Title: Cell-Cell Interactions, T-Independent Antigens, CD5 B Cells, Cytokines
1Cell-Cell Interactions, T-Independent Antigens,
CD5 B Cells, Cytokines
2T Cell-B Cell Interactions(hapten-carrier effect)
- Th cells recognize carrier, B cells recognize
hapten - Th and B cells cooperate by interacting
- Interactions are class II self-MHC restricted
3Uniqueness of B Cells
- Express both immunoglobulin (Ig) and class II MHC
on cell surface - Capable of producing antibody of same specificity
as that of its surface Ig - AND
- Capable of functioning as an antigen presenting
cell
4Mechanism of Hapten-Carrier
- Hapten recognized by Ig receptor on B cell
- Hapten-carrier endocytosed
- Carrier processed and presented on class II MHC
to Th cell - Activated Th cell produces cytokines
- Cytokines enable B cell to be activated to
produce anti-hapten antibodies
5 Antigen
CD40
T helper cell
TCR
B cell
B cell
MHC II
1. Antigen presentation to Th cell
CD28
B7
2. B7 expressed
Immunoglobulin receptor
3. Th cell is activated and expresses CD40
ligand, Cytokines secreted
Cytokine receptor
4. Cytokine binds to cytokine receptor, CD40
ligand binds to CD40
CD40 ligand
T helper cell
B cell
5. B cell activated
Cytokine
6. B cells proliferate, differentiate, secrete Ig
6 7B cell takes up and presents antigen
Th cells are primed by antigen-presenting cell
B-T cell cooperation B cells receive signals from
T cells
B cells divide
8B Cells In Secondary Responses
- Memory cells created during primary response
- Have high-affinity Ig receptors
- Can therefore take up antigens at much lower
concentrations than other antigen presenting
cells that lack Ig antigen receptors
9Thymus-Independent Antigens
- Activate B cells at high concentrations
- Large polymeric molecules with repeating
determinants - Poorly degraded
- Some activate both immature and mature B cells
some only mature cells - Responses dominated by CD5 B cells
10CD5 B (B-1) Cells
- First B cells appearing in development
- Express surface IgM, little or no IgD
- Produce mainly IgM from unmutated or minimally
mutated germline genes - Antibodies are of low avidity and bind multiple
different antigens (polyreactive) - Contribute most of the IgM in adult serum
11CD5 B Cells (continued)
- Do not develop into memory cells
- Are self-renewing
- Reside in peripheral tissues
- Predominant lymphocyte in peritoneal cavity
12CD5 B Cells and Conventional B Cells
13Tumors of B Cells
Tumor Equivalent normal cell
Location
Chronic lymphocytic leukemia
CD5 B-1 B cell
Blood
Lymphoid progenitor
Acute lymphoblastic leukemia
Bone marrow Blood
Pre-B cell leukemia
Pre-B cell
Periphery
Follicular center cell lymphoma Burkitts lymphoma
Mature B cell
B cell IgM secreting
Waldenstroms macroglobulinemia
Multiple myeloma
Plasma cell secreting various Ig isotypes
Bone marrow
Adapted from Immunobiology Janeway/Travers
Garland
14Cytokines
- Non-antibody proteins acting as mediators
between cells, termed - Monokines mononuclear phagocytes
- Lymphokines activated T cells, especially
helper T cells - Interleukins abbreviated IL with a number
15Properties of Cytokines
- Produced by cells involved in both natural and
specific immunity - Mediate and regulate immune responses
- Secretion brief and limited
- not stored pre-formed
- synthesis initiated by gene
transcription - mRNA short-lived
- cytokines produced as needed
16Properties of Cytokines(continued)
- Can be produced by many cell types and act on
many cell types (pleiotropic) - Can have similar actions (redundant)
17Properties of Cytokines (continued)
- 6. Can influence synthesis of other cytokines
- - produce cascades
- - enhance or suppress production of other
cytokines - - exert positive or negative regulatory
mechanisms for immune responses - Influence action of other cytokines - can be
antagonistic, additive, synergistic
18Properties of Cytokines (continued)
- Bind to receptors with high affinity
