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
What type of molecules are blood group Ag?
Difference between blood groups A and B?
Carbohydrates,
N-acetyl-galactosamine on antigen A, missing on Ag B
Describe different types of allergies
Type 1: Ag causes crosslink between IgE-bound mast cell and basophils -> release of granules -> vasoactive mediator
Type 2: Ab (IgM, IgG) mediates cell destruction through complement activation or antibody-dep.-mediated-cytotoxicity (ADCC) -> often on red blood cells
Type 3: Ab-Ag complex induce complement activation -> and massive neutrophile recruiting -> huge inflammatory response
Type 4: delayed-type hypersensitivity (DTH): sensitized T-cell release cytokines activating macrophages or Tc cells -> tissue damage
What is the difference between type II hypersensitivity and autoimmunity?
In type II hypersensitivity antibodies are against non-self targets on cells (Transfusion reaction)
In autoimmunity, B cells detect self-antigens and produce auto-antibodies
Why is screening for maternal Rh factors important?
Rh-negative maternal blood develops antibodies when the fetus is Rh-positive during 1st pregnancy
In 2nd pregnancy with Rh-positive fetus blood -> the mother’s antibody binds the fetus’s red blood cells and activates the complement system
How can drugs cause Hemolytic Anemia?
-drugs can bind non-specifically to proteins on RBC membranes
stimulating antibody production -> Ab on red blood cells activates the complement system
-f.e. Penicillin
How can drugs cause T cell response, in addition to antibody response?
Other compounds like penicillin can covalently (permanently)
attach to proteins and change the structure of the protein
-> That protein is no longer self and can also generate Tcell response
How does Urushiol in poison ivy cause Dermatitis?
Modified proteins (by Urushiol?) are taken up by DCs, carried to regional lymph nodes, and presented on MHC class II -> TH1 formation
-Th1 returning to the skin, activating macrophages -> release of inflammatory cytokines, lytic enzymes, ROS causing tissue damage
What is the benefit of Conjugated vaccines?
A conjugated vaccine improves immunogenicity and
outcome
-> a molecule causing a weak immune response, coupled with an antigen with a strong immune response
thereby stimulating the preferred immune response to the weak molecule
example: H. influenza vaccine coupled with tetanus toxoid -> activates T-cells and induces B-cell memory
