WEEK 14: GENETICS OF IMMUNITY

• importance of cell surfaces

  • Genes encode antibodies and cell surface antigens
  • Blood typing is done according to the surface antigens in RBCs
  • Genes encode the 6-million-base-long DNA sequence on the short arm of chromosome 6, known as the major histocompatibility complex (MHC) –confers about 50% of the genetic influence on immunity
• • MHC CLASS III = encode proteins in the plasma which provide immune functions
  • MHC class I and II = encode human leukocyte antigens (HLA)
  • HLA glycoproteins bind bacterial and viral proteins in such a way that will alert other immune system cells
• • Class I HLA – 6 genes = 3 genes found in all cell types +3 genes with more restricted distribution
  • Class II HLA – 3 major genes found mostly on antigen-presenting cells
  • Ankylosing spondylitis – resulting from two subtypes of HLA B27
• • Innate = immediate, generalized
  • Adaptive = slower, specific
  • Inflammation = creating hostile environment for pathogens at injury site
• INNATE IMMUNITY

  • Complement - consists of plasma proteins which assist several other defenses
  • Collectins – protect against bacteria, fungi, and some viruses by detecting differences in their cell surfaces
  • Cytokines
  • Interferons – alters components of the immune system to the presence of infected cells
  • Interleukins – cause fever, which directly kills or inhibits the growth some infecting bacteria and viruses
• ADAPTIVE IMMUNITY

  • B cells carry out the humoral immune response which produces antibodies
  • T cells carry out the cellular (or cell-mediated) immune response which produces cytokines
  • B and T cells differentiate in the bone marrow, and migrate to the lymph nodes, spleen, and the thymus, and circulate in the blood and tissue fluid
• ADAPTIVE IMMUNITY

  • Diverse - can tackle various types of pathogens
  • Specific - distinguishes “self” from “non-self”
  • Remembers - responds faster to a previous infection
  • primary and secondary immune response
• HUMORAL IMMUNE RESPONSE

  • Macrophage activates a T cell
  • T cell contacts a B cell with surface receptors that can bind the presented by the macrophage
  • T cell releases cytokines that stimulate B cells to divide
  • B cells give rise to plasma cells and memory cells
• ANTIBODY STRUCTURE

  • idiotypes - parts that contact the antigen on antigen-binding sites
  • epitopes - parts of the antigen that bind to the idiotypes
  • Antibodies have several functions, which can range from neutralization, inactivation, clumping of pathogens for removal of phagocytes(opsonization), and activation of the complement system
• ANTIBODY ASSEMBLY (Variable regions)

  • VDJ, heavy chains = chromosome 14
  • light chains = chromosome 2 and 22
• IgA


  location: milk, saliva, urine, and tears; respiratory and digestive secretions

  function: protects against pathogens at points of entry into body
• IgD


  location: on B cells in blood

  function: stimulates B cells to make other types of antibodies, particularly in infants
• IgE


  location: in secretions with IgA and in mast cells in tissues

  function: acts as receptor for antigens that cause mast cells to secrete allergy mediators
• IgG


  location: blood plasma and tissue fluid; passes to fetus

  function: protects against bacteria, viruses, toxins, especially in secondary immune response
• IgM


  location: blood plasma

  function: fights bacteria in primary immune response; includes anti-A and anti-B antibodies of ABO blood groups
• T CELL MATURATION PROCESS

  • T cells descend from stem cells to the bone marrow
  • Travels to thymus gland
  • Thymocytes (immature T cells) approach the lining of the thymus gland, which are studded with “self” antigens
  • Thymocytes which do not attack these cells mature into T cells, while those who harm the lining die by apoptosis
• T CELL TYPES

  • Helper T cells – recognize foreign antigens, stimulate B cells to produce antibodies, secrete cytokines, activate cytotoxic T cells (has CD4 receptors)
  • Cytotoxic T cells – binds to antigens and releases perforin, which kills the cell membrane of the ‘nonself’ cell (has CD8 receptors)
  • Regulatory T cells – suppress immune response
  • Cluster-of-differentiation (CD) antigens enable T cells to recognize foreign antigens displayed on macrophages
• colony-stimulating factors


  stimulate bone marrow to produce lymphocytes
• interferons


  block viral replication, stimulate macrophages to engulf viruses, stimulate b cells to produce antibodies, attack cancer cells
• interleukins


  control lymphocyte differentiation and growth, cause fever that accompanies bacterial infection
• tumor necrosis factor


  stops tumor growth, releases growth factors, stimulates lymphocyte differentiation, dismantles bacterial toxins
• macrophage

