Infection and Immunity

• Edward Jenner discovered vaccination in the late 18th century by inoculating individuals with cowpox to protect against smallpox.
• Robert Koch proved that infectious diseases are caused by microorganisms.
• Smallpox was officially eradicated in 1980.

Commensal Microorganisms

• More than 1000 different microbial species live in the healthy adult human gut.
• Commensal microorganisms "eat at the same table".
• Animals are both tolerant to and dependent upon their commensal species.
• Taking oral antibiotics can destroy beneficial commensal bacteria, allowing pathogenic strains to populate the colon and cause disease.

Pathogens

• Any organism with the potential to cause diseases is a Pathogen.
• There are four kinds : bacteria, viruses, fungi, and internal parasites.
• Pathogens have evolved special adaptations to invade hosts, replicate, and be transmitted.

Barriers Against Infection

• The skin is the body's first tough defense: an impenetrable barrier of epithelium protected by layers of keratinized cells.
• Physical damage, such as wounds, burns, or surgical procedures can violate the Skin.
• Mucosae lining the respiratory, gastrointestinal, and urogenital tracts are other epithelia.

Innate Immune Response

• Consists of Recognition via soluble or surface-bound receptor proteins (primitive non-specific recognition: mainly phagocytes).
• Recruitment of effector mechanisms to kill and eliminate the pathogen.
• Serum proteins of the complement system are activated in the presence of a pathogen.
• A piece of complement tags the pathogen as dangerous.
• The soluble complement fragment binds to a receptor on the surface of a WBC, and summons it to the site of complement activation.
• The receptor and its bound ligand are taken up into the cell by phagocytosis.
• Inflammation is a key aspect of the innate immune response at infection sites.
• Inflammation is characterized by heat, pain, redness, and swelling (calor, dolor, rubor, and tumor, respectively).
• Inflammation enables cells and molecules of the immune system to be brought rapidly and in large numbers into the infected tissue.

Adaptive Immune Response

• Adaptive Immunity is better understood than innate immunity

Hematopoietic Stem Cells

• Immune system cells with different functions all derive from hematopoietic stem cells.
• Blood cells are first made in the yolk sac of the embryo, and later in the embryonic liver and spleen and start to be made in the bone marrow before birth.
• By the time of birth, the bone marrow is the only tissue in which hematopoiesis occurs.
• Natural killer cells kill cells infected with certain viruses
• Neutrophil: Phagocytosis and killing of microorganisms
• Monocyte: Circulating precursor cell to macrophage
• Macrophage: Phagocytosis and killing of microorganisms, activation of T cells and initiation of immune responses.
• The relative abundance of the leucocyte cell types in human peripheral blood: Neutrophil 40-75%, Lymphocyte 20-50%, Monocyte 2-10%, Eosinophil 1-6%, Basophil <1%.
• Large reserves of neutrophils are stored in the bone marrow and move in large numbers to sites of infection, where they act and then die.
• After one round of ingestion and killing of bacteria, a neutrophil dies.
• The receptor of bacterial surface constituents are needed for macrophages to stimulate phagocytosis and cytokine secretion.

Immunoglobulins and T-Cell Receptors

• Immunoglobulins and T-cell receptors are the diverse lymphocyte receptors of adaptive immunity
• B-Cell Receptor Y-shaped immunoglobulin (glycoprotein)
• Membrane-bound: anchored by a transmembrane tail
• Two identical Ag-binding sites

Antibody Function

• Facilitate the engulfment and destruction of foreign bodies by phagocytes.
• Neutralization of toxins: Ab binds to toxins and prevents its interaction with receptors on human cells.
• Opsonization of bacteria: IgG can coat the bacterium through binding with its variable region, is recognized by receptors on a macrophage and phagocytosis then occurs

Lymphoid Tissues

• Primary lymphoid tissues: sites of development and maturation of lymphocytes, the BM and thymus
• Secondary lymphoid tissues: sites of stimulation in response to pathogens, all other lymphoid tissues.

Secondary Lymphoid Tissues

• Adaptive immunity is initiated in secondary lymphoid tissues
• Small kidney-shaped organs Composed of a cortex and a medulla.
• Packed with lymphocytes, macrophages, and other cells of the IS, between which the lymph percolates.
• Effector cells are selected against specific antigens.

