The immune system

A SIMPLICTIC OVERVIEW
 Immune System

COMPONENTS RESPONSE
Cells and Organs Compliment activation
Antigen Inflammation
Antibodies Antigen-antibody
Major interactions
Histocompatibility B- and T- cell
Complex generation and
T and B cell receptors activation
Cytokines Cell mediated effector
Compliment response
Hypersensitivity
 Immune
System

Innate Adaptive
(Nonspecific) (Specific)

Cellular Humoral Cellular Humoral

Components Components Components Components
Humoral Component Mechanism

Complement Lysis of bacteria and some viruses

Opsonin
Increase in vascular permeability
Recruitment and activation of phagocytic cells
Coagulation system Increase vascular permeability
Recruitment of phagocytic cells
-lysin from platelets a cationic detergent
Lactoferrin and Compete with bacteria for iron
transferrin
Lysozyme Breaks down bacterial cell walls

Cytokines Various effects

Interleukins,
Interferones
 Cellular Components
Cell Functions

Neutrophils Phagocytosis and intracellular killing

Inflammation and tissue damage
Macrophages Phagocytosis and intracellular killing
(Monocytes) / Extracellular killing of infected or altered self
Dendritic cells targets
Tissue repair
Antigen presentation for specific immune
response
NK and LAK cells Killing of virus-infected and altered self targets

Eosinophils Killing of certain parasites

Basophils Allergy
Cells and Organs of the Immune
System
Cellular and acellular components of blood
Hematopoiesis
 Identifying Cell Using the CD
Nomenclature

CD-Cluster Of
Differentiation
About 371 CD Markers for
humans (till date)

Fluorescence Activated Cell Sorting (FACS)

Type of cell CD markers
stem cells CD34+,CD31-
all leukocyte groups CD45+
Granulocyte CD45+,CD15+
Monocyte CD45+,CD14+
T lymphocyte CD45+,CD3+
T helper cell CD45+,CD3+,CD4+
Cytotoxic T cell CD45+,CD3+,CD8+
CD45+,CD19+ or
B lymphocyte
CD45+,CD20+
Thrombocyte CD45+,CD61+
Natural killer cell CD16+,CD56+,CD3-
Cells of the Immune System

WHITE BLOOD CELL: after centrifugation of a blood

sample, the white cells are found in the buffy coat, a thin,
typically white layer of nucleated cells between the
sedimented red blood cells and the blood plasma.

Also called LEUKOCYTE (Greek leukos - white, and kytos

cell)

Blood plasma may sometimes be green if there are large

amounts of neutrophils in the sample, due to the heme-
containing enzyme myeloperoxidase that they produce.
Ficoll or Ficoll-Paque method : Density gradient centrifugation
1 2 3 4 5

1. Whole blood in the collection tube

2. Blood after centrifugation
3. WBCs and RBCs after plasma removal
4. Top view of the WBCs (buffy coat)
5. Top view of sample after WBC removal
 Types
Agranulocytes Granulocytes
(mononuclear leucocytes) (polymorphonuclear leukocytes)

Apparent absence of granules Presence of differently staining

in their cytoplasm when viewed granules in their cytoplasm when
under light microscope. viewed under light microscopy.

Although the name implies a These granules are membrane-

lack of granules these cells do bound enzymes which primarily act
contain non-specific azurophilic in the digestion of endocytosed
granules, which are lysosomes. particles.

