Download (b) activate the adaptive immune response

#3 Anatomy of the Immune System I
Immunology 297
July 28, 2015
Ikuo Tsunoda, MD, Ph.D.
Associate Professor
Department of Microbiology and Immunology
LSUHSC
Homepage: http://tsunodalaboratory.web.fc2.com/
E-mail: [email protected]
Textbooks and online
resources
2007
2014
Cellular and Molecular Immunology:
with STUDENT CONSULT Online
http://www.oup.com/uk/orc/defranco/
http://www.oup.com/uk/orc/bin/9780199206148/ Access, 8e (Abbas, Cellular and
Molecular Immunology)
2011
http://lib-sh.lsuhsc.edu/ebooks/ebooks.php
Dictionary
Stedman's Medical Dictionary - 28th Ed. (2006)
Immune
1. Free from the possibility of acquiring a given
infectious disease; resistant to an infectious
disease.
2. Pertaining to the mechanism of sensitization in
which the reactivity is so altered by previous
contact with an antigen that the responsive
tissues respond quickly on subsequent contact,
or to in vitro reactions with antibody-containing
serum from such sensitized people. [L.
immunis, free from service, fr. in, neg., + munus
(muner-), service]
•The term immunity; derived from the Latin word
immunitas, which was referred to the protection from
legal prosecution offered to Roman senators during
their tenures in office
•Historically, immunity meant protection from
infectious disease
•The cells and molecules responsible for immunity
constitute the immune system
•Their collective coordinated response to the
introduction of foreign substances is called the
immune response
•The physiologic function of the immune system is
defense against infectious microbes
•Noninfectious foreign substances can elicit immune
responses
1-0 Overview: The Protective Mechanisms of Immunity
•The immune system protects us against
infectious organisms
•Four pathogens
•Virus
•Bacteria
•Fungus
•Parasites
•The first critical barrier to infectious
disease are the skin and the mucosal
epithelia of the gastrointestinal, respiratory
and urogenital tracts
Three lines of protection against infectious agents
• Natural barrier
– Restrict entry of infectious agents; skin, mucus, gastric acid
• Innate immune response
– Antigen-nonspecific; interferon, complement, neutrophil,
macrophage
• Adaptive immune response
– Antigen specific; antibody and T cells
Table 2-3
Barriers to Infection
• Skin and mucous
membranes serve as
barriers
• Free fatty acid, lactic
acid, low pH
• Mucosal epithelium
protected by mucus
and cilia
• Antimicrobial
substances
(defensins,
lysozyme, lactoferin)
γδ T cells, B1 B cell (natural antibody), mast cells
Janeway’s Movie 3-6 Lymphocyte Homing
https://www.facebook.com/photo.php?v=876855242363491
Two waves of the immune response
innate
adaptive
Immune mechanisms are divided
into those of innate immunity
and adaptive immunity
Innate immunity
• Distinguish host cells from
those of infectious agents by
recognizing conserved
constituents of microorganisms
• Activated within hours
• Phagocytes: neutrophils and
macrophages
Adaptive immunity
• Recognize a variable component
of microorganisms
• Effective after 96 hours (4 days)
• B and T lymphocytes
Two waves of the immune response
Two waves of the immune response
The nonspecific innate immune response is critical to control the
early stages of infection and the extent of pathogen replication
and spread.
The adaptive immune response provides a mechanism to
specifically target foreign pathogens, protecting the host from
excessive damage.
PMN: polymorphonuclear cell, neutrophil
MAC: macrophage
T/B: T and B lymphocytes
1-1 Cells of the Immune System:
Differentiation in the bone marrow
Hematopoietic stem cell in the bone marrow gives rise to all immune
cells (white blood cells), red blood cells (erythrocytes) and
megakaryocytes, whose fragments form platelets that initiate blood
clotting
The primary lymphoid organs
Sites where cellular components of immunity are generated
 All precursor cells are generated in the
bone marrow.
 Myeloid lineage cells develop in the
bone marrow.
