Immune Cells and Organs

Elizabeth Repasky, Sept. 1, 2016

Dept of Immunology
[email protected]
 Immune system
Purpose/function?
• First line of defense= epithelial integrity=
skin, mucosal surfaces
• Defense against pathogens
– Inside cells= kill the infected cell (Viruses)
– Systemic= kill- Bacteria, Fungi, Parasites
• Two phases of response
– Handle the acute infection, keep it from
spreading
– Prevent future infections
 The Immune
System
“Although the lymphoid
system consists of various
separate tissues and
organs, it functions as a
single entity. This is mainly
because its principal
cellular constituents,
lymphocytes, are
intrinsically mobile and
continuously recirculate in
large number between the
blood and the lymph by way
of the secondary lymphoid
tissues… where antigens
and antigen-presenting
cells are selectively
localized.”
-Masayuki, Nat Rev Immuno. May 2004
 Not all who wander are lost…..

Tolkien

Lord of the Rings

…..some are searching

Overview of the Immune System

Immune System
• Cells
– Innate response- several cell types
– Adaptive (specific) response- lymphocytes
• Organs
– Primary where lymphocytes develop/mature
– Secondary where mature lymphocytes and
antigen presenting cells interact to initiate a
specific immune response
• Circulatory system- blood
• Lymphatic system- lymph
Cells= Leukocytes= white blood cells
Plasma- with anticoagulant
Granulocytes Serum- after coagulation
1. neutrophils
2. eosinophils
Plasma (56%)
3. basophils

Non-granulocytes After centrifugation in

Ficoll, leukocytes are
4. monocytes
found in the “buffy
5. lymphocytes
coat” 1%
RBCs
Where do all these cells come
from?
Cells of the Immune System

The cells of the immune system arise

from pluripotent hematopoeitic stem
cells (HSC) through two main lines of
differentiation
• Myeloid lineage produces phagocytes
(neutrophils..) and other cells
• Lymphoid lineage produces lymphocytes
 Hematopoeisis
• Pleuripotent Hematopoeitic Stem Cells give
rise to second generation stem cells with
restricted lineage potential

A. Hemosiderin: A protein that

stores iron in the body,
derived chiefly from the
hemoglobin released
during hemolysis
B. Erythroid precursor
C. Band cells
• Neutrophil
D. Megakaryocytes
• platelets
(Dog)

Univ Penn, Vet School, http://cal.nbc.upenn.edu/histo

 HSC- Pleuripotent
“First Responders”
Common
Myeloid
Progenitor

Granulocyte
lineage

Eosinophil
Neutrophil
Basophil

(Myeloid = of or
relating to the bone
marrow)
 Granulocytes

• Front line of attack during immune

response~ part of innate immune
response
• Identified by characteristic staining
patterns of “granules”
– Released in contact with pathogens
– Proteins with distinct functions: killing,
regulation of other cells, tissue remodeling
• All have multilobed nuclei
 Neutrophils
• One of the main effector cells in the
innate immune system
• 50-70% of white blood cells
• Released from bone marrow, circulate 7-
10 hrs, enter tissues, live only a few days
• Numbers & recruitment increases during
infections~ “leukocytosis”~ diagnostic
• shown to kill microorganisms by
phagocytosis 100 years ago
• Main cellular component of pus
Neutrophil
• Named based on staining
qualities of granules
• Multilobed nucleus=
polymorphonuclear
leukocyte= PMN
• Neutrophilic granules stain
lightly blue to pink
• 7-10 hrs in blood, then
migrates into tissues
• First responders- Motile &
phagocytic
• “Leukocytosis” indicates
infection
• Extracellular “traps”
http://www.youtube.com/watch?v=f
pOxgAU5fFQ
COVER
Scanning electron micrograph of
Staphylococcus aureus bound to
neutrophil extracellular traps
(NETs). These novel structures
formed by activated neutrophils
can disarm and kill bacteria before
they reach host cells
NETS

neutrophils resting neutrophils activated

Brinkman/Zychlinsky Nat Rev Micro 5: 2007

“Beneficial suicide: why neutrophils die to make
NETS”

Brinkmann et al, Science 303, 2004

Stimulated neutrophil with NETs and some trapped Shigella
(orange). Colored scanning electron micrograph.

