Cell and organs of immune system

Chapter 2

Kuby

Key concepts from last lecture

• Pathogen

• Antigen

• Antibody?

• B cells (Plasma cells)

• T cells (Th&Tc)

• Innate immunity

• Adaptive immunity

• Passive immunity

• Active immunity

• History

• Overview of immune response

• Cell mediated immunity

• Humoral immunity

• Phases of immune response

• Adaptive immunity has memory

• Primary and secondary response

• What happens on immunization

1. What are the main cell types of the immune

response?

2. Where are they, where do they come from, what

do they look like, what are their major functions?

3. How does this package fit together to give you a

circulating immune system?

4. Describe the overall physical organization of the

immune system and the different roles played by

primary and secondary lymphoid organs.

Today’s Objectives

Blood composition

– 55% Plasma (fluid matrix of water, salts, hormones,

proteins, Ab, metabolites, etc.)

– 45% Cellular elements:

Red Blood Cells (RBCs): 5-6 million RBCs/ml of blood.

Contain hemoglobin which transport oxygen and CO2.

White Blood Cells (WBCs also called leukocytes):

5,000-10,000 WBCs/ml of blood. Play an essential role

in immunity and defense. Include:

Lymphocytes: T cells, B cells and NK cells

Macrophages (phagocytes)

Granulocytes: Neutrophils, basophils, and

eosinophils.

Platelets/Thrombocytes: Cellular fragments. 250,000-

400,000/ml of blood. Important in blood clotting, release

growth factors/cell differentiation/proliferation/blood

cells/blood vessel/healing properties.

Name two types of fluid that circulate in our body?

1. Blood

2. Lymph:

• Tissue fluid/interstitial fluid/intercellular fluid

• Colorless,

• composition similar to blood serum.

• Collected from tissue into lymph vessels by diffusion

• Along with it are collected Antigens (pathogens/toxins)

• Added to blood in the heart

Blood

Serum Proteins White Blood

Cells

(Leucocytes)

•Immunoglobulins

•Complement

•Clotting factors

• Growth factors

• Many others

Phagocytic/den

dritic cells

(macrophages,

dendritic cells,

NK cells etc)

Lymphocytes (T

cells, B cells &

NK cells)

Where are they (immune components)?

Where are they?

Lymphocytes 15-40%

Neutrophil

Eosinophil

Basophil

Macrophage

Hematopoiesis

• The process of

– proliferation

– differentiation

&

– maturation

of blood cell

• Mostly in bone marrow from stem cells

• Regulated by cytokines & growth factors

Hematopoiesis

Blood Cell (RBCs and WBCs)

Self renewing

Differentiation and Maturation

Routes for hematopoietic stem cell (HSC)

HSC HSC

Stromal cells

Non-hematopoietic cells found in bone marrow

Form a meshwork for HSC growth

Provide microenvironment consisting of

cellular matrix + hematopoietic growth factors

(these proteins/Growth factors induce differentiation and maturation)

Thus stromal cells support HSC differentiation

and maturation

When infection occurs: Activated T cell and macrophages produce hematopoitic

growth factors stimulate hematopoiesis

Myeloid

Progenitor

Lymphoid

Progenitor

HSC

Development of immune cells

B cell

Progenitor

T cell

Progenitor

B cell

TC cell

TH cell

Dendritic cell

Natural killer

(NK) cell

Dendritic cell

Macrophage

Monocyte

Neutrophil

Eosinophil

Basophil

Platelets

RBC Erythroid

progenitor

Megakaryocyte

Basophil

progenitor

Eosinsophil

progenitor

Granulocyte

monocyte

progenitor

Where do they come from?

Where do they come from?

Cytokines and Growth factors

IL = Interleukins

In Vitro Hematopoiesis

Adherent layer of

stromal cells

Bone marrow cells added (HSCs)

Cell culture in semisolid agar

Used for detection and identification of HGFs

Eg. Cytokine called colony stimulating factors (CSFs)

• Acidic glycoproteins

• Induce the formation of hematopoitic cell lines

Eg. Cytokine Erythropoietin (EPO)

• Glycoprotein involved in terminal development of RBCs

Growth of

bone marrow

cell colonies

Cells of the Immune System

Immune

System

Myeloid

Cells

Lymphoid

Cells

Granulocytic Monocytic T cells B cells

Neutrophils

Basophils

Eosinophils

Macrophages

Dendritic cells

Helper cells

Cytotoxic cells

Plasma cells

NK cells

Bone marrow lymph

Lymphocytes

• Group of WBC (20 - 40%)

