Transcript January 6, 2014 - Immunology Overview

An Overview of the Immune System
Elizabeth Crabb Breen, MT(ASCP), Ph.D.
Associate Professor
David Geffen School of Medicine at UCLA
Co-Director, Inflammatory Biology Core Laboratory
UCLA Cousins Center for Psychoneuroimmunology
a) The cells of the immune system
b) Essential cell surface molecules
c) Innate immune responses
d) Adaptive immune responses
i. What happens in an antibody response?
ii. What happens in a cell-mediated response?
a) The cells of the immune system
Figure from Parham, P., 2000, The Immune System, Garland Publishing
Figure from Parham, P., 2000, The Immune System, Garland Publishing
Figure from Parham, P., 2000, The Immune System, Garland Publishing
b) Essential cell surface molecules
MONOCLONAL ANTIBODY =
HOMOGENEOUS PREPARATION OF ANTIBODY
MOLECULES, ALL OF WHICH RECOGNIZE THE
SAME ANTIGEN
Produced by hybridomas, which are
clones of cells resulting from the fusion of a
normal, antibody-secreting B cell
and an immortal myeloma cell
CLUSTER OF DIFFERENTIATION (CD) =
ALL MONOCLONAL ANTIBODIES
THAT REACT WITH A PARTICULAR
LEUKOCYTE MEMBRANE MOLECULE
As of 2010 HLDA Workshop, up to CD363;
HDLA  HCDM
http://www.hcdm.org/HLDA9Workshop/tabid/60/Default.aspx
Commonly used CDs:
Cell Types
CD3: ALL T CELLS
CD4: T HELPER CELLS
CD8: T CYTOTOXIC CELLS
CD19, 20, 21: B CELLS
CD14: MONOCYTE/MACROPHAGE
CD16, CD56: NATURAL KILLER CELLS
Activation, Differentiation Markers
CD25: Interleukin-2 Receptor
CD28: Co-stimulatory receptor on T cells
CD34: Stem cell marker
CD38: Activation marker
•
MHC = MAJOR HISTOCOMPATABILITY COMPLEX
in humans: HLA = HUMAN LEUKOCYTE ANTIGENS
MHC
CLASS
I
II
HLA TYPES
A, B, C
LOCATION
VIRTUALLY ALL
NUCLEATED CELLS
DP, DQ, DR
B CELLS, MONOCYTES/
MACROPHAGES,
DENDRITIC CELLS;
ACTIVATED T CELLS
Markers of self vs. non-self
ANTIGEN RECEPTORS
Required for specificity of immune system
B cells: membrane-bound immunoglobulin
a.k.a. B cell receptor (BCR)
T cells: T cell receptor (TCR)
Figure from Parham, P., 2000, The Immune System, Garland Publishing
Responsible for tremendous diversity
of immune system
Dr. Breen ,
c) Innate immune responses
Anatomic, Physiologic barriers
• Intact skin
• Salivary enzymes
• Stomach acid
• Etc.
If breached  rapid but non-specific responses to
low dose, low virulence antigen/pathogens
Inflammation
• PMNs, monocyte/macrophage = phagocytosis
• Induction of complement cascade, acute phase
proteins (C’-reactive protein or CRP)
• Fever response (Interleukin 1 or IL-1)
c) Innate immune responses
Rapid but non-specific responses to
low dose, low virulence antigen/pathogens
Inflammation
• phagocytosis
• complement cascade, acute phase proteins
• fever response
Non-specific cell-mediated responses
• abnormal cells  NK cells
Figure from Parham, P., 2000, The Immune System, Garland Publishing
c) Innate immune responses
Rapid but non-specific responses to
low dose, low virulence antigen/pathogens
Inflammation
• phagocytosis
• complement cascade, acute phase proteins
• fever response
Non-specific cell-mediated responses
• abnormal cells  NK cells
• bacteria  “toll-like receptors” (TLR)
Figure from Kindt, Goldsby, & Osborne, 2007, Kuby Immunology 6th Ed., W.H. Freeman and Co.
c) Innate immune responses
Rapid but non-specific responses to
low dose, low virulence antigen/pathogens
Require no previous exposure to antigen
Do not improve with repeated exposure to same antigen
d) Adaptive (antigen-specific) immune responses
Four hallmarks of specific immune responses:
1. Self/non-self recognition
2. Specificity
3. Diversity
4. Memory
Immunologic Memory
Faster response, Greater magnitude, Longer duration
Figure from Kindt, Goldsby, & Osborne, 2007, Kuby Immunology 6th Ed., W.H. Freeman and Co.
Immunologic Memory
» Faster response
» Greater magnitude
» Longer duration
“Citius, Altius, Fortius”
(Faster, Higher, Stronger)
Photo by E. Rosenberger,
from Games of the XXIIIrd Olympiad Los Angeles 1984 Commemorative Book
Not cleared by innate response and/or
high dose, high virulence antigen/pathogens
2 types of antigen-specific immune responses:
HUMORAL RESPONSE
CELL-MEDIATED RESPONSE
HUMORAL RESPONSE = antibodies produced by
immunoglobulin-secreting B cells (plasma cells)
• Directed against soluble antigens, i.e., freefloating bacteria, proteins, etc.
CELL-MEDIATED RESPONSE = killing of cells by
cytotoxic T lymphocytes (CTL)
• Directed against infected/defective cells, nonself cells
What happens in an antibody (humoral) response?
What happens in a cell-mediated response?