The cells include lymphocytes, There are three types of

monocytes, macrophages and granulocytes which are named
dendritic cells according to their staining
properties: neutrophils, basophils,
and eosinophils
WBC, when active they die off soon, when passive they survive a few days longer.
1. neutrophil (non activated)- 24 hrs in blood , few days in tissues
neutrophil active- less than 12 hrs
2. eosinophil and basophils - few hrs in blood when active and 8-12 days in tissues
when not active
3. Life span of lymphocytes ranges from a few hours to a few Years depending on
whether it is active or present inactive as a memory cell.
4. Intravascular lifespan of monocytes is 2-8 days...average half life is 3 days.
5. In tissues monocytes (now called macrophage) can stay longer upto 20 days.
 Lymphocytes
Lymphoid Cells
B-cells, T-cells and Natural Killer cells
20-40% of bodys leukocytes
99% of lymph node
If inactivated said to be nave
Nucleus occupies almost entire cell
6 m diameter
Lymphoid Cells
 B-Lymphocytes
Site of maturation- bursa of Fabricius (birds),
bone marrow
Mature B-cell: 1.5X105 molecules of antibody
Other membrane proteins include
MHC-II: permits antigen presentation
CR1(CD35), CR2 (CD21): complement receptors
FcgRII (CD32):receptor for IgG
B7-1 (CD80), B7-2 (CD86): interacts with regulatory
molecules on T cells
CD40: interacts with ligand on helper T cells, that helps
development into plasma or memory cells
Plasma cells are terminally differentiated B cells that have a life span of 1 or
2 weeks
 T-Lymphocytes
Site of maturation- thymus
T cell receptor does not recognize free antigens
CD3, CD4, CD8
CD4 restricted T cells: recognize antigen bound
to MHC II (helper T cell or TH)
CD8 restricted T cells: recognize antigen bound
to MHC I (cytotoxic T cell or TC)
Other membrane proteins include
CD28: receptor for co-stimulatory molecule B7 on APC/B-cells
CD45: a signal transduction molecules
 T-Lymphocytes
Sub-population of T cells
Inflammation and cell
TH 1 response
CD4+ T-cells (TH cells): mediated immunity

TH 2 response Humoral immunity

CD8+ T-cells (TC cells): Cytotoxic T lymphocytes

Suppressor T-cells (TS cells): Suppress humoral and cell mediated

Regulatory T cells (Treg)
T cells (gamma delta T cells)
branches
The TCR of -chain and one -
chain. (2% of total T cells) highest
abundance in the gut mucosa, within
a population of lymphocytes known
as intraepithelial lymphocytes (IELs).
 Regulatory T cell

Act to suppress activation of the immune system and thereby

maintain immune system homeostasis and tolerance to self-antigens

Regulatory T cells come in many forms, including those that express

the CD8, CD4, CD25 and Foxp3 (CD4+CD25+ regulatory T cells or
"Tregs")

CD4+Foxp3+ regulatory T cells have been referred to as "naturally-

occurring" regulatory T cells to distinguish them from "suppressor" T
cell populations that are generated in vitro.
Overview Of Mode of Action: T cells
 Natural Killer Cells
~ 2 % of lymphocytes, effectors of innate immunity
(innate lymphoid cells)
specialized to kill virus infected or cancerous host cells
Can recognize stressed cells in the absence of
antibodies and MHC , they do not require activation to
kill cells that are missing "self" markers of MHC class 1

Express Low Affinity FcgRIII (CD16)

Using CD16 (a membrane receptor for COOH end of
IgG) they Can Carry Out ADCC
Reduction of MHC I Can Activate them
 NKT Cells
Natural killer T (NKT) cells are a heterogeneous group of T cells that
share properties of both T cells and natural killer (NK) cells.

The term NK T cells was first used in mice to define a subset of T

cells that expressed the natural killer (NK) cell-associated marker NK1.1
(CD161).

Like T cells - co-express an T cell receptor (TCR).

TCRs are far more limited in diversity and in that they recognize lipids
and glycolipids presented by CD1d molecules, a member of the CD1
family of antigen presenting molecules, rather than peptide-MHC
complexes.

Like NK cells - CD16 and CD56 expression and granzyme production.

They constitute only 0.2% of all peripheral blood T cells.

Concept of professional phagocytes
 MononuclearCells
Mononuclear Cells
Monocytes in Blood, Macrophages (M) in
Tissues
Monocytes 5-10 times smaller than M
M Increases Phagocytic Ability
Secretes cytokines and Produces Hydrolytic
Enzymes
Named Based on Tissue They Reside
Alveolar (lungs), Kupffer (liver), Microglial (brain),
Osteoclasts (bone), Histiocytes (connective tissue),
Mesangial (Kidney)
Activated By Phagocytosis or Cytokines (IFNg)
Antigen Presenting Capacity Through MHC II
 Monocyte vs M

Intravascular lifespan of monocytes is 2-8 days...average half life is 3 days.

In tissues macrophage can stay longer upto 20 days
NEUTROPHILS
-Garnulocyte
-Produced in bone marrow
-Most abundant (54-62%) of WBCs
-part of the polymorphonuclear cell
family (PMNs), nucleus divided into 2-5
lobes
-stain a neutral pink, on hematoxylin and
eosin (H&E) histological or cytological
preparations
-average diameter of 12-15m
-Life span: 7-10 hrs in peripheral blood
before migrating to tissue where these
live for 1-2 days
 First to arrive at the site of infection

Neutrophils undergo a process called

chemotaxis.

