Immune system (part 2)

 Immune system  (part 2) 

Dendritic cells (DC)

• are phagocytes in tissues that are in contact with the external environment; therefore, they are located mainly in the skin, nose, lungs, stomach, and intestines 

• named for their resemblance to neuronal dendrites, as both have many spine-like projections, but dendritic cells are in no way connected to the nervous system

 • serve as a link between the bodily tissues and the innate and adaptive immune systems, as they present antigen to T cells, one of the key cell types of the adaptive immune system   

CELLS OF INNATE AND ADAPTIVE IMMUNITY 

• Lymphoid Lineage 

             – Large lymphocytes (large granular lymphocytes)

                 • Natural killer (NK) cells (CD16, CD56)

                 • Innate immunity to viruses and other intracellular                                 pathogens

                 • Participate in antibody-dependent cell-mediated                                     cytotoxicity (ADCC) 

            – Small lymphocytes

                 • B cells (CD19) 

                 • T cells (CD3, CD4 or CD8)

                 • Adaptive immunity 

            – Lymphocytes refers to small lymphocytes 

Lymphocytes; B cells; T cells

• B cells & T cells carry receptor molecules that recognize specific targets

 • T cells recognize a “non-self” target, such as a pathogen, only after antigens (small fragments of the pathogen) have been processed and presented in combination with a “self” receptor called a major histocompatibility complex (MHC) molecule 

• There are two major subtypes of T cells: the killer T cell and the helper T cell

 • Killer T cells only recognize antigens coupled to Class I MHC molecules, while helper T cells only recognize antigens coupled to Class II MHC molecules 

• A third, minor subtype are the γδ T cells that recognize intact antigens that are not bound to MHC receptors 

• In contrast, the B cell antigen-specific receptor is an antibody molecule on the B cell surface, and recognizes whole pathogens without any need for antigen processing. Each lineage of B cell expresses a different antibody, so the complete set of B cell antigen receptors represent all the antibodies that the body can manufacture 

Lymphocytes

• Many types; important in both humoral and cell-mediated immunity

 • B-cells produce antibodies

 • T- cells 

        – Cytotoxic T cells 

        – Helper T cells 

• Memory cells 

A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates.^[1] Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic adaptive immunity), and B cells (for humoral, antibody-driven adaptive immunity).^[2][3] They are the main type of cell found in lymph, which prompted the name "lymphocyte".^[4] Lymphocytes make up between 18% and 42% of circulating white blood cells.

• Plasma Cell (in tissue) 

        – Fully differentiated B cells, secretes Ab

 • Natural Killer cells

        – Kills cells infected with certain viruses 

        – Both innate and adaptive

        – Antigen presentation   

Typical recognition markers for Lymphocytes

Comparison of T and B cells

T-cells                                                        

 • responsible for cell mediated immunity 

 • Life span is long 

 • Differentiate inside Thymus Gland

 • Absence of surface antibodies 

 • Transformed in small lymphocytes by antigens

 • secrete Lymphokines

 • sub population are Cytotoxic T, Helper cells and suppressor     cells.

 • stimulate phagocytes and B-cells into activity. 

B-cells 

 • responsible for Humoral immunity

 • Life span is short

 • Differentiate inside Bone Marrow 

 • Surface Antibodies present

 • Transformed to plasma cells by antigens 

 • secrete antibodies 

 • sub population are memory cells and plasma cells

 • B-cells or B-lymphocytes produce antibodies .  

