Cells of the immune system

Humoral response

B-cells, plasma release

Cell mediated response

CD4 T helper cells, CD8 cytotoxic cells

G-CSF

Granulocyte colony stimulating factor

Released from fibroblast and endothelial cells

M-CSF

Macrophage colony stimulating factor

Released from fibroblast and endothelial cells

GM-CSF

Granulocyte/macrophage colon stimulating factor

Produced by T cells

Il-3

Interleukin 3, proliferation of all cell lines

PMN functions

Primary WBC in circulation respond

Circulating and margination

Diapedesis and Cyto-destructive

PMN granules

myeloperoxidase, elastase, alkaline phosphatase, acid phosphatase, lactoferrin, NADPH oxidase, lysozyme

Eosinophils

Destroy parasites and extracellular degranulation

Allergies and parasites

Neutralize basophil production

Basophils

Histamine and heparin release

Degranulation when 2 IgE mollecules attach to allergen

Vasodilation, vascular permeability, smooth muscle contraction

Monocytes and macrophages

Phagocytosis

Process antigen and present to T-helper cells

Secrete interleukin 1 = enhance Tcell growth

Liver and spleen

CD16 surface receptors

Cytokines

soluble product of any cell type that affects the behavior of other cells, regulates local and systemic inflammatory responses

Inactivated by serum proteases

Il-1

produced by macrophages to enhance T cell growth by stimulating Il-2 receptor expression

Increase production of acute phase reactants and chemotaxins

Il-2

Produced by CD4 cells, stimulate T and B cells to divide

Induce lytic activity of NK cells

Il-3

Produced by T cells, stimulates growth in all hematological cell line

Il-4

induces B cell proliferation, activation, and differentiation

Interferrons

enhance cellular resistance to viruses; involved in first line defense, alpha, beta, gamma

Produced by lymphs and macrophages

TNF

tumor necrosis factor

Alpha and beta

Tumor and transformed cell lines are targeted

Lymphocytes

Stem cells produced by bone marrow migrate to primary and secondary tissue

only 1% are in PB

Primary lymphoid organs

Thymus and bone marrow

Secondary lymphoid organs

Lymphatics, lymph nodes, spleen, peyer’s patches, appendix, tonsils, or MALT

Lymph node structure

Cortex

Paracortex

MedullaL

Lymph node function

Contact with antigen cause lymph node to swell

Flow shuts down

Lymphadenopathy

Secondary lymphatic system

Antigen necessary to stimulate development

Open ended

Lymph originates in interstitial fluid

Circulates and returns blood through thoracic duct

Spleen

Filters blood like lymph nodes

Process old RBCs

Prime site for immune response to bloodborne infections

Thymus

Atrophy overtime

Houses thymocytes, connected to lymphatics by efferent vessels only

T-cell differentiate into CD4 or CD through positive and negative selection

Negative selection

T-cell reacts too strongly to HLA/MHC during maturation

Indicates possible autoimmune disease

Positive selection

T-cell react to self HLA/MHC normal amount

Bone marrow

Involved in production of WBC, RBC, and platelets

Differentiation of B-cells

T-cells general

60-80% of circulating lymphocytes

Cellular immunity

Delayed hypersensitivity

T cell cellular immunity

Assist B cells with antibody production,

Production of cytokines

cytotoxic response, graft rejections

CD4 cells

T-helper cells 55-70%

TcR

CD3/CD4

CD8

T-cytotoxic cells 25-40%

TcR

CD3/CD8

NK cell markers

CD16 - FC receptor

CD56 - Cell adhesion

B cell markers

CD19 - CD receptor

CD20 - activation/ proliferation

IgM/ IgD

TdT

Terminal deoxynucleotidyl transferase

Kill viral infected self cells, recognize antigen HLA class I (Nucleated cells)

Immature T-cells

CD3 marker

Pan T cell marker, function as signal with TCR

CD4:CD8 ratio

2:1 CD4:CD8

B cell humoral immunity

Memory cells or differentiate into plasma cells

B-cell surface markers

Kappa/Lambda

Surface immunoglobulins

TdT

CD19, CD20

HLA-DR

Natural killer cells

Do not need antigen exposure

Produce interferon = TNF, GM-CSF

Cytotoxic reaction

Stimulated by interleukin 2

75% are large granulocytic lymphocytes

ADCC

CD56 and CD16

NK cells ADCC

antibody dependent cell cytotoxicity

Immunoglobulins purpose

Bind antigen

Bind complement

Bind PMNs or macrophages

Immunoglobulins structure

Heavy chain = constant, GAMDE

Light chain = variable, Kappa and Lambda

Fab = fragment for antigen binding

FC - complement receptors

Hinge

J chain

Isotypes

heavy chain unique to each immunoglobulin class. SHARED by all members of a species

Allotypes

Genetic traits that differentiate individuals

Idiotypes

Variations in the variable region that give individual antibody molecules specificity

B cell class switching

Initially make IgM, switch to making other classes (isotypes) with the same (idiotype) antigen binding site

IgG

70-75%, ½ life 23-25 days

Crosses placenta

Anamnestic or secondary response (memory)

Found in blood and tissue not external secretions

Can activate complment

IgA

15-20% ½ life 6-8 days

Monomers or dimers

Body fluids (secretory piece)

Cannot fix complement by classic pathway

J chain

Secretory piece IgA

Prevents it from being digested by enzymes

Secreted by plasma cells in mucosa associated lymphoid tissue

IgM

10% ½ life 5 days

Does not cross placenta

First immunoglobulin produced

Present in blood not tissue

Activates complement

Increased IgM

Waldenstrom’s macroglobulinemia

Polyclonal gammopathies

Infections

IgD

<1%

Seen in association with IgM on mature B cells

IgE

Mediates hypersensitivity reactions, allergies, anaphylaxis, invading parasites

Binds FC receptor on mast cells, basophils, eosinophils

Mainly in respiratory and intestinal tract

Monoclonal antibodies

Hybridoma technique

B cells to produce specific antibodies

Malignant plasma cells

Only binds viable cells