Lecture 13/14: Tumors, Transplants/Immunodeficiency Flashcards
(31 cards)
4 mechanisms of tumor immune evasion
- Failure to produce tumor Ags
- MHC I deficiency
- Secretion of inhibitory proteins
- Expression of inhibitory cell surface proteins
Enhancing tumor immunity
Passive: mAb, autologous T cell transfer
Adaptive: Chimeric Ag Receptor T cells
Chkpt: anti-CTLA-4, anti-PD-1/anti-PD-L1
Combo
Immunological approaches to cancer
- Prevent
- Passive immunization
- Adaptive T cell therapy
- Immune chkpt blocking
Transplant immunology
Syngeneic = identical genes
Allogeneic = same species, diff. individual
Xenogeneic = diff. species
Autologous = to/from self
MHC transplant Ags
MHC has several antigenic sites that recipient T cells may recognize as foreign or recognize alloMHC::self peptide as selfMHC::foreign peptide
Transplant immune response
- AlloAg transport to LNs
- T cell activation, expansion, migration
- Inflam. cytokine secretion
- Graft cell killing -> rejection (direct vs indirect)
- Direct: donor MHC recognized
- Indirect: alloAg is processed
Types of graft rejection
- Hyperacute
- W/in minutes; Abs recognize endothelial Ags -> complement, coag. -> ischemia - Acute
- Days to wks; graft alloAg processing -> Abs/T cells - Chronic
- Months to yrs; alloreactive T cells -> chronic inflam. -> arteriosclerosis
Methods to prevent transplant rejection
- HLA type matching
- Immunosuppression
- Therapies vs Ab mediated rejection (steroids, anti-thymocyte globulin, soluble CTLA-4)
Agglutination between blood types
ABO Ags define blood groups; recognition of allo-Abs -> agglutination
Graft versus host disease
Occurs after HSC transplant i.e. bone marrow
- Mature T cells from graft attack host; similar to T cell autoimmunity
Types of immunodeficiencies
- Primary (congenital)
- Secondary (acquired
Primary (congenital) immunodeficiency
- Caused by gene defects, rare, inherited
- Present early
- Usually autosomal recess. or X-linked
- Suscept. to recurrent infections, viral cancers
Common defects = lymphocyte maturation/activation, effector defects
- Many req. bone marrow transplant
- Maternal IgG protects for first 6 months of life
Chronic Granulomatous Disease (CGD)
Primary innate immune deficit
- Phagocyte oxidase complex Mx -> reduced ROS production -> inhib. pathogen killing
- Granulomas form due to recognition w/o degradation
Leukocyte Adhesion Deficiency (LAD)
Primary innate immune deficit
- Cell trafficking defect
- LAD-1 Mx -> CD18 (integrin beta chain)
- LAD-2 Mx -> E/P-selectin ligand defect
- Issues w/ transport to infection sites or LNs
- Increased WBC count
Complement deficiencies
Primary innate immune deficit
- C3 gene Mx -> no functional complement pathways
- Suscept. to pyogenic bacteria (opsonization), Neisseria infections (MAC)
Primary adaptive defects in lymphocyte maturation
- SCID
- Bare lymphocyte syndrome
- DiGeorge’s Syndrome
SCID
Severe Combined ImmunoDeficiency
- Loss of T+B cell function
- B cell functional defect may be secondary to T cells
- X-linked
- Autosomal recessive
X-linked SCID
- Mx in cytokine R gamma chain gene -> signal tranduction defect for many cytokines
- T/NK cell deficiency w/ secondary humoral deficiency
Autosomal recessive SCID
Secondary to ADA, PNP deficiency OR to RAG1/2 Mx
- Adenosine deaminase
- Purine Nucleoside Phosphorylase
Toxic purine metabolite buildup -> dividing T cell loss -> secondary B deficit
Bare Lymphocyte Syndrome
MHC II Mx -> no MHC II; lymphocytes nonfunctional
DiGeorge’s Syndrome
Fetal developmental defect -> complete/partial missing thymus
- T cell defect, normal B cells
Primary B cell defects
- X-linked agammaglobulinemia
- X linked hyper IgM syndrome
X-linked agammaglobulinemia
- BTK defect -> B cell maturation failure
X-linked hyper IgM syndrome
CD40L Mx -> no class switching; nearly all Abs stay IgM
