MICROBIOLOGY – ALCAMO LECTURE: Specific Immune System B Cells & T Cells

Specific Immune System Late 1800’s: –not sure how body responded to disease –knew there were certain proteins in blood involved (Bence Jones proteins) 1922: –these proteins were unlike other serum proteins

Specific Immune System 1950’s: –post-war explosion in biological research –realized that specific resistance applied to disease, organ transplant, allergies, resistance to cancer 1960’s: –structure of antibodies deciphered –maturing of immunology as a key scientific discipline

Specific Immune System Last defense mechanism of the body –failure to beat the invader means death “Man to Man” defense against invaders Specific immune system cells: –Only Lymphocytes – type of WBC

Antigens Substances capable of mobilizing the immune system and provoking immune responses Large complex molecules not normally present in the body They are anything non-self: Mo’s, Cells, Cells containing MO’s, or chemicals Epitope – small area of antigen that stimulates the immune response

Antigens Exhibit 2 important properties: –Immunogenicity – ability to stimulate the proliferation of the immune system cells –Reactivity – ability to react with the products of the immune system cells or the immune system cells themselves

Antigens Specific Immunologic Tolerance – before birth, the proteins and polysaccharides of the body contact and inactivate immune system cells These substances are now seen as “self” and will be tolerated by immune system

Origins of Immune System General term for a complex series of cells, factors, and processes that provide a specific response to antigens Lymphocytes – the cornerstone of the immune system: –Spread throughout the body –Small cells (10-20 um) with a large nucleus –Can be B-lymphocytes or T-lymphocytes

Origins of Immune System Immune system arises in a fetus ~ 2 months after conception Lymphocytes arise from precursor cells in the bone marrow (stem cells) Stem cells can be: –Erythropoietic – become RBC’s –Lymphopoietic – become WBC’s

T Lymphocytes Original cells from bone marrow Memory programmed in thymus gland Circulate in blood, colonize lymph tissue Interact directly with antigen marked cells and destroy them Antigens: Infected body cells, fungi, protozoa, cancer, transplants

T Lymphocytes 2 “T” cell types (total 4 “T” Cells) –Effector “T” Cells: Killer T - worker Delayed Sensitivity T - allergies –Regulator “T” Cells: Helper T – don’t kill Suppressor T – lower immune response Active chemical: Lymphokines ( a group of glycoproteins)

T Lymphocytes Process Phagocytic cell finds antigen in tissue (cell’s surface looks different if infected) Brings it to lymph tissue containing memory cells (spleen or lymph node) May remember antigen If “Yes”Yes If “No”No Cell mediated Immunity (CMI)

T Lymphocytes If “Yes” Clones 2 Cell Types Memory T Cells and Killer T which makes lymphokines Lymphokines kill or inactivate antigens and stimulate phagocytosis Back

T Lymphocytes If “NO” In thymus, program blank T cells for antigen memory To lymph tissue in nearest war zone Now: Clone Memory T and Killer T Back

B Lymphocytes Profile Original cells from bone marrow Memory programmed in bone marrow Circulate in blood and colonize lymph tissue Antigens: Bacteria, Viruses, Chemicals Active chemical: Antibody

B Lymphocytes Process Phagocytic cell finds antigen in blood Brings it to lymph tissue containing memory B cells May remember antigen from before –We all have 1,000s of memory B cells If “YES”YES IF “NO”NO

B Lymphocytes If “Yes”: –Clones 2 cell types –Memory B cell (so it won’t forget) and plasma cell to make antibodies (2,000 molecules/sec/cell 4-5 days) –Antibodies kill or inactivate antigen and stimulate phagocytosis Back

B Lymphocytes If “No”: –Blank B cells in bone marrow program for antigen memory to lymph tissue nearest “war zone” –Now clone memory and plasma cells Back

B Lymphocytes Process (continued) Antibodies: Stimulate complement proteins to attack Monocytes and macrophages clean up Antibody Mediated Immunity (AMI)

Antibodies Edelman and Porter described the structure of antibodies (1972) Basic Antibody Protein: Has 4 polypeptide chains –2 identical heavy chains (400 AA) –2 identical light chains (200 AA) –Joined together by disulfide bonds to form a “Y” shaped structure Is called a monomer and has 2 identical halves (1 heavy and 1 light chain each)

Antibodies Have constant and variable regions Constant regions – identical in all antibodies (AB) Variable regions – differ among 100’s of thousands of different AB –Form a very specific, 3-D structure –Uniquely shaped to “fit” a specific antigen –Each arm can bind an antigen

Types of antibodies Five Types – based on differences in heavy chain: –1. IgM – five monomers joined to form a pentamer, First AB to appear after stimulation of B-cells –2. IgG – monomer, the major AB in the blood that appears hrs after antigen appears, provides long-term resistance, crosses placenta to give immunity to fetus

Types of antibodies Five Types – based on differences in heavy chain: –3. IgA – dimer shaped AB that accumulates in body secretions in respiratory and GI tracts, in tears and saliva, and in the 1 st milk secreted by a nursing mother –4. IgE – monomer that is involved in allergic reactions –5. IgD – monomer – function unknown

Antigen antibody Interaction Neutralizing AB’s – react with viral capsids and prevent entry into cells Antitoxins – alter toxin molecules released by antigen Agglutinins – cause clumping of antigens and enhances phagocytosis Precipitins – react with dissolved antigens and convert them to solids