- Cells responding to cytokine can be
- - same cell (autocrine)
- - nearby cell (paracrine)
- - distant cell by circulation (endocrine)
- Cellular responses to cytokines are slow, require
new mRNA and protein synthesis
19Mediators and Regulators of Natural Immunity
- Tumor Necrosis Factor-alpha (TNF-a)
- Interleukin-1 (IL-1)
- Chemokines (Chemotactic cytokines)
- Type I Interferons (IFN-a and IFN-ß)
- Interleukin-12 (IL-12)
- Interleukin-10 (IL-10)
20Tumor Necrosis Factor (TNF-a)
- Produced by activated macrophages
- Most important mediator of acute inflammation in
response to microbes, especially Gram-negative
bacteria (LPS) - Mediates recruitment of neutrophils and
macrophages to site of inflammation - Acts on hypothalamus to produce fever
- Promotes production of acute phase proteins
21Interleukin-1 (IL-1)
- Produced by activated macrophages
- Effects similar to those of TNF-a
22Chemokines
- Produced by many different leukocytes and tissue
cells - Large family of gt50 substances
- Recruit leukocytes to sites of infection
- Play a role in lymphocyte trafficking
23Type I Interferons (IFN-a and ß)
- IFN-a a family of many proteins produced by
macrophages, IFN-ß a single protein produced by
many cells - Both IFNs inhibit viral replication
- Both increase expression of class I MHC
- Both activate NK cells
24Interleukin-12 (IL-12)
- Produced by activated macrophages and dendritic
cells - Stimulates production of IFN-?
- Induces differentiation of Th cells to become Th1
cells - Enhances cytolytic functions of cytotoxic T cells
and NK cells
25Interleukin-10 (IL-10)
- Produced by activated macrophages, Th2 cells
- An inhibitory cytokine
- Inhibits cytokine production by activated
macrophages - Inhibits expression of class II MHC and
costimulatory molecules on macrophages
26Mediators and Regulators of Specific Immunity
- Interleukin-2 (IL-2)
- Interleukin-4 (IL-4)
- Interleukin-5 (IL-5)
- Interleukin-10 (IL-10)
- Interferon-gamma (IFN-?)
27Interleukin-2 (IL-2)
- Produced by ThgtgtTc
- Main growth factor for T cells
28Autocrine Function of IL-2
29Interleukin-4 (IL-4)
- Produced by Th2 cells
- Stimulates Ig class switching to IgE isotype
- Stimulates development of Th2 cells from naïve Th
cells - Promotes growth of differentiated Th2 cells
30Interleukin-5 (IL-5)
- Produced by Th2 cells
- Promotes growth and differentiation of
eosinophils - Activates mature eosinophils
- IL-4 and IL-5 can work together Helminths
opsonized with IgE can be killed by activated
eosinophils
31Interleukin-10 (IL-10)
- Produced by activated macrophages, Th2 cells
- Inhibits production of IFN-? by Th1 cells needed
to activate macrophages
32Interferon-gamma (IFN-?)
- Produced by Th cells gtgt Tc and NK cells
- Numerous functions in both natural and specific
immunity
33Stimulators of Hematopoiesis
Colony-Stimulating Factors (CSF)
- Granulocyte-macrophage CSF (GM-CSF) promotes
growth and differentiation of bone marrow
progenitors - Macrophage CSF (M-CSF) is involved in development
and function of monocytes and macrophages - Granulocyte CSF (G-CSF) stimulates production of
polymorphonuclear leucocytes (PMN)
34Cytokines Regulate Ig Class Switching
- Fc region of antibodies determines effector
function in different anatomical locations - Class (isotype) switching produces class or
subclass of antibody most effective in host
defense - Cytokines acting alone or in combination regulate
class switching
35Cytokine Network
- Many cytokines have effects on many cells and
organ systems in addition to functions in immune
systems - Referred to as the cytokine network
36Effects on Cells of Immune System
Activation of cells of immune system
Proliferation, Differentiation, Ig secretion and
selection
Proliferation, Differentiation, Cytokine productio
n
Cytokine production
IL1 IL2 IL4
IL1 IL2 IL4 IL5 IL6 IFN?
cytokines
37Cytokine Effects on Organ Systems
38Cytokine Effects on Various Cells