Lecture 7: Immune II Flashcards
Autoimmunity
- Immune rxn to self Ag
- Destruction of normal tissue
- Often chronic, never ending
- Can be temp. relieved w/ immune regulatory mechanisms
- Can be systemic or single organ
Cause of autoimmunity
Loss of tolerance, mainly T cells
Types of immune tolerance
Central: maturation/selection
Peripheral: Tregs, exhaustion, induced death
Hypersensitivity types
Type I: IgE mediated (allergy)
Type II: ADCC, complement, IgG, IgM (Ab)
Type III: Ag/Ab soluble complex (complex)
Type IV: Macrophages + direct T cell lysis (T cell)
Type I hypersensitivity
- Most allergies; pre-existing IgE in sensitized host
- Mast cells, basophils, PMNs, eosinophils, B cells
- Degranulation -> mediator release (histamine, heparin)
- Evolved vs. parasites
Type II hypersensitivity
- Ab vs cell surface/matrix Ags
- Immune response or affect molecule activity (e.g. receptors)
- e.g. AIHA, ITP, Goodpasture’s, pemphigus vulgaris, Graves’, myasthenia gravis
Autoimmune Hemolytic Anemia
AIHA = type II hypersensitivity
- Abs vs RBC surface Ags
- Premature RBC destruction by complement/phagocytes (spleen phagocytosis or intravasc. hemolysis)
- Treatment w/ steroids, splenectomy, rituximab
- Coombs test diagnosis
Coombs test
Direct antiglobulin test; anti-human Ab -> agglutination in positive results
Immune Thrombocytopenic Purpura
Type II hypersensitivity
ITP = Abs vs platelets; spleen phagocytes, complement
- Prone to bleeding/bruising
- Steroids, splenectomy, IV-Ig
Goodpasture’s Syndrome
Type II hypersensitivity vs basement memb. collagen IV
- Hemoptysis, hematuria
- Steroids, rituximab, plasmapheresis
Pemphigus vulgaris
Type II hypersensitivity; blistering disease vs epidermal cadherin (desmosomes)
Graves’ Disease
Type II hypersensitivity vs TSH receptor -> hyperthyroidism, goiter
- AutoAb stimulates receptor
- Can transfer disease from mother to fetus (Abs cross placenta)
- Beta blockers, anti-thyroid meds, radiation, thyroidectomy
Myasthenia gravis
Type II hypersensitivity vs ACh receptor
- Steroids, plasmapheresis, IVIg, rituximab
Rituximab
Anti-CD20 mAb that inhibits B cell functions
Type III hypersensitivity phases
Immune complex
1. Deposition of Ab-Ag complex on tissue
2. Complement activation
3. Inflam. rxn
4. Cell injury
3 etiologies of Type III hypersensitivity
- Persistent low-grade infection
- Extrinsic environmental Ags
- Autoimmune process
Post-Streptococcal Glomerulonephritis
Type III hypersensitivity
PSGN = autoimmune injury init. by group A β-hemolytic Strep. infection leading to kidney failure
Systemic Lupus Erythematosus
Type III hypersensitivity
SLE = multi-system Abs vs nucelar Ags (ANA)
- Acute onset -> chronic phase
- AutoAbs create circulating immune complexes that deposit in tissues -> vasculitis, etc.
- Heavy immunosuppression required
Type IV hypersensitivity
Aka delayed type hypersensitivity - T cell mediated vs soluble or cell-assoc. Ag
- Th1 vs soluble Ag -> macrophages
- Th2 vs soluble Ag -> IgE, mast cells, eosinophils
- CTLs vs cell-assoc. Ag -> ADCC
- e.g. tuberculin TB test, Type I diabetes, rheumatoid arthritis, MS
Type I diabetes
Type IV hypersensitivity vs pancreatic β cell Ag
- Destruction by CTLs -> no insulin production
Rheumatoid arthritis
Type IV hypersensitivity vs synovial joint Ags -> joint inflam./destruction
- V. difficult to resolve due to low vascularization in joints
Multiple Sclerosis
Type IV hypersensitivity vs myelin basic protein, proteolipid protein -> demyelination, brain degen., paralysis
Autoimmunity risks
Combo of genes + environment; HLAs, smoking, drugs, physical trauma, etc.
