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Microbiology 204: Cellular and
Molecular Immunology
Class meets MWF 11-12:30
Lectures are open to auditors
Discussions are restricted to those
enrolled in class (or by permission)
Textbook recommended: Janeway et al
Immunobiology or Abbas and Lichtman
Cellular and Molecular Immunology
Microbiology 204: Cellular and
Molecular Immunology
Grades: 2/3 take-home final and 1/3
participation in discussions
My office hours: Mondays 4-5PM HSE1001F
([email protected])
The central questions
• How does the immune system respond to different
infections?
– Microbes are recognized by two mechanisms, evolved
broad recognition mechanisms (innate immunity), and by
highly specific lymphocyte antibodies and T cell receptors
(adaptive immunity)
– Different types of microbes are eliminated by different
effector mechanisms, which are designed to best combat
each type of microbe
• Why does the immune system not respond to self
antigens?
• What are the pathogenic mechanisms and clinicopathologic consequences of abnormalities in the
immune system?
Cells of the immune system
• Lymphocytes
– Mediators of adaptive immune responses; only
cells with specific receptors for antigens
• Antigen-presenting cells (APCs)
– Specialized to capture, concentrate, and display
antigens for recognition by lymphocytes
– Dendritic cells; macrophages, B cells; follicular
dendritic cells
– Different APCs serve different roles in adaptive
immune responses
• Effector cells
– Function to eliminate microbes; include
lymphocytes, granulocytes (neutrophils,
eosinophils), macrophages
Cells of the
myeloid
lineages
Innate vs. Adaptive Immunity
Examples of Innate Immune Recognition
Inna te Imm une componen t
Recogn it ion Property
Func tion
Toll-li ke receptors
Cell wall compon ents;
Nuc leic acids
Trigge r inflamm ation
Promote adaptive response
Coll ectins
Carbohyd rate structures
Agg lutination, phagocy tosis,
complement activation
Alt ernative p athway of
complement
Membranes lacking p roteins
that block it
Damage to cell s; promote
phagocy tosis
Apop totic sensors wit hin
cells (p53, etc.)
Stress wit hin c ell,
uns chedu led DNA repli c.
Presenc e of dsRNA
Killi ng o f vir us-infected cell
Principal mechanisms of defense against microbes
Antibodies
Phagocytes
T cells (CTLs)
(may work with antibodies, T cells)
All microbes
All microbes
Intracellular
microbes, esp.
viruses
Pathogen recognition by adaptive
immunity: great variety, selectivity
Great variability of antigen recognition
is created by combination of gene
segments during lymphocyte
development
Two types of T cells
CD Nomenclature
•
•
•
Structurally defined leukocyte surface molecule that
is expressed on cells of a particular lineage
(“differentiation”) and recognized by a group
(“cluster”) of monoclonal antibodies is called a
member of a cluster of differentiation (CD)
CD molecules (CD antigens, CD markers) are:
• Identified by numbers
• Used to classify leukocytes into functionally
distinct subpopulations, e.g. helper T cells are
CD4+CD8-, CTLs are CD8+CD4• Often involved in leukocyte functions
Antibodies against various CD molecules are used to:
• Identify and isolate leukocyte subpopulations
• Study functions of leukocytes
• Eliminate particular cell populations
Two types of MHC
Coordination of properties with functions of two types
of T cells: source of peptide and cells expressing
Two types of T cells: coordination of function
with properties of antigen-presentation
CD4 T cells
.
Help other immune cells
Recognize peptide + MHC II
MHC II is expressed
primarily on immune cells
Peptides are from
endocytosed antigen
CD8 T cells
.
Kill virus-infected cells
Recognize peptide + MHC I
MHC I is expressed on all
nucleated cells
Peptides are from cytosolic
antigen
Generation of lymphocytes
of many specificies
Clonal deletion to remove
self-reactive lymphocytes
Clonal selection to expand
pathogen-reactive
lymphocytes during an
immune response
Anatomy of the
lymphoid
system
Anatomy of a
lymph node
Naïve lymphocytes
circulate between
blood and lymphoid
tissues; antigen in
tissue arrives at
draining lymph node
via lymph flow and
being carried by
dendritic cells
Mechanism for
directing the
immune response
against microbes
and not against
self, food, etc.
Applies to B cells
and T cells
For T cells:
costimulatory
molecules include B7-1
and B7-2 on dendritic
cells
Sequence of Events in an
Immune response
Stages of lymphocyte activation
• Naïve lymphocytes
– Mature lymphocytes that have not previously encountered
antigen; function -- antigen recognition
– Preferential migration to peripheral lymphoid organs (lymph
nodes), the sites where immune responses start
• Effector lymphocytes
– Activated lymphocytes capable of performing the functions
required to eliminate microbes (‘effector functions”)
– Effector T lymphocytes: cytokine secretion (helper cells),
killing of infected cells (CTLs)
– B lymphocytes: antibody-secreting cells (e.g. plasma cells)
• Memory lymphocytes
– Long-lived, functionally silent cells; mount rapid responses
to antigen challenge (recall, or secondary, responses)
Immune responses often can be
characterized as type 1 or type 2
• Type 1 immune
responses: Killing
microbes
– Pro-inflammatory;
neutrophils and
macrophages
– Antibody classes
involved in
phagocytosis and
complement activ.
– Macrophage
activation
• Type 2 immune
responses: Defense at
epithelium
– Allergic inflammation:
eosinophils, basophils
– Antibody classes: IgE
and IgG1 (mast cell
activation)
– Expulsion type
reactions (diarrhea,
coughing, sneezing,
etc.).
LYMPHOCYTE DEVELOPMENT
Congenital immunodeficiency diseases are often caused by blocks
at different stages of lymphocyte maturation
The Immunoglobulin Superfamily
(a few examples)
Integrins: Regulated Cell-cell and
cell- ECM adhesion
Cytokine receptor families
Chemokines: lymphoid or homeostatic chemokines