Transcript Characteristics of Immune Cells

September 27, 2016
Characteristics of Immune
Cells
Christa Chun
Yujin Lee
Cathy Nguyen
Jin Roh
PHM142 Fall 2016
Instructor: Dr. Jeffrey Henderson
What is an immune cell?
• Part of the immune system that provides non-specific and
specific defence against pathogens
Immune System
Innate (non-specific)
1. Granulocytes
2. Natural Killer cells
Adaptive (Specific)
MONOCYTE
1. Dendritic Cells
2. Macrophages
1. T cells
2. B cells
Granulocytes
1. Basophils (< 1% of circulating
WBC)
• Allergic response and
inflammation
• High-affinity immunoglobulin
E receptors (FcεRI)
• IgE bind to α-subunit
• Release inflammatory
mediators (eg. histamine)
and cytokines (eg. IL-3, IL-4)
Garman, S.C., et al (2000)
Granulocytes
2. Eosinophils (4-6% of
circulating WBC)
• Combat infection,
allergic reaction
• Eosinophilia
• High-affinity
interleukin-5 receptor
(IL-5R)
• Release of cytotoxic
contents
Maskal, P. (2004)
Granulocytes
3. Neutrophils (50-60% circulating WBC)
•
•
First responder to site of infection
• Pattern Recognition Receptors
(Toll-like receptors, C-type lectin
receptors, NOD-like receptors)
• Fc receptors (Fcγ, FcγRIIA,
FcγRIIIB)
Release cytotoxic granules to attack
target cells and release cytokines to
recruit other immune cells to site
Scordino, T. (2016)
Granulocytes
4. Mast cells
•
•
•
•
Similar in function to
basophil cells
Allergic response and
inflammation
High-affinity immunoglobulin
E receptors (FcεRI)
Release of inflammatory
mediators, cytokines, and
cytotactic factors
Radinger, M. K. (n.d.) from LAD/NIAID/NIH
Natural Killer Cells
• Activating and inhibitory
receptor mechanism
• Inhibiting receptors (KIR,
LIRs) ligated by MHC class I
molecules
• Activating receptors (NKG2D)
ligated by MHC class Irelated proteins (MICA, MICB)
and UL16-binding proteins
(ULPB1-5)
Dendritic Cells (DC)
• Hematopoietic stem and
progenitor cells(HSPC) in bone
marrow
• Resident, migratory and
inflammatory DCs
• Major antigen-presenting cells
• Connection between adaptive
and innate
• Toll like receptors for
discrimination between foreign
and host
Macrophages
• Phagocytosis of apoptotic and
necrotic cells, and cell debris
• Secretes inflammatory
mediators such as cytokines
and chemokinesn for signalling
• Antigen presentation and
activation of T and B cells
• Wound healing and tissue
repair
B-cells and T-cells
• The most abundant lymphocytes:
– B lymphocytes (often simply called B cells) and
– T lymphocytes (likewise called T cells).
• Lymphocytes are one of the five kinds of white blood
cells or leukocytes), circulating in the blood.
• B cells are produced in the bone marrow.
• The precursors of T cells are also produced in the bone
marrow but leave the bone marrow and mature in
the thymus.
T-Cell and B-Cell receptors
• Each B cell and T cell is specific for a particular antigen.
(each is able to bind to a particular molecular structure)
• The specificity of binding resides in a receptor for antigen
• Both BCRs and TCRs:
– integral membrane proteins
– present in thousands of identical copies exposed at the
cell surface
– encoded by genes assembled by the recombination of
segments of DNA
– a unique binding site.
– This site binds to a portion of the antigen called
an epitope.
Primary Immune Response: clonal expansion results in the
generation of effector T cells and memory T cells
effector cells
plasma cellz
effector CD4+ (Th) cell
effector CD8+ (CTL)
memory cells
memory B cell
naïve cells
B cell
naive Th cell
naive CTL
memory
Th cell
memory CTL
Days after exposure to a pathogen
Where?
• The TCR binds a bimolecular complex displayed at the surface
of some other cell called an antigen-presenting cell (APC).
Naïve
Th Cells
Naïve
CTLs
Effector CTLs
effector Th cells
CD4+ (Helper T-cells) and CD8+ (Cytotoxic T-cells)
Which of these molecules is present determines what types of cells the
T cell can bind to.
