IMMUNOLOGY

De p a rtm e n t o f Scien c e & Engine ering

 BMS 205: IMMUNOLOGY I
• This course is four credits (three hours of class and one hour of laboratory
session.
• It is a pre-requisite for BMS 302: Immunology II.
• The purpose of the course is to make the learner acquire basic facts on the
immune mechanisms in man, in particular, the cells, tissues, organs, molecules
and interactions involved to bring about the defense in humans against foreign
substances.
• The course will be blended having online lectures as well as physical practical
sessions.
• Assessments will be through laboratory practical 10%; assignments 10%,
Continuous assessments 30% and a Final Exam 50%.
• Reference: Kuby Immunology, 7th ed., 2013. W.H. Freeman Company.
 Expected learning outcomes:
By the end of the course the learner will be able to:
• define the terms immunity and identify the immune cells, tissues and organs in
man;
• draw well labeled diagrams showing cross sections of the spleen, and lymph nodes
in humans;
• describe the mechanisms of innate (non adaptive) immunity in humans;
• describe the origin, features and functions of immuno-competent cells in humans;
• Discuss cell mediated immunity
• discuss the immunoglobulins in relation to their structure, functions and role in cell
mediated and humoral immunities;
• describe different types of cytokines and outline their application in medical
research.
• Discuss hypersensitivity reactions. Explain the principle of vaccines.
 Content
• Immune system: Structure, characteristics and organization;
• Innate defenses: skin, phagocytes, natural killer cells, inflammation, antimicrobial
proteins, fever; Organs and cells of the immune system:
• Types and structure of lymphoid organs, characteristics of immuno-competent
cells of the immune system.
• Adaptive defenses of the body: mechanisms and characteristics;
• Antigens, antigenic determinants, self antigens and major histocompatibility
complex (MHC);
• Cells of the adaptive immunity (overview)- Lymphocytes: development of
immuno-competence and self tolerance, generation of antigen receptor diversity
of lymphocytes; Antigen presentation, antigen processing, dual recognition of
antigen.
 Content cont.
• Humoral immune responses: differentiation of B cells; immunological memory;
• Active and passive humoral immunity;
• Antibodies: basic structure of immunoglobulins; Classification;
• Mechanisms of antibody diversity; Antibody targets and functions; Monoclonal
and polyclonal antibodies;
• Adjuvants; Lymphocyte hybridomas;
• Cell mediated Immunity: Overview; Clonal selection and differentiation of T
cells: antigen recognition and MHC restriction, T cell activation, antigen binding,
cytokines.
• Hypersensitivity reactions
• Vaccines.
 Introduction to Immunology:
• Every nation invests heavily in the area of defense: being able to identify
internal and external threats and how to deal with the threats in order to
protect the country.
• Human bodies equally are faced by threats both internal and external.
Thankfully, God has inbuilt a mechanism of defense to take care of these
threats.
• Immunity refers to how our bodies defend themselves against agents that
threaten our wellbeing.
• The body needs defense mechanisms since our environment (air, water,
soil) is polluted.
Immune Cells = Leukocytes
• The cells of the immune system arise from pluripotent hematopoeitic
stem cells (HSC) in the bone marrow.
• There are two major pathways / main lines of differentiation: lymphoid
and myeloid progenitor cells.
• The lymphoid lineage produces T lymphocytes, B lymphocytes and
Natural Killer (NK) cells.
• The myeloid pathway gives rise to mononuclear and polymorphonuclear
leukocytes, as well as platelets and mast cells.
• Platelets are involved in blood clotting and inflammation.
 Properties of WBCs.
• 1. Diapedesis: leukocytes are able to squeeze through the narrow blood
vessels.
2. Ameboid Movement: Neutrophils, monocytes and lymphocytes show
amebic movement, characterized by protrusion of the cytoplasm and
change in the shape.
3. Chemotaxis: this is the attraction of WBCs towards the injured tissues
by the chemical substances released at the site of injury.
4. Neutrophils and monocytes engulf the foreign bodies by means of
phagocytosis
White Blood Cells = Leukocytes
a) Phagocytes
• these are cells that engulf a pathogen and kill it using enzymes.
• They respond immediately incase there is a threat. They are part of
innate immunity. Two categories:
i. Granulocytes – phagocytic cells that contain granules. Each granule is
a pocket/ bag containing enzymes such as proteases… The granules
pick a certain stain and become very conspicuous.
ii. Agranulocytes – phagocytic cells that do not contain granules.
Examples include monocytes/ macrophages and dendritic cells.
Mechanism of phagocytosis