 B lymphocytes mature exclusively
in the bone marrow.
 T lymphocytes start in the bone
marrow as pre-T cells, but develop into
mature T cells in the thymus.
Cytokines (haematopoietins) promote
differentiation of immune cells
• Erythrocytes: erythropoietin
• Megakaryocyte (platelets): thrombopoietin
• Lymphoid and myeloid cells: interleukins (IL) and
colony-stimulating factors (CSFs)
• Cytokines are produced constitutively by a
number of different cell types
• Infection induces the production of cytokines by
immune cells and non-immune cells
All white
blood cells
(WBCs)
develop
from the
HSC
Effector cells can
activate or destroy
other cells
WBCs derive from common progenitors
Myeloid lineage
Figure 1-5 Cells of the myeloid lineage
•Granulocytes / polymorphonuclear
leukocytes (PMNs)
•Neutrophil
•Eosinophil
•Basophil
•Monocyte / macrophage lineage
cells
•Monocyte
•Dendritic cell
•Macrophage
•Mast cells
Neutrophils are
the most
abundant WBC
•Basophils and
mast cells release
molecules
including
histamine,
important
mediators of
allergic responses
•PMNs are
distinguished
by the different
staining
properties of
the granules
• faint stain:
neutrophil
• red:
eosinophil
• blue:
basophil
•Short-lived (a
few days)
Figure 2-1
A. Neutrophil
B. Mast cell
C. Basophil
D. Eosinophil
Mast cell
•Blood-borne precursor
is not well defined
•Defense against
parasites (helminth)
•Allergic diseases
•Blue (basophilic)
granules
Monocyte / macrophage
lineage cells
Myeloid lineage
“phagocytes”
[phago- + G. kytos, cell]
phagoto eat]
Eating, devouring. [G. phago,
PMNs, Polymorphonuclear
leukocytes, neutrophils
Polymorphonuclear: Possessing a nucleus
consisting of several parts or lobes
connected by fine strands
Mononuclear: Having one nucleus, particularly
a blood cell such as a monocyte or lymphocyte
Mononuclear cell (MNC) = monocyte and
lymphocyte
Monocytes
A and B. Monocyte; C. Macrophage
Figure 2-6
IV_10_2_Chemotaxis-H264
(Janeway’s Immunobiology)
Phagocytosis of intracellular destruction of microbes
http://www.studentconsult.com/content/9780323054706/abbas_sped-up_animations/index.html
Macrophages induce the inflammatory response
macrophages encounters antigen
activation of the macrophage
phagocytosis
killing
induction of inflammatory response
neutrophils
complement
pro-inflammatory cytokines
Inflammatory response
An immune process involving components of innate immune
response, especially macrophages and neutrophils
Inflammation
A pathologic process consisting of a dynamic complex
of histologically apparent cytologic changes, cellular
infiltration, and mediator release that occurs in the
affected blood vessels and adjacent tissues in response
to an injury or abnormal stimulation caused by a
physical, chemical, or biologic agent, including the local
reactions and resulting morphologic changes; the
destruction or removal of the injurious material; and the
responses that lead to repair and healing. The cardinal
signs of inflammation are rubor, redness; calor, heat (or
warmth); tumor, swelling; and dolor, pain; a fifth sign,
functio laesa, inhibited or lost function, is sometimes
added. All these signs may be observed in certain
instances, but none is necessarily always present. [L.
