure, subsides within 60
-Mediated by mast cell degranulation
Type 1 Late-phase response
-2-8 days after first phase
- Result of lipid mediators and cytokines in inflammatory response
- Influx of eosinophils and leukocytes to site of allergen causing tissue destruction
Possible mechanisms for tissue-specific rxns (type 2)
- Complement-mediated lysis
- Opsonization and phagocytosis
- Antibody-dependent cell-mediated cytotoxicity
- Modulation of cellular function
Graves Disease
Type 2 rxn
AB binds to pit and stims TSH release = thyroxine release
Examples of type 2 rxn
Autoimmune hemolytic anemia, blood transfusion or Rh, medications are antigens and bind to cells, NK cells target killer cell, Graves Disease
Type 3 rxn
Produce damage - elicit inflammatory response - recruitment of neutrophils and other inflammatory cells responsible for injury
Glomerulonephritis
Thickening of glomerular capillary wall from immune complex deposition and destruction of ET cells by neutrophils
Symptoms of glomerulonephritis
Hematuria, proteinuria, hypertension, edema
Type 4 rxn responds to
Fungi, protozoa, parasites, poison ivy
Type 4 rxn mediated by
Sensitized T lymphocytes
Type 4 rxn t-cells
Macrophages/other cells release lysosomal enzymes that kill tissue cells with antigen on cell membrane
ex. poison ivy causing contact dermatitis
Types of Type 4 rxns
Direct cell-mediated cytotoxicity
Delayed-type hypersensitivity
Type 4 Direct cell-mediated cytotoxicity
Cytotoxic T lymphocytes kill target cells that show peptides from antigens prevented in association with class 1 major histocompatibility complex molecules
Type 4 rxn Delayed-type hypersensitivity
Activation of antigen-presenting cells, result in release of cytokines and recruitment/activation of inflammatory cells`
Type 4 rxn Delayed-type hypersensitivity
-24-72 hours to develop
- Cause of several diseases like contact dermatitis
- Patch testing can be used
- Treatment usually limited to removal of irritant and topical preparations
Autoimmune diseases are
Familial
Autoimmunity
Self-tolerance breaks down and cytotoxic T cells/antibodies mistakenly attack the body’s own cells
Two primary factors believed to cause autoimmune disease
Heredity and environment
T cell anergy
Self tolerance mechanism in which the T cell is inactivated after antigen encounter, but remains alive for an extended period of time in a hyporesponsive state.
Proposed environmental factor mechanisms include
- Breakdown of T cell anergy
- Release of sequestered antigens
- Molecular imagery
- Superantigens
Testing/diagnosis of autoimmune testing
- Demonstration of antibodies that are directed against tissue antigens or cellular components
- Assays involve diluting individual’s serum and allow to react with antigen-coated surface
- Serum serially diluted until it no longer produces a rxn
Treatment of autoimmune disease
Immunosuppressive drugs and corticosteroids, plasmapheresis, potential development of vaccines
Lupus
Chronic multisystem inflammatory disease
Manifestations: fatigue, rashes, myalgia/arthritis, weight change and fever
Lupus characterization
Production of large variety of autoantibodies against: nucleic acids, erythrocytes, coagulation proteins, phospholipids, lymphocytes, platelets, etc.
Lupus Autoantibodies
Combine with antigens and form circulating immune complexes that can get stuck in various organs like kidneys, brain, heart, spleen, skin
Some symptoms result from T3 rxn, others T2
Lupus - Clinical manifestations
Vasculitis, renal disease, hematologic changes, cardiovascular disease
Lupus - Common Findings
Need 4
Butterfly rash, discoid rash, photosensitivity, oral or nasopharyngeal ulcers, nonerosive arthritis, serositis (fatigue), renal disorder, neurologic disorder, hematologic disorder, immunologic disorder, presence of antinuclear antibodies
Lupus - Treatment (nonpharmaceutical)
Protection from sunlight, maintaining adequate nutrition, exercise, smoking cessation, receiving appropriate immunizations
Lupus - treatment (pharmacologic)
Hydroxychloroquine
Other meds depending on severity and combination of clinical manifestation
Rheumatoid arthritis
Inflammatory joint disease characterized by inflammatory destruction of synovial membrane, articular cartilage, joint capsule, and surrounding ligaments and tendons.
First joint affected is synovial membrane
What does rheumatoid arthritis affect
Heart, lungs, kidneys, skin, joints
Rheumatoid arthritis - antibodies
Antibodies against IgG fragments w/presence of rheumatoid factors (IgG and IgM) against self-antigens in blood and synovial membranes
Rheumatoid nodules could invade
Skin, lung, spleen, small and large arteries
Synovial fibroblasts
SFs undergo changes and develop exaggerated immune response. Produce proinflammatory cytokines, enzymes, and prostaglandins that thicken synovial tissue
Rheumatoid arthritis pathogenesis
Neutrophils in synovial fluid activated
Inflammatory cytokines secreted by SFs
T-cells interact with synovial fibroblasts
Inflammation spreads to fibrous joint capsule and surrounding ligaments/tendons
Rheumatoid arthritis - manifestations
Insidious onset
Inflammation - fever, fatigue, weakness, anorexia, weight loss, aching/stiffness
Joints become painful, tender, swollen, warm, boggy
Joint deformities
Rheumatoid arthritis evaluation
4 or more
Morning joint stiffness
Arthritis of 3+ joint areas
Arthritis of hand joints
Symmetric arthritis
Rheumatoid nodules
Abnormal amounts of serum rheumatoid factor
Radiographic changes
Rheumatoid arthritis - treatment
Methotrexate, NSAIDS or corticosteroids, Leflunomide, Infliximab
Biologics like Enbrel
