Transcript Chapter 2
Chapter 2
Cells and Organs of the Immune System
Dr. Capers
Kindt • Goldsby • Osborne
Kuby IMMUNOLOGY
Sixth Edition
Chapter 2:
Cells and Organs
of the Immune System
Copyright © 2007 by W. H. Freeman and Company
Hematopoiesis
All blood cells arise from Hematopoietic
Stem Cells (HSC)
Study of these cells is difficult
○ Scarce
○ Difficult to grow in vitro
Hematopoiesis
Early in hematopoiesis, stem cell
differentiates to either
○ Lymphoid progenitor cell
○ Myeloid progenitor cell
- Progenitor cells have lost ability for self renewal
and are committed to particular cell lineage
Organized hierarchy
Most of proliferation
takes place in
differentiated
precursors (that are
NOT self-renewing)
rather than
hematopoietic stem
cell
Lowers chance of
cancer
Hematopoiesis
Regulated at gene level
○ Transcription factors play important roles in
hematopoiesis
○ Studies using “knockout” mice
- Gene inactivated, if RBC or a particular WBC fails
to develop, it is concluded that protein was involved
in development of that cell
Hematopoietic Homeostasis
Erythrocyte
○ Average life span: 120 days
○ Phagocytosed by macrophages in spleen
WBC - LEUKOCYTES
○ Life spans from 1 day to 20-30 years
Apoptosis – programmed cell death
Normal WBC
WBC going through
apoptosis
Cells of the Immune System
Lymphocytes
○ 20-40% of WBC
○ 3 populations
- B cells
- T cells
- Natural Killer Cells
Lymphocytes
B cells and T cells
Adaptive immunity
Small lymphocytes
Those that have not interacted with antigen
are called naïve
Interaction with antigen – proliferation into
effector cells (i.e. plasma cells) and memory
cells
Lymphocytes
B and T cells
Lymphocytes
B Lymphocytes (B cells)
Site of maturation
○ Bursa of fabriscus in birds
○ Bone marrow in mammals
Display membrane-bound immunoglobulin
(antibody)
Once antigen is encountered:
Differentiation
- Plasma cells – antibody can be secreted, die within 12 weeks
- Memory B cells – same membrane-bound antibody
as parent B cell, longer life span
Lymphocytes
T Lymphocytes (T cells)
Site of maturation
○ Thymus
T cell receptor
○ Only recognize antigen that is bound to cell membrane
proteins called major histocompatibility complex (MHC)
○ Once antigen in encountered with MHC:
Differentiation
- Effector T cells
- Memory T cells
2 subpopulations
T helper (TH)
T cytotoxic (TC)
And now T regulatory (Treg)
Lymphocytes
T helper cells
○ CD4 glycoprotein
○ “help” activation of B cells, TC cells,
macrophages in immune response
Lymphocytes
T cytotoxic cells
CD8 glycoprotein
Recognition of MHC-antigen complex
initiates differentiation into effector cell called
cytotoxic T lymphocyte
Eliminates infected cells or cancerous cells
Lymphocytes
T regulatory cells
CD4 and CD25 glycoproteins
Help suppress the immune system
Lymphocytes
Natural Killer Cells
Innate immune response
Large, granular
Recognize tumor or virus-infected cells
CD16 – which can recognize a region of
antibody that has attached to cell infected by
virus
Other Leukocytes
Mononuclear phagocytes
Monocytes circulate in blood and then migrate into
tissue and differentiate into specific macrophage
Macrophages
Intestinal macrophages in gut
Alveolar macrophages in lung
Histiocytes in connective tissue
Kupffer cells in the liver
Mesangial cells in the kidney
Microglial cells in the brain
Osteoclasts in bone
Activated macrophages are more effective than resting ones
Other Leukocytes
Mononuclear phagocytes
○ Complex antigens are phagocytized, the resulting
phagosome fuses with a lysosome
○ The digested antigen is then eliminated through
exocytosis
- Some of it is presented on membrane on MHC
○ Phagocytosis is enhanced when antibody is
attached to the antigen
- Antibody acts as opsonin: molecule that binds to both
antigen and phagocyte
Macrophage and bacteria
Other Leukocytes
Granulocytes
○ Neutrophils
○ Eosinophils
○ Basophils
Other Leukocytes
Granulocytes – Neutrophils
Multi-lobed nucleus, light granules
1st to arrive at site of inflammation
High #’s is 1st indication of infection
Phagocytize
Generate antimicrobial agents
Other Leukocytes
Granulocytes – Eosinophils
Phagocytize
Play a role in parasitic organisms
Other Leukocytes
Granulocytes – Basophils
Nonphagocytic
Play a role in allergic reactions
Other Leukocytes
Mast cells
Play important role in development of
allergies
Other Leukocytes
Dendritic cells
Long membranous extensions, look like
dendrites on nerve cells
Antigen presentation
4 major groups:
Langerhans DC
Interstitial DC
Monocyte-derived DC
Plasmacytoid-derived DC
Follicular dendritic cells
Involved with B cell maturation
Organs of the Immune System
Primary
○ Thymus and bone marrow
○ Place of maturation of lymphocytes
Secondary
○ Lymph nodes, spleen, mucosa-associated
lymphoid tissues such as gut-associated
lymphoid tissues
○ Mature lymphocytes interact with antigen
Primary Lymphoid Organs
Bone marrow
Lymphocytes arise there, T cells go to
thymus to mature
B cells mature here
90% of plasma IgG and IgA comes from B
cells in the bone marrow
Primary Lymphoid Organs
Thymus
○ T cell development and maturation
○ Bilobed organ above heart
- Surrounded by capsule and divided into lobules
- Outer part of lobule is cortex, inner is medulla
- Network of epithelial cells, dendritic cells, and
macrophages
○ Thymus will induce death of those T cells that
can’t:
- Recognize self-MHC molecules
- Those that interact with MHC molecules too strongly
(could produce autoimmune disorder)
○ Function decreases with age
Lymphatic System
Interstitial fluid (the portion that doesn’t
enter venous system) is returned to
circulatory system by lymphatic vessels
Largest lymphatic vessel – thoracic duct
○ Enters left subclavian vein
○ Lymph from right arm and right side of head enters
through right lymphatic duct, drains into right
subclavian
Antigen is carried by lymph to lymph nodes
Secondary Lymphoid Organs
Primary follicle
Unactivated lymphoid
follicle
Secondary follicle
Follicle that is
activated by antigen
Ring of B cells that
surround germinal
center
Proliferating B cells
and T helper cells
Secondary Lymphoid Organs
Lymph Nodes
Encapsulated
3 regions:
○ Cortex
B cells, macrophages, dendritic cells
Primary follicles
○ Paracortex
T cells, dendritic cells
○ Medulla
Plasma cells secreting antibody
Secondary Lymphoid Organs
Spleen
Filters blood, traps blood-bourne antigens
○ Important in systemic infections
Blood enters through splenic artery
Encapsulated
Structure:
○ Projections from capsule form trabeculae
○ Compartments:
Red pulp
- Macrophages, red blood cells
White pulp
- Surrounds branches of splenic artery
- Forms PALS (periarteriolar lymphoid sheath)
- Primary follicles rich in B cells
Secondary Lymphoid Organs
Mucosa-Associated Lymphoid Tissue
MALT
Organized areas along digestive, respiratory,
and urogenital tracts
Very well organized areas in intestine are referred to
as Peyer’s patches
Includes tonsils and appendix