Part 1Terry Kotrla, MS, MT(ASCP)BB

Unit 3 Immunology and Complement

Overview of Immunity

Immunologic ResponseThree functions:

Defense HomeostasisSurveillance

Components of the Immune SystemFour components to be discussed:

Cells and tissues of the immune systemMonocyte-Macrophage Cell SystemT Lymphocytes (T cells)B lymphocytes (B cells)

Cells and tissues of the immune systemPluripotential hematopoietic stem cellsLocated within the bone marrow, fetal liver

and yolk sac of the fetusStem cells differentiate into 2 types of

“committed” stem cells Those which produce platelets, erythrocytes

(red blood cells), monocytes or granulocytes.Those which produce cells of the lymphoid

line only

Hematopoietic Stem Cells

Cells and Tissues of the Immune SystemCells of the immune system are found

within the blood, body tissues, thymus, spleen, liver, lymph nodes and body areas exposed to the external environment.

These organs comprise the reticuloendothelial system (RES).

Reticuloendothelial System

Monocyte-Macrophage Cell SystemDerived from stem cell in the bone marrow.Monocytes circulate to sites of

inflammation or migrate to various tissues.Macrophages have cell surface receptors,

one of them being a receptor for the Fc portion of the immunoglobulin molecule.

Tissue macrophages possess a receptor for the complement component C3b.

The presence of antibody and/or complement enhances phagocytosis.

The term used to describe any substance which enhances phagocytosis is “opsonin”.

MacrophagesHave receptors for Fc portion of immunoglobulin

molecule.Antigens coated with antibody will be bound to

macrophages.Causes removal through phagocytosis

Have receptors for complement component C3bAntigens coated with C3b will bind to macrophages.Some blood group antibodies, especially ABO, are

capable of activating complement.RBCs will be destroyed, cytolysis.

Involved in cellular immunity, important in rejection of transplanted tissues.

Monocyte-Macrophage Cell System Macrophages participate in

phagocytosis, inflammation, and cellular immunity.

Macrophages are mainly involved in nonspecific immunity and include the

phagocytic cells: mononuclear phagocytes, polymorphonuclear phagocytes (neutrophils), eosinophils and

mediator cells: basophils, mast cells and platelets.

T Lymphocytes (T cells)Derived from stem cells in the bone

marrow.Leave bone marrow and travel to the

thymus to matureApproximately 75 to 80% of lymphocytes

are T cells.Important in recognizing foreign material

that is fixed in the tissues of cells. Do NOT secrete antibody Important in transplant rejection. Differentiate into different types.

T Lymphocytes (T cells)Play an important role in regulating the

production of antibodies by B cellsT Helper cell T Suppressor cell T Cytotoxic cells (Killer T cells)

T cells have surface proteins known as cluster determinants (CDs)Helper T cells are CD4 positive cells enhance and

promote the action of other immune cells.Suppressor T cells are CD8 positive and have

suppressive or cytotoxic effects65% helper and 35% suppressor, ratio of 2:1,

important in monitoring HIV infection.

T Lymphocytes (T cells)Two T-cells, one which recognizes a target

Activated T Cell

B lymphocytes (B cells)Derived from stem cells in the bone

marrow.Involved in humoral immunity

Transform into plasma cells. Produce a family of proteins known as

antibodies or immunoglobulins.Activated B cells begin antibody production

and undergo a process called clonal expansion.

Overview of Antibody ProductionAntigen presented to

T cell and processed.Presented to B cellB cell produces

specific antibodyAntibody attaches to

specific antigen

Final Phase Memory Cells

Immune Response Two types of immunity:

Innate or nonspecific immune response. Adaptive or specific immune response.

Innate immunityInvolves the body’s first line of defense.Physical barriers which include intact skin

and mucous membranes.Physiological factors.

