LEC-02 Basic Immunology 1

2 Summery of the Total immunology unit  Kill the pathogen and don’t harm the host

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Immunity  The term “immunity” derived from the latin word immunitas meaning exemption from legal prosecution.  Historically immunity means protection from disease and, more specifically,infectious disease.  Chinese made children inhale powder from crusted smallpox lesions. 4

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Immunity: resistance to infectious disease The immune system is:  Defense body mechanism an interacting set of specialized cells and proteins designed to identify and destroy foreign invader(non-self).  The system is able discriminate between foreign and self molecules/ cells/ proteins. 6

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Basic concept (Recognition) Antigen: A substance that when introduced into the body stimulates the production of an antibody/ the specific immune response. Antigens include toxins, bacteria, foreign blood cells, and the cells of transplanted organs.  Molecular weight of 10,000 Da or higher  Nature of Ag- To be immunogenic, an antigen must possess three characteristics: –be of high molecular weight, –exhibit chemical complexity, and –exhibit foreignness (recognized as non-self by the body). Eg. Microbial Antigen-Bacteria (whole cell or coats, capsules, cell walls, flagella, fimbrae, and toxins ), viruses, and other microorganismsBacteriavirusesmicroorganisms Non-microbial antigen-pollen, egg white, and proteins 8

Substances that act as antigens In terms of infectious diseases, the following may act as antigens: a.microbial structures, such as bacterial and fungal cell walls, protozoan cell membranes, bacterial and fungal capsules, microbial flagella, bacterial pili, viral capsids, viral envelope- associated glycoproteins, etc.; and b. microbial toxins 9

Certain non-infectious materials may also act as antigens if they are recognized as "nonself" by the body. These include: a. allergens, including dust, pollen, hair, foods, dander, bee venom, drugs, and other agents causing allergic reactions; b. foreign tissues and cells from transplants and transfusions; and c. the body's own cells that the body fails to recognize as "normal self," such as cancer cells, infected cells, cells involved in autoimmune diseases. 10

Chemical nature of antigens Chemically, antigens are large molecular weight (>10KDa) proteins (including conjugated proteins such as glycoproteins, lipoproteins, and nucleoproteins) and polysaccharides (including lipopolysaccharides). These protein and polysaccharide antigens are found on the surfaces of viruses and cells, including microbial cells (bacteria, fungi, protozoans) and human cells. 11

Classification of antigen  Depending on origin three types- 1.Exogenous antigens-entered the body from the outside, for example by inhalation, ingestion, or injection (usually not virus)inhalationingestioninjection 2.Endogenous antigens-generated within normal cells (viral or intracellular bacterial infection)infection 3.Autoantigens (self protein or complex of proteins (and sometimes self DNA or RNA) ) 12

Antigens Epitope/ Antigenic determinants:  The portion of antigen molecules which can be specifically bound by antibody or antigenic receptor of lymphocytes.  The size of an epitope is generally equivalent to 5-15 amino acids or 3-4 sugar residues or 6-8 nucleotide.  Any given antigen may have several epitopes.  Each epitope is recognized by a different antibody. 13

14 Two different epitopes 1.B cell epitope, a portion of antigen molecule that is recognized by B cell receptors. 2.T cell epitope, the region of antigen molecules that are recognized by T cell receptors. B-lymphocytes have B-cell receptors that recognize epitopes directly on antigens. T-lymphocytes recognize epitopes only after they have been placed on the body's own cells by way of MHC molecules.

Epitopes: Antigen Regions that Interact with Antibodies 15

Basic concept (Response) The discrimination between “self” and “non-self” and the subsequent destruction and removal of foreign material is accomplished by the two arms of the immune system 1) The innate (natural/native or nonspecific) immune system –Include both first and second line of defense 2) The adaptive (acquired or specific) immune system- Include third line of defense *These two systems perform many of their functions by cooperative interactions 16

17 1. Innate or Genetic Immunity: Immunity an animal is born with. –Genetically determined –Nonspecific –That exists prior to exposure with Ag 2. Acquired /Adaptive Immunity: Immunity that an animal develops during lifetime. – Not genetically determined. – May be acquired naturally or artificially – But only protein Ag can cause adaptive immune response

Overview of immune system  First line of defense: Physical barriers that viruses, bacteria must cross ◦ skin covers ~2 m 2 ◦ Mucous membranes that line digestive, respiratory, reproductive tracts cover ~400 m 2  Second line of defense: Innate immune system - no adaptation to specific pathogens) ◦ Macrophages (Greek for “big eater”), neutrophils, natural killer (NK) cells ◦ Cytokines – antimicrobial proteins that mediate inflammation, Complement proteins  Third line of defense (vertebrates only): Adaptive immune/Acquired system (adapts to defend against specific pathogens using variable receptors) ◦ B cells make antibodies that vary -- can make an antibody specific for any new antigen ◦ T cells mediate cellular responses using variable receptors (T cell receptors; TCRs) ◦ Cytokines – antimicrobial proteins that mediate inflammation, Complement proteins 18

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Types of Acquired/Adaptive Immunity (Depending on Immune response) 1.Active immunity: form of immunity that is induced by exposure to a foreign antigen is called active immunity.  Antigens or pathogens enter body naturally /through vaccine  Body generates an immune response to antigens.  Immunity may be lifelong (chickenpox or mumps,oral polio vaccine) or temporary (influenza or intestinal infections or tetanus toxoid). 21

Continue… 2.Passive immunity: is conferred by adoptive transfer of antibodies or serum specific for the microbe from a specifically immunized individual.  Antibodies pass from mother to fetus via placenta or breast feeding (colostrum). Protects until child’s immune system develops  Preformed antibodies (antiserum) are introduced into body by injection.  Snake antivenom injection from horses or rabbits.  Immunity is usually short-lived (weeks to months).  Show rapid response. 22

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Types of Acquired Immunity (Depending on Immune components involved) I.Humoral immunity:  Host defense are mediated by Ab present in plasma, lymph and tissue fluids  Protect against exogenous bacteria and foreign molecules – Antibodies are produced by a subset of lymphocytes called B cells. – Antibodies are found in  Secretary form in extracellular fluids (blood plasma, lymph, mucus, etc.) and  Receptor form as the surface of B cells. 25

II. Cell Mediated Immunity –Involves specialized set of lymphocytes called T cells. Helper T(T H ) cells Cytotoxic T(T C ) cells –Defense against: 1. Helper T(T H ) cells give protection to cells (APC) which carry microbes and process it show Ag to T H cells 2.Cytotoxic T(T C ) cells give protection to which carry microbes but microbes survive within it 26 Types of Acquired Immunity (Depending on Immune components involved)

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29 Innate Vs. Adaptive immunity