Principles of Immunology

Presenter: Dr. Ireri Victor

Moderator: Prof. J. Nyagol

February 5, 2025
 Outline of the Lecture
• Cells and Organs of the Immune System

• Mechanisms of Innate and Adaptive Immunity

Cells and Organs of the Immune System
 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
 We didn’t know….
• What triggers innate immunity-
• What mediates communication between
innate and adaptive immunity-
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
3. basophils Plasma (56%)

Non-granulocytes After centrifugation in

4. monocytes Ficoll, leukocytes are
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= progenitors

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
 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 increase 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=fpO
xgAU5fFQ
 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
 Monocyte
• Mononuclear
• Circulate in blood~ 8 hrs
• Bean-shaped nucleus
 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; 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
from Ag capture to Ag presentation
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
Examples of lymphocytes:
 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
• Seeded cells in adult
stem cells from both •B-cell maturation
•RBC’s are large and outside •T-cells to thymus
nucleated=primitive sources
• Cannot form • Max 6 mos
lymphoid progeny
then declines to
 •Tonsil
Organs of the •Lymph nodes 2. Distribution to
s
Immune Secondary lymphoid
•Spleen 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)
The thymus in the adult lies behind the sternum, abov
the heart
The Thymus is the Site of T-cell Maturation
• Epithelial cells (thymic stroma)
– forming a sponge-like meshwork of epithelial
cells= reticular epithelial cells
• T-cells- Lymphopoiesis (proliferate and
mature)
• mature T-lymphocytes leave via venules in the
medulla and travel through the blood to populate
peripheral organs
• If the thymus fails to form, and T-cells do not
develop
The cortex contains immature thymocytes which move into the
medulla as they mature.
 Adult thymus

• Rate of T-cell production peaks prior to

puberty
• Greatly reduced but continuous through
adulthood
• Thymus undergoes Involution
– Fatty infiltration
– Lymphocyte depletion
 DiGeorge syndrome

• deletion on chromosome 22
• defect of cranial neural crest cell migration into
arches
• congenital thymic hypoplasia= anlage of the thymus does
not form
• variety of other defects involving facial, thyroid,
parathyroid and cardiovascular system
“Anlage”- an organ in its earliest stage of development; the foundation for subsequent
development, primordium
 Secondary lymphoid organs

• Specialized for trapping antigen facilitating presentation to

lymphocytes
• Characterized by:
– Localized areas for T-cells and B-cells
– Follicles where B cells mature
Schematic diagrams Lymphoid follicle
of various types of Diffuse
lymphoid tissue

• Diffuse
Peyer’s patch Tonsil
• Solitary follicle
• Aggregated follicle
• Lymph Node Spleen
• Spleen
• Thymus

Lymph Node Thymus

 Lymphoid follicle

Germinal Centers

• Are formed when activated B cells enter lymphoid

follicles and proliferate
– Somatic hypermutation
– Affinity maturation
– Isotype switching of Ab class
• Selected B cells will mature to plasma cells or
become memory cells
 Encapsulated peripheral lymphoid organs

• Lymph nodes-
– filter Ag from lymph
– Receive Ags and APCs from local sites
• Spleen-
– filters Ag from blood
– Ags from systemic infections
 The Lymph Node: filters lymph
• Filters lymph
• Filtering stations interposed in the lymphatic
vessels
• Present everywhere, but large and numerous ones are
found in certain sites: axillary, groin (inguinal LNs),
near the abdominal aorta (coeliac LNs), in the neck
(cervical LNs) and in the mesentery (mesenteric LNs)
• Regional nodes: draining particular regions or
organs
Lymph nodes
filter lymph
Lymphatic vessels

Lymph node
 The Spleen: filters blood

• In contrast to lymph nodes, which are inserted in the

lymph circulation, the spleen is inserted in the blood
circulation.
• Oblong, purplish body the size of a fist, on the left side
• Smooth surfaced except for hilus, where blood vessels
enter and leave

* There are no lymphatics leading to the spleen.

 The Spleen has 2 major regions
• White Pulp: lymphatic
– Small arterioles surrounded by sheaths of
lymphocytes= Peri-Arteriole Lymphoid Sheaths
(PALS- human arrangement slightly different)
– Surrounded by marginal zone
• Red Pulp: clears RBCs
– “Cords” of cells: Erythrocytes, macrophages,
dendritic cells, few lymphocytes and plasma cells
– Also contains venous Sinusoids
Spleen- surface of a fresh cut appears stippled due to
red and white pulp
 Function of the spleen cont.
• Erythrocytes enter the red pulp, push through
the masses of macrophages filling the splenic
cords and enter the sinuses.
– Macrophages engulf old rbcs and antigens in blood
• Lymphocytes are brought into the spleen by the
arteries and arterioles; they enter the marginal
sinus and then migrate to their respective
domains
– B cells to the follicles, T cells to the PALS
 Mucosal Immune System
MALT- Mucosal Associated Lymphoid
Tissue
• Mucosal surfaces of mouth, respiratory and
reproductive tracts are colonized by
lymphocytes and accessory cells
• Respond to ingested, inhaled antigens
• BALT (bronchial) :
• GALT (gut) :
– Tonsils
– Peyer’s Patches
– Appendix
 Tonsils
• Latin tonsa (stake set up on the shore)
• At entrance to GI tract:
– 1 pharangeal= “adenoids”
– 2 tubal
– 2 palatine= “tonsils” (from pouch 2)
– 1 lingual
 Human Tonsils
1.Palatine
3.Pharyngeal