  • presents antigens
  • performs phagocytosis
• dendritic cell

  • presents antigens
• mast cell

  • releases histamines in inflammation
  • releases allergy mediators
• b cell

  • matures into antibody-producing plasma cell or into memory cell
• T CELLS

  • helper
  • recognizes nonself antigens presented on macrophages
  • stimulates b cells to produce antibodies
  • secrete cytokines
  • activates cytotoxic t cells
• T CELLS

  • cytotoxic - attacks cancer cells and cells infected with viruses upon recognizing antigens
• T CELLS

  • neutrophil - attacks bacteria
• T CELLS

  • natural killer - attacks cancer cells and cells infected with viruses without recognizing antigens; activates other white blood cells
• T CELLS

  • suppressor - inhibits antibody production
• inherited immune deficiencies

  A) Chronic granulomatous disease

  B) Immune defect due to absence of thymus

  C) Neutrophil immuno-deficiency syndrome

  D) Adenosine deaminase deficiency

  E) IL-2 receptor mutation

  F) X-linked lymphoproliferative disease

  G) X1'

  
• AUTOIMMUNITY

  • Immune system attacks the body’s own tissues (autoantibodies)
  • Most autoimmune disorders are not inherited as single-gene diseases
  • Ways by which the immune system turns against self
  • Virus replicating in a cell incorporates proteins from the cell’s surface onto its own
  • Some thymocytes that attack ‘self’ cells escape the massive die-off
  • A nonself antigen coincidentally resembles a self-antigen and the immune system attacks both
• autoimmune disorders

  A) Diabetes mellitus (type 1)

  B) Graves disease

  C) Hemolytic anemia

  D) Multiple sclerosis

  E) Myasthenia gravis

  F) Rheumatic fever

  G) Rheumatoid arthritis

  H) Systemic lupus erythematosus

  I) Ulcerative colitis

  
• ALLERGIES

  • Immune system response to allergens
  • Involves humoral and cellular immunity(IgE)
  • IgE binds to mast cells, which stimulate these cells to release allergy mediators(histamine and heparin)
  • Allergens also activate a class of T helper cells that produce cytokines, whose genes are clustered on chromosome 5q
  • Regions of chromosomes 12q and 17q have genes that control IgE production
• ALTERING IMMUNITY

  • Vaccines – stimulate immune system to alert B cells to produce antibodies
  • Monoclonal antibody technology – from the principle that B cells release a single type of antibody to target specific infections
  • Cytokines – interferons are now tested to treat many diseases, including cancer, genital warts, multiple sclerosis, and some other conditions
• TYPES OF TRANSPLANTS

  • Autograft – from one part of a person’s body to another
  • Isograft – from a monozygotic twin
  • Allograft – individual not genetically identical to the recipient but of same species
  • Xenograft – from one species to another
• REJECTION REACTIONS AND HOW TO AVOID THEM

  • Hyperacute rejection reactions can happen in xenografts
  • Graft-versus-host disease can develop when the transplanted organ attacks its recipient body
  • Problems also arise when the donor’s part is too closely matched – can result to not treating the disease
  • Immunosuppressant drugs inhibit production of antibodies and T cells that attack transplanted tissue
• GENOMICS TO FIGHT INFECTION

  • Reverse Vaccinology – researchers consult genome sequence information to identify genes that encode “hidden” antigens that can be the base of a vaccine
  • Metagenomics – sequences random pieces of DNA or entire genomes in a particular environment, can track outbreaks
• UPDATES

  • T-cell Activation Inhibitor, Mitochondrial (TCAIM) - This gene was mapped to chromosome 3p21.31 based on an alignment of the sequence with the genomic sequence (April 15, 2024)
  • Hyper-IgD syndrome (HIDS) - Evidence that the disease is caused by homozygous or compound heterozygous mutation in the gene encoding mevalonate kinase on chromosome 12q24