Unit 3 Flashcards
(24 cards)
Self-tolerance
- Clonal deletion of relevant effector cells
- Active regulation by T cells
- Majority of T cells processed through the thymus do not survive
- Loss of T cells encourage production of Autoantibodies.
Central-tolerance
- Induced in the Thymusand Bone Marrow
- Process happens when B cells mature in the bone marrow.
- Newly developing T cells and B cells are rendered non-reactive to self.
- Immune system learns to discriminate self from non-self
Peripheral tolerance
- Induced in the other tissues and lymph nodes
- Develops after T and B cells mature and enter periphery
- Suppression of autoreactive cells by regulatory T cells
- Key to preventing over-reactivity of the immune system
Major histocompatibility complex
- Influence antigen recognition or nonrecognition-By determining peptides that can be presented to T cells
- The expression of class II molecules on host cells may result in presentation of antigens for which there is no tolerance
- Inheritance of specific MHC molecule
Molecular mimicry
- Viral or bacterial agents contain antigens that closely resemble self-antigens
- Exposure may trigger antibody production that reacts with similar self-antigens
Polyclonal B-cell activation
B-cell defects -Abnormal expression -Function of signaling molecules -Dysregulation of cytokines -Fc receptor polymorphisms Defects may be enhanced by -Gram-negative bacteria -Several viruses -Induces proliferation of clones of B-cells
Effects of SLE-
1) Nonspecific involvement-diverse and nonspecific enough to start looking at autoimmunity; fatigue, weight loss, malaise, fever, anorexia
2) Joint involvement-specific enough to start looking at autoimmunity
3) Uncommon appearance-BUTTERFLY rash
4) Systemic effects-renal involvement common (deposition of immune complexes in kidney tissue leading to renal failure); also cardiac, CNS, hematologic abnormalities
What are the major contributing factors to autoimmunity? What are the other three?
1) Self-tolerance
2) Central-tolerance
3) Peripheral tolerance
4) Major histocompatibility complex
Other mechanisms contributing to autoimmunity:
-Sequestered antigens
-Molecular Mimicry
-Polyclonal B-cell activation
SLE
Systemic lupus erythematosus; chronic and systemic inflammatory disease caused by immune complex formation
- Genetic (HLA-DR and HLA-DQ) and environmental
- Complement C1q, C2, C4
- More common in women, caucasian, 20-40 yrs
Why are women more prone to SLE?
estrogen enhances B cell activation leading to more B cell issues
What are the 4 types of autoantibodies found in SLE? Explain the corresponding pattern with each with immunofluorescence testing.
Homogenous Pattern -Anti-DNA -Anti-DNP -Anti-histone Peripheral Pattern -Anti-DNA Speckled Pattern -Anti-RNP -Anti-SSA/SSB
FANA
Fluorescent anti-nuclear antibody (ELISA); very sensitive, indirect assay; subjective but simple and inexpensive
Principle: animal/human cells fixed to slide, patient serum added and incubated, washed to remove unreacted antibody, addition of anti-human globulin labelled with fluorescent tag of enzyme
ENA
Extractable nuclear antigen; similar to ELISA; 6 main antigens used for detection: anti-Sm, anti-RNP, anti-La, anti-Ro, Anti-Scl-70, and anti-Jo
What are the 2 main cell division stages for reading fluorescence?
Interphase and metaphase
SLE treatments
No cure; High dose of anti-inflammatory, Anti-malarials/topical steroids, Systemic corticosteroids
Symptoms of Rheumatoid arthritis
1) Nonspecific involvement: malaise, fever, weight loss, and transient joint pain
2) Joint involvement: Morning stiffness, swelling around hand and wrist joints, Swelling around soft tissue of 3+ joints, joint erosion
3) Systemic effects: inflammation affecting heart, lungs and blood vessels
RA Genetics
associated with certain MHC II genes: DR4 alleles
Characteristics of RF in RA
IgM antibody against the Fc portion of the IgG molecule; Immune complexes form and activate complement and inflammatory response; Latex particles covered in IgG, if RF present then agglutination occurs
Characteristics of anti-CCP in RA
More specific, ELISA for anti-CCP; Other autoantibodies found in RA patients (anti-keratin, anti-perinuclear, anti-filaggrin, anti-Sa) they target citrullinated proteins
Treatments available for RA
No cure; non-steroidal anti-inflammatory drugs, anti-rheumatic drugs, joint replacement
Autoantibodies and symptoms of Sjorgrens disease
Inflammation of glands in body: lacrimal glands-decreased water production and dry eyes, salivary glands-mouth dryness, also joint pain, skin rashes/dry skin, vaginal dryness, persistent dry cough, prolonged fatigue; Complications: dental cavities, yeast infections, vision problems, peripheral neuropathy, lung-liver-kidney
Anti-SSA
Anti-SSB
RF pos
speckled pattern on ANA
Autoantibodies and symptoms of Schleroderma
excessive deposits of collagen–>thickening and tightening of skin, scarring, reddish/scaly skin, visible blood vessels, CREST
Anti-Scl-70
RF pos
centromere pattern on ANA
Autoantibodies and symptoms of Myasthenia gravis
damaged acetylcholine receptors–> varying degrees of weakness of the skeletal muscles of the body, facial weakness, difficulty chewing/swallowing, inability to support trunk/neck/head
Binding Ab
Blocking Ab
Modulating Ab
Striated muscle Ab
Titin Ab
Autoantibodies and symptoms of Goodpasture’s Syndrome
Renal failure–>foamy bloody dark urine, decreased urine, cough with bloody sputum, difficulty breathing after exertion, nonspecific chest pain, pale skin, fatigue, weight loss, weakness, nausea/vomiting
Anti-GBM
