MOLECULES, CELLS AND

ORGANS OF THE IMMUNE

SYSTEM
BY
APIO FAITH MBASANI
KASOZI FRED
Overview
• Specialized cells of the immune system
• Organs of the immune system
• Molecules of the immune system
• Cell homeostasis
Immune System
• Is a network of biological processes that protects organisms from
disease.
• It is composed of the innate and adaptive immune systems.
• The innate system provides immediate defense against attacking
microorganisms while the adaptive system kicks in later, in aid of the
innate immune system.
• Through the adaptive system, organisms are able to retain memory of
past attacks.
Organs of the immune system
Organs of the immune system are grouped into;

Primary lymphoid organs Secondary lymphatic tissues

• Thymus • Spleen
• Bone marrow • Tonsils and adenoids
• Lymph nodes
• Appendix
• Peyer’s patch
Thymus
• Located in the upper chest
• Large and very active in neonates and pre-adolescents.
• Shrinks after puberty and is smaller in adults
• It facilitates the maturation of T-cells
• Failure of thymus development causes T-cell deficiency
Bone Marrow
• Found in interior of flat and long bones
• Contains hematopoietic stem cells that mature into blood cells and
platelets in red bone marrow.
• Is the site of B-cell maturation
• Hematopoietic cytokines are produced by stromal cells and
macrophages in the bone marrow. Activated T-cells and macrophages
also produce these cytokines.
• Houses numerous long-lived antibody producing plasma cells and
some long-lived memory T-cells
Spleen
• Main function is to remove ageing and damaged blood cells and
particles like immune complexes and opsonized cells and microbes (by
macrophages in the spleen’s red pulp).
• It also initiates adaptive immune responses to blood-borne pathogens in
its white pulp.
• Those without a spleen are susceptible to encapsulated bacteria e.g
pneumococci and meningococci which are cleared by opsonization and
phagocytosis
• Provides site for the interaction of APCs, B-cells and T-cells.
• Becomes a secondary site for hematopoiesis during bone marrow failure
Tonsils and adenoids
• Protect the body from pathogens invading the upper respiratory tract.
• Some adenoid lymphocytes secrete IgA, IgG and IgM which are essential in antigen phagocytosis
• Adenoid secretions also contain activated T-cells which participate in cellular immunity.
• The tonsils contain both B and T cells.

Skin
• Is a barrier organ of the immune system together with the mucosal membranes of the digestive,
respiratory and urogenital tracts.
• These barrier organs are lined by epithelial cells which are defended by mucosa-associated
lymphoid tissue (MALT).
• MALT in barrier organs are active in both innate and adaptive immunity and are our first line of
defense against invading pathogens.
Lymph nodes
• Distributed widely around the body and are linked by lymph vessels
through which flow circulating lymph
• Structurally composed of the cortex, paracortex and medulla.
• The cortex contains lymphocytes (mostly B-cells), macrophages &
dendritic cells
• The paracortex is populated largely by T-cells but contains some
dendritic cells
• The medulla is the innermost layer. It is the site where outgoing
lymphocytes exit the lymph node
Cells of the immune system
Cells of the immune system
Innate Immune cells Adaptive Immune cells
• Neutrophils • T cells
• Eosinophils • CD4 T cells (Th1, Th2, Th17)
• Basophils • CD8 T cells
• Mast cells • Regulatory cells
• Monocytes and Macrophages • B cells
• Dendritic cells
• ILCs (ILC1, ILC2, ILC3)
Cell Types
Phagocytes
These are innate immune cells and they include;
• Neutrophils
• Macrophages
• Dendritic cells
Functional responses of phagocytes in host defense consist of sequential
steps;
• Recruitment of the cells to sites of infection
• Ingestion of microbes by phagocytosis
• Destruction of ingested microbes
 Neutrophils

• Are the most abundant circulating leukocytes.