THE CLUSTER OF DIFFERENTIATION (CD) 

• CD nomenclature established in 1982

            – 1 st International Workshop and Conference on Human Leukocyte Differentiation                 Antigens (HLDA) held in Paris

• protocol for identification and investigation of cell surface                   molecules 

• intended for classification of many monoclonal antibodies                  generated by different laboratories around the world against           epitopes  on the surface molecules of leukocytes

 • CD number assigned on basis of 1 cell surface molecule                 recognized by 2 specific m Ab 

cluster of differentiation

• The (cluster of designation) (often abbreviated as CD) is a protocol      used for the identification and investigation of cell surface                  molecules present on White blood cells 

• CD molecules can act in numerous ways, often acting as receptors     or ligands (the molecule that activates a receptor) important to the     cell

• A signal cascade is usually initiated, altering the behavior of the         cell

• Some CD proteins do not play a role in cell signaling, but have            other functions, such as cell adhesion

• CD for humans is numbered up to 350 most recently (as of 2009). •  If the molecule has not been well-characterized, or has only one        mAb, it is usually given the provisional indicator "w" (as in                 "CDw186")  

THE CLUSTER OF DIFFERENTIATION (CD)

• CD markers on leukocytes

        Granulocyte                          CD45+, CD15+ 

        Monocyte                              CD45+, CD14+ 

        T lymphocyte                        CD45+, CD3+ 

        T helper lymphocyte             CD45+, CD3+, CD4+

        T cytotoxic lymphocyte        CD45+, CD3+, CD8+ 

        B lymphocyte                       CD45+, CD19+ 

        Natural killer cell                 CD45+, CD16+, CD56+, CD3-  

Components of blood

COMPLETE BLOOD COUNT WITH 

 DIFFERENTIAL (CBC WITH DIFF)

                                                References Ranges

 Erythrocytes (RBC)               4.0 to 5.4 M/uL 

 Thrombocytes (Platelets)      145 to 400 K/uL 

 Leukocytes (WBC)               4.8 to 10.8 K/uL 

 Neutrophils                            40 to 74 % 

 Band neutrophils                      0 to 9

 Eosinophils                              0 to 6 

 Basophils                                 0 to 1 

 Lymphocytes                         15 to 47 

 Monocytes                               0 to 12

Other Blood Cells

• Megakaryocyte                                          

        – Platelet formation

        – Wound repair

 • Erythrocyte

        – Oxygen transport

LYMPHOCYTES, LYMPHOID TISSUES AND ORGANS

• Lymphocytes originate in bone marrow

 • Lymphoid tissues and organs

         – Primary 

                 • Development and maturation of lymphocytes

                 • Bone Marrow (B cells) and thymus gland (T cells)

         – Secondary 

                 • Mature lymphocytes meet pathogens 

                 • Spleen, adenoids, tonsils, appendix, lymph nodes,                               Peyer’s patches, mucosa-associated lymphoid tissue                          (MALT) 

THE LYMPHATIC SYSTEM

• Lymph

         – Fluid and cells in lymphatic vessels 

• Lymphatic vessels

         – Collect and return interstitial fluid to blood

         – Transport immune cells throughout body 

         – Transport lipid from intestine to blood

 

• Lymph nodes 

         – Kidney shaped organs at intervals along lymphatic vessels

 • Other secondary lymphatic tissues and organs  

   

LYMPHOCYTES AND THE LYMPH NODES

• Naïve lymphocytes circulate between blood, lymph and secondary    lymph nodes 

• Pathogens from infected tissue sites are picked up by lymphatic       vessels and arrive at closest lymph node 

• T and B cells congregate at specific regions of nodes 

• Architecture and size of nodes change in response to activation of      lymphocytes       

LYMPHOCYTES AND THE SPLEEN

• Spleen 

        – Lymphoid organ in upper left abdomen 

        – Functions 

                • Remove damaged or old erythrocytes 

                     • Activation of lymphocytes from blood borne pathogens 

• Architecture of Spleen 

        – Red pulp 

                • Erythrocytes removed 

        – White pulp 

                • Lymphocytes stimulated  

SECONDARY LYMPHOID TISSUES ASSOCIATED WITH MUCOUS MEMBRANES

• Primary portals of entry for pathogens 

        – Respiratory tract

        – Gastrointestinal tract 

• Secondary lymphoid tissues 

        – Bronchial-associated lymphoid tissue (BALT) 

        – Gut-associated lymphoid tissues (GALT) 

                 • Tonsils, adenoids, appendix, Peyer’s patches 

• Pathogens are directly transferred across mucosa by “M” cells