cells of immune system

inhibitory receptors:

(Ly-49 in mouse, Kir in humans) that detect the presence of class I MHC proteins on the cell surface. If a cell displays sufficient class I MHC proteins, that cell is not killed by the NK cell. Many virus-infected cells and tumor cells display a significantly reduced amount of class I MHC proteins, and it is those cells that are recognized by activating NK receptors (NKRP-1 in mouse, numerous receptors in humans)) and are killed this is known as the missing self recognition.

what are main markers used to identify human B cells

CD19, CD20, CD22

what do Th cells carry

CD4 marker, helps or induces immune responses

what do Tc cells carry

CD8 marker, predominantly cytotoxic

example of stimulator ligand expression

For example, NK cells detect the presence of cancer cells by recognizing a protein called MICA found on the surface of many cancer cells but not normal cells. Interaction of MICA with an activating receptor on NK cells triggers the production of cytotoxins by the NK cell and death of the tumor cell. Thus, even in the presence of MHCI, if an abnormal self protein is expressed on the surface of a cell, NK cells will be activated and induce killing of the transformed cell.

TH1 subset

secretes IL-2 and IFN-important in combating viruses, **intracellular bacteria and parasites) cell-mediated response - only expresses certain kind of cytokines

TH2 subset:

secretes IL-4, IL-5, IL-6, and IL-10 , IL-13(stimulate B cells to proliferate and produce antibodies and is the main effector against helminths (worms) - humoral response, expression of IgE--> allergic response--> making antibodies-->IL 4 -->B-cell proliferation and class switch (IgM to IgE) **IL5, IL13 , class switching

TH17 subset

secretes IL17 and protects against the spread of bacterial and fungal infections at mucosal surfaces; IL-17 attracts neutrophils to the site of infection

what does B cell express

MHC class II antigens which is important for B-T cell interactions, as well as MHC class I; they express CD40 (important for class switching), Fc receptors. Complement receptors and PRRs

T cell expression once matired

some become CD4 expressing, others become CD8 expressing

CD4 positive T cells recognize

specific antigens in association with MHC class II molecules

T cell makers

T cell receptors; TCR 1 and TCR2

T cell structure

T-cells - majority are small, non-granular with a high N:C ratio **all B cells, 90% of T-helper cells, about ½ of T cytotoxic cells - carry a "Gall body"= Lipid droplet + primary lysozomes - about 10% of TH and 50% of Tc cells display LGL (large granular lymphocyte ) morphology with primary lysosomes dispersed in the cytoplasm and a well developed Golgi apparatus

non-differentiated T cell

TH0 cell (zero) - will make all cytokines, can activate cell mediated and humoral response. When infection becomes chronic, it decides to become TH1 or TH2

which CD4+ T cell populations are made after exposure to antigen

TH1, TH2, TH17

what are both TCR1 and 2 associated with

a set of five polypeptides, collectively known as the CD3 complex, to give the T-cell receptor complex (TCR-CD3) complex

Natural killer cells

third population of lymphocytes do not express antigen receptors

T reg subset

aka T suppressor cells -a subset of T cells called regulatory T cells (TR) can suppress the effector functions of CD4 (helper) and CD8 (cytotoxic) T cells. TR cells are 5% to 10% of the CD4-positive cells and are characterized by possessing the CD25 marker. These cells also produce FoxP3, a regulator of transcription of various genes. A hallmark of TR cells that are expressing FoxP3 is the synthesis of the inhibitory surface protein, CTLA-4. Individuals whose TR cells lack the ability to make FoxP3 are predisposed to autoimmune diseases such as systemic lupus erythematosus

CD8 positive T cells recognize

antigens in association with MHC I molecuels

surface IgM

assoc. with IgA and IgB to form "be cell antigen receptor complex" (BCR)

where do T cells develop

thymus

primary lymphoid organs:

thymus bone marrow

where do B cells develop in adult

bone marrow

CD3 complex

both receptors form cluster designation 3, different antibodies recognize polypeptide chains on CD3 cluster of antibodies

how are lymphocytes identified

by characteristic markers: lymphocytes express a large number of different molecules on their surfaces which can be used to distinguish cell populations.