BIO 111 12
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BIO 111 13
 GRANULOCYTES: Eosinophils.
• They are bilobed;
• They have cytoplasmic ‘granules’ that stain orange or red in color.
• They take the acidic stain called eosin.
• They are motile and phagocytic;
• Eosinophilia is an increase in eosinophil count; it occurs when worm
(parasitic) or fungal infections come in to fight the pathogens and when
there is allergy.
• They kill pathogen that aree too largee to be engulfed.
• The lifespan of an eosinophil is 7-12 days.
• Proportion is 2-4%
 GRANULOCYTES: Basophils

• Basophils – they increase when there is injury resulting in inflammation,

or incase of allergic responses.
• They are non-phagocytic.
• They take basic stain; cytoplasmic granules stain dark blue to black.
• Lifespan is 12-15days; their proportion is 0-1%.
• They release the following:
a) histamine that regulate inflammation;
b) Heparin to prevent intravascular clotting;
c) Proteases and myeloperoxidases for killing of pathogens.
 GRANULOCYTES: Neutrophils

• Neutrophils are multilobed (2-5 lobes);

• They are most abundant of circulating WBCs: 50-70%.
• Lifespan of a neutrophil is 2-5days.
• They take both acidic and basic stain hence cytoplasmic granules appear
violet/ lavender /lilac color.
• Their granules contain numerous microbicidal molecules.
• they increase in case of bacterial infections in the body.
BIO 111 17
Monocytes

• They are mononuclear; have a clear cytoplasm;

• Have a bean / kidney shaped nucleus at the center of a cell.
• They enter tissues where they become fully mature macrophages.
• They are phagocytic; have many lysosomes.
• They have various cell membrane receptors to aid thee binding and
ingestion of foreign material.
• They are the largest leukocytes.
• Lifespan of a monocyte is 2-5days.
• Proportion is 2-6%
Macrophages
• They have a kidney shaped nucleus. Macrophages live long (several
months or years)!
• Macrophages are agranulocytes that are large in size.
• They are produced in most infections, regardless of the causative agent.
• They are actively phagocytic and can engulf large targets.
• Some are free while others are fixed in tissue such as liver (Kupffer cells),
lungs (alveolar macrophages), brain (microglia) spleen and bone marrow.
• Macrophages and monocytes are capable of producing various
complement components and monokines such as interleukin I,
prostaglandins, interferons and tumour necrosis factor.
• They can process and present antigens
Dendritic cells:

• Dendritic cells have extensions (long processes)

• Some are of myeloid others of lymphoid origin.
• They are the best antigen presenting cells to naïve T cells.
• They are found in the
a) Spleen where thy trap antigens in blood
b) Follicular dendritic cells in lymph nodes
c) Skin where they trap organisms in contact with the body surface.
Mast cells:

