Immune system, lymphoid organs

1. ORGANIZATION OF
THE IMMUNE SYSTEM
DR. SUFI H. Z. RAHMAN
MBBS, MD (Immunology)
Lecturer, Medical Faculty, AUCMS

2. Objectives
◆Identify the major components of the lymphatic system
(organs, cells and vessels) and explain their functions
◆List the primary and secondary lymphoid organs
◆Discuss the development of lymphoid organs in brief
◆Explain the functions of the immune system

4. Introduction
There is a huge number
of microorganisms
in our environment
that can infect us,
but we are remaining
uninfected How are we defending them?
Our immune system defends these organisms
and provides immunity to infection

5. Introduction
Immunity
State of protection
from infections or
resistance to
infections
Immune system
Collections of cells,
tissues and molecules
that mediate
resistance to infections
Immune response
The coordinated
reaction of cells and
molecules to eliminate
the invading organisms

6. Major components of the
Immune System
◆Lymphoid organs
• Primary or central
• Secondary or peripheral
◆Lymphatic vessels
◆Cells
• Lymphocytes
• Antigen presenting cells
• Other leukocytes
◆Molecules
• Antibody
• Complement
• Cytokines

7. Primary or Central
Lymphoid Organs
◆These organs are the sites of maturation of
lymphocytes before they encounter any antigen
◆Primary or central lymphoid organs include
1. Bone marrow
2. Thymus
◆During their maturation in these organs lymphocytes
• Acquire phenotypic features
• Become self tolerant
• Acquire clonal diversity
• Become capable of recognizing and responding to
specific foreign antigen (become immunocompetent)

8. Secondary or Peripheral
Lymphoid Organs
◆These organs are the sites of interaction of
mature lymphocytes with antigens and antigen
presenting cells (APCs)
◆Mature lymphocytes from circulation migrate and
reside in these organs
◆Microorganisms and APCs carrying microbial or
tumour antigens also migrate to these organs
through blood or lymph
◆Lymphocytes, antigens and APCs come in close
proximity and can interact in these organs

9. Secondary or Peripheral
Lymphoid Organs
◆These organs also bring different types of
lymphocytes (helper T cells, cytotoxic T cells and B
cells) in close proximity
◆This close proximity of different types of
lymphocytes optimizes their interaction with each
other by direct contact or by cytokines
◆Interaction between different lymphocytes
generates effective immune response

10. Secondary or peripheral lymphoid organs include
1. Lymph nodes
2. Spleen
3. Mucosa associated lymphoid tissue (MALT)
• Tonsils
• Peyer’s patches
• Lymphocytes in the mucosa of GIT, Respiratory and Urinary tract
1. Cutaneous associated lymphoid tissue (CALT)
Secondary or Peripheral
Lymphoid Organs
CALT is some times called tertiary lymphoid organ

11. Lymphoid Organs

12. T helper
cell
Lymphocytes in Lymphoid Organs

13. Bone Marrow
Primary Lymphoid Organs
Found in the medullary cavity of compact bones and interstices of spongy bone
Consists of haematopoitic and stromal tissue
Stromal tissue support maturation of cells by providing growth factors and cytokines

14. Bone Marrow
◆Site of haematopoisis
◆Site of maturation of B cells
◆B cells rearrange their
immunoglonulin gene segments
to generate clonal diversity
◆Acquire B cell receptors for
antigen recognition (mIgM)
◆Self-reactive B cells undergo
apoptosis (clonal deletion)
◆B cells that are not self reactive
enter circulation
Primary Lymphoid Organs

15. Thymus
Primary Lymphoid Organs
◆It is a flat, bi-lobed organ situated
above the heart
◆At birth it weighs 10- 15 gm
◆Its size increases up to puberty
(30- 40 gm)
◆Subsequently its size reduces and
much of the organ is replaced by
fat
◆Each lobe is surrounded by a
connective tissue capsule that
sends trabeculae inside and divide it
in to lobules