how are TCR2 cells distinguished

by their expression of CD4 of CD8

B cells and their markers

characterized by surface (transmembrane) Ig

transformation or infection might induce expression of stimulatory ligands on infected cell or tumor cell

constitution inhibition delivered by inhibitory receptors is overcome, induced-self reocgnition

granulocyte nucleus

distinctive lobed, irregularly shaped (polymorphic) nucleus)

what do T cells express when they mature in thumus

double positive express CD4 and CD8

when do T reg cells form

during selection (others already went through selection) regulatory cells, turn down immune response, when cells become overly activated, TGF beta - transforming growth factor beta - dampens IR, IL-10 shuts down IFN Gamma (TH1 subset turns off), allergic reactions- not able to turn down immune response

endothelial cells

express molecules recognized by certain lymphocytes

B cells in peripheral blood

express two immunoglobulin isotypes on their surface: IgM and IgD

megakaryocytic lineage

gives rise to platelets, involved in inducing inflammation

TCR-1

heterodimer of two disulfide-linked polypepitdes and (5-10% of T cells)

TCR-2

heterodimer of two disulfide-linked polypeptides A and B, 90-95% o T cells

polymorphonuclear granulocytes

includes neutrophils, eoisonophils, basophils

receptors on NK cells

inhibitory receptors, stimulating (activating receptor)

APCs in thumus and medulla

interdigitating cells -interestingly, they play a role in deleting T cells that react against self antigens during selection IMPORTANT IN SELECTION PROCESS

accessory cells

interdigitating dendritic cells (IDCS), follicular dendritic cells

platelets

involved in clotting and inflammation. •Platelets release histamines that increase permeability • activate complement makes C3A and C5A • attract leukocytes •Type 3 hypersensitivity rxn

-another specialized population of APCs

is the follicular dendritic cells found in the B cell areas of the lymph nodes and spleen. they present NATIVE antigen to B cells and lack class II MHC molecules, but express high levels of FcR and complement receptors for interaction with immune complexes.

morphology of NK cells

large granular lymphocytes (LGLs)

where do B cells develop in fetus

liver

follicular dendritic cells

located in the B-cell-containing germinal centers of the follicles in the spleen and lymph nodes (secondary lymph organs). They do not present antigen to helper T cells because they do not produce class II MHC proteins. Rather, they capture antigen-antibody complexes via Fc receptors located on their surface. The antigen-antibody complexes are then detected by activated B cells. present native antigen to B cells. Primarily macrophages

what does presence of CD4 or CD8 restrict

types of cell with which the T cell can interact--MHC restiction

activation of B and T cell

- T and B cells are activated upon binding to their specific antigen -T cells 'see' the antigen in association with an MHC molecule on antigen-presenting cells - B cells can bind free antigen but generally need help from the TH cells to become activated

antigen presenting cells

- They are a heterogeneous population of leucocytes -B cells, macrophages -cells other than leucocytes, such as endothelial or epithelial cells can also acquire the ability to present antigens when stimulated by cytokines -APCs are found primarily in the skin, lymph nodes, spleen and thymus

B cell structure

- do not display Gall bodies or LGL morphology, cytoplasm scattered with ribosomes; resting B cells have a high N:C ratio - Resting B Cell - no antigen communication yet-- just circulating -activated B cells are blast cells - Have seen ANTIGEN, presenting on MHC II to T helper cells and have developing rough endoplasmic reticulum, RER -plasma cells are antibody producing cells (short lived) Plasma cell - Antibody producing cells, more ER, more golgi here

NK cell expression

- express neither TCR nor BCR antigen receptors -NK cell function is to recognize and kill certain tumor cells and virus-infected cells

monocyte characteristics

- large in comparison to lymphocytes -has a horse-shoe shaped nucleus, often contains azurophilic granules Ultrastructurally, they contain peroxidase and several acid hydrolases which are important for intracellular killing (granules with digestive enzymes)

how do lymphocytes migrate

- migrate via circulation to the secondary organs; the spleen, lymph nodes, and mucosa-associated lymphoid tissue (MALT)

what are B cells rich in

-B cells are rich in class II MHC molecules and can process and present antigen to T cells.