nodes
Pharyngeal
2.Lingual
Tubal
Palatine
4.Tubal
Lingual
 Diagram of the
Pharynx
Tonsil
• Aggregated
lymphoid follicles
• Corrugated surface with
cracks and pits CRYPTS
lined with stratified
squamous epithelium
• become filled with
sloughed off cells,
dead lymphocytes
and fluid
• good culture
medium for bacteria
 Peyer’s Patches (~30) are found in the ileum (small intestin
in the wall opposite the mesentary

Each is a collection of X-section showing the

many individual lymphoid follicles in the submucosa
follicles (pink) scattered
between the microvilli “like
puffballs on a lawn”
Plane of cross section shown in next slide
Identify the lymphoid organ indicated by the
green arrows.
 Appendix

• Worm-like projection of the human large

intestine, 10-15 cm long and up to 8mm in
diameter.
• The lamina propria contains dense, diffuse lymphoid
tissue packed with some 200 lymphoid follicles.
Appendix

There is a
network of
lymphatics
surrounding
each follicle
Mechanisms of Innate and Adaptive Immunity
The Immune
System

Basic Immunology, 6e
 The Innate Immune System
• First line of defence

• Includes
• Physical barriers and biochemical barriers – skin, body secretions etc.

• Soluble components – Complement, cytokine, acute phase proteins

• Cellular components – PMNs, monocytes/macrophages, NK cells

• Develops in utero
• Response to pathogens is rapid but nonspecific
• Activation of innate immune system results in Inflammation
 The Innate Immune System
Complement systems
Activated by/on microbial surfaces

© Amboss
 The Innate Immune System
The Alternative Pathway of
Complement Activation
Activated by/on microbial surfaces

Basic Immunology, 6e
 The Innate Immune System
Antigen Recognition
• Germline-encoded pattern-recognition receptors (PRR)

• 3 classes of PRR:
• Signaling receptors

• Endocytic receptors

• Secreted proteins
Bind to microorganisms and target them for phagocytosis or
complement-mediated destruction
 The Innate Immune System
Antigen Recognition
• The ligands for PRR are termed pathogen-associated molecular
patterns (PAMPs)

• PAMPs are chemical structures that characterize whole groups

of pathogens

• The recognized structures are distinct from self-antigens

• Overall effect of immune recognition is labelling and destruction of

the target
 The Innate Immune System
Effector Cells - Polymorphonuclear Leukocytes (PMNs)
Neutrophils respond to infective stimuli via a sequential series of activities
• Chemotaxis
Anaphylatoxins, cytokines, microbially-derived peptides

• Target recognition and attachment

• Sugar residues e.g. mannose (C-lectin type receptors)
• LPS receptors (TLRs)
• Specific Fc and complement receptors – opsonization

• Ingestion, killing and degradation

Phagocytosis and killing by oxygen dependent and non-oxygen-dependent
mechanisms

NETosis
 The Innate Immune System
Effector Cells - Polymorphonuclear Leukocytes (PMNs)
Eosinophils have a central role in defense against parasitic infection

Basophils and mast cells play a role in mucosal immunity

Type I hypersensitivity
reactions
 The Innate Immune System
Effector Cells – Natural Killer cells (NK cells)
• Large granular lymphocytes (non-B, non-T lymphocytes)
10-15% of circulating lymphocytes

• Kill pathogens, infected cells and tumour cells

• Lack antigen-specific receptors, but have

• Carbohydrate-binding lectins on their cell surface as well as

• MHC class I binding motifs and

• Fc receptors for IgG1 and IgG3 – Antibody-dependent Cellular

Cytotoxicity
The Innate Immune
System
Effector Cells – Natural Killer cells
(NK cells)

Cytotoxic mechanisms:
• Perforins (cause membrane
destruction) and
granzymes (proteases)

• Induction of apoptosis
(Fas-FasL pathway)

Basic Immunology,
 The Innate Immune System
Macrophages
• Circulating monocytes leave the circulation and migrate into tissues; mature
macrophages
into

• Phagocytes

• Antigen-presenting cells – process ingested antigens and present them

immune effector cells in association with MHC on their membranes
to
T cells are not activated by soluble antigens, and so presentation of antigens is
necessary for T cell stimulation and induction of cell-mediated immunity

• Effector cells for some types of cell-mediated immunity (e.g.

hypersensitivity)
delayed
 The Innate Immune System
Dendritic Cells
• Antigen-presenting cells

• Dendritic cells (found in lymphoid tissues and in interstitial regions of

other organs) and Langerhans cells (found in the epidermis) have
extensive dendritic cytoplasmic processes that are rich in MHC class
II molecules