16. Thymus
◆Each lobule is organized into
•Outer cortex: Densely packed
with maturing T cells called
thymocytes
•Inner medulla: Sparsely populated
with thymocytes
◆Both the cortex and medulla
are crisscrossed by a stromal-
cell network consisting of
thymic epithelial cells, dendritic
cells, and macrophages
◆Site of maturation of T cells
Primary Lymphoid Organs

17. Thymus
◆Progenitor T cells (pro T cells) migrate to thymus from
bone marrow to mature in its microenvironment
◆During their maturation in the thymus, maturing T cells
• Rearrange their T cell receptor (TCR) gene segments to
generate clonal diversity
• Acquire TCRs and surface CD molecules (CD4 or CD8)
• Undergo positive selection that result in self MHC restriction
• Undergo negative selection that result in self tolerance
• Positive and negative selection is called thymic education
◆Mature T cells with TCRs that are not self reactive enter
circulation and migrate to secondary lymphoid organs
Primary Lymphoid Organs
CD= Cluster of differentiation

18. Secondary Lymphoid Organs
◆In the normal immune system, there are very
few lymphocytes (T and B) specific for any one
antigen
◆Anatomic organization of peripheral lymphoid
organs enable the APCs to concentrate antigens
in these organs so that the specific lymphocyte
clone can locate and respond to the antigen

19. Lymph nodes
◆Lymph nodes are nodular
aggregates of lymphoid tissues
located along lymphatic channels
throughout the body
◆Fluid (lymph) from epithelia,
connective tissue and most
parenchymal organs is drained by
lymphatic channels to lymph nodes
Secondary Lymphoid Organs

20. Lymph nodes
◆Encapsulated bean (or kidney)
shaped structures containing a
reticular network packed with
lymphocytes and APCs
◆Morphologically, a lymph node can
be divided into three roughly
concentric regions
•Cortex: Rich in B cells, also contains
macrophages and dendritic cells
•Paracortex: Rich in T cells, also contains
macrophages and dendritic cells
•Medulla: Contains T cells, B cells and
Plasma cells
Secondary Lymphoid Organs

21. Lymph nodes
◆Lymph enter into the lymph nodes
through afferent lymphatic vessels and exit
through the efferent lymphatic vessel
◆Microorganisms carried in lymph come in
contact with lymphocytes and APCs while
passing through the lymph nodes
◆In addition, APCs can pick up microbes
from tissue and parenchymal organs and
transport them to the lymph nodes
through lymphatic channels
◆Antigens that enter through tissue and
parenchymal organs interact with
lymphocytes in the lymph nodes and
induce immune response
Secondary Lymphoid Organs

22. Spleen
Secondary Lymphoid Organs
◆A large lymphoid organ
◆Situated in the upper part of the
left side of the abdominal cavity
◆The whole organ is covered by
peritoneum except the hilum
◆Splenic artery enters and splenic
vein exits through the hilum

23. Spleen
•Red pulp: Network of sinusoids, populated with macrophages, numerous red
blood cells and a few lymphocytes
•White pulp: Surrounds the branches of the splenic artery, forming periarteriolar
lymphoid sheath (PALS) populated mainly by T lymphocytes
• Primary lymphoid follicles: Attached to PALS rich in B cells
• Marginal zone: Peripheral to PALS contain Lymphocytes and macrophages
Secondary Lymphoid Organs
It is surrounded by
connective tissue
capsule that sends
trabeculae inside and
divide it in to
compartments

24. Spleen
Secondary Lymphoid Organs
◆Largest secondary lymphoid organ
◆More recirculating lymphocytes pass through the
spleen daily than all lymph nodes combined
◆Blood borne microorganisms enter spleen,
interact with APCs and lymphocytes and induce
immune response
◆Site of clearance of immune complexes

