Cell Biology - Class Notes for Exam #3

Link to remaining Exam #3 Notes

LSc 202 Immune Response: Molecules and Cells Notes Winter 1999

Chapter 19 p. 270

Cells and Molecules of the Immune System

Antibodies (Immunoglobulins): found on B lymphocytes and secreted by B lymphocytes

• Antibodies (Ab) bind antigens (Ag) typically in their 3-dimentional conformation
• Epitope: the region of antigen that is recognized and bound by antibodies

How do antibodies function?

• bind antigens on surfaces of invading viruses – blocking viral entry into host cells, neutralize virus
• bind antigens on surface of free organisms in circulation (ex: bacterium) – mark the pathogen for engulfment and destruction by macrophages
• bind free antigens in circulation, can cause agglutination of antigen -- marks antigens for engulfment and elimination by macrophages

Macrophages engulf antibody-coated particles and agglutinated antigens by binding the Fc fragment (constant regions of antibody heavy chains) via an Fc Receptor.

Antibody Structure p.792 Fig 19-1

• tetramer: 2 heavy and 2 light chains each with variable and constant regions
• 2 variable regions confer antigen binding specificity
• constant region of antibody confers function (see Table 19-1 for classes of heavy chain constant regions and their functions)
• diversity of antibodies is accomplished by gene rearrangement (combinatorial factors splicing different component regions of DNA together to form the variable regions), introduction of new nucleotides at junctions, and somatic mutations in the DNA to create further diversity

Clonal Selection Theory

• normal unstimulated B cell life is ~5 days
• B cells with many different antibody specificities are generated (~10⁸ different specificities in humans)
• "virgin" B cells circulate through blood and lymph systems
• if the B cell encounters its specific antigen it is selected and clonally expanded
• with T helper cell help – stimulated B cells grow and differentiate into effector cells (plasma cells which secrete antibodies) and memory B cells (which are long-lived and poised for a subsequent encounter with specific antigen)

Immunoglobulin Superfamily of Proteins : share structural similarity – immunoglobulin domain Fig. 19-12

Immune Response is the coordinated response involving macrophages, T cells (both cytotoxic or killer cells and helper cells) and B cells

MHC antigens : review structure and function from exam #2 notes & Fig. 19-13 class I

Fig. 19-14 depicts antigen processing by B cells and presentation by MHC class II

Antigen processing and presentation

• Ag binds cell surface receptor (Ab for B cells or FcR for macrophages)
• Ag is endocytosed by the class II positive cell (Ex. B cells)
• Ag is cleaved into smaller pieces in endosomal compartments (processing)
• Ag fragment is bound to newly synthesized class II n\molecules within the cell
• Ag fragment is "presented" on the cell surface bound to class II
• T helper cell receptor which is specific for antigen binds to the Ag peptide/MHC complex (see Fig. 19-16)
• T helper cell secretes growth factors which help the B cell to differentiate

T cell Receptor

• similar mechanism for generating variability in antigen binding regions as antibody gene rearranging
• heterodimer with a and b chains (Fig. 19-16) and variable and constant regions
• recognize only a small piece or antigenic peptide of the antigen, not 3-d structure
• autoreactive T cells are eliminated in the thymus during T cell development

T killer cells (CTLs) CD8+	T helper cells CD4+
recognizes specific antigens presented by class I MHC molecules	recognizes specific antigens presented by class II MHC molecules
typically endogenously-produced antigens (Ex: viral proteins made by and infected cell)	typically exogenously-produced antigens that are endocytosed from the extracellular fluid
action: destroys target cells by creating pores in the plasma membrane	action: secretes growth and differentiation factors (interleukins), stimulate B cells to produce and secrete antibodies and differentiate into memory B cells
recognition of foreign MHC I molecules à lyse cells (without additional antigenic peptides)	recognition of foreign MHC II molecules à help stimulate immune responses

 

Immune system goes awry – Autoimmunity and Allergies

Autoimmune diseases – recognition and immune response to self antigens

• insulin-dependent juvenile onset diabetes – antibodies to b - cells of pancreas à destroys these cells à no insulin
• acquired hemolytic anemia – immune response to red blood cells
• Lupus erythematosis – autoantibodies against red blood cells, clotting factors, DNA etc.
• Rheumatoid arthritis – attack of connective tissue in joints
• multiple sclerosis – antibodies against myelin basic protein
• seen more often in women
• certain autoimmune diseases are linked to MHC haplotypes, a certain MHC polymorphism may increase susceptibility to a particular autoimmune disease

Allergies – overzealous immune response to some antigens (allergens)

• mediated by IgE subclass of antibodies which produce symptoms of allergy
  (Ex: IgE promotes histamine release from mast cells)
• allergic response typically gets stronger with each exposure to allergen (just like an immune response to foreign antigens)
• some common allergens include dust mites, ragweed pollen, bee toxin, animal dander

Link to remaining Exam #3 Notes