The Immune System
4BBY1030
Dr. Brian Stramer
[email protected] The Immune System
Aims
To understand the general structure/function of
the immune system.
Objectives
• To understand and have knowledge of the
cellular components of the immune system.
• To be able to distinguish between the innate and
adaptive immune responses.
• To understand how the innate and adaptive
immune responses interact with one another.
• To have a general understanding of the tissues
where the immune components act.
The Immune System
Represents a number of surveillance mechanisms:
• that respond to infection by micro-organisms.
• which can help repair damaged tissues.
• that may help retard cancer development
How?
• The system is capable of recognizing self vs non-self
• Can secrete protective substances into bodily fluids
(humoral immunity)
• Can launch a cellular response
(cellular immunity)
The Immune System
There are several mechanisms which protect the
body before the immune system is invoked.
Barriers
• Both physical and chemical in nature.
• The skin, mucous membranes and cilia are examples of
physical barriers.
• Chemical barriers include mucous and the acidic properties
of the stomach.
• Surface epithelia can secrete specific microbicidal
substances e.g. lysozyme and phospholipase in saliva and
tears, and cryptidins and defensins in the gut.
• Blood also contains antimicrobial substances e.g.
complement
The Two Arms of the
Immune System
Ilya metchnikoff Paul Ehrlich
Innate Immunity Adaptive Immunity
Innate Immunity
Innate Immunity
• Non specific.
• Rapid.
• Response to infections (non-self).
• Response to altered self.
• Can be humoral
• or cell mediated.
Adaptive Immunity
Adaptive Immunity
• Specific.
• Slower to develop.
• Response to infections (non-self).
• Response to altered self.
• Can be humoral
• or cell mediated.
• Has memory.
Cells of the Innate Response
Macrophage Neutrophil
• Highly phagocytic
• Contain lysosomal and microbiocidal proteins which
destroy engulfed bacteria, cellular debris or foreign
particulate matter.
• Neutrophils die after having disposed of their target
• Macrophages can produce new lysosomes and continue to
engulf and destroy foreign material.
Macrophage
s
Macrophages can reside in a tissue or
wander and survive for several weeks or
even months. In certain locations they have
specific names as well as specific functions:
1. Liver - kupffer cells
2. Bone - osteoclasts
3. Kidney – mesangial cells
4. Brain - microglia
They are also found in lung, lymphoid
organs and connective tissue.
Kupffer
Cells
Osteoclasts
Neutrophil Action
Neutrophils
survive for only a
few days on
leaving the
circulatory system
and have to be
constantly
replaced which
explains their high
concentration
among circulating Neutrophil wound response
white blood cells
Other “Killer” Cells
Eosinophil Natural Killer Cell
• Natural killer cells (lymphocyte lineage)
attach to virally infected cells, transplanted
cells, and some tumor cells by causing
pores to form in the target cell membrane
which induces apoptotic death.
• Eosinophils contain granules with cytotoxic
proteins that attach to, and kill, parasites.
Adaptive Immune Cells
• Cells are slower to react than innate
immune cells.
• Respond to a near infinite range of
different organisms.
• Recognize foreign, possibly harmful
substances termed antigens.
• Cells act to neutralize or destroy these
foreign substances.
• Adaptive response can be both cellular
and humoral in nature.
Adaptive Immune Cells
lymphocytes
• Make up about 30% of
WBC population.
• Different functional
classes of lymphocyte:
B Cell
T Cell
• Circulate in the blood
and lymph and become
activated in secondary
lymphoid organs
B vs T cells
B Cells T Cells
• Arise in bone marrow • Arise in bone marrow
• Mature in the bone • Mature in the thymus
marrow
• Activated in 2 lymphoid • Activated in 2 lymphoid
organs organs
• Secrete antibodies • Activated to induce a cell-
specific to the target mediated adaptive
antigen immune response.