inflammo, pp. -atus, fr. in, in, + flamma, flame]
Stedman's Medical Dictionary - 28th Ed. (2006)
Inflammation
•A protective response to get rid of damaged or
necrotic tissues and foreign invaders, such as
microbes and toxins
•A complex reaction in tissues that consists of
responses of blood vessels and leukocytes
•Acute inflammation versus chronic inflammation
•Inflammation may be harmful in some situations;
immunopathology
Characterized by
four signs :
• rubor (redness)
• calor (heat)
• tumor (swelling)
• dolor (pain)
http://globalwarming-arclein.blogspot.com/2011/01/inflammation-thoughts.html
Infection triggers inflammation
The accumulation of fluid and cells causes the
redness, swelling, heat and pain
Acute inflammation
• A rapid host response that serves
to deliver leukocytes and plasma
proteins to sites of infection or
tissue injury
• 1) Expansion of vascular caliber to
increase blood flow
– Causing redness or a rash and
releasing heat
– 2) Increase in permeability of the
microvasculature structure to allow
escape of fluid, plasma proteins,
and leukocytes from the circulation
• Swelling, edema
– 3) Recruitment and activation of
leukocytes
Edema: a local or generalized condition in which body tissues
contain an excessive amount of tissue fluid in the interstitial
spaces
Two roles of phagocytes of
innate immunity
 Release cytokines and chemokines
which are signaling molecules with
a wide range of functions: eg.
interleukin (IL)-1, IL-6, tumor
necrosis factor (TNF)
 Activate the adaptive immunity
phagocytes (dendritic cells) display
a component (antigen) of
microoorganism for recognition by T
cells (antigen presentation), and
activate T cells
Antigen: molecule or part of a molecule
recognized by antibody or T cell
receptor
Macrophages and dendritic cells are known as
“antigen presenting cells” (APCs): they engulf
pathogens and present antigens to activate T cells
The innate response acts very early to:
(a) control the pathogen
(b) activate the adaptive immune response
Figure 1-1: Innate and adaptive immunity.
The mechanisms of innate immunity provide the initial defense against infections. Adaptive immune responses develop later and
require the activation of lymphocytes. The kinetics of the innate and adaptive immune responses are approximations and may vary
in different infections. ILC, innate lymphoid cell; NK, natural killer.
PAMPs
Table 2-1
1-3 Macrophage and Dendritic Cell Subsets
Macrophage
•Defense against
infection, scavenging
debris and tissue
repair and
maintenance
•Spleen; marginal
zone macrophage,
metallophilic
macrophage
•Brain; microglia
•Lung; alveolar
macrophage
•Liver; Kupffer cell
•Bone; osteoclast
Figure 2-2: Maturation of mononuclear phagocytes.
Tissue resident macrophages, which differentiate into specialized forms in particular organs, are derived from precursors in the yolk sac and
fetal liver during fetal life. Monocytes arise from a precursor cell of the myeloid lineage in the bone marrow, circulate in the blood, and are
recruited into tissues in inflammatory reactions, where they further mature into macrophages. Subsets of blood monocytes exist, which have
distinct inflammatory or reparative functions (not shown).
Dendritic cell
•Antigen capture and the
induction of T cell responses to
protein antigen
•Epidermis; Langerhans cell
•Dermis; dermal dendritic cell
•Blood; plasmacyotoid dendritic
cell
Follicular dendritic cell
(FDC)
•Lymph nodes, spleen, mucosal
lymphoid tissues
•Not derived from bone marrow;
non-hematopoietic cell
•Capture antigen for recognition
by B cells
NK cells
•Large granular
lymphoid-like cells
•Kill tumor cells and
infected cells
•Lack antigen specific
receptor
•Part of the innate
immune system: Group
1 innate lymphoid cell
(ILC)
New online resources
http://www.oup.com/uk/orc/defranco/
http://www.oup.com/uk/orc/bin/9780199206148/
1-1 Cells of the Immune System:
Differentiation in the Bone Marrow
1. Which of the following cells belong to the myeloid lineage?
a)
macrophages
b)
neutrophils
c)
mast cells
d)
NK cells
2. Which of the following statements are true?
a)
Hematopoietins do not stimulate the production of myeloidlineage cells.
b)
Growth factors required for the production of different
types of hematopoietic cells are produced both
consititutively by some tissue cells and inducibly by tissue
cells and immune cells in response to infection.
c)
Interleukins are cytokines that signal between immune cells
and can also serve as growth factors for specific cell types.
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