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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

Todays Objectives
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.

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. 250,000400,000/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

Where are they (immune components)?

Blood

Serum Proteins

White Blood Cells (Leucocytes)

Immunoglobulins Complement Clotting factors Growth factors Many others

Lymphocytes (T cells, B cells & NK cells)

Phagocytic/den dritic cells (macrophages, dendritic cells, NK cells etc)

Where are they?


Eosinophil

Neutrophil
Macrophage Lymphocytes
15-40%

Basophil

Hematopoiesis
The process of
proliferation differentiation & maturation of blood cell

Hematopoiesis
Mostly in bone marrow from stem cells Regulated by cytokines & growth factors

Routes for hematopoietic stem cell (HSC)


HSC

HSC

Self renewing

Differentiation and Maturation

Blood Cell (RBCs and WBCs)

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

Development of immune cells


HSC
Dendritic cell Myeloid Progenitor Macrophage Monocyte
Granulocyte monocyte progenitor

Lymphoid Progenitor

Natural killer (NK) cell

Neutrophil

T cell Progenitor

TH cell

Eosinsophil progenitor

TC cell B cell Progenitor

Eosinophil
Basophil progenitor

B cell

Basophil
Megakaryocyte

Platelets

RBC

Erythroid progenitor

Dendritic cell

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 Growth of bone marrow cell colonies


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

Cells of the Immune System


Immune System
Bone marrow lymph

Myeloid Cells

Lymphoid Cells

Granulocytic

Monocytic

T cells

B cells

NK cells

Neutrophils Basophils Eosinophils

Macrophages Dendritic cells

Helper cells Plasma cells Cytotoxic cells

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 B Lymphocytes T lymphocytes a) Helper T cell Function Antibody production

b)

-Stimuli for B-cell growth and activation - Release cytokines for macrophage activation Cytolytic T cell - Phagocytic, Lysis of pathogen infected cells - Lysis of pathogen infected cells, virus infected cells, tumor cells etc

Natural Killer cells

Lymphocyte subsets
CLP Common Lymphoid Progenitor
Naive T cell Naive B cell

Antigen activation

Antigen activation

TC cell CYTOTOXIC T LYMPHOCYTES Kill pathogen infected cells

TH cell

T HELPER CELLS Activate B cells and macrophages Secrete cytokines

B cell PLASMA CELLS Produce antibodies

Adaptive immunity
Naive Lymphocyte

Antigen activation

Effector cells Short life (days to weeks) Eliminate antigen

Memory cells Long lived years Give life long immunity against a particular antigen

TC cell CYTOTOXIC T LYMPHOCYTES

B cell T HELPER CELLS PLASMA CELLS


TH cell

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 nave 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

Regulatory T cells (Treg)


CD4+CD25+Foxp3+ regulatory T cells, or "Tregs" Also known suppressor T cells (Ts) 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.

Functions of T reg cells


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 .
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


NK cells recognize potential target cells by the following ways

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

The cells of the immune system


White Blood Cells

Lymphocytes

Other WBCs

B, T, NK

Phagocytic APC

Phagocytic

Secretory

Dendritic Macrophages

Neutrophil Eosinophil

Basophil Mast cell

Big in size Fix or moving Professional APC Secrete hydrolytic Enz. Innate immunity

Professional APC Present to TH cells

Most abundant WBCs Migrate to infection sites kill the invader

Phagocytic

Phago = eating Cyte = cell

Read from Kuby

Phagocytic Motile Damage parasite memb

Non-phagocytic Allergic responses


Heparin (stop blood coagulation) +Histmine (allergic reaction)

Non-phagocytic MC Precursor in Bone marrow Migrate blood tissue Differentiate in tissue Role in allergic reactions

The cells of the immune system


White Blood Cells

Lymphocytes

Other WBCs

B, T, NK

Phagocytic APC

Phagocytic

Secretory

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 Peyers Patches, tonsil, appendix,)

The tertiary lymphoid tissue


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

CALT (Cutaneous Associated Lymphoid Tissues)

Thymus
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.

Age and Thymus

With age cell content of thymus decreases Size decreases Fat content increases Decline in thymic function Leads to decline in immune function

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

Evolution and lymphoid cells and organs

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

Break

Clotting factors in serum