Phagocytic cells
Azurophilic granules contain:
myeloperoxidase, phospholipase A2, acid
hydrolases, elastase, defensins, neutral serine
proteases, bactericidal/permeability-increasing
protein, lysozyme, cathepsin G, proteinase 3, EXTRAVASATION
and proteoglycans.

NOT APC

When two is better than one: macrophages and neutrophils work in concert
in innate immunity as complementary and cooperative partners of a myeloid
phagocyte system
Their common origin also explains that these two professional
phagocytes share several characteristics:

(i) Like macrophages, neutrophils are avidly phagocytic,

(ii) both phagocytes use a large array of antimicrobial mechanisms that

involve oxidants, granule proteins, and iron-withholding molecules.

(iii) ROS are produced by a NADPH oxidase complex.

(iv) can also produce RNS, and induced NO synthase is involved in the
production of the microbicidal NO.

(v) Macrophages and neutrophils have overlapping expression of cell surface

receptors for Igs and complement and for several chemokines, which
explains that under infectious/inflammatory situations, neutrophils and
monocytes are concomitantly recruited.

(vi) Monocytes/macrophages and neutrophils express Pattern Recognition

Receptors
 M/Neutrophils : Phagocytosis
The process of phagocytosis is
greatly enhanced by antigen
opsonization.

Opsonins (such as
antibody molecules and
complement components) bind
Ag, making the Ag
much more susceptible to
phagocytosis.

This is because the opsonin

cross-links Ag to the phagocytic
cell.

As phagocytes, neutrophils play a more important role in the acute stages of an

infection, while macrophages are principally involved in chronic types of infections.
Macrophages are the main scavenger phagocyte in a tissue.
The pattern of distribution of neutrophils and macrophages correlates with
their different antimicrobial capacities (and associated cytotoxicity) and
different life spans.

1. The abundant and powerful antimicrobial neutrophil

granule molecules and oxidants are not selective against
microorganisms but rather, unspecific biocidal molecules with
high cytotoxicity and potential tissue-damaging activity . This
makes the activated neutrophil a dangerous cell that must be
tightly controlled.

2. In contrast, the lesser microbicidal and thus, less cytotoxic

resident macrophage is long-lived and has species
variable, self-renewal capacity . Therefore, it is a cell well
suited to reside in all body compartments as the first phagocyte
that invading pathogens encounter, irrespective of their route of
entry.
 Methods of killing
within the phagocyte outside of the phagocyte
(intracellular killing) (extracellular killing).

Oxygen- Interferon-gamma
dependent Oxygen-
independent stimulates macrophages
intracellular to produce nitric oxide.
intracellular

Intracellular
Nitric oxide is then released
digestion:
from the macrophage and,
Enzyme
because of its toxicity, kills
dependent lysis
microbes near the
inside
macrophage and also engulfed
phagolysosome
bacteria.

M Capturing Bacteria
 Cytotoxic activities
Respiratory Burst
The respiratory burst results from the activation of an enzyme, dormant in
resting cells, that catalyzes the one-electron reduction of oxygen to O2- at
the expense of NADPH:

Enzyme: NADPH oxidase, Cytochrome b558: the flavin-binding

component of the phagocyte NADPH oxidase

Most of this O2- reacts rapidly with itself, dismuting to produce oxygen and
H2O2

Enzyme: Superoxide dismutase

 Cytotoxic activities
Respiratory Burst
G-6-P-dehydrogenase
+
Glucose +NADP Pentose-P + NADPH
hexose monophosphate
shunt pathway

O2-, OH., and H2O2 are activated oxygen species

that are potent oxidizing agents in biological
systems which adversely affect a number of
cellular structures including membranes and
nucleic acids.
 Myeloperoxidase system, or
MPO
1. In the case of neutrophils, these reactive oxygen intermediates can act
in concert with a lysosomal enzyme called myeloperoxidase to function
as the myeloperoxidase system, or MPO

2. Myeloperoxidase is one of the lysosomal enzymes of neutrophils which

is released into the phagocytic vacuole during fusion to form the
phagolysosome.

3. Myeloperoxidase uses H2O2 generated during the respiratory burst to

catalyze halogenation (mainly chlorination) of microbes contained within
the phagolysosome. Such halogenations are a potent mechanism for
killing cells.