25. Mucosa Associated Lymphoid Tissue
(MALT)
◆Group of lymphoid tissues located under the
epithelium of the gastrointestinal, respiratory and
urogenital systems
◆Their structure ranges from loose, barely organized
clusters of lymphoid cells in the mucosa (e.g. in lamina
propria) to well organized structures like
• Tonsils
• Peyer’s patches
◆Majority of the lymphocyte in MALT are memory cells
Secondary Lymphoid Organs

26. Tonsils
◆Palatine, nasopharyngeal, lingual and tubal tonsils form Waldeyer’s ring at the
site of entry of pathogens through digestive and respiratory tracts
◆Contain lymphocytes, macrophages and plasma cells
Secondary Lymphoid Organs

27. Peyer’s patches
◆Present in the submucosal
layer of the ilium beneath
the lamina propria
◆These are nodules of 30–40
lymphoid follicles
◆Lamina propria of the
intestine also contains
lymphocytes, plasma cells
and macrophages
Secondary Lymphoid Organs

28. Cutaneous associated lymphoid tissue
(CALT)
Collection of lymphocytes under the epithelium of skin
Majority are memory cells
These are the sites of immune responses to antigens
that breach the epithelium of skin
Secondary Lymphoid Organs
At any time, more than half of the body’s
lymphocytes are in the MALT and CALT
reflecting their large size

29. Lymphatic Vessels
◆The lymphatic system is a part of the circulatory system
◆It comprises a network of lymphatic vessels that carry a
clear fluid called lymph unidirectionally toward the heart
◆Blood does not directly come in contact with the tissue
cells
◆Constituents of the blood exit the microvascular exchange
blood vessels (capillaries) to become interstitial fluid, which
comes into contact with the tissue cells
◆Lymph returns excess protein and excess interstitial fluid to
the circulation
◆Lymph also transports fats from the digestive system

30. Lymphatic Vessels
◆Lymphatic vessels from tissue
drain to the regional lymph
nodes through afferent
lymphatic vessels
◆Efferent lymphatic vessels from
these nodes drain into another
group of lymph nodes

31. Lymphatic Vessels
◆Efferent lymphatic vessels form
lymphatic trunks that ultimately
drain into lymphatic ducts
(thoracic duct on the left and right
lymphatic duct on the right side)
◆Thoracic duct and right lymphatic
duct drain into the internal jugular
veins at their junction with
subclavian veins
◆Thereby it carries fluid from
tissue to the blood circulation

32. Lymphatic Vessels
◆Lymph may pick up microorganisms and cancer cells
from tissue and parenchymal organs, bring them to
lymph nodes where they come in contact with APCs
and lymphocytes and induce immune response
◆Macrophages, dendritic cells and lymphocytes that
migrate to tissues can also return back to circulation
through lymphatic vessels
◆So lymphatic system is an important part of the
immune system

33. Lymphocyte Recirculation
Lymphocytes are
recirculating cells that
migrate to secondary
lymphoid organs in search of
antigens
If they do not encounter
antigen, they can come back
to the circulation again

34. Cells of the Immune System
◆Cells of the immune system are
generated in the bone marrow
◆The process of generation is
called haematopoisis
◆The microenvironment of the
bone marrow stroma support cell
generation and maturation
◆From bone marrow the cells are
released into the circulation

35. Cells of the Immune System
Functionally cells of the Immune System
can be classified as
1. Immunocompetent cells
2. Antigen presenting cells
3. Effector cells

36. Cells of the Immune System
◆Capable of recognizing specific antigens and providing
immune response to that particular antigen
◆These cells possess 4 attributes of adaptive immunity
1. Antigenic specificity
2. Diversity
3. Immunological memory
4. Self/ non-self recognition
◆Only mature T and B lymphocytes have these
characteristic attributes and are called ICC
Immunocopmpetent cells
(ICC)