• CD8+ T cells bind epitopes that are part of class I
histocompatibility molecules (MHC I).
– Almost all the cells of the body express class I molecules.
• CD4+ T cells bind epitopes that are part of class II
histocompatibility molecules (MHC II).
– Only specialized antigen-presenting cells (APC) express class II
molecules. These include:
• dendritic cells (mature)
• phagocytic cells like macrophages and
• B cells!
B-Cells
•
•
•
•
•
Adaptive Immune
Produce Antibodies
Humoral Immunity
Antigen presenting
Memory Cell
How B-Cells Make Antibodies
1.Expression of proteins that promote survival
2.Antigen presentation, Increased B7
3.Increased Cytokine receptors
4.Increased CCR7
1. Antigen uptake and processing, B cell activation - CCR7
2. B present antigen to activated helper T cells in T-cell zone
3. Initial T-B interaction produces short lived plasma cells
4. Rest of T-B cells migrate to germinal center and go through somatic
mutation to produce high affinity antibodies, memory B cell, isotype switching.
B-Cell Receptor
•
Antigen in native form
•
Antigen in blood or lymph
using membrane bound B
cell receptor
Sources Of Antibody Diversity
• VDJ recombination
• Somatic
hypermutation
• Recombination
inaccuracy
• Assortment of heavy
and light chains
Types Of B-Cells
Follicular B Cell
(Spleen)
● Protein Antigen
● Helper T-cell
Marginal zone B Cell & B-1 Cell
(Mucosal, Tissue)
Polysaccharide
(Mucosal,
Tissue)
● Polysaccharide, Lipid, T-independent, IgM,
shortlive
● Lipids, Polysaccharide, T-independent, IgM,
shortlived
Antibody
Def.
Immunoglobulin: any protein in serum that functions as
antibody (Y shaped)
IgM : Predominant in Primary Immune response
IgG : Opsonize (phagocytosis easier), activates
complement, longer half life than IgM
IgE: Worm infection, hypersensitivity
IgA: tears, saliva, prevents microorganism
IgD: fuction is elusive
Summary
•
•
•
•
•
•
Neutrophils are first responders to site of infection
• Pattern Recognition Receptors recognize pathogens via PAMPs
Eosinophils combat infection
Basophils and mast cells involved in allergy response
• FcεRI receptor binds IgE with high affinity
• release of inflammation mediators & cytotactic signals
NK cells: inhibitory/activating receptors
• ligated by MHC class I molecules/MHC class I-related protein
Dendritic cells are antigen presenting cells.
• Mechanism: DCs encouter tumor cells => cell death => DCs capture antigens from
tumors => Present them to MHC => Activates T-cells => Tumor lysis
Macrophages are phagocytic cells
• Ligand binding to phagocytic receptors => Activates signalling patyways =>
Rearrangement of actin cytoskeleton => Internalization of pathogen into vacuole =>
Acdification and lysosome degradation of pathogen => Present antigen to T and B
cells
● T lymphocyte (T cell) and B lymphocyte (B cell) are the most abundant lymphocytes.
● Both B cell receptors and T cell receptors are integaral membrane proteins and bind to a portion of the antigen called
an epitope.
● TCR (T cell receptors) binds a bimolecule complex displayed on the surface of antigen presenting cell (APC).
● CD8+ T cells bind epitopes that are part ofMHC class I.
● CD4+ T cells bind epitopes that are part of MHC class II.
○ Only specialized antigen-presenting cells (APC) express class II molecules.
■ dendritic cells (mature)
■ phagocytic cells like macrophages and
■ B cells
● B cell is part of adaptive immunity. It can become either plasma cell (secretes antibodies) and memory cells.
● Activation of B cells increase cytokine receptors, increase B7 expression for T cell interaction, and express proteins to
promote survival and cell cycling.
● Diversity of Antiodies comes from VDJ recombination, somatic hypermutation, and recombination inaccuracy of heavy
and light chain reassortment.
● B cell is activated by antigen uptake and this will lead to CCR7 increase on B cells which will lead B cell to T cell zone.
Then B cell will be activated by interacting with T cells. Initial T-B cell interaction will produce short lived plasma cells.
Rest of T-B cells migrate to light zone and dark zone of Germinal Center. Now, B cell will start making high affinity
antibodies through hypermutation and also produce long lived memory B cells.
Reference
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