Soluble Immune Response Mediators

What are biological response mediators (BRMs)?

• general term for substances that regulate immune responses

• secreted by mononuclear leukocytes

  • B lymphs - antibody

  • T lymphs - interleukins, interferon, and TNF

  • NK cells - IFN alpha

  • monocytes and macrophages - IFN alpha, interleukins

What are therapeutic modifiers, and what are the 4 types?

• biological response mediators that are used therapeutically to fight disease

• types:

  • active: adjuvants

  • adaptive: interleukins

  • passive: transfer of preformed antibodies

  • restorative: interferons

List the 4 categories of cytokines

• interleukins

• interferons

• tumor necrosis factor (TNF)

• chemokines

What are cytokines?

• polypeptides from activated cells that regulate the immune response

• active and innate immunity

• released in response to an antigen

• performs multiple acts on all kinds of cells

• very potent

• usually limited to the site of infection, but can work systemically

What is a cytokine storm?

• an exaggerated response when cytokines are used in immune reactions

• severe damage occurs as the immune system destroys self cells and tissues in response to an invader

What are interleukins?

• cytokines produced by leukocytes that act on other leukocytes

  • examples: lymphokines, monokines

• assigned numbers (38 have been identified)

• each interleukin is a distinct molecule

What are interleukins responsible for?

• mediating interactions between white blood cells

• regulates inflammation and the immune response by regulating growth, mobility, and differentiation of lymphoid cells

What are interferons (IFNs)?

• substances initially found in virally infected cells “interfering” with viral replication

• acts as a natural defense to foreign components such as microbes, tumors, and antigens

• two types

  • type 1 IFNs: IFN alpha and IFN beta

    • mediates early innate immune response to viral invasion

  • type 2 IFNs: IFN gamma

    • activates macrophages and segs

    • acts on B cells to promote IgG class switching

    • stimulates NK cells

What is tumor necrosis factor (TNF) responsible for?

• recruits neutrophils and monocytes to the site of infection by chemotaxis

• activates cells to eradicate microbes

• the primary mediator in acute inflammatory responses, especially against Gram-negative bacteria

• induces apoptosis

• TNF alpha and TNF beta

What can happen if the body produces too much tumor necrosis factor during a severe infection?

TNF can enter circulation and induce septic shock, resulting in death (gram-negative sepsis)

What are chemokines?

• cytokines that stimulate leukocyte migration (neutrophils and macrophages) from the blood to the tissue site of infection

• regulates lymphocyte and leukocyte traffic through lymphoid tissues

  • maintains normal migration of immune cells into lymphoid organs

What are acute phase reactants

• glycoproteins that rise at different rates and varying levels in response to tissue injury

• made in the liver

• increases after trauma and is sustained by proinflammatory cytokines

• used to:

  • monitor the progress of diagnosed diseases

  • assess therapy for diseases

  • and detect known disease complications

Describe the following acute phase reactant: C reactive protein

• used to monitor:

  • infection

  • inflammation

  • autoimmune disorders

  • and healing after an MI

• it acts as an opsonin and activates the complement system

• non-specific indicator of inflammatory responses

Describe the following acute phase reactant: procalcitonin

• used to identify sepsis and diagnose bacterial infection

• increased in systemic inflammation caused by bacterial infection

Describe the following acute phase reactant: ceruloplasm

• used to monitor Hodgkin disease

• measured as serum copper

Describe the following acute phase reactant: haptoglobin

• main function is to bind free hemoglobin in the blood

• as an acute phase reactant, it increases in infection, inflammatory responses, and tissue damage