4. When the NADPH oxidase and myeloperoxidase systems are operating

in concert, a series of reactions leading to lethal oxygenation and
halogenation of engulfed microbes occurs.
 Respiratory Burst

- myeloperoxidase -
H2O2 + Cl OCl + H2O

- 1O -
2OCl + H2O 2 + Cl + H2O

Toxic compounds Hypochlorite (OCl-), and Singlet oxygen (1O2)

Hypochlorite is also the precursor of the chloramines, a group of microbicidal

oxidized halogens that are formed by the reaction between hypochlorite
and ammonia or amines
 Respiratory Burst
Detoxification Reactions

-
Superoxide dismutase
2O2 + 2H+ H2O2 + O2

Catalase
2 H2O2 H2O + O2

Catalases: peroxisomes
GSH peroxidases, which are selenoproteins: cytosol and mitochondria

Am J Respir Crit Care Med Vol 166. pp S4S8, 2002

 Nitric Oxide Dependent Killing

TNF

TNF
Nitric Oxide
Nitric Oxide

Bacterial cell wall

components like LPS
and Muramyl
dipeptide

Activates expression of nitric oxide synthetase: NOS

(inducable nitric oxide synthetase i NOS)

L-arginine +O2 +NADPH NO + L-citrulline + NADP

Nitric oxide synthase: models and mechanisms Groves and Wang
Reactive Nitrogen Intermediates
Nitric oxide and peroxynitrite
Macrophages: (iNOS) induced by
inflammatory cytokines (IFNg, TNFa) and
bacterially-derived products (LPS)
Highly labile; oxidizes nucleic acids,
membranes, proteins
Nitric oxide reacts with superoxide anion
forming peroxynitrite (ONOO, It is an
unstable "valence isomer" of nitrate, NO3)
 Oxygen-Independent Killing in
the Phagolysosome

Effector Molecule Function

Cationic proteins and cathepsin Damage to microbial
membranes
Lysozyme Hydrolyses mucopeptides in
the cell wall
Lactoferrin Deprives pathogens of iron
Hydrolytic enzymes (proteases) Digests killed organisms
Defensins Ion-permeable channels in
the bacterial cell wall
 Neutrophil Extracellular Traps (NETs).
Neutrophil extracellular traps (NETs) are networks of extracellular fibers, primarily
composed of DNA from neutrophils, which bind pathogens

Composed of decondensed chromatin and antimicrobial proteins, NETs bind and kill
a variety of microbes including bacteria, fungi, and parasites.

peptidylarginine deiminase 4

Front.Immunol., 04 October 2012

Nature 468, 9 (04 November 2010)
Science 5 March 2004:
 Degranulation of Neutrophils
Neutrophils also release an assortment of proteins in of granules by a
process called degranulation

Azurophilic granules (or "primary granules"): Larger and Denser

granules
myeloperoxidase, bactericidal/permeability increasing protein (BPI),
Defensins and the serine proteases neutrophil elastase and cathepsin
G, peroxidase, lysozymes etc

Specific granules (or "secondary granules"): Lactoferrin and

Cathelicidin (anti-bacterial peptides)

Neutrophils shuttle to lymph node microorganisms and bacterial antigens,

regulate macrophage/DC functions , deliver bacterial antigens to these
cells, helping in presentation of bacterial antigens to T cells, indicating that
neutrophils cooperate with macrophages in the orchestration of adaptive
immune responses
 Dendritic Cells
Professional APCs
Several Types
Langerhans (LC) found in skin
Circuilating DCs
Myeloid (CD11c+ DCs, the CD141+ DCs )
Plasmacytoid (lymphoid) (CD303+)
- Interstitial DCs, populate organs such as heart,
lungs, liver, intestines
Interdigitating DCs, T-cell areas of lymph nodes and
Thymic medulla

http://lab.rockefeller.edu/steinman/
Developmental Pathway of DCs
 Dendritic Cells

Constitutively express high levels of MHC-II and B7

Immature dendritic cells: high endocytic activity and low T-

cell activation potential.

Immature dendritic cells constantly sample the surrounding

environment for pathogens such as viruses and bacteria

Become activated into mature dendritic cells when presented

with antigen.

Upregulate CCR7, a chemotactic receptor that induces the

dendritic cell to travel through the blood stream to the spleen
or through the lymphatic system to a lymph node
 Dendritic Cells
Dendritic cells have a very large contact surface area relative to their overall
cell volume.