37. Cells of the Immune System
Immunocopmpetent cells
TH= T Helper, TC= T Cytotoxic

38. Cells of the Immune System
◆Constitute 40- 60% of circulating WBC population
◆Only cells that bear specific receptors for antigens
◆All lymphocytes are morphologically similar but they differ
in lineage, function and phenotype (e.g. CD molecules)
◆Lymphocyte population can be classified as
• B lymphocytes
• T lymphocytes
• Natural Killer (NK) cells
Lymphocytes
CD= Cluster of Differentiation
NK cells do not bear specific receptors for antigen

39. Cells of the Immune System
◆Mature in bone marrow
◆Constitute 30- 40% of circulating lymphocytes
◆Express membrane bound antibodies or
immunoglobulins (mIg) on their surface that serve
as receptors for antigen recognition
◆Other important surface markers include: Class I
and II MHC molecules, CD20, CD21 (CRII) , CD35
(CRI), CD40, CD45, CD80 (B7.1), CD86 (B7.2)
B lymphocytes
CR= Complement Receptor

40. Cells of the Immune System
◆Express B cell receptors (mIg) by
which they can recognize soluble or
free antigens in circulation or tissue
◆They can recognize antigens that are
chemically protein, polysaccharide,
nucleic acid or phospholipid in nature
◆Upon activation they differentiate to
plasma cells and memory B cells
◆Plasma cells secrete antibodies
specific for the inciting antigen
◆Antibodies are effector molecules
that eliminate the invader
◆Provide humoral immunity
B lymphocytes

41. Cells of the Immune System
◆Mature in the thymus
◆Constitute 60- 70% of the circulating lymphocytes
◆Express T cell receptors (TCRs) on their surface for
recognition of specific antigen
◆Other important surface markers include Class I MHC
molecule, CD3, CD4/ CD8, CD28, CD40L, CD45
◆TCRs can recognize antigens only if it is presented on the
surface of APCs by self MHC molecule (self MHC restricted)
◆Can recognize only protein antigens
◆ Provide cell mediated immunity (CMI)
◆Regulate Humoral Immunity and CMI
T lymphocytes

42. Cells of the Immune System
Functionally there are 3 subpopulations of T cells
Helper T (TH) lymphocytes
CD4+ T cells, recognize antigen presented by APCs with Class II
MHC
Kill cells harbouring intracellular pathogens by macrophages
Help Cytotoxic (CD8+) T cells and B cells
Cytotoxic T (TC) lymphocytes
CD8+ T cells, recognize antigen presented by APCs with Class I MHC
Recognize specific antigens on cell surface and kill virally infected cells
and tumour cells
Regulatory T lymphocytes
Usually CD4+ T cells (some times CD8+)
Limit immune response
T lymphocytes

43. Cells of the Immune System
T lymphocytes

44. Comparison of B and T lymphocytes
Attribute B lymphocytes T lymphocytes
Site of maturation Bone marrow Thymus
Antigen receptor Membrane immunoglobulin (mIg) T cell receptor (TCR)
Surface markers
MHC molecules
CD molecules
Class I & II
CD20, CD21 (CRII) , CD35 (CRI),
CD40, CD45, CD80 (B7.1),
CD86 (B7.2)
Class I
CD3, CD4/ CD8, CD28,
CD40L, CD45
Antigen recognition Can recognize free antigens
Do not require antigen presentation
Can recognize antigens only when
presented on the surface of APCs with
self MHC molecules
Chemical nature of
antigen recognized
Proteins, polysaccharides, nucleic
acids, phospholipids
Only proteins because MHC can
present only peptides
Role as APC Yes No
Cells of the Immune System

45. Cells of the Immune System
◆Large granular lymphocytes
◆5- 10% of circulating lymphocytes
◆Do not express clonally
distributed specific antigen
receptors like B or T lymphocytes
◆Capable of rapidly attacking and
killing virally infected cells and
tumour cells (antigen non- specific)
◆Component of innate immunity
◆Also play a role in adaptive
immunity by participating in
antibody dependent cell mediated
cytotoxicity (ADCC)
Natural Killer (NK) cells