• Long term immunity
• Long term immunity
maintained by “memory B
maintained by “memory T
cells”
cells”
T Cells
• Direct and recruit other cells of the immune
system
• as well as attacking diseased cells directly.
• Specific T cell receptors (TCR) are responsible for
recognition of antigen.
There are four functional subsets :
1.Helper T cells - can activate B cells and/or…
2.Cytotoxic T cells - which can specifically kill
infected cells.
3.Regulatory T cells - Help modulate responses.
4.Memory T cells.
B Cells
• Activated by antigen and helped along by helper
T cells
• Secrete antibody when activated.
• Antibodies can then either:
1. neutralize the pathogen
2. facilitate uptake by phagocytes (opsonization).
There are two functional subsets :
1. Plasma cells
2. Memory cells
Antigens
• Substance that may or may not be harmful which
activates the immune system.
• It can be a protein, lipid, carbohydrate, or nucleic
acid.
• Can induce a T cell and/or a B cell response.
Antibodies
• Glycoprotein (immunoglobulins) that interacts
with a specific antigen.
• Can neutralize the antigen (if harmful) or they
can coat the antigen to induce phagocytosis
(opsonization) by macrophages.
• Staggering array of diversity.
~ 5x1013 or 5,000,000,000,000 varieties!!
Antibodies
Antibodies
T Cell Receptor
Diversity generated by a similar somatic
recombination mechanism to antibodies.
~1018 or 1,000,000,000,000,000,000 varieties!!
Lymphocyte
Activation
Antigen
presentation via
an antigen
presenting cell
B T
B
B Th T
T
Clonal Expansion Clonal Expansion
Plasma Cells • T helper
• Cytotoxic
B T
B T
B B B T T
Memory B Cells T Memory T Cells
B T
B B T T
The Link Between Innate and
Adaptive Immunity
The Antigen Presenting Cell (APC):
• Vital for activation of lymphocytes.
• Include macrophages, dendritic cells, and B
lymphocytes.
• The antigen is taken up by phagocytosis by an
APC (e.g. macrophage or a professional APC).
• These cells then migrate to lymphoid tissue to
present antigen to the lymphocytes.
• The antigen is presented on the surface of the
APC and shown to a T cell.
• If the T cell has the correct receptor to bind to
the antigen the immune response will proceed.
The Professional APCs:
Dendritic Cells
Sentinels of the Immune System
• Derived from bone marrow blood cell precursors.
• Reside in many tissues but can also circulate.
• Resident DCs often given special names
dependent on their localization (e.g. langerhans
cells of the skin).
• Often in close contact with the external
environment where they search for antigen.
• Capable of migrating to lymph nodes where they
have a chance to present their antigen to T cells.
Dendritic Cells
Langerhans Cells
The Immune System as a
Defence Organization
1) Its function is selective destruction.
2) It is large, complicated and elaborate.
3) It is expensive.
4) It is wasteful.
5) It has distinct components performing apparently
identical functions.
6) It is slow to react.
7) It is prepared for events that never happen.
8) It fights today’s threats with the solutions of past
problems.
9) It is susceptible to corruption.
10) It can destroy that which it protects.
Parnham Nature 1990; 344;709-11
The Tissues of the
Immune System
The Tissues of the
Immune System
• Primary Lymphoid Tissues - where immature
lymphocytes acquire the capacity for antigen
recognition.
Bone marrow- T cell development, and B cell development
and maturation
Thymus- T cell maturation
• Secondary Lymphoid Tissues- Sites of lymphocyte
activation
Lymph nodes- Screens lymph
Spleen- Screens blood borne antigens
Mucosa Associated Lymphoid Tissue (MALT)- Screens mucosa
Thymus
• A bilobed encapsulated organ located in the
lower neck.
• Site of T cell maturation
1) acquisition of T cell immunocompetence
2) development of immunological self tolerance
• Once immunocompetent T cells have been
selected they enter the circulation and migrate to
other lymphoid organs.