• 99% cells in lymph

• Three classes of lymphocytes

• Morphologically similar

• Each has distinct function

• Circulate in blood and lymph

• Migrate to tissue spaces and lymphoid organs

Lymphocytes Classes

Class Function

B Lymphocytes Antibody production

T lymphocytes

a) Helper T cell

b) Cytolytic T cell

-Stimuli for B-cell growth and activation

- Release cytokines for macrophage activation

- Phagocytic, Lysis of pathogen infected cells

Natural Killer cells - Lysis of pathogen infected cells, virus

infected cells, tumor cells etc

Lymphocyte subsets

CLP

Common

Lymphoid

Progenitor

Naive

T cell

TC cell

CYTOTOXIC T

LYMPHOCYTES

Kill pathogen

infected cells

TH cell

T HELPER CELLS

Activate B cells

and macrophages

Secrete cytokines

Naive

B cell

B cell

PLASMA CELLS

Produce antibodies

Antigen activation Antigen activation

TC cell

CYTOTOXIC T

LYMPHOCYTES

TH cell

T HELPER CELLS

B cell

PLASMA CELLS

Adaptive immunity

Naive Lymphocyte

Antigen activation

Effector cells Memory cells

• Short life (days to weeks)

• Eliminate antigen

• Long lived years

• Give life long immunity

against a particular antigen

Name and Maturation

B cell mature in bone marrow

Called B cell (not true) B cells got their name because B cell differentiation was first demonstrated in

the bursa of Fabricius of chicken embryos.

T cell mature in thymus therefore called T cell

B cell

• Membrane bound Immunoglobulins (Ig)/Antibodies (Ab) on surface

• These are receptors for Ag: recognize free Ag

• ~1.5 x 105 Ab on B-cell surface

• Other molecules on B-cell surface are

CD40 (interaction with TH cell),

MHCII (APC), (Major histocompatibility complex)

CR1 and CR2 (receptor for complement products)

• B cell Ab binds to Ag and also interacts with TH/macrophages

• Activation of naïve B-cell

• B cell divides and differentiate

• Plasma cells + Memory cells

• Plasma cells secrete Ab and die in 1-2 weeks

T cell • Membrane bound T cell receptor (TCR) on surface

• TCR receptor for Ag

• Does not recognize free Ag

• Recognizes Ag bound to MHC molecules on self-cells

• TH cells express CD4 = CD4+T-cell

• TC cells express CD8 = CD8+T-cell

• CD4+T-cell recognize Ag bound to MHC II

• CD8+T-cell recognize Ag bound to MHC I

• CD4+T-cell: CD8+T-cell/TH:TC = 2:1

TH cells

Ag on MHCII

Activated

Effector cells

Secrete cytokines

Cytokines activate Bcell,

Tcell and macrophages

Tc cells

Ag on MHCI

Interaction + Cytokines =Activated

Effector cells= cytotoxic Tcell (CTL)

Recognize and eliminate infected cells

• The immune system must discriminate between self and non-self.

• When self/non-self discrimination fails, the immune system destroys cells and

tissues of the body and as a result causes autoimmune diseases (AID).

• Autoimmunity against hematopoietic stem cell causes Aplastic anemia

• Bone marrow transplant /Stem cell transplant

• Regulatory T cells actively suppress activation of the immune system and prevent

pathological self-reactivity, i.e. autoimmune disease.

• The critical role regulatory T cells play within the immune system is evidenced by

the severe autoimmune syndrome that results from a genetic deficiency in

regulatory T cells.

Regulatory T cells (Treg)

Also known suppressor T cells (Ts)

CD4+CD25+Foxp3+ regulatory T cells, or "Tregs"

1. Prevention of autoimmune diseases by establishing and

maintaining immunologic self-tolerance .

2. Suppression of allergy and asthma.

3. Induction of tolerance against dietary antigens, i.e. oral

tolerance.

4. Induction of maternal tolerance to the fetus .

Functions of T reg cells

Still research is ongoing?

A third kind of lymphocytes

Release lytic granules that kill

Virus infected cells

+ Tumor cells

•Granules contain porins and granzyme (serine) proteases

•Cause lysis or apoptosis of infected/tumor cells

Natural Killer cells

Tumor cells and virus infected cells display Ags on surface

Antibodies (produced against these Ags by immune

system) bind to theses Ags on the surface of infected cells

CD16 receptor on NK cells recognizes antibodies (Fc)

Destroys the target cell

Process is called Antibody dependent cell mediated

cytotoxicity (ADCC)

NK cells also recognize abnormalities on infected or tumor cells

• Reduction in display of MHCI on surface

• Unusual profile of surface Ags

NK cells recognize potential target cells by the following ways

White Blood Cells

Other WBCs Lymphocytes

The cells of the immune system

Phagocytic

Phagocytic

APC Secretory B, T, NK

Dendritic

Macrophages

Neutrophil

Eosinophil

Basophil

Mast cell

Most abundant WBCs

Migrate to infection sites

kill the invader

Big in size

Fix or moving

Professional APC

Secrete hydrolytic Enz.