• Their granules contain proteases, antimicrobial proteins, histamine and protease
inhibitors
• Circulate in blood for 7-10 hours before migrating into tissues where they have a
life span of only a few days
• Mediate earliest phases of inflammatory reactions
• Swarm in large numbers to site of infection and they function for 1 to 2 days and
then die.
• They then phagocytose pathogens and release the contents of their granules
into the phagosomes
Macrophages
• Circulating versions are called monocytes
and tissue resident versions are
macrophages.
• Most tissue-resident macrophages arise
from embryonic cells
• Inflammatory monocytes can also migrate
into tissue and differentiate into
macrophages
• Recognition of pathogens by macrophages is
enhanced by pathogen opsonization
• They also serve as APCs for T-cells
• They clean up after an infection and promote
the repair of damaged tissues
Dendritic cells (DCs)
• Are widely distributed in lymphoid tissue, mucosal epithelia and organ
parenchyma and are thus sentinels of the immune system
• They are tissue resident but also circulate in the body, sensing and phagocytosing
microbes and displaying them to T-cells to initiate adaptive immune response.
• Classical DCs mainly capture microbe antigens and present them to T-cells
• Plasmacytoid DCs produce the antiviral cytokine type I interferon (IFN) in
response to viruses and may capture blood born microbes and carry their
antigens to spleen for presentation to T cells. Play a major role in innate antiviral
defense
• Monocyte-derived DCs arise from inflammatory monocytes but carry out DC
function. They express both DC and monocyte markers.
Basophils and eosinophils
Basophils
• Are nonphagocytic
• Respond to parasites particularly parasitic worms
• When they bind to parasites, they release the contents of their granules. Histamine, one
of the contents increases blood vessel permeability and other released cytokines recruit
more immune cells
• In the absence of parasites, this histamine causes allergic reactions
Eosinophils
• Coordinate defense against multicellular parasites
• Cluster around worms and damage their membranes with the contents of their granules
• May release cytokines that regulate B and T cells
Mast cells
• Also act against parasitic worms and have histamine in their granules
that can contribute to allergies.
• They leave the bone marrow undifferentiated and mature in tissues
like the skin and epithelial tissue
• Were once thought to be tissue basophils but were discovered to be
distinct from basophils
Lymphocytes (Ly)
• Comprise of B-cells, T-cells and ILCs
• Lymphocytes perform major roles in the adaptive immune system
• B-cells mature in the bone marrow in mammals and in the bursa of
Fabricius in birds while T-cells mature in the thymus
• Activated B-cells differentiate into plasma and memory cells after
receiving cytokines from T-cells
• Plasma cells are majorly involved in the production of antibodies. They
lose their surface immunoglobulin and only secrete antibodies to the
presented antigen
• T-cells recognize antigens bound to MHC molecules.
• There are T helper (CD4) and T cytotoxic cells (CD8) at a healthy ratio of
2:1. Changes in this ratio indicate immunodeficiency disease
Lymphocytes contd
NKT cells
• They have T cell receptors like T cells but only recognize lipids and glycolipids
presented by CD1
• Activated NKT release cytotoxic granules that kill target cells and also release large
quantities of cytokines that can both enhance and suppress the immune response
ILCs
• Comprise ILC1, ILC2 and ILC3
• Provide a first defense against pathogens in the skin and mucosa
• Include cytotoxic NK cells that attack cells that do not express the MHC I molecule
e.g virus infected cells or malignant cells
Molecules of the Immune system
• Antibodies
• Cytokines
• Major Histocompatibility Complex
• Immune phase reactants
Antibodies
• Antibodies are the antigen binding protein present
on the B-Cells membrane and secreted by the
Plasma cells
• Recognize specific configurations (epitope or antigen
determinants) on the antigen surface.
Antibody Structure
• 4 polypeptide chains (2
identical heavy chains and 2
identical light chains) joined
by disulfide bonds to
produce a Y configuration.

• The heavy and light chains

are divided into a variable (V)
region and a constant (C)
region
 Antibodies
The classes are defined by their type of heavy chain:
• mu (μ) for IgM,
• gamma (γ) for IgG,
• alpha (α) for IgA,
• epsilon (ε) for IgE
• delta (δ) for IgD.
There are also 2 types of light chains: kappa (κ) and lambda (λ). Each of
the 5 Ig classes can bear either kappa or lambda light chains.
SN Immunoglobulin Description Function
1 IgM  The first antibody formed after exposure to new it complexes with and agglutinates
antigen antigens and can activate
5 Y-shaped molecules (10 heavy chains and 10 light complement, thereby facilitating
chains), linked by a single joining (J) chain phagocytosis.

Present in the intravascular space

2 IgG Most prevalent Ig isotype in serum and is present in • IgG1 and IgG3 are efficient
(IgG1,IgG2,IgG3& intravascular and extravascular spaces mediators of antibody-
IgG4) Most dependent cellular cytotoxicity
the primary circulating Ig produced after
reexposure to antigen (secondary immune
response) and is the predominant isotype
contained in commercial gamma-globulin products.

