BS Biotchnology Course Lecturs

1. Cellular and Molecular Basis of
Immunity
Lecture-6
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Dr Farheen Bhatti

2. Cytokines are polypeptides secreted by immune and other
cells when the cell interacts with a specific antigen, with
pathogen-associated molecules such as endotoxin, or with
other cytokines. Main categories include
• Chemokines
• Hematopoietic colony-stimulating factors (CSFs)
• Interleukins
• Interferons (IFN-alpha, IFN-beta, IFN-gamma)
• Transforming growth factors (TGFs)
• Tumor necrosis factors (TNF-alpha, lymphotoxin-
alpha, lymphotoxin-beta)
Cytokines
2

3. • Although lymphocytes interact with a specific antigen that
triggers cytokine secretion, cytokines themselves are not
antigen-specific; thus, they bridge innate and acquired
immunity. They may act in an autocrine or paracrine manner.
• Cytokines deliver their signals via cell surface receptors. For
example, the interleukins-2 (IL-2) receptor consists of 3
chains: alpha (α), beta (β), and gamma (γ). The receptor’s
affinity for IL-2 is:
• High if all 3 chains are expressed
• Intermediate if only the beta and gamma chains are expressed
• Low if only the alpha chain is expressed
• Mutations or deletion of the gamma chain is the basis for X-
linked
Cytokines
3

4. • Chemokines induce chemotaxis and migration of leukocytes.
There are 4 subsets (C, CC, CXC, CX3C), defined by the
number and spacing of their amino terminal cysteine residues.
Chemokine receptors (CCR5 on memory T cells,
monocytes/macrophages, and dendritic cells; CXCR4 on
resting T cells) act as co-receptors for entry of HIV into cells.
Chemokines
4

5. Granulocyte-colony stimulating factor (G-CSF) is produced
by endothelial cells and fibroblasts.
The main effect of G-CSF is:
• Stimulation of neutrophil precursors growth
Clinical uses of G-CSF include:
• Reversal of neutropenia after chemotherapy, radiation
therapy, or both
Colony-stimulating factors (CSF)
5

6. Granulocyte-macrophage colony stimulating factor (GM-
CSF) is produced by endothelial cells, fibroblasts, macrophages,
mast cells, and TH cells. The main effects of GM-CSF are:
• Stimulation of growth of monocyte, neutrophil, eosinophil,
and basophil precursors
• Activation of macrophages
Clinical uses of GM-CSF include
• Reversal of neutropenia after chemotherapy, radiation
therapy, or both
Colony-stimulating factors (CSF)
6

7. Macrophage colony stimulating factor (M-CSF) is produced
by endothelial cells, epithelial cells, and fibroblasts.
The main effect of M-CSF is
• Stimulation of monocyte precursor growth
Clinical uses of M-CSF include
• Therapeutic potential for stimulating tissue repair or both
Colony-stimulating factors (CSF)
7

8. Stem cell factor (SCF) is produced by bone marrow stromal
cells.
The main effect of SCF is
• Stimulation of stem cell division
Clinical uses of SCF include
• Therapeutic potential for stimulating tissue repair
Colony-stimulating factors (CSF)
8

9. • IFN-alpha is produced by leukocytes
• IFN-beta is produced by fibroblasts
• IFN-gamma is produced by natural killer (NK) cells,
cytotoxic type 1 (Tc1) cells, and T helper type 1 (Th1) cells.
Interferons
9

10. • IL-1 (alpha and beta) is produced by B cells, dendritic cells,
endothelium, macrophages, monocytes, and natural killer
(NK) cells
• IL-2 to IL-35 have different sites of synthesis and functions
Interleukins
10

11. TGF-beta is produced by B cells, macrophages, mast cells, and
Th3 cells.
The main effects of TGF-beta are:
• Proinflammatory activity (eg, by chemoattraction of
monocytes and macrophages) but also anti-inflammatory
activity (eg, by inhibiting lymphocyte proliferation)
• Induction of switch to IgA
• Promotion of tissue repair
• Clinical trials of TGF-beta antagonists (eg, antisense
oligonucleotides) in cancer are ongoing.
Transforming growth factors (TGF)
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12. The main effects of TNF-alpha include
• Cytotoxicity to tumor cells
• Cachexia
• Induction of secretion of several cytokines (eg, IL-1, GM-
CSF, IFN-gamma)
• Induction of E-selectin on endothelium
• Activation of macrophages
• Antiviral activity
Tumor necrosis factors (TNFs)
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13. The major histocompatibility complex (MHC) is a set of genes
that code for cell surface proteins essential for the acquired
immune system to recognize foreign molecules in vertebrates,
which in turn determines histocompatibility.
Once a T-cell response has been initiated, macrophages and B
cells that have taken up specific antigen also become targets for
armed effector T cells. Dendritic cells, macrophages, and B cells
are often known as antigen-presenting cells (APCs).
Peptides from intracellular pathogens that multiply in the
cytoplasm are carried to the cell surface by MHC class I and
MHC class II and CD4 T cells respectively.
Major Histocompatibility Complex
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14. These T cells can differentiate into two types of effector T cells,
called TH1 and TH2. Pathogens that accumulate in large
numbers inside macrophage and dendritic cell vesicles tend to
stimulate the differentiation of TH1 cells, whereas extracellular
antigens tend to stimulate the production of TH2 cells. TH1 cells
activate the microbicidal properties of macrophages, and induce
B cells to make IgG antibodies that are very effective at
opsonizing extracellular pathogens for uptake by phagocytic
cells. TH2 cells initiate the humoral immune response by
activating naive antigen-specific B cells to produce IgM
antibodies. These TH2 cells can subsequently stimulate the
production of different isotypes, including IgA and IgE, as well
as neutralizing and/or weakly opsonizing subtypes of IgG.
Continued...
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