• Consequently, they are very efficient at presenting antigens

(and priming naïve T cells)
 The Adaptive Immune Response
• Comprises humoral and cellular responses via B and T lymphocytes

• Antigen specificity and memory

• T and B lymphocytes bear cell surface receptors of a single

specificity

• The specificity of these receptors is determined by a process

of genetic recombination that occurs during development
 Maturation of B and T Lymphocytes
• Genetic programming - Ag
receptor genes rearranged
to produce receptors that
are invariant in their Ag
specificity for the life span of
that lymphocyte, as well as
for all its descendant cells

• Selection - self-reactive
lymphocyte eliminated;
thymocytes that can
recognize antigens
through interactions with
MHC molecules are
retained Basic Immunology, 6e
 The Adaptive Immune Response
T Lymphocytes
• 60% to 70% of all lymphocytes in the blood; also found in paracortical areas
of lymph nodes and within periarteriolar lymphoid sheaths in the spleen

• T Cell Subsets:
• CD4 is found on about 60% of CD3+ cells - Helper T cells
• Direct the functions of other cells of the immune system by secreting cytokines that stimulate
various functions

• CD8 is found on about 30% of T cells – Cytotoxic T cells

(Thus the normal ratio of CD4+ to CD8+ cells in the blood is typically 2 : 1)

• Kill virally infected cells, tumour cells

Maturation of T
Lymphocytes
and Induction of
Tolerance

Basic Immunology, 6e
 The Adaptive Immune Response
B Lymphocytes
• 10% to 20% of all lymphocytes in the blood; also found in bone
marrow, lymph nodes, spleen and other lymphoid tissues

• In the spleen and lymph nodes, they aggregate into lymphoid

follicles

• Antigenic stimulation of B cells leads to the formation of plasma

cells that secrete immunoglobulins—the basis of specificity in
humoral immunity
Model of B cell
Differentiation

Clinical Immunology, Principles & Practice, 5e

 Tolerance Induction of Immature B
cells
• Self Ags that cross-link immature BCRs (multivalent Ags) induce apoptosis
–
• Self Ag in this context are macromolecules present in the BM that could be bound
Clonal deletion
the BCR
by
E.g. molecules on surface of healthy cells, or present in solution in the
ECM
• Small soluble proteins/Ags (cannot crosslink BCR) in high doses lead
downregulation
to of IgM expression
• These cells are rendered incapable of becoming activated upon subsequent
antigenic challenge – Anergy

• B cells that survive negative selection express increased IgM levels and
also begin to express membrane-bound IgD
• Expressed after alternative splicing of heavy chain
transcripts
 The Adaptive Immune Response
Antigen Recognition by B and T cells
• B cells recognise antigen directly via the BCR (surface expressed
Ig molecule)

• T cells do not recognize antigen directly

• They recognize specific peptide sequences derived from the antigen that are
bound to Major Histocompatibility Complex (MHC) class I or class II
molecules

• MHC class I is expressed by nucleated cells

• MHC class II is expressed by antigen presenting cells

 The Adaptive Immune Response
Antigen Presenting Cells
• Dendritic cells (DCs)
• Macrophages
• B cells

• All of them can stimulate memory T

cells

• Only DCs activate naive T cells

 The Adaptive Immune Response

Antigen Processing

Basic Immunology, 6e
Distinct subpopulations of
CD4+ helper
cells:

• Th1 subset secretes cytokines associated with inflammation,

e.g. IFN-γ & TNF-α; & induce cell-mediated immune responses
Activation of naïve CD8+ T cells and macrophages

• Th2 subset produces cytokines such as IL-4 & IL-5 that help B cells
to proliferate and differentiate; associated with humoral-type
immune responses

• Th17 subset secrete cytokines associated with

Basic Immunology, 6e
neutrophilic inflammation, e.g. IL-17
Cell Mediated
Immunity

Basic Immunology, 6e
Humoral Immunity

Basic Immunology, 6e
 Humoral Immunity
• Activated B cells differentiate into
immunoglobulin/antibody-secreting plasma cells

• 5 classes of immunoglobulin
IgM, IgA, IgG, IgD, IgE

• Comprise of a basic unit of 2 identical light and 2 identical heavy

chains, linked by disulphide bonds

• The heavy chains differ between classes and mediate the different
antibody effector functions
© Amboss
Antibody Effector
Functions

Basic Immunology, 6e
 References
1. Abbas, A. K., Lichtman, A. H., & Pillai, S. (2023). Basic Immunology E-Book: Basic Immunology
E-Book. Elsevier Health Sciences.
2. Helbert, M. (2016). Immunology for Medical Students: Immunology for Medical Students E-Book.
Elsevier Health Sciences.

3. Doan T, Melvold R, Viselli S, Waltenbaugh C. Immunology. Lippincott Williams & Wilkins; 2012

4. Levinson W. Review of Medical Microbiology and Immunology. Lange; 2012

5. Gartner LP. Textbook of Histology. Elsevier; 2017

THANKS
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