General Microbiology and

Immunology
Competency- MI1.8
Lecture 4
Prof Pradyot Prakash
Department of Microbiology
IMS, BHU, Varanasi
 Specific Learning Objectives

• Describe the organization of the lymphoid system, into

lymphoid cells and central and peripheral organs

• Describe the characteristics of T & B cells.

• Explain the importance of Phagocytic cells, null cells, &

other cells in the immune system.

[This lecture is covering only few SLO addressing competency MI1.8]

 Topics to be covered

• Anatomy of Immune response: Organs which

are responsible for generation or harbouring
the immuno-competent cells.

• Cells involved in Immune response

 2 Major types of Organs involved
Primary Lymphoid organs: in which lympho-reticular cells
develops and matures---Bone marrow and Thymus

Secondary Lymphoid Organs: in which lymphoid cells and

antigens react…. Lymph nodes, Spleen, MALT

Lymphoreticular system (Mononuclear-phagocytic system) –

complex organisation of cells---distributed widely in different--
-Organs and tissues:
Blood, connective tissues, spleen, liver, lungs, bone marrow
and lymph nodes
 Mononuclear Phagocytic system
• Lymphoid cells: Lymphocytes and plasma cells
(Role in specific immune response)

• Phagocytic cells: Monocytes and Macrophages

(Ingesting and digesting exogenous antigens, remove
microbes from the blood and tissues, role in specific immunity
response also)
 Reticular connective tissues
The reticular connective tissues are found in
the kidney, the spleen, lymph nodes, and bone
marrow.

Their function is to form a stroma and provide

structural support to lymphoid organs.

Reticular connective tissue is a type of

connective tissue with a network of reticular
fibers, made of type III collagen (reticulum = net
or network).
 Functional anatomy of Lymphoid
system enables--
• Humoral immunity : Plasma cells (activated B cells)

• Cellular Immunity: Activated T cells

• Cells of Immunological importance originates from

HSC.

• Both T & B cells: develops through different channels –

but interact for the execution of both types of
immunity.
Hematopoteic stem cells
Lymphoid systems
 Lymphoid organs
Thymus gland: Thymic Lymphocytes or T cells
• L progenitor Cells which get processed in Thymus

• T cells which either do not recognize the self antigen

–MHC complex or Ag-MHC complexes get
destroyed.

• T cells are mainly associated with Cell mediated

immunity

• Clinical significance: Thymus dysfunction ---

Deficient CMI as well as Humoral immunity
• Bone Marrow: B cells
• Origin and development in Bone marrow

• Immature B cells ---differentiate within

BM.

• Clinical significance:
• Bone marrow dysfunction---leads to
hypo or agammaglobulinemia– recurrent
bacterial infections
Peripheral (Sec)Lymphoid organs
 Lymph nodes

Sub-capsular
Sinus
1. Germinal centre:
B cells
2. Mantle zone:
activated B cells
Dendritic
3. Paracortical region: macrophages,
plasma cells,
Dendritic cells
T cells
 Activities of Lymph nodes
• Site for Phagocytosis

• Site for proliferation and circulation of T and B

cells
• Clinical significance
• Enlarged nodes: Sign of local antigenic
stimulation (local infections)
 Spleen
1. Periarteolar lymphoid sheath (PALS): T cells & APCs
2. Marginal zone: B cells

Capsule

Trabecula Primary
follicle
Vascular
sinusoids
Marginal
zone White pulp

Periarterial
lymphatic
sheath (PALS)

Red pulp Germinal center

Vein Artery
 Functions of spleen
• Clearance of damaged cells
• Host resistance to bacterial infections, primarily against
blood borne antigens—Pneumococcal and Meningococcal
infections.

• Clinical significance of splenectomy

• Children: Leads to increased incidence of bacterial sepsis
by S pneumoniae, Meningococcus, H influenzae
• Adults: May lead to bacterial infection leading to
bacteremia.
 Mucosa associated Lymphoid tissue
Mucosa lining alimentary tract, respiratory, genitourinary tracts and
other Lumina and surfaces are exposed to numerous antigens.