46. Cells of the Immune System
◆APCs are specialized cells that display antigens on their
surface by MHC molecules to activate T lymphocytes
◆The common portals of entry of microorganisms- the
skin, gut and the respiratory tract contain APCs in their
epithelium
◆These cells can capture antigens, transport them to
peripheral lymphoid organs and display them to T cells
Antigen presenting cells (APCs)

47. Cells of the Immune System
◆Professional APCs include:
• Dendritic cells
• Macrophages
• B lymphocytes
◆APCs express both Class I and Class
II MHC molecules on their surface to
display antigen to T cells
◆They also express B7 (B7.1 and B7.2)
molecules to provide co-stimulatory
signal to activate T cells
Antigen presenting cells (APCs)
Signal 1: Stimulatory signal
Signal 2: Co-stimulatory signal
TC

48. Effector cells
Cells that eliminate microbes
◆Lymphocytes
◆Neutrophils
◆Monocytes and Macrophages
◆Eosinophils
◆Basophils and Mast cells
◆Natural Killer (NK) Cells
Cells of the Immune System

49. • Plasma cells
• Derived from B lymphocytes
• Produce antibodies
• Antibodies eliminate extracellular pathogens
• Effector TH cells
• Derived from CD4+ T lymphocytes
• Produce cytokines that activate macrophages
to eliminate intracellular pathogens
• Cytotoxic T cells
• Derived from CD8+ T lymphocytes
• Induce apoptosis of infected cells
Cells of the Immune System
Effector cells
Humoral
Immunity
Cell mediated
Immunity
Effector Lymphocytes

50. Other effector cells and their roles in Innate and Adaptive Immunity
Cells of the Immune System
Effector cells
Cells Role in Innate Immunity Role in Adaptive Immunity
Neutrophils Phagocytosis ADCC
Macrophages
(Monocytes)
Phagocytosis ADCC
Pathogen elimination by TH cells
Type IV Hypersensitivity
Eosinophils ADCC in parasitic infections
Type I Hypersensitivity
Mast cells and
Basophils
Inflammation Type I Hypersensitivity
NK cells Kill virus infected and tumour cells ADCC
ADCC= Antibody dependent cell mediated cytotoxicity

51. Development of lymphoid organs
◆The epithelia of thymus is developed from 3rd
pharyngeal pouch
◆During the late stages of the development of the thymic
epithelium, haematopoitic bone-marrow precursors migrate into
the thymus and form thymocytes
◆The spleen develops from mesenchymal cells between layers of
the dorsal mesentery of the stomach
◆Lymphatic vessels develop from lymph sacs that arise from
developing veins, which are derived from mesoderm
◆With the exception of the anterior part of the sac from which
the cisterna chyli develops, all lymph sacs become invaded by
mesenchymal cells and are converted into groups of lymph
nodes

52. Functions of the Immune System
◆The main function of the immune system is
defense against microbial infections
• Prevents entry of organisms inside the body
• Kills and eliminates organisms that enter the body and
prevents establishment of infection
• Eradicates established infection
◆Another major function of the immune system is
protection from tumours
• Continuous surveillance for tumour cells
• Kill any tumour cell developed
(Tumour develop only when it can evade the immune surveillance)

53. Importance of the Immune
System
◆Individuals with defective immune responses are
susceptible to serious, life-threatening infections
◆Stimulating immune responses by vaccination is the
most effective method for protecting from infections
◆Immune response is a barrier to successful organ
transplantation
◆Clinical trials are showing that cancers can be treated by
stimulating the immune response
◆Abnormal immune response (hypersensitivity and
autoimmunity) may cause diseases with serious
morbidity and mortality

54. Further Review
◆Levinson W. Review of Medical Microbiology
and Immunology. 11th
edition. McGraw Hill, 2008.
◆Kindt TJ, Goldsby RA, Osborne BA. Kuby
Immunology. 6th
ed. WH Freeman, 2006.
◆Abbas AK, Lichman AH. Basic Immunology. 3rd
edition. Elsevier, 2011.