Download cells of the immune system

Lecture Outline
Lymphocytes
T-cells
B-cells
Natural Killer (NK) cells
Acquired Immune Responses
Humoral
Cell-mediated
Antigen Presentation
(Introduction)
Cytokines
CELLS OF THE IMMUNE SYSTEM
THE LYMPHOCYTES (25-40% of WBC)
CELLS OF THE IMMUNE SYSTEM
THE LYMPHOCYTES
T-lymphocytes (T-cells)
-Different subpopulations:
-helper T-cells, cytotoxic/suppressor T-cells, intraepithelial
lymphocytes (IELs)
-Subpopulations of helper T-cells: TH1 & TH2 cells
-Specific molecules or surface “markers” (i.e. CD4 and CD8)
-T cell receptor (TCR).
-T cells mature and further develop in the thymus.
-Destroy infected cells, Cytokine Production, and Memory
T-lymphocytes are Generated in the Thymus
Specific molecules or surface “markers” of T-cells
TCR !
CELLS OF THE IMMUNE SYSTEM
THE LYMPHOCYTES
B-lymphocytes (B-cells)
-Mature and develop in lymphoid tissues.
-The antibody producing cells of the immune system.
-Antibody secreting B-cells are also known as Plasma Cells.
-B-cells also express antibody (immunoglobulins) on their surface.
-Surface expressed antibody is called the B-cell receptor (BCR).
-Clonal expansion of antigen-specific B-cells.
-Exhibit immunological memory.
Antibody production, Antigen Presentation, Memory
Specific molecules or surface “markers” of B-cells
BCR !
B-cells and T-cells are both found in Lymph Nodes
CELLS OF THE IMMUNE SYSTEM
THE LYMPHOCYTES
Natural Killer (NK) cells
-Large granular lymphocytes.
-Central cell of innate immune responses.
-Participates in Cell Mediated Immune (CMI) Responses.
-Efficient at recognizing and killing pathogen-infected host cells.
-Also recognize and destroy damaged or altered host cells (i.e. tumors).
-Not antigen specific.
-NK-specific markers include;
-CD56+ (CD3 negative)
-Killer Ig-like Receptor (KIR+)
-Low affinity FcR (CD16+)
-Do NOT express TCR nor BCR!
COOPERATION, COORDINATION, and
COMMUNICATION
The WBC of the immune system work together through a
variety of complex interactions to defend the host.
These interactions are essential and have evolved to rid the
body of pathogens and other foreign substances.
There are two sites at which pathogens may be located:
1. Extracellular sites
2. Intracellular sites
Depending on the location of the pathogen, the immune
response can be;
1. Humoral
2. Cell mediated (CMI)
Innate
Humoral
Acquired
Cell Mediated
CD4+
TH1
TH2
CD8+
HUMORAL RESPONSE (TH2)
vs. EXTRACELLULAR PATHOGENS
Antibodies are important for;
Neutralization
-Bind to bacterial toxins.
-Bind to molecules that pathogens use to attach to host cells.
Opsonization
-Facilitate uptake of pathogens by phagocytes.
Complement Activation
-Complement factors also act as opsonins.
-Lyses of certain bacteria.
** Antibodies are NOT effective vs. intracellular pathogens **
1. Neutralization
http://pathmicro.med.sc.edu/bowers/toxin-endo1.jpg
2. Opsonization
http://pathmicro.med.sc.edu/bowers/bact1.jpg
3. Complement
Activation
http://pathmicro.med.sc.edu/
bowers/bact-comp.jpg
CELL-MEDIATED RESPONSE (TH1)
vs. INTRACELLULAR PATHOGENS
Intracellular pathogens can reside in;
Cytosol
-Continuous with nucleus via nuclear pores.
-Site of viruses and some bacteria.
-Cells harboring pathogens in cytosol are recognized and killed by
cytotoxic CD8+ T cells.
CELL-MEDIATED RESPONSE (TH1)
INTRACELLULAR PATHOGENS
Intracellular pathogens can reside in;
Vesicular System
-Comprises the endoplasmic reticulum (ER), Golgi apparatus, endosomes,
lysosomes, and other intracellular vesicles.
-Site of bacteria and some parasites.
-Cells with pathogens in vesicular system are recognized by helper T cells
(TH1), which then release products called cytokines that enable the
infected cell to kill the pathogen.
Complex Cellular Interactions
During Immune Responses
Antigens
bacterial
viral
CD4+
WBCs
APC; macrophages
T-cells
B-cells
CD4+
Receptors
TCR
BCR
CD4, CD8, MHC
Soluble Proteins
Cytokines
Antibodies
CD8+
Antigen Presentation
CD4+
CD4+
CD8+
INITIATION OF RESPONSES
DETECTION, PROCESSING & PRESENTATION of Antigens
TH1 cytokines
CD4+
TH2 cytokines
CD4+
CD4+
CD8+
Humoral Response
(TH2)
HUMORAL RESPONSE
Response to EXTRACELLULAR PATHOGENS
CD4+
Produce
Antibodies
CD4+
CD4+
Cell-Mediated
Response
(TH1)
CD8+
CELL-MEDIATED RESPONSE
INTRACELLULAR PATHOGENS
CD4+
CD8+
CYTOKINES
“Hormones” of the Immune System
The complex interactions among cells of the immune
system are mediated by a group of proteins
known as cytokines
-Also referred to as Lymphokines, Interleukins, and Chemokines.
-Cytokines are produced by a wide variety of cells types.
-Cytokines can have effects on both nearby cells or throughout the body.
CYTOKINES
CYTOKINE ACTIONS
CYTOKINE-MEDIATED RESPONSES
Effects of Cytokines on cells can be:
Pleiotropic
-Cytokine elicits different biological activities in different cell types.
Redundant
-Different cytokines can mediate similar responses.
Synergistic
-The combined effect of two different cytokines greater than the effect of
either cytokine alone.
Antagonistic
-The effect of one cytokine inhibits the effect of another.
TYPES OF CYTOKINES
Interferons - alpha, beta, and gamma
Interleukins - IL-1 through IL-30
Tumor Necrosis Factor - alpha, beta
Transforming Growth Factor - alpha, beta
Colony Stimulating Factors
Chemokines
CYTOKINES produced by CD4+ Helper T-cells
Cytokine
TH1
TH2
Cytokines produced by helper TH1 and TH2 cells
regulate immune responses
Dominant TH1 Response
Strong cell-mediated immunity.
Dominant TH2 Response
Strong humoral (antibody-mediated) immunity.
Cross-regulation
TH1 cytokines such as Interferon-gamma inhibit TH2 responses.
TH2 cytokines such as IL-4 and IL-10 inhibit TH1 responses.
Interferon-gamma and IL-4
provide different signals
to helper T-cells:
Interferon-gamma acts through
Stat-1 which promotes
TH1 cell activation.
IL-4 acts through Stat 6
which promotes TH2 cell
activation.
The end result
is cytokine induced
cross-regulation of helper
T-cell function