HCL in stomach Ciliated epithelium Flushing action of urine Unsaturated fatty acids on skin Sweat Tears Commensal normal flora

InflammationInflammation is the body's reaction to

injury and is known as the body's second line of defense which results in:Increased blood supply to the area.Increased capillary permeability.Migration of leukocytes into the surrounding

tissue.These three events manifest symptoms

which include pain, heat, redness and swelling.

Adaptive (specific) ImmunityInvolves ability to recognize self and non-

self.Encounters with non-self or foreign

materials results in production of antibodies (humoral immunity) or actions of T-cells (cell mediated immunity).

Interaction between both humoral and cell-mediated.

Immunohematology primarily concerned with the causes and effects of humoral immunity.

AntigenAny substance which is recognized as

foreign by the body and is capable, under appropriate conditions, of provoking a specific immune response.

It is capable of:Stimulating the formation of antibody and

the development of cell-mediated immunity.Reacting specifically with the antibodies or T

lymphocytes produced.

Physical Nature of AntigensForeign nature Molecular sizeMolecular complexity and rigidityGenetic factorsRoute of administration and dose –

although not a “physical nature” important for response

Antigenic Determinants or epitopesStructures on antigens that are recognized as

foreign by the immune system.An immune response is directed against

specific determinants and resultant antibodies will specifically bind to them.

Multivalent antigens may elicit antibodies of different specificities.

Antibodies produced in response to one antigen may cross react with other antigens having a common determinant.

Blood bank concerned with allogeneic antigens (from other humans) and autologous (self) antigens.

Epitopes

Blood group antigensChemical structures embedded in or

protruding from RBCs, WBCs, and platelets and have three common forms:Glycoproteins - HLA system.Glycolipids - ABH, Lewis, Ii, and P blood group

systems.Proteins - Rh, M, N blood group systems.

HaptensSubstances, usually of low molecular

weight, that can combine with antibody but cannot initiate an immune response unless it is coupled to a larger carrier molecule.

Most important in drug-induced hemolysis covered later in this course.

Cellular ImmunityImportant defense mechanism against viral

infections, some fungal infections, parasitic disease and against some bacteria, particularly those inside cells.

Responsible for delayed hypersensitivity, transplant rejection and possibly tumor surveillance.

T cells involved, T helper and T suppressor regulate intensity of immune response.

Review your Immunlogy notes from Fall for more information.

Cellular ImmunityLymphokines

Attract neutrophils and monocytes to site of infection.

Cause aggregation of macrophages at site of infection.

Activate macrophages to phagocytose and destroy.

Combined result is amplification of inflammatory reaction.

The Humoral Immune ResponseProduction of antibodies induced when the

host's immune system comes into contact with foreign antigenic substance and reacts to this antigenic stimulation.

Two types of responses:PrimarySecondary (anamnestic)

Mediated by B lymphocytes

Primary Immune ResponseAntigen ingested by antigen processing cell

(APC).Presented to helper T cell which as receptor for

antigen.Activated helper T cell present the antigen to the

B cells and secrete lymphokines which activates B cells.

B cells proliferate and differentiate into plasma cells (which secrete antibody) and memory cells.

Initially low affinity and avidity.IgM produced first, followed by IgG.Takes weeks to months.

Secondary Immune ResponseExposure to same antigen agan.Activates B memory cells to proliferate into

plasma cells.Production of IgG antibody with high affinity

and avidity.Some production of IgM due to immune

cells which have not seen this antigen, but IgG is predominant antibody produced.

Rapid production with high titer.Takes hours to days.

Humoral Immune ResponseAntibody production occurs in four phases

following antigen challenge:Lag phase when no antibody is detectable.Log phase in which antibody titer rises

logarithmically.Plateau phase during which the antibody titer

remains steady.Decline phase during which antibody levels

gradually decline.

Humoral Immune ResponseYou must be able to differentiate a primary

vs secondary immune response based on the following:TimeAntibody TiterAntibody ClassAntibody affinity and avidity

These are critical to understanding reactions obtained in Blood Banking

The following chart nicely illustrates the concepts.

Memorize!

End of Unit 3 Part 1