• They play an important role in hypersensitivity reaction like allergy and

anaphylaxis.
• They are developed in the bone marrow but mature in body tissue.
• They have similarity with basophils.
 Lymphocytes
• Lymphocytes form 20-40% of all WBCs in adults.
• Their nucleoli is present; no granules in cytoplasm; nucleus occupies much part of
the cytoplasm, dense heterochromatin.
• They recognize specific antigenic determinants. They are responsible for specificity
and memory of adaptive immunity.
• Lymphocytes that mature in thymus gland are called T cells or T-Lymphocytes. T
and B cells cannot be distinguished morphologically.
• Lymphocytes that mature in the bone marrow are B cells or B-lymphocytes. These
produce antibodies for killing pathogens or neutralizing toxins.
• Lymphocytes use unique mechanisms to destroy pathogens.
• They are part of adaptive immunity that comes in later to help where phagocytes
have already started and need assistance.
 T-Lymphocytes
• They possess molecules on their surface unique to their function.
• The molecules, also called markers, are used to distinguish the cell types and
their stages of differentiation.
• The markers are also named by the Cluster of Differentiation system.
• T-lymphocytes produce lymphokines; lymphokines enhance macrophage work.
 T –lymphocytes:
1. T- helper cells – promote and coordinate immune responses in the body e.g.,
CD4 cells. They coordinate B cells, phagocytes.
2. T-cytotoxic cells – kill infected cells of the body
3. T-suppressor /regulator cells – they avoid overproduction of WBCs.
 B-lymphocytes
• B- lymphocytes (B-cells) become plasma cells.
• Plasma cells produce antibodies.
• Antibodies are protein molecules also called immunoglobulins (Ig).
• Antibodies bind to antigens and neutralize the destructive action of the
pathogen or the toxin responsible for its virulence.
Marker Proposed function
CD1 presentation of glycolipids to NK T-cells
CD2 Adherence of T cell to target cell;

CD3 Signal transduction as a result of antigen recognition.

CD4 Binding to MHC class II molecules

CD8 Binding to MHC class I molecules

CD 11 a CD11b Leukocyte adhesion

CD 14 Co-receptor for binding lipoproteins.

Marker Proposed function
CD 16 Receptor for immunoglobulin G
CD18 Beta -2 integrin
CD19 & 20 Found on B lymphocytes for Bcell signal transduction and B cell
calcium channel activation respectively.

CD21 B cell activation

CD 25 Interleukin 2 receptor
CD 28 T cell costimulatory molecule

CD 32 Immunoglobulin G receptor.
Marker Proposed function
CD 34 Haematopoietic stem cell marker
CD 40 Class switching on B cells
CD 45 Lymphocyte activation; 45RA is a naïve T-cell marker; 45RO is a
memory T cell marker
CD54 Adhesion molecule
CD 56 NK cell marker
CD 58 Adhesion marker

CD 59 Complement membrane attack complex regulator

 Clusters of differentiation
• Read about CD 62, 69, 80, 86, 95, 106, 152, 154, 178, 274, 278, 279.
• There are genes that code for CD formation.
 NK cells
• Large in size compared to T-cells and B-cells
• They contain cytoplasmic granules
• NK cells are able to kill certain tumour cells and virally infected cells.
• They destroy cells coated with immunoglobulin (in antibody-dependent cell -
mediated immunity.
• They kill intracellular parasites using extracellular killing mechanism – they
release molecules that damage the host cell.
• NK cells respond to production of interferons by infected cell. IFNs attract NK
cells.
 ANTIGEN PRESENTING cells (APCs)
• APCs of myeloid origin include: monocytes, macrophages and dendritic cells.
• They are phagocytic cells
• They ingest pathogen, digest and present antigens on their cell surface
• They secrete proteins that attract and activate other immune cells.
 Immune System
• Defense is carried out by various organs or tissues that are part of the
lymphatic system.
• Unlike other systems, immune organs and tissues are separate from
each other but work together.
• Organs are classified as
a) Primary that is where lymphocytes develop/mature e.g. thymus gland.
b) Secondary – that is where mature lymphocytes and antigen presenting
cells interact to initiate a specific immune response
• Lymphoid organs contain lymphocytes at various stages of development.
 Primary Lymphoid Organs
• Primary lymphoid organs are major sites of lymphopoiesis.
• In mammals T-lymphocytes develop in the thymus and B cells in the bone
marrow (and fetal liver).
• In primary lymphoid organs, lymphoid progenitor cells proliferate and mature
into functional effector cells.
• Lymphocytes acquire their repertoire of specific antigen antigens in order to
cope with antigenic challenges that thee individual receives during its life.
• Ability to distinguish between self and non-self is acquired in these tissues.
 Thymus gland:
• Thymus is situated above the heart.
• It is bilobed structure.
• The thymus is internally zonated into many lobules.
• They are separated from each other by connective tissue strands called
trabeculae.
• Each lobule consists of central medulla and the outer cortex.
• The medulla is sparsely populated by thymocytes, whereas the cortex is
densely packed with immature T cells called thymocytes. It is believed that
the progenitor T cells enter the thymus and start proliferating rapidly within
the cortex.
 Thymus Gland
• Thymus is organized into an outer cortex where immature proliferating thymocytes
are found and an inner medulla that contains more mature cells.
• It has three cell types: Thymocytes, Phagocytic reticulum, Reticular epithelial cells
• Cells produced in the bone marrow migrate to the thymus gland.
• The cells are rich in MHC class II molecules.
• They are involved in thymic education; thymocytes learn to recognize self antigens.
• Lymphoid progenitor cells → prothymocytes → thymocytes → mature T cells
• Surface molecules develop on mature T lymphocytes.
• Mature T-cells leave via the post –capillary venules at the cortico-medullary junction.
Some mature T cells remain in the thymus gland.
• They migrate by the blood into specific areas of the secondary lymphoid organs.
 Bone marrow:
• It is the source of all types of blood cells
• It in the bone marrow that B lymphocytes are produced and matured.
• B lymphocytes develop without contact with antigens.
• Antigen –stimulated B cells (activated B cells) proliferate and differentiate into
plasma cells.
• Some activated B cells undergo class switch and begin to produce other
isotypes.
• Some activated B cells develop to memory cells; they can survive for months
without further antigen stimulation.
• Plasma cells secrete antibodies. Fully mature plasma cells lose their surface
immunoglobulin and MHC class II antigens.
 Secondary Lymphoid organs
• They create an environment in which lymphocytes can interact with each other
and with antigen, and then disseminate the effector cells and molecules
generated.