Spleen

• Is a large lymphoid organ in the upper left part of the abdomen

• It Weighs about 150 grams, serving as a filter for the blood

  • Removes damaged or senescent RBCs (red pulp)
  • Works as a secondary lymphoid organ by defending the body against blood-borne pathogens (white pulp)

• The spleen is an organ in the upper left of the abdomen

Gut Associated Lymphoid Tissue, (GALT)

• The gastrointestinal and respiratory tracts are particularly vulnerable to infections since they are heavily invested with secondary lymphoid tissue.
• in the GI tract, including the tonsils, adenoids, appendix, and Peyer's patches.
• The GALT is organized similarly to the lymph node and the white pulp of the spleen.
• M cells in the gut epithelium deliver pathogens from the gut lumen to the lymphoid tissue within the gut wall.

Commensal Microorganisms as Protection

• Physical barriers colonized by commensal microorganisms protect against infection by pathogens
• Mammalian babies have no commensal microorganisms before birth.
• After birth: commensals from environment (family members, pets) begin to populate the skin and mucosal surfaces.
• The microbiota is an integral part of a healthy human body influencing and shaping the development of the Immune System. Physical barriers are colonized by commensal microorganisms

Pathogens Types Require Different types of Immune Response

• Live and replicate in the spaces between human cells or inside cells.
• Extracellular pathogens
  • Accessible to soluble, secreted molecules of the Immune System.
• Intracellular pathogens
  • Must be killed in order to expose pathogen to the soluble immune system molecules

Complement

• Many are proteases circulating as inactive "zymogens", until their activation upon infection.

• Complement proteins activate each other in cascade, by proteolytic cleavage

• Activation results covalent attachment pathogen surface

Pathways of Activation

• There are three pathways:
  • The alternative first to be activated, initiated by direct interaction with pathogen
  • Lectin is initiated by mannose-binding lectin in plasma
  • Classical Initiated in the innate response by the binding of C-reactive protein to pathogen surfaces.
• First at the start of an infection, at the start of an infection, complement activation proceeds by the alternative pathway: Constituents of bacterial surfaces induce changes in the local physiochemical environment
• These changes trigger the hydrolysis of serum C3, fragments covalently attach to the pathogen surface
• The alternative C3 convertase C3bBb molecules have been assembled, they cleave more C3 and fix more C3b at the pathogen surface, leading to the assembly of even more convertase
• Regulatory proteins determine the extent and site of C3b deposition: factor P, Disrupt C3bBb on human cell surface: DAF and MCP

Macrophages

• Provide a first line of cellular defense against invading microorganisms
• Mature forms circulating monocytes that have left the blood to take up residence in the tissues
• Prevalent in connective tissues, GI and respiratory tracts, and liver and Participate in both innate and adaptive immunity
• Complement receptors on phagocytes trigger the uptake and breakdown of C3b-coated pathogens.
• CR1 on the surface of macrophages recognize C3b-coated pathogens.
• Upon recognition, CR1 generates intracellular signals enhance phagocytosis and the fusion of the phagosome with lysosomes.

Terminal Complement Proteins Cause Lysis

• The terminal complement proteins lyse pathogens by forming membrane pores.
• On activation the soluble C5b fragment initiates assembly of the membrane-attack complex in solution Bb produced for alternative pathway and component also can be activated as C5b to cause C5a to cleave.

Small Complement Peptides

• C3a and C5a fragments induce anaphylactic referred to anaphylatoxins
• Have receptors on phagocytes, endothelial cells, and mast cells: Increase blood flow, increase vascular permeability, serve as chemoattractants (C5a)
• Increase blood and migration
• Plasma and coagulation, enzyme blood with pathogens prevented

Antimicrobial Peptides

• Antimicrobial peptides kill pathogens by perturbing their membranes
• Defensin interacts with the charged surface of a cell membrane and then insert into the lipid bilayer producing pores forming integrity and disrupt and peptides
• defensins: are made secreted other by also lysozyme include factors Paneth cells and HD6 ( cryptds. and are not considered cells can cells of of they hematopoietic, the or IS although, lyase origin origin. defensive and are in tissue and origin: a more is factors of and the secretion and Paneth cell are and other more

Pentraxins

• Are plasma proteins of innate immunity that bind microorganisms and target them to phagocytes play a role similar to the antibodies.
• pentraxin principal member principal is C-reactive protein CRP

Brief information about the discovery of vaccination. Also contains information about commensal microorganisms, pathogens and body's barriers against infection. Oral antibiotics destroy commensal bacteria allowing pathogens to thrive.