CHAPTER III - MHC & CYTOKINES Flashcards
– discovered how to fuse lymphocytes to produce a cell line that is both immortal and a producer of specific antibodies
Georges Kohler and Cesar Milstein (1975)
- Purified antibodies cloned from a single cell.
MONOCLONAL ANTIBODIES
- Exhibit purity and specificity
MONOCLONAL ANTIBODIES
- Able to recognize and bind to a specific antigen
MONOCLONAL ANTIBODIES
- Used in-vitro diagnostic testing
MONOCLONAL ANTIBODIES
- Immunoglobulins derived from a single clone of cells
MONOCLONAL ANTIBODIES
- Process of producing Mab’s takes 3 to 6 months.
MONOCLONAL ANTIBODIES
Used to treat various types of cancers
MONOCLONAL ANTIBODIES
- metastatic breast cancer
Trastuzumab (Herceptin)
- an antibody directed against HER-2/neu
protein
Trastuzumab (Herceptin)
-present in large numbers on tumor cells
Trastuzumab (Herceptin)
- has been helpful in slowing the disease’s progress
Trastuzumab (Herceptin)
- non-Hodgkin lymphoma
Rituximab (Rituxan)
- approved by the FDA
Cetuximab (Erbitux)
- colorectal cancer
Cetuximab (Erbitux)
- head and neck cancers
Cetuximab (Erbitux)
- approved by the FDA
Beva-cizumab (Avastin)
- lorectal, non-small lung, and breast cancers
Beva-cizumab (Avastin)
- Identifying and quantifying hormones
USES OF MONOCLONAL ANTIBODIES
- Typing tissue and blood and delivering immunotherapy
USES OF MONOCLONAL ANTIBODIES
- Identifying infectious agents
USES OF MONOCLONAL ANTIBODIES
- Identifying clusters of differentiation for the classification of leukemias and lymphomas and follow-up therapy
USES OF MONOCLONAL ANTIBODIES
- Identifying tumor antigens and autoantibodies
USES OF MONOCLONAL ANTIBODIES
First named as “?” by a French scientist named Dausset
Human Leukocyte Antigen (HLA)
o Observed in responses of circulating WBCs
MAJOR HISTOCOMPATIBILITY COMPLEX
- Tightly linked cluster of genes
MAJOR HISTOCOMPATIBILITY COMPLEX
o Products of MHC plays a role in intracellular recognition of Ags and in the discrimination of self from nonself
MAJOR HISTOCOMPATIBILITY COMPLEX
- Participates in the development of Humoral-MI and Cellular-MI
MAJOR HISTOCOMPATIBILITY COMPLEX
- Partly determines response of an individual to antigens of
infectious disease and graft rejection
MAJOR HISTOCOMPATIBILITY COMPLEX
o Determines whether a transplanted tissue is histocompatible (to reject or to accept and organ for receipient)
MAJOR HISTOCOMPATIBILITY COMPLEX
o Organ donation considers blood type and compatibility of donor with recipient’s major histocompatibility genes
MAJOR HISTOCOMPATIBILITY COMPLEX
- Implicated in susceptibility to disease and development of autoimmunity
MAJOR HISTOCOMPATIBILITY COMPLEX
- Genes are found on the short arm of chromosome 6
MAJOR HISTOCOMPATIBILITY COMPLEX
– locations where the alleles are present
Loci
– alternative form of a gene found on the same chromosome
Allele
CLASS 1 MOLECULE
Loci
Coded for three different loci
• A, B and C
CLASS 1 MOLECULE
Chain structure
• a-chain and B2- microglobulin
CLASS 1 MOLECULE
Cells distribution
Expressed on all nucleated cells
• Highest on lymphocytes
• Low or undetected on liver, neural cells, muscle cells and sperm
CLASS 1 MOLECULE
Function
Presentation of peptide antigen to Tc cells (T cytotoxic cells/CD8 cells)
CLASS I1 MOLECULE
Loci
Coded for several loci
• DR, DQ and DP
CLASS I1 MOLECULE
Chain structure
a-chain and b-chain
CLASS I1 MOLECULE
Cells distribution
Antigen Presenting Cells
• B- lymphocytes, monocytes, macrophages and dendritic cells
CLASS I1 MOLECULE
Function
Presents processed antigenic peptides to Th Cells
CLASS II1 MOLECULE
Loci
Encodes for components of the complement system and inflammation
CLASS II1 MOLECULE
Chain structure
—-
CLASS II1 MOLECULE
Cells distribution
—-
CLASS II1 MOLECULE
Function
Secreted proteins that have immune function but are not expressed on cell surface
• Bone marrow – 1st
MOST IMMUNOGENIC
• Skin
MOST IMMUNOGENIC
• Islets of Langerhans
MOST IMMUNOGENIC
• Heart
MOST IMMUNOGENIC
• Liver
MOST IMMUNOGENIC
• Bone
MOST IMMUNOGENIC
• Xenogeneic valve replacements
MOST IMMUNOGENIC
• Cornea
LEAST IMMUNOGENIC
- located at a privilege site; not patrolled by the immune system; easier to transplant
• Cornea
- Polypeptide products that will control a variety of cellular response, thereby regulating the immune response
CYTOKINES
- Assists in regulating the development of immune effector cells
CYTOKINES
- Cytokine activity produces several cascades leading to rapid
generation of innate and adaptive immune response
CYTOKINES
- Under the humoral-mediated immunity
CYTOKINES
- Low molecular weight regulatory proteins or glycoproteins
secreted by the WBC and various other cells in the body in
response to a number of stimuli
CYTOKINES
- Named based on their activities and types of cell from which they were isolated
CYTOKINES
- Over 200 different cytokines
CYTOKINES
- Most fall into one of the following families:
hematopoietins,
interferons, chemokines and tumor necrosis factors
o Major:
TNF, IF, TGF, CSF