Brinkmann: Max Planck Institute for Infection Biology

 Basophil
• <1% all leukocytes
• Non-phagocytic
• Nucleus obscured by
coarse blue (H&E)
granules
• Important in some
allergic responses
• Critical to response to
parasites
• Bind circulating Abs and
release histamine-
increasing permeability
of blood vessels
 Mast Cell

• Leave bone marrow as undifferentiated

cells and mature in tissues; histamine
• May be related to basophils (?)
Eosinophil
• Bilobed nuclei
• Motile, phagocytic
• Killing of antibody
coated parasites
• Degranulation of
substances that
kill parasites,
worms
Myeloid antigen presenting cells:
Monocytes, macrophages, dendritic cells
• Phagocytic
• Ingest, digest into peptides, present on
cell surface
• Bridge between innate and adaptive
immune responses
• Make contact with antigens in periphery
and then interact with lymphocytes in
lymph node
• Secrete proteins that attract and activate
other immune cells
 Pleuripotent Stem Cell

Myeloid
lineage

Monocyte

Monocytes- macrophages & DCs

 Monocyte
• Mononuclear
• Circulate in blood~ 8 hrs
• Bean-shaped nucleus
• Enter tissues and become
fully mature macrophages or
dendritic cells
– Enlarges
– Becomes phagocytic
• Free vs fixed tissue mΦ
– Special names in different
organs- Kupffer cells-liver
• Digest and/or present Ag
• Surface receptors for Abs
(opsinized Ags)
Macrophage
• Monocytes enter tissues and become fully mature macrophages
or dendritic cells
– Enlarge
– Become phagocytic
• Free vs fixed tissue mΦ
– Special names in different organs- Kupffer cells-liver
• Digest and/or present Ag
• Surface receptors for Abs (opsinized Ags)
 Dendritic cells:
heterogeneous myeloid & lymphoid origins
• Best APC for presenting to naïve T-cells
• Ralph Steinman discovered them in mid
1970’s; just received Nobel Prize 2011
• Critical
• Named for long processes; actively extend
and retract sampling Ags & examining T cells
• Capture Ag in one place- then migrate-
present Ag in another place (eg. LN)
• Immature to mature; change in functionality
Hematopoesis (3) Pleuripotent Stem Cell

Myeloid
lineage

Mega-

Platelets
Platelets
Blood Clot: fibrinogen
Hematopoesis (4) Pleuripotent Stem Cell

Myeloid
lineage

Erythroid
Mature human and mouse RBCs have no nuclei

Salamander RBCs
Adaptive Immune HSC-
Response
Lymphoid
lineage

Lymphocytes, NK
 Lymphocytes: 3 types
• 20-40% of WBC
• Cannot be distinguished morphologically
• T-cells
– helper CD4+ recognize Ag in context of MHCII
– cytotoxic CD8+ recognize Ab in MHCI
• B-cells
– become antibody producing plasma cells
• NK cells
– part of the innate immune response
 T and B
Lymphocytes
• Large nucleus with
dense
heterochromatin
• Thin rim of
cytoplasm
• Recognizes
specific antigenic
determinants
• Therefore are
responsible for
specificity and
memory of the
adaptive immune
response
Condensed heterochromatin= resting
Decondensed chromatin= active
 Plasma cell
Perinuclear golgi
and abundant
layers of
endoplasmic
reticulum

Figure 2.8e The Biology of Cancer (© Garland Science 2007)

Usually lives 1-2 weeks
Secretes 100’s- 1000 Ab molecules/sec
 Mononucleosis

• Caused by Epstein-Barr virus

– DNA herpes-types virus
• Infects 2 cell types
– First epithelial cells of salivary gland- virus released in saliva
– Then B lymphocytes via CD21
• Circulating B cells spread virus
– to “reticuloendothelial system (liver, spleen, lymph nodes)
• Symptoms
– Adenopathy, hepatosplenomegaly, fever, pharyngitis
– Characteristic peripheral blood smear showing reactive
lymphocytes
 Dendritic cells Macrophage B-cell

Antigen
Presenting Cells

3 kinds of cells
present Ag to T-
cells

Dendritic cells:
Several types

Capture, process,
present Ag
 Organs of Hematopoesis…

•spleen

Yolk Sac Fetal Liver Bone Marrow

•3 weeks •5-6 weeks •Source of all stem
•Blood islands
•Erythro-myeloid stem
•Seeded from cells in adult
cells both outside •B-cell maturation
•RBC’s are large and sources •T-cells to thymus
nucleated=primitive •Max 6 mos then
•Cannot form lymphoid declines to
progeny
neonatal stage
 Organs of Hematopoesis

Hepatocytes Adipose cells

Bone spicules
Hematopoetic colonies Hematopoetic colonies

Fetal Liver Bone Marrow

 •Tonsils
Organs of the •Lymph nodes 2. Distribution to
Immune •Spleen Secondary lymphoid
organs for engagement
System •Peyer’s
with antigens
Patches
•Appendix

Thymus Bone Marrow

1. Development &
maturation in primary
lymphoid organs
Stem cell
(in bone marrow)
 In birds, the Bursae of Fabricius is the site of B-
cell maturation
• Outpocketing of cloaca day 4-5
• Day 11-12, nodules form from lining: cortex and medulla

Bursae
 Bursae of Fabricius

•In mammals, B-cell maturation occurs

in fetal liver and bone marrow after
birth
Maturation of
T cells-

1. Hematopoesis/
development of myeloid
and lymphoid cells
2. Maturation of myeloid
and B-cells