Exam #3: Immuopathology II Flashcards
What is conditioning regime?
Irradiation therapy to destroy the immune system and create a graft bed
What is timeline for acute GVHD?
Days to weeks post engraftment
What is the mechanism of acute GVHD?
Immunocomptent T-cells in the donor bone marrow recognize recipient HLA antigens as foreign & react to them
- CTL response= direct destruction
- CD4+= cytokines production and inflammation
What are the manifestations of acute GVHD? Why?
Mainly the immune system and the epithelial of the skin, liver, and intestines are effected
- Skin= dequamating rash
- Liver= small bile duct destruction leading to jaundice
- Intestines= mucosal destruction leading to bloody diarrhea
**Profound IMMUNOSUPPRESSION
What is chronic GVHD?
Follows resolution of acute CVHD or may evolve insidiously
What is the mechanism of chronic GVHD?
Autoreactive T-cells deried from donor stem cells that cannot be clonally deleted due to immune compromise of recipient
What are the manifestations of chronic GVHD?
Generally, this is a worsening of acute GVHD that mimics systemic sclerosis
- Destruction of skin appendages and fibrosis of the dermis
- Chronic liver damage leading to jaundice
- GI damage leading to esophageal stricture
**Patients also experience recurrent life-threatening infections
What is bronchiolitis oboliteratans?
Obstructive lung disease that results from chronic GVHD
Generally, what are autoimmune diseases?
Immune reactions against self-antigens
What are systemic autoimmune diseases?
Connective tissue or collagen-vascular diseases that target widely distributed intracellular molecules
Generally, what are the criteria for the diagnosis of an autoimmune disease?
1) Immune reaction for a self-antigen or self-tissue
2) Reaction is NOT secondary to tissue breakdown but is PRIMARY
3) Absence of other well-defined cause of disease
What are the two general mechanisms of self-tolerance?
1) Central tolerance
2) Peripheral tolerance
What is central tolerance?
Process by which self-reactive B & T-cells are killed during their maturation process in the central lymphoid organs i.e. bone marrow & thymus
- Negative selection= T-cells, random rearrangement of somatic genes generates indiscriminate lymphocytes; these cells are presented with self antigens & those that react, die by apoptosis
- Receptor editing= auto-reactive B-cells in the bone marrow get another shot at gene rearrangement to be non-self reactive
What is peripheral tolerance?
Process by which auto-reactive B & T-cells are silenced in peripheral lymphoid organs i.e. lymph nodes
What are the mechanisms of peripheral tolerance?
Anergy=
- T-cells–normal tissues do NOT express the costimulatory molecules needed for activation–T-cells that react to self-antigen undergo a silencing reaction
- B-cells–need helpter T-cells for activation, without, also undergo silencing reaction
Suppression by regulatory T-cells
Deletion by activation induced cell death= CD4+ T-cells that recognize self-antigens recieve signals that promote their apoptosis
What locus is associated with autoimmunity?
Expression of certain MHC alleles (D locus) confers higher susceptibility to loss of self tolerance
What is the genetic polymorphism is most commonly associated autoimmunity & RA?
PTPN-22 gene
- Encodes a tyrosine phosphatase
How do microbes precipitate autoimmunity?
Antigenic mimicry
Which gender is associated with higher incidence of autoimmunity? Why?
Female, which potentially suggests a role of sex hormones in autoimmunity
Generally, what balance is interrupted to cause autoimmunity?
Genetic background + enviornmental factors= autoimmunity
What is SLE?
Systemic Lupus Erythematous: prototypical multisystem autoimmune disorder
What gender is SLE more common in? What race?
African american females
What are the ACR diagnostic criteria for SLE?
1) Malar/ butterfly rash on face
2) Discoid rash–erythematous raised patches with adherent keratotic scaling & follicular plugging
3) Photosensitivity
4) Oral ulcers (painless)
5) Arthritis
6) Serositis–pleuritis or pericarditis documented by ST elevation in all leads (except aVR)
7) Renal disorder i.e. proteinuria/ casts
8) Neurologic disorder i.e. seizures or psychosis
9) Hematologic disorder i.e. hemolytic anemia, leukopenia, lymphopenia, or thrombocytopenia
10) Immunologic disorder
11) Antinuclear antibodies
Outline the pathogenesis of SLE.
- UV irradiation or other environmental insult results in apoptosis
- Inadequate clearance of these cells= high burden of nuclear antigens
- Underlying genetic defect e.g. HLA-DQ= defective self-tolerance
- Self-reactive lymphocytes remain active
- Activation of helper T-cells & B-cells that produce autoantibodies to nuclear antigens
