Properties of Cells involved in the Immune Response
Intro
- all blood cells and Lymphocytes come from pluripotent stem cells in the bone marrow
- We can distinguish stem cells from other bone marrow components
- Developmental Pathway
Platelets, Erythrocytes, Eosinophils, Neutrophils, Basophils, Monocytes, Macrophages
Myeloid Stem Cell
Bone Marrow Pluripotential Stem Cell
Lymphoid Stem Cell
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T Cell Precursor B Cell Precursor
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Thymus Mature B Cells (B cell areas)
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Mature T Cell
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TH, TDTH, TC, TS (effector cells)
Cluster Determinants
- monoclonal antibodies permitted the ID of many surface proteins on lymphocytes and other cell types
- CD-Specific antibodies have been useful for:
- determining functions of CD proteins
- IDing the distribution of CD proteins in different cell populations in normal individuals
- measuring changes in proportion of cell carrying these markers in patients (esp. HIV)
- developmenting therapeutic measures for increasing or decreasing the numbers or activities of certain cell populations
Top 6 CDs (as stated in class)- someday we will order tests to determine levels of these in patients
T Cell Markers
1. CD3- T cells and precursors expressing TCR; vital importance in TCR structure
2. CD4- TH and TDTH cells; immature T cells; Binds to MHC Class II; involved in interaction with APCs
3. CD8- TC and TS cells; binds to MHC class I; inv. in interaction w/ APCs;
B Cell Markers
4. CD19- B cells; used to ID B cells
NK Cells (Fc receptors)
5. CD 16/56- Null lymphocytes, granulocytes, some T cells and macrophages
Leukocytes during development
- “Don’t worry about numbers, these change. What doesn’t change is the proportions.”
Age Other Leukocytes/mm3 to Lymphocytes
Birth 15-25,000 Low
2 weeks 40 60
4 YEARs 50 50
>14 yrs 60 40
- Important to remember is the magic number of 4 years, because this is when the % of lymphocytes is less than the other Leukocytes
- After 14 years, for the rest of normal life, the Lymphocytes proportion should normally be 40:60, with less lymphocytes than other leukocytes.
Development of B lymphocytes
- These are distinguishing markers of the different cells in B cell development
- Pre-Pre B Cell- VDJ rearrangement of m chain
- Pre B cell- Cytoplasmic m chain and MHC Class II molecules
- Immature B cell- VJ rearrangement of L chain and synthesis of IgM
- Mature B cell- synthesis of IgM and IgD
Proliferation and Differentiation occurs
- Plasma Cells and Memory cells with surface Ig
Important B Cell Markers
- prior to Ag exposure, B cells express monomeric surface IgM and IgD
- Antigen-specific receptor- required for B cell activation
- After antigen exposure, memory B cells have undergone class switching and now have IgG, IgA, or IgE
- Fc receptors- may suppress B cell function by Ag-spec. serum Ab
- CD19, CD20- may serve as receptors for hormones, T cell products like cytokines
- CD21= Complement Receptor 2 (CR2) and CD35= CR1
- EBV binds to CD 21 infecting B cells
- MHC Class I and Class II (APCs)
Development of B lymphocytes
- Selection of T cells in the Thymus
- Negative selection
- Apoptosis (not necrosis)
- Destined to die
- components retained and recycled
- programmed cell death
- Positive Selection
- selecting developing T cells capable of reacting with foreign Ag associated with either class I or Class II MHC proteins
Important T Cell Markers
- TcR and CD3 complex- “Beans and Cornbread”; they go together
- CD4- on THELPER cells
- CD8- on TCYTOTOXIC cells
- MHC Class I
- MHC Class II- only on activated cells
- CD2- on all T cells
T Cell Receptor
- remember 90% ab and 10% gd, never both
- binds to antigen fragment- MHC protein complexes
- GENES
- ag use V and J gene seg., like light chains
- bd use V,D,and J like heavy chains
- gd type may be used in mucosal immunity
- lack CD4, but may have CD8 (CD8 or nothing)
- have CD3
CD3 Complex
- 6 invarient proteins that bind noncovalently with the TcR
- all T cells
- mediates signal transduction into the cell leading to cell activation
CD4 and CD8
- both are on immature T cells; then one gets lost
- selection of CD4 or CD8 determines function
- CD8- MHC Class I
- CD4- MHC Class II
Adhesion molecules
- “Get em rounded up together in a close packed bunch and hook them bad boys up (Antigen) to the T cell.
- LFA-3 (CD2), ICAM-1(LFA-1)
Subsets of CD4 T cells
1. BOTH produce IL-2, and IL-10, and IL-3
TH1 subset
- help in cellular immunity (T cells)
- produce IFNg
- CD45Ro, CD29
TH2 Subset
- help in Humoral Immunity (B cells)
- produce IL-4,5,6
- CD45RO, but not CD29
Null Lymphocytes
- Non-B or non-T lymphocytes
- CD 16/56
- LGL=NK cell (Large granulolymphocyte)
- Two activities
- Natural Killer activity
- can kill in absence of Ag-specific receptors (Don’t need no license)
- Antibody-Dependent Cellular Cytotoxicity (ADCC)
- activates NK cells; can recogniz & kill cells that are coated with Ab by binding Ab via Fc receptor
Antigen Presenting Cells
- Class I (CD8) and Class II (CD4) MHC
- Express adhesion proteins
- “KNOW THESE TYPES AND LOCATIONS”; “Remember Langerhans cells are a cousin or identical twin to follicular dendritic cells”
Monocyte- Blood
Macrophage- Various tissues
Follicular dendritic cell (Langerhans)- Secondary follicles of lymph nodes)
Interdigitating reticular cell- Paracortical regions of lymph nodes
Langerhans cell- SKIN
B cells- Various tissues
Tags: adhesion molecules, Basophils, bone marrow, CD8, D4, Eosinophils, erythrocytes, Langerhans, Lymphocytes, lymphoid, Macrophages, Monoclonal Antibodies, Monocytes, Myeloid Stem Cell, Neutrophils, Null Lymphocytes, Platelets, Pluripotential Stem Cell, T cell markers, T Cell Receptor, TcR and CD3 complex, thymus