CD (cluster designation) system

-CD (cluster designation) system - a system of nomenclature, CD refers to clusters of antibodies that recognize a particular cell marker.

B cell differentiation leads to formation of plasma cells and memory cells

-Following B cell activation, the B cell matures into terminally differentiated plasma cells. - these plasma cells are short-lived, surviving only a few days -the activated B cell expresses new surface markers upon activation, such as MHC class II markers, IL-2R, as well as, IL-3, IL-4, IL-5 and IL-6 receptors

The archetypical APC is the dendritic cell called Langerhan's cells of the skin which travel as 'veiled cells' into the lymph nodes

-Good mechanism of carrying antigens from the skin to the T cells in the lymph nodes -APCs are rich in class II MHC molecules; important for presenting antigen to T helper cells during the primary IR

macrophage/monocyte cell markers

-PRRs -Fc receptors for IgG -trigger extracellular killing, opsonization (complement binds to immune complexes) and phagocytosis -Complement receptors -Class II MHC molecules -cytokine receptors, IL-2, IL-4 and IFN-- their functions can be enhanced by T cells through these receptors

lymphocytes

made in primary lymphoid organs -they are long-lived, as memory cells Lymphocytes are morphologically heterogeneous Looking at lymphocytes -can take 2 forms - depends on nucleus: cytoplasm ratio (N:C) - differences are in the Nuclear:Cytoplasmic ratio, the nucleus shape and the presence of granules

CD4+ T cell subpopulations

1. TH1 subset 2. TH2 subset 3. TH17 subset 4. T reg cells

2 main lines of immune cell differentiation

1. lymphoid 2. myeloid lineage

purpose of CD3

1. need in order for TCR to be expressed on surface 2. activates T cells

mononuclear phagocytes

2 functions performed by two different types of bone-marrow derived cells: 1."Professional" phagocytic macrophages- role is to remove particulate antigens 2. Antigen presenting cells (APCs)- role is to take-up, process and present antigen to T cells - Phagocytic macrophages are found in many organs - Cells from the blood migrate into the tissues to become macrophages.

3rd immune cell differentiation lineage

megakryocytic

two basic kinds of phagocytes

monocyte/macrophage and polymorphonuclear granulocytes

TCR 1 cells are mainly

non-MHC restritced

how are TCR2 cells classified

on basis of cytokine secretion: After the encounter of antigen and co-stimulatory molecules presented by antigen-presenting cells, naive CD4+ T cells can differentiate into (4) different subpopulations

CD40

on surface, important for activating B cell causing class switch: need T helper cell to make certain cytokins, also associates with B cell, when B cell presents peptide on MHC II, T helper cell associates, makes cytokines. CD40 on B cell and CD40 ligand on T helper cell interact-important for inducing class switch in B cell

TCR 2 is unique

only ones that express CD4 and CD8 upon maturation TCR2 becomes CD4 positive or CD8 positive, not both

where do cells of immune system arise from

pluripotent stem cells through to main lines of differentiation: signal from IL-3 and CSF

interdigitating dendritic cells

present antigen to T cells; they are primarily located under the skin and the mucosa (e.g., Langerhans' cells in the skin); they migrate to local lymph nodes, where they present antigen to helper T cells. are also important during selection in thymus - Antigen presenting cells - presenting MHC II with peptide to T cells

lymphoid lineage

produces lymphocytes

myeloid lineage

produces phagocytes: monocytes, macrophages, neutrophiles and other cells

how does CD3 activate T cells

Attached to cytoplasmic side of CD4 and CD8 -attchament of p56lck (tyrosine kinase) - adds phosphate - phosphorylates tyrosine on zeta chain of CD3 to activate T cell à makes IL-2

what happens in primary lymphoid organs

B and T cells acquire ability to recognize antigens through development of specific surface receptors

stimulating (activating receptor on NK cells)

protection

bone marrow: primary or secondary?

Bone marrow is primary and secondary lymphoid organ*** T cell that mature in thymus can enter bone marrow and interact with T cells in bone marrow