• Secondary lymphoid organs include lymph nodes, spleen, and mucosal

associated lymphoid tissue (MALT) e.g., tonsils and Peyer’s patches of the gut.
 Lymph nodes:
• Lymph nodes of man are round or bean shaped organs; 1-25mm in diameter.
They are encapsulated.
• They are strategically placed to filter antigens from lymph (tissue fluid).
• Tissue fluid collected from limbs and organs flow in lymphatic vessels.
• Lymphatic vessels are connected with lymph nodes.
• Lymph nodes are surrounded by a collagenous capsule with trabeculae
extending radially from the sub-capsular marginal sinus through the cortex to
the medulla.
• B cells are predominant in the cortex.
 Lymph nodes
• Cells enter lymph nodes via the
afferent lymphatics which
brings cells from the body
spaces or other lymph nodes.

• Lymphocytes leave via efferent

lymphatics and eventually
reenter the blood at the thoracic
duct.
Lymph
nodes
 SPLEEN
• The spleen is enclosed by a capsule and divided by trabeculae into
communicating compartments.
• The tissue consists of:
a) White pulp found around the branches of splenic artery
b) Red pulp – composed of splenic sinuses filled with blood and splenic cords.
Between the cells are cells: reticulum cells, erythrocytes, lymphocytes and
phagocytes. The red pulp is involved in destruction of old erythrocytes.
c) Periarteriolar lymphoid sheath (PALS) – has T-lymphocytes
d) Germinal centers – have macrophages and dendritic cells
 MUCOSAL ASSOCIATED LYMPHOID
TISSUE (MALT)

• These are non-encapsulated lymphoid tissue;

• They are found in sub-mucosal areas of gastrointestinal, respiratory and
genitourinary tracts; MALT protects such mucosal areas.
• They provide protection at the main portals of entry.
• The organized MALT tissues include tonsils, appendix, Peyer’s patches (found
in the gut.
• Some tissues are not in aggregate forms (rather they are dispersed).
• Tonsils are located at the base of tongue, at the side of the back of the mouth
and the adenoids, in the nasopharyngeal roof.
 Review of organs involved:
a) The bone marrow is responsible for production of immune cells.
b) Thymus gland: Some cells mature, differentiation, in the thymus gland.
c) Spleen: it filters blood ridding it of pathogens such as Plasmodium. It is
involved in destruction of old, worn out RBCs.
d) Lymph nodes: they filter lymph (fluid collected from tissue fluid).
There are several lymph nodes in the body
• They occur in clusters; are bean shaped and small in size.
e) Mucosal Associated Lymphoid Tissue (MALT)