In primates, two main groups: the myeloid dendritic cells (mDCs) and the
plasmacytoid dendritic cells (pDCs).

mDCs are similar to monocytes

subdivided into the more abundant mDC-1 which is a major stimulator of T
cells and the less common mDC-2 that helps fight infections caused by
wounds.
The mDCs secrete the cytokine interleukin-12 and they display the Toll-like
receptors (TLRs) TLR 2 and TLR 4.

The pDCs resemble plasma cells but share some features of mDCs.
interferon-producing cells, these can secrete large amounts of interferon-alpha
and they display TLR 7 and TLR 9.
 Follicular DCs
non-migratory population found in primary and
secondary follicles of the B cell areas of lymph
nodes, spleen, and Mucosa-associated Lymphoid
Tissue (MALT).
these dendritic cells are not of hematopoietic origin
mesenchymal origin but are located in lymphoid follicles
and possess dendrites
Do Not Express MHC II Molecules
Found in Lymph Follicles (Rich in B Cell)
Express FcR For Antibodies and Complement
Ag-Ab Complex Shown To Last Very Long (weeks to
months)
Follicular Dendritic Cells
Kidney International (2008) 74, 57. doi:10.1038/ki.2008.189
 Antigen Presenting Cells of our Immune System

The most relevant property of APCs is that, in addition to antigen presentation, they
provide co-stimulatory signals via B7.1 and B7.2.

It is important to note that APC's do not constitutively express these co-stimulatory

molecules. (Except Dendritic cells).

Upon this recognition, the APC's will up regulate their co-stimulatory molecules
(namely B7's), and only then will they activate T cells, by interacting with the B7
receptor called CD28.
 Summary table of Antigen Presenting Cells

Macrophage Dendritic Cell B cell

Low levels. Always Expressed.
MHC-II Expression Induced by Bacteria Always Expressed. Inducible upon
and/or Cytokines Activation
Extracellular Antigens:
pinocytosed
Intracellular by MHC-I
exogenous antigen via
Extracellular Antigen
MHC class I whereas Intracellular &
binds
Antigen type and antigen ingested by Extracellular Antigens:
to specific Ig
presentation by MHC receptor-mediated presentation via MHC-
receptors:
endocytosis is I & II
presentation via MHC-
presented via MHC
II
class II

Low levels. Low levels.

Co-Stimulation Always expressed
Induced by Bacteria Inducible upon
(B7 expression) at high Levels
and/or Cytokines Activation
Lymphoid tissue Lymphoid tissue
Lymphoid tissues.
Location Connective tissue Connective tissue
Blood
Body Cavities Epithelium
 Cellular components that
mediate allergic responses
 Eosinophils
-Phagocytic motile cells
-make up about 1-6% of white blood cells, and are
about 12-17 micrometers in size
-persist in the circulation for 8-12 hours, and can
survive in tissue for an additional 8-12 days in the
absence of stimulation
 Functions of eosinophils

Effector functions following activation

-Cationic granule proteins and their release by degranulation

-Reactive oxygen species such as superoxide
-Release of cytokines such as IL-1, IL-2, IL-4, IL-5, IL-6, IL-8,
IL-13, and TNF alpha
-play a role in fighting viral infections, which is evident from
the abundance of RNAses in their granules
-Eosinophils along with basophils and mast cells, are
important mediators of allergic responses and asthma
-They also fight helminth (worm) colonization and may be
slightly elevated in the presence of certain parasites.
 Functions of eosinophils

Effector functions following activation

-Cationic granule proteins and their release by degranulation

-Reactive oxygen species such as superoxide
-Release of cytokines such as IL-1, IL-2, IL-4, IL-5, IL-6, IL-8,
IL-13, and TNF alpha
-play a role in fighting viral infections, which is evident from
the abundance of RNAses in their granules
-Eosinophils along with basophils and mast cells, are
important mediators of allergic responses and asthma
-They also fight helminth (worm) colonization and may
be slightly elevated in the presence of certain parasites.
Opsonization of a Helminth by IgE and
Eosinophils
 Basophils

least common of the granulocytes, 0.01% to 0.3%

Basophils contain large cytoplasmic granules which obscure the
cell nucleus under the microscope. However, when unstained, the
nucleus is visible and it usually has 2 lobes.

