Phagocytosis and Immunogenicity Flashcards
Which molecules are secreted during phagocytosis?
-Reactive oxygen and nitrogen species (ROS and RNS) generate free electrons (O(-), H2O2, NO) to kill pathogens
-protective mechanism by host and some pathogens:
-> Catalase and glutathione (GSH) converting H2O2 to H2O
What are common Immunodeficiencies in the innate immune system?
-Complement activation: genes and pathways
-C4 defects: failure to activate complement (no C2/C4 )
-Entire Alternative pathway failure
-for bacterial/fungal infections:
often due to defects in late complement components C5–C9 and MBL formation
What are the outcomes of NK-cell deficiencies (innate)?
-susceptibility to viral infections and cancer
-occur in lymphoid lineage development or NK development
itself
-
How do innate Immunodeficiencies impact the adaptive immune system?
-Mendelian susceptibility to mycobacterial diseases
-usually in IFN signaling (Cytokines) or receptor pathways
-leads to problem in getting rid of intracellular bacterial infections (like mycobacteria)
Innate Immunodeficiencies in Granulocytes:
Chronic granulomatous disease
-> Defect in NADPH oxidative pathway (to generate ROS)
-> antifungal/antibacterial drugs needed
Chediak-Higashi syndrome
-> disorder of lysosomal storage and transport leading to o recurrent bacterial infections
-> antibacterial treatments or bone marrow transfusion
What is the structure of Immunoglobins?
(Ab, or B-cell receptors with transmembrane domain)
- two identical heavy chains and two identical light chains connected by disulfide bonds
How is the heavy chain generated?
-Through recombination of the Heavy-chain gene V, D, J, and C segments -> producing single expressed VDJ segment
-Eight CH regions for different isotypes (IgM, IgD, IgG, IgA, and
IgE)
How is the light chain generated?
-Light-chain genes include V, J, and C segments with 2 types: lambda and kappa
-T cell receptors have a similar composition
What is the meaning of Central Tolerance?
– The deletion of lymphocytes in the primary lymphoid organs
for B-cells: Bone marrow
for T-cells: Thymus
What is the meaning of peripheral Tolerance?
-occurs outside bone marrow and thymus
Outcomes are:
-apoptosis of the self-binding lymphocyte
-state of anergy: functionally inactivated
- production of inhibitory lymphocytes (pTreg) suppressing the immune response
What is an epitope?
-the specific binding sites of single TCRs and BCRs
Any part of an Ag can be an epitope
What are T-cell and B-cell epitopes?
T-cell receptor
-typically a fragment of the linear protein polypeptide chain
B-cell receptor: bind the 3D protein
-can be linear or conformational
1. Conformational: Determinant lost after denaturation
2. Lineal: Ig binds to determinant in denatured protein only or Ig binds the determinant in native or denatured protein
3. new determinant created by proteolysis
Explain T-dependent B-cell responses
-require help from T cells
BCR binds to Ag -> ingest it and displays a piece on MHC-II to T-helper cell
-> secretion of cytokines by T-helper cell
-often for peptide PAMPs
-T-cells helps the B-cell to switch Isotypes (from M,D to D,A,E)
Explain T-independent B-cell responses
-exposure to multivalent/polymerized Ag is required to activate B-cells without the help of T-cells (binding of a few PAMPs won’t activate a B-cell)
-also for non-peptide PAMPs (lipids, carbohydrate, nucleic acid)
-> TI-1 Ag includes bacterial cell wall components and LPS binding to PRRs (TLR) and BCR
-> TI-2 Ag. crosslink a large number of BCR
How does the body react to incompatible blood transfusions?
- Attachment of antibodies to donor blood -> triggering complement proteins