Thymus
progenitor cells from
bone marrow
lobule
cortex
cortex proliferation &
(Immature T cells) selection
capsule
medulla medulla
Mature T cells septa
enter circulation
Thymus
cortex
capsule
lymphoblasts
mitotic cells
macrophages
Thymus
Degeneration
of the thymus
in adults
adipose
tissue
Secondary Lymphoid
Organs
Secondary Lymphoid Tissues- Sites where immune
responses are carried out.
Lymph nodes- Screens lymph
Spleen- Screens blood borne antigens
Mucosa Associated Lymphoid Tissue (MALT)- Screens mucosa
Lymph Nodes
Lymph Nodes
• Small organs found in groups or chains in
sites where lymphatic vessels drain an
anatomic region.
They have two main functions:
1. Phagocytic cells within the nodes act as
non specific filters of particulate matter e.g.
carbon & micro-organisms, preventing them
from reaching the general circulation.
2. Location where lymphocytes can interact
with new antigens and APCs, which
facilitates activation of an immune
response.
Lymph Nodes
Structure-
• Surrounded by a fibrocollagenous capsule from
which trabeculae extend into the node forming a
supportive network.
• The surface is penetrated by a number of afferent
vessels which drain into the node leading to the
hilum where the efferent vessels transport the
lymph into the collecting vessels.
• The parenchyma consists of an extracellular
matrix supporting regions of lymphocyte
aggregates (follicles) where immune activation
takes place.
Lymph Nodes
Lymph Nodes
follicles
subcapsular capsule
sinus
paracortex
cortex
hilum
medulla
Lymph Nodes
Lymphoid follicle Follicles- regions of B
cell activation
• The germinal
mantle center consists of
activated, dividing B
germinal cells, with a few T
center cells.
• The mantle zone is
primarily resting B
cells.
• T cells make up the
majority of cells in
the paracortex.
Secondary Lymphoid
Organs
Secondary Lymphoid Tissues- Sites where immune
responses are carried out.
Lymph nodes- Screens lymph
Spleen- Screens blood borne antigens
Mucosa Associated Lymphoid Tissue (MALT)- Screens mucosa
Spleen
• Responsible for
immunological responses
against blood antigens.
• Removes aged or
defective blood cells.
• Haematopoietic organ in
the embryo.
Spleen
Trabeculae Fibrous capsule
Red Pulp
White Pulp White Pulp
Spleen
Red Pulp-
Responsible for
filtering blood
White Pulp-
Immunological
region of the organ
macrophages
Spleen
mantle
Splenic follicles
zone similar in structure -
and function - to
follicles of lymph
nodes.
germinal
center
Secondary Lymphoid
Organs
Secondary Lymphoid Tissues- Sites where immune
responses are carried out.
Lymph nodes- Screens lymph
Spleen- Screens blood borne antigens
Mucosa Associated Lymphoid Tissue (MALT)- Screens mucosa
Mucosa Associated Lymphoid Tissue
(MALT)
• Populations of immune cells in the mucosa
of many epithelial tissues.
• They may be organized aggregations of
immune cells or simply be a collection of
scattered lymphocytes within the tissue.
• Functionally analogous to lymph nodes.
Mucosa Associated Lymphoid Tissue
follicle
Peyer’s Patch
(Gut Associated Lymphoid Tissue)
Mucosa Associated Lymphoid Tissue
Ileum Diffuse
collection in
the lamina
propria
Appendix
Mucosa Associated Lymphoid Tissue
Tonsil
Aims
To have knowledge and understanding of the
structure and function of the immune system.
Objectives
To know and understand:
• The two arms of the immune system
• and the cells and components responsible for
their function (B&T cells, APCs, antibodies,
antigens).
• The origins of lymphocytes (1 lymphoid tissues).
• Recognize the general structure of 2 lymphoid
tissues (Lymph nodes, Spleen, MALTs).
