Immunology III

lymphocytes

• born in liver and spleen → fetus

• born in bone marrow → postnatal

central tolerance

• during T-cell maturation in thymus, this process eliminates T cells that recognize self-antigens (auto-reactive)

• similar elimination process for auto-reactive B cells in bone marrow

• ensures immune system does not attack itself

thymus

most active from development to puberty, then becomes atrophic → less development of new T cells in adults

T-cell receptors

• also called non-antibody antigen receptors

• recognize and bind to a specific protein antigen on a host cell surface MHC

• require coreceptor CD4 or CD8 (depends on subclass)

major histocompatibility complex (MHC)

presents antigens on cell surface

killer (cytotoxic) T cells

• only type of T cell that can directly kill another cell

• activated only by its target antigen presented on MHC 1

  • MHC 1 is expressed in all nucleated host cells (not on RBC)

• expresses CD8 → helps bind antigen-MHC1 complex on target cell

• target abnormal host cells

  • usually infected host cells (most often virus)

  • immunological surveillance against cancer cells

  • transplant rejection

killer T cell: mechanism

1. activated by antigen-MHC1 complex on abnormal host cell

2. secretes perforins → punch holes in target cell membrane

3. secretes granzymes → enter target cells and induce apoptosis

   • need perforins first so granzymes can enter cell through pores

helper T cells

• enhance immune response

  • promote killer T cell proliferation (ex: IL-2)

  • stimulate B cell hypermutation for clonal selection

  • help activate macrophages and recruit more neutrophils

• activated only by its target antigen presented on MHC 2 on APC

  • MHC 2 is only expressed in professional APC (dendritic cells, macrophages, and B cells)

• express CD4 → helps bind antigen-MHC2 complex on APC

• activated cells proliferate and mature → release cytokines

regulatory T cells

• dampen immune response → inhibit B cell and killer T cell responses

• help prevent autoimmune disease

• can be activated by pathogen or cancer cell that survives immune response

APC: extracellular pathogen

• dendritic cell and macrophage:

  • engulfs pathogen

  • fragments are processed, picked up by MHC 2

  • presents antigen-MHC2 to helper T cells

• B cell:

  • BCR/surface Ab (IgD) binds free antigen

  • Ab-antigen complex endocytosis

  • fragments processed, picked up by MHC 2

  • presents antigen-MHC2 to helper T cells

APC: intracellular pathogen

• pathogen propagates in infected host cell

• host links pathogen fragment to MHC 1

• presents anitgen-MHC1 complex to killer T cells

• abnormal antigen in cancerous cells presented on MHC 1 as well

leukocyte infiltration

1. neutrophils → “first responders”

2. monocytes → mature into macrophages and dendritic cells

3. T lymphocytes → activated by APC and get called in

natural killer cells

• non-specific immune response

• kill virus infected or cancerous host cells by recognizing lack of MHC 1 expression

hypersensitivity (allergy)

• abnormal immune response to allergen

• immediate vs. delayed

immediate hypersensitivity

• abnormal B cell response (IgE-mediated)

• common allergens → food, pollen, bee stings, allergic asthma

delayed hypersensitivity

• abnormal T cell response (cell-mediated) → release of lymphokines (IL-2, IFN)

• common allergens → contact dermatitis → poison ivy, poison oak, topically applied medications

immediate hypersensitivity: mechanism

• first exposure:

  1. B cells are activated and secrete IgE

  2. IgE don’t circulate and concentrate in mucosal membrane

  3. attach to mast cells and basophils → no allergy response

• subsequent exposure:

  • allergen binds to attached IgE → stimulates mast cell and basophil degranulation

  • hitamine and other substances released → allergy response → increased capillary permeability (swelling/edema), smooth muscle contraction in airways (bronchoconstriction), and inflammation

autoimmunity

• disruption of central tolerance

• immune system targets self-antigens

• ex: rheumatoid arthritis, T1DM, lupus, multiple sclerosis, myasthenia gravis, Hashimoto’s disease, Grave’s disease

immunodeficiency

• unable to mount an immune response (usually specific immune response)

• ex: HIV targets helper T cells → inhibits both B cell and killer T cell responses

cancer

• transformed cells that escape immune detection

• ex: express/secrete molecules that inhibit immune detection