WEEK TWO: Autoimmunity & Hypersensitivity (TAE) Slides 43 - 68 Flashcards
Autoimmunity
when the body recognizes itself as foreign and attacks itself
Autoimmune diseases
self tolerance is lost and immune system reacts to self
Generally…what the immune system does when it goes right
- T and B cells are programmed by the THYMUS to identify self as OK
- Thymus is the organ that helps eliminate ‘self-reactive cells”
- In autoimmune diseases this doesn’t happen right
Antigens vs antibodies
- An antigen is a foreign substance that enters your body
- An antibody is a protein produces by immune system
- Autoantigens, or self-antigens, are made by body to fight own cells and are usually a sign of an illness such as an autoimmune condition
Specific antibodies (immunoglobulins)…what are they?
- Antibodies are also called immunoglobuins or Ig.
- They are Y-shaped proteins made by immune system’s B lymphocytes or B cells
B-cells and specific antibodies
- B cells attack and eliminate viruses and other toxins outside the cell.
- They do this by making specific antibodies for a single type of antigen
- These tailored antibodies lock on to their specific antigens and tag them for attack.
- Antibodies also block these antigens, keeping them away from healthy cells
- Ultimately, antibodies kill these antigens, stopping infection
Specific antibodies (immunoglobulins): IgG
IgG. These are the most abundant types of antibodies in the plasma. They detoxify harmful substances and provide long-term protection. Small, versatile, short lasting.
Specific antibodies (immunoglobulins): IgM
These are the first antibodies made by B cells in response to antigens. Broad spectrum, large, stay in blood.
Specific antibodies (immunoglobulins): IgA
Antiviral specific against local infections. Seen in body secretions and other body fluids such as saliva, nasal, respiratory.
Specific antibodies (immunoglobulins): IgE
These antibodies trigger allergies and protect against parasites. Small amounts are in your skin, lungs, and mucosal membranes.
Specific antibodies (immunoglobulins): IgD
- These antibodies bind to B cells and signal them to release IgM antibodies. - No specific functions.
- Each antibody guards against its target antigen, and many types of antibodies are found throughout the body.
A theory of HOW autoimmune disease occur
- Theory of mimicry → parts of our own cells look a lot like foreign cells
- And/or the “bad” cells have adapted to look like “normal cell” and the immune system is confused
- Shirley basically said not to study these theories too much.
- Regardless of cause…autoimmune diseases injure body tissue through hypersensitivity reactions & chronic inflammation
Hypersensitivity - what it is and how many types
- A normal immune response at the wrong time or excessive action
- Immune reaction that causes inflammation and destruction of healthy tissue
- 4 types
Hypersensitivity reactions with antibodies and/or cell mediators: Type I
IgE → mediated immediate reaciton. Allergen associated. May be mild or severe, 15 - 30 minutes after exposure
Hypersensitivity reactions: type II
Reaction to antigens on cells. 15 - 30 minutes. Antibody-mediated reaction (IgG or IgM antibodies)
Hypersensitivity reactions: Type III
Immune complex-mediated reaction-persistent inflammation and destruction (SLE)
- Can be chronic and damaging
Hypersensitivity reaction: Type IV
Cytotoxic, cell mediated, delayed hypersensitivity reaction (T cells instead of antibodies)
Hypersensitivity reactions: Immediate vs delayed
- The 1st three types are considered immediate hypersensitivity reactions because they occur within 24 hours
- The fourth type is considered a delayed hypersensitivity reaction because it usually occurs more than 12 hours after exposure to the allergen, with a maximal reaction time between 48 and 72 hours.
IgE hypersensitivity physiology
IgE is bound to mast cells via its Fc portion. When an allergen binds to these antibodies, crosslinking of IgE induces degranulation. Destroys the cell.
IgG mediated cytotoxic hypersensitivy: physology
Cells are destroyed by bound antibody, either by activation of compliment or by a cytotoxic T cell with an Fc receptor for the antibody (ADCC)
Immune Complex mediated hypersensitivity: Physiology
Antigen-antibody complexes are deposited in tissues, causing activation of compiment, which attracks neutrophils to site. Causes more inflammation + damage. Seen in Lupus + Rheumatoid arthritis.
Cell mediated hypersensitivity: physiology
Th1 cells secrete cytokines, which activate macrophages and cytotoxic T-Cells and can cause macrophage accumulation at site.
Systemic lupus Erythematosus
- Chronic, autoimmune, multi-system, inflammatory disease
- With unpredictable exacerbations and remissions
- Not a rare disease
- Effects mostly women in childbearing years - who then get older
- Especially effects non-caucasians
Etilogy of Lupus
- Unknown exactly
- Possible triggers → Genetics, gender (hormones), UV light, chemicals, infectious agents and STRESS
Pathophysiology of Lupus
- Production of auto-antibodies gainst own cell’s DNA
- The auto-antibodies get deposited in tissues and make inflammation and destruction
- Auto-antibodies enter cells and destroy cell DNA
S/S of Lupus
- Arthritis and arthralgias (acute or insidious pain!)
- Skin has butterfly rash on face, hair loss, MM ulcers, patchy skin
- Blood: anemia, and thrombocytopenia
- Plus: Kidney, cardiac and lung damage.
- Any cell can be affected
Systemic Lupus erythematosus
-DX: Hard to diagnose
- S/S: vary so much from person to person
- Basically rule out everything else
Treatment of Lupus
- Decrease inflammation so tissue destruction is reduced
- Malaria drugs are commonly used: they decrease antibody production, pain and inflammation
- used in combo with corticosteroids which decrease inflammation
Treatment of lupus: antimalarials
- Examples: Chloroquine (Aralen) and hydroxychloroquine (Plaquenil) are approved for the treatment of SLE
- Have been shown to reduce the frequency of disease flares (particularly of Lupus nephritis), Maintain remission, prolong the onset of disease and reduce the risk of complications