Basophils: inflammatory reactions, allergic symptoms

When activated, basophils degranulate to release histamine,
proteoglycans (e.g. heparin and chondroitin), and proteolytic
enzymes (e.g. elastase and lysophospholipase). They also secrete
lipid mediators like leukotrienes, and several cytokines
 Mast Cells

Basophil
 Mast Cells
- best known for their role in allergy and anaphylaxis

- originate from bone marrow precursors expressing the

CD34 molecule.
The basophil leaves the bone marrow already mature,
whereas the mast cell circulates in an immature form, only
maturing once in a tissue site

- Mast cells are present in most tissues in the vicinity of blood

vessels, and are especially prominent near the boundaries
between the outside world and the internal milieu, such as
the skin, mucosa of the lungs and digestive tract, as well as
in the mouth, conjunctiva and nose
** Leukotrienes are a family of eicosanoid inflammatory mediators
The molecules thus released into the
extracellular environment include:

* preformed mediators:
histamine (2-5 pg/cell)
serotonin
proteoglycans, mainly heparin (active as
anticoagulant)
serine proteases
* newly formed lipid mediators:
prostaglandin D2
leukotriene C4
* cytokines:
Eosinophil chemotactic factor
 Lymphoid Organs

Primary Secondary

Microenvironment for Site for effective

maturation of interactions between
lymphocytes antigen and mature
lymphocytes
 Organs Of Immune System
Primary Lymphoid Organs
Bone Marrow and Thymus
Maturation Site
Secondary Lymphoid Organs
Spleen, lymph nodes,
MALT (mucosal associated lymph tissue)
GALT (gut associated lymph tissue)
Trap antigen, APC, Lymphocyte Proliferation
Tertiary Lymphoid Organs
CALT (cutaneous-associated lymph tissue)
 Thymus
Bilobed Organ on Top of Heart
Reaches Max. Size During Puberty
Age Mass
birth about 15 grams;
puberty about 35 grams
twenty-five years 25 grams
sixty years less than 15 grams
seventy years as low as 5 grams

95-99% Of T Cells Die in Thymus

self reactivity or no reactivity to Ag
Consists of Cortex and Medulla
 Thymus

Hassall's corpuscles composed of concentric arrays of epithelial cells which contain

keratohyalin and bundles of cytoplasmic filaments.
potent source of the cytokine Thymic stromal lymphopoietin .
Helps in the maturation of T cell populations through activation of antigen presenting cells.
TSLP is produced mainly by non-hematopoietic cells such as fibroblasts, epithelial cells
Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human
thymus.
Bone Marrow
 Lymphatic System
Plasma From Blood Seeps Into Tissue
Interstitial Fluid Either Goes Back or
Becomes Lymph
Lymph Enters Lymphatic Vessels
Thoracic Duct Is Largest Lymphatic Vessel
Empties Into Left Subclavian Vein
Lymphatic Vessel Depends On Muscle
Contractions For Movement
One Way Valves Ensure One Direction
Lymph Nodes Act As Filters For Antigens
Lymphatic System

Secondary Follicle
Secondary lymphoid organs
Lymph
Node
 Lymph Node
Multiple Afferent Lymphatics
Cortex
B-cells, Follicular DCs, M, Primary and Secondary
Follicles
Paracortex
TH, M, interdigitating DCs
Medulla
Plasma Cells
Post Capillary Venule
Allow Lymphocyte Migration From Circulation Into
Lymph Node
One Efferent Lymphatic
Rich In Abs and Lymphocytes
 Spleen

Red Pulp: Clusters of Macrophages and

Red Blood Cells.
White Pulp: Lymphocytes suspended on
reticular Fibers

The spleen serves two major functions in the body:

1. It is responsible for the destruction of old red blood cells
(RBC),
2. It is a major site for mounting the immune response.
Spleen
 Mucosal Associated Lymphoid
Tissue (MALT)
Mucous Membranes S.A=400m2
Mucous Membr. Most Common Pathogen Entry
Site
M.M Protected by MALT
Organization Varies (most organized Peyers
patch, Tonsils, appendix
GI Tract, Intra Epithelial Leukocytes Unique g
TCRs
Lamina Propria (below epithelium) M, B cells,
TH
M Cell Allows Ag Entry, Unique Architecture
 TONSIL

1. Pharyngeal Tonsil
2. Palatine Tonsil
3. Lingual Tonsil
4. Epiglottis
Cutaneous Associated Lymphoid Tissue
Jawless Fishes Amphibians Reptiles Aves Mammals
vertebrates

??

Germinal
centres

Lymph nodes

Bone marrow

Thymus and
Spleen

GALT