Innate immunity

Professional APC

Present to TH cells

Phago = “eating”

Cyte = “cell”

Phagocytic

Read from Kuby

Non-phagocytic

Allergic responses Heparin (stop blood coagulation)

+Histmine (allergic reaction)

Phagocytic

Motile

Damage parasite memb

Non-phagocytic

MC Precursor in Bone marrow

Migrate blood tissue

Differentiate in tissue

Role in allergic reactions

White Blood Cells

Other WBCs Lymphocytes

The cells of the immune system

Phagocytic

Phagocytic

APC Secretory B, T, NK

Dendritic

Macrophages

Neutrophil

Eosinophil

Basophil

Mast cell

Organs of the immune system

Lymphatic system:

It is a network of lymph vessels

that collects the fluid and

lymphocytes that escape into

the tissues from blood

capillaries and returns these

back to the circulating system.

Lymph organs + lymph

Based on Function:

MALT: Mucosal associated lymphoid tissue: (less organized compared to lymph nodes, includes: small

Intestine – Peyer’s Patches, tonsil, appendix,)

• Far fewer lymphocytes

• Assumes an immune role only when challenged with antigens

• Generally result in inflammation.

• It achieves this by importing the lymphocytes from blood and lymph

The tertiary lymphoid tissue

CALT (Cutaneous Associated Lymphoid Tissues)

Thymus:

• Site for Tcell dev and maturation

• Flat

• Bilobed organ

• Situated above the heart

• Each lobe has two compartments

Cortex: outer

Medulla: inner

• Cortex: densely packed with

immature T cells called thymocytes

• Medulla: few thymocytes

Thymus

•Cortex+Medulla has stromal cell

network

• Stromal cell network help in

differentiation and maturation of T

cells

• Composed of epithelial cells,

dendritic and macrophages

• Thymic epithelial cells called

Nurse cells

Nurse cells form membrane

extensions

surround many thymocytes

form multicellular complexes

Selection process in thymus

• Only 5% of T cells recognize Ag

on MHC complex of APC

• Rest 95% die (these cannot

recognize Ag/or recognize self Ag)

Thymus does not work, No T cells, no cell mediated immunity, infectious diseases inc.

Thymus

With age cell content of thymus decreases

Size decreases

Fat content increases

Decline in thymic function

Leads to decline in immune function

Age and Thymus

Birds (Bursa), primates+ rodents (primary lymphiod organ),

cattle+sheep (spleen) different site of B cell maturation

Largest lymphatic vessel

in the body.

Collects most of the

lymph in the body

Empties it into left

subclavian vein

•Blood flowing with pressure

•Plasma seeps through the walls

of capillaries

• This fluid is called interstitial

fluid

• Most of it returns back to blood

• Rest of this interstitial fluid is

called lymph

• Lymph collected by lymphatic

capillaries network

• Flows to large lymph vessels

• Largest lymph vessel called

Thoracic duct empties it in heart

vein

• Flow in the lymph achieved by

muscles in the body

•Ag is picked by lymph syst and

carries to secondary lymphoid

organs: lymph nodes and traped

there

• Lymph system also transports

immune components to various

sites

• Bean shaped structure

• divided into three regions

• Outer most: Cortex

Contains lymphocytes

( B-cells mostly), Mac

+ dendritic cells =

Primary follicle (PF)

Ag challange

PFs enlarges to

Secondary follicles (SFs)

Each SF has a

germinal centre (GC)

GC where B cell

proliferate

• Paracortex

Contains ( T-cells

mostly + dendritic cells

APC:MHCII) to Th cells

• Medulla

Few cells

mostly Plasma cells

secreting Ab

•Afferent vessel carries lymph containing pathogens to lymph nodes into Cortex, paracortex

medulla.

•Macrophages/dendritic cells of lymph attack and present Ag by MHC molecules.

•Activate B cells and T cells

•Efferent vessel carries lymph away from the lymph nodes

•Lymph leaving the lymph node is rich in Abs secreted by Plasma cells in medulla and other

activaed lyphocytes

Spleen • Mounts immune response in

blood

• Large ovoid secondary

lymphoid

organ

• traps blood born Ag

• not connected with

lymphatic vessles

• Ag supplied by splenic

artery

• It has a capsule

• Projection from capsule

goes to the interior of

spleen

• compartments are formed

• Two compartments

•Red pulp (old RBCs

removed here)

•White pulp

•Red pulp: Mac+RBCs

• White pulp: mostly T

cells, DC and few B cells,

forms PALS

• Marginal zone Primary

follicles + GC

Self-reading

MALT intestine

Mucosal membrane of gastrointestinal tract (stomach+intestine)

•Loose clusters:

B cells,

Plasma cells

Th cells

Macrophages

•Ab are secreted

in the lumen

M-cells

Epithelial cells specialized for Ag transport

M cells

M cells lie above

Inductive site:

Self-reading

• Innate immunity found in invert. +

plants

• Addaptive immunity mediated by

Ab+Tcells found in vertebrates

• All lyphoid tissues are not present

in all vert.

• With evolution new lymphid organs

were added

• Retains the old ones

• Eg B and T cells not present in jaw

less fish (Lamprey = GALT gut

associated)

• Shark is has jaws and it also has B

and T cells

Evolution and lymphoid cells and organs

Break

Clotting factors in serum