3 IgA Occurs in mucosal surfaces, in serum, and in Provides an early antibacterial and
secretions antiviral defense.
4 IgD Coexpressed with IgM on the surface of naive B
cells.
5 IgE present in low levels in serum and in respiratory If antigen bridges 2 IgE molecules
and gastrointestinal mucous secretions bound to the mast cell or basophil
surface, the cells degranulate,
releasing chemical mediators that
cause an inflammatory response
Cytokines
• Polypeptides secreted by immune cells when the cell interacts with specific
pathogen-associated molecules such as endotoxin, or with other cytokines.
• Classes include:
i. Chemokines (C, CC, CXC, CX3C)
ii. Hematopoietic colony-stimulating factors (G-CSF, GM-CSF & M-CSF)
iii. Interleukins (IL1 - IL-38)
iv. Interferons (IFN-alpha, IFN-beta, IFN-gamma)
v. Transforming growth factors (TGFs)-(TGF-alpha &TGF-beta)
vi. Tumor necrosis factors (TNF-alpha, lymphotoxin-alpha, lymphotoxin-
beta)
Major Histocompatibility Complex (MHC)
• Genetically diverse glycoproteins found on all cell membranes
• MCH act as Antigen Presenting receptors
• Involved in:
 Cell-cell interaction
 Antigen presentation
 Recognition of self and non-self molecules
 Participation in both humoral and cell mediated immunity
 Major Histocompatibility Complex (MHC)
A complex of genes encoding cell-surface molecules that
are required for antigen presentation to T-cells

• Fundamentally important for:

• basis of self / not self distinction
• presentation of processed antigen

• MHC-I (on nearly all nucleated cells of vertebrates)

MHC-II (on APCs)
MHC- I & MHC-II
Immune Phase Reactants
• Many immune phase reactants are made in the liver. Plasma proteins whose
levels dramatically increase or decrease in response to the elevated
circulating levels of interleukin (IL-1 and IL-6) that occur when infection or
tissue damage occurs
• Functions
•they may help limit tissue injury
•enhance host resistance to infection
•promote tissue repair and resolution of inflammation
• Types include
• C-reactive protein (CRP) fixes complements and act as opsonins
• Mannose-binding lectin
• Alpha-1 acid glycoprotein
• Serum amyloid P component
Cell Homeostasis
• Tendency to resist change in order to maintain a stable relatively
constant environment by the cell
• Involves maintaining a balance of several factors that make the cell
health.
• These factors include;
• Ions
• Water balance(volume)
• Temperature
• Waste products
• ATP
Structure and Role of Cell Membrane in cell
homeostasis
• The cell membrane is made up of
phospholipid bilayer with embedded
proteins that separate the internal
components of a cell from its
surrounding. Proteins act as transporters
for hydrophilic molecules like glucose

• The plasma membrane controls the

passage of organic molecules, ions, water,
and oxygen into and out of the cell.
Wastes (such as carbon dioxide and
ammonia) also leave the cell by passing
through the plasma membrane.
Ions
• A proper concentration of ions needs to be maintained inside a cell
especially for neurons that send electric signals by allowing ions to
flow through them. Cells have more sodium ions outside and more K+
inside. That concentration difference is maintained through the
protein channel.
• The sodium and potassium move against their concentration
gradients.  The sustained concentration gradient is crucial for
physiological processes in many organs and has an ongoing role in
stabilizing the resting membrane potential of the cell, regulation of
the cell volume and in the cell signal transduction. 
Membrane Fluidity
• The cell membrane is a phospholipid bilayer. The head region is
electrically charged (phosphate) and the tail region is oily (lipids). The
phospholipid molecules are free to rotate and move.
• Such fluidity is a critical property of membranes and is determined by
both temperature and lipid composition. For example, the interactions
between shorter fatty acid chains are weaker than those between longer
chains, so membranes containing shorter fatty acid chains are less rigid
and remain fluid at lower temperatures.
• Lipids containing unsaturated fatty acids similarly increase membrane
fluidity because the presence of double bonds introduces kinks in the
fatty acid chains, making them more difficult to pack together.
Acidic Lysosomes
• These are organelles which serve as cell recycling centres.
• They digest unwanted proteins, DNA, RNA, Carbohydrates and fats.
whole organelles like damaged mitochondria.
• Inside of a cell is pH 7 but inside of a lysosome, pH is 5. This is
because enzymes in lysosome work best at pH 5.
• These are essential for homeostasis of the cell. Otherwise damaged
proteins and organelles build up and clog up the cell
Water
• Due to osmosis, water will want to flow into a cell with a lot of ions.
• The cell membrane is hydrophobic and slows the movement of water
into or out of the cell, which helps the cell maintain a proper water
volume.
• This allows the cell to maintain a certain concretion of ions inside it.
• This maintained cellular balance of water molecules and ions
maintains an optimal environment for cellular function
Homeostasis and The Immune System
• The immune system’s clearance of foreign substances is a maintenance of
homeostasis.
• Cytokines like IL-1 and TNF are pyrogenic substances that raise body
temperature.
• Signal transduction dependent TLRs in the intestines induce the repair of
intestinal tissues
• TLR-4, TLR-2 and enterobacteria in the intestines are also essential for the
maintenance and regulation of intestinal homeostasis.
• TNF and IL-1B suppress GLUT2 and glucokinase in the pancreas making it less
sensitive to blood glucose levels increasing energy levels for immune
response.
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