The components of MALT are sometimes subdivided into the

following:
• GALT (gut-associated lymphoid tissue. Peyer's patches are a
component of GALT found in the lining of the small intestines.)
• BALT (bronchus-associated lymphoid tissue)
• NALT (nasal-associated lymphoid tissue)
• CALT (conjunctival-associated lymphoid tissue)
• LALT (larynx-associated lymphoid tissue)
• SALT (skin-associated lymphoid tissue)
• VALT (vulvo-vaginal-associated lymphoid tissue)
• TALT (testis-associated lymphoid tissue)
 GALT
• Mucosa lining alimentary tract, respiratory, genitourinary
tracts and other Lumina and surfaces are exposed to
numerous antigens.
BALT
• Contains both lymphoid as well as phagocytic cells.
• Predominant Ig produced is IgA
• Also produces IgG, IgM and IgE locally

Clinical significance:
• Existance of common mucosal and secretory immune
system may explain the superiority of oral and nasal
immunization over parenbteral route for many enteric
and respiratory infections.
• Oral Polio vaccine
 Cells of Lymphoreticular system
Lymphocytes
• 20-40% body WBCs and 99% of the cells in the lymph.
Types based on functions and cell membrane components:
1. T cells
2. B cells
3. Null Cells

Lymphocytic circulation: Through blood, lymph, lymphatic

organs and tissues---ensures their contact with antigens in
any part of the body
• T and B calls after priming in central lymphoid organs---
ICC---Naïve cells before they encounter any antigen

• Function:
• Recognition of antigens
• Storage of immunological memory
• Immune response to specific antigens

Each clone of a lymphocyte is able to recognize only one

antigen.
• Stimulated T cells produce Lymphokines and
induces CMI.

• Stimulated B cells divide and transform into

Plasma cells which synthesizes Ig
Surface markers of different subset of
lymphocytes
 T cells
Origin – Bone marrow
Development- Thymus
Important role in adaptive immune response
Possess T cell receptor
Types of T cells:
Effector T cells
1. Cytotoxic cells (CD8+)
2. Helper T cells (CD4+): TH1, TH2, TH17
3. Memory T cells
Regulatory T cells
Treg cells
• Regulatory T cells are CD4+ specialized subpopulation of
T cells that act to suppress immune response, thereby
maintaining homeostasis and self-tolerance.

• It has been shown that Tregs are able to inhibit T cell

proliferation and cytokine production and play a critical
role in preventing autoimmunity.
 B cells
Origin and development: Bone marrow

Type :
Naïve B cells
Activated B cells—mature B cell –Plasma cells—
Ig—each subset reacting with different
epitopes
Memory B cells
Role of B cells:

Major player in Humoral immunity, responsible for

producing immunoglobulins
Difference between T and B cells
 Null cells
• 5-10% of circulating lymphocytes lacks features of T and
B cells

• LGL are heterogenous group of cells with different

surface markers and functional characterstics.

• 3 types of Null cells

• NK: Natural killer cells
• ADCC: Antibody dependent cytotoxic cells
• LAK: Lymphokine activated killer cells
 Natural Killer cells
 Part of Innate immunity
 Active mainly against tumor cells
and virus infected cells
 Cytotoxicity is not AD or MHC restricted
 Activity does not require prior sensitization.
 Activity augmented by Interferons.
 ADCC: Antibody dependent cytotoxic
cells
• Subset of NK cells possessing surface receptors for Fc
portion of Ig..
• Kill the target cells sensitized by IgG antibodies
• ADCC is distinct from action of Cytotoxic T cells, which are
independent of the antibody.
 LAK cells
• NK lymphocytes which in conjuction with IL-2, are cytotoxic
to wide range of tumor cells.

• Shown promise in treatment of RCC.

 PHAGOCYTIC CELLS
Macrophages: (Mononuclear Macrophages)
• Circulating Macrophages: Monocytes
• Fixed tissue macrophages (histiocytes)

Microphages: Polymorphonuclear Microphages

• Neutrophils, Eosinophils
 Macrophage

 Larger monocyte with some changes

1. 5-10 times larger than monocyte
2. More lysozyme and cell organelle
3. Produces more lytic enzymes and cytokines
4. Have greater phagocytic activity
5. Have longer life in tissues
 Action:
1. Antigen presenting cells
2. Phagocytosis
3. Microbial destruction by myeloperoxidase activity
4. Granuloma formation
 Polymorphonuclear Microphages
Neutophil:
Part of innate immunity
Phagocytosis Eosinophil

PMNs
Comparison of PMNs
to eosinophil
 Eosinophil

Eosinophil:
Minor role in phagocytosis
 Antigen presenting cells
T helper cells recognize only those antigen which are
displayed together with MHC Class II antigen by APC----
after confronting the complex produces cytokines produced
by Th Cells

Dendritic cells are Major Antigen presenting cells

 Assessment- Written/ Viva voce
• Comment on differences between T and B cells

• Short notes on:

a. B cells b. Null cells c. MALT

• Enumerate types of T cells and their functions

• MCQ/ Short answer type questions