‭UNIT 4 CHAPTER 1: INTRODUCTION TO IMMUNOLOGY‬

‭Learning Objectives:‬
‭1.‬ ‭Give the definition of immunology‬
‭2.‬ ‭Explain the different types of immunity and the underlying factors involved‬
‭3.‬ ‭Identify the body’s first line of defense and explain their roles in the body‬
‭4.‬ ‭Identify and explain the body’s second line of defense‬
‭5.‬ ‭Discuss the elements of specific immunity and differentiate the body’s immune‬
‭responses‬
‭6.‬ ‭Briefly explain the types of acquired immunity.‬

‭IMMUNOLOGY‬
‭➢‬ ‭The branch of biomedicine concerned with the structure and function of the immune‬
‭system‬
‭➢‬ ‭It involves study of:‬
‭○‬ ‭Innate and acquired immunity‬
‭○‬ ‭Bodily distinction of self from non-self‬
‭○‬ ‭Laboratory techniques involving the interaction of antigens with specific‬
‭antibodies‬
‭OVERVIEW OF THE BODY’S DEFENSES‬
‭➢‬ ‭A pathogen can cause disease only if it can:‬
‭○‬ ‭Gain access either by penetrating the surface of the skin or by entering‬
‭○‬ ‭Attach itself to host cells‬
‭○‬ ‭Evade the body’s defense mechanisms long enough to produce harmful‬
‭changes‬
‭➢‬ ‭Hence, it is important to examine the structure, processes, and chemicals that‬
‭respond in a general way to protect the body from all types of pathogens because‬
‭the cells and certain basic physiological processes of humans are incompatible with‬
‭those of most plant and animal pathogens‬
‭➢‬ ‭Humans: innate or inborn‬
‭○‬ ‭Acquired upon birth‬

‭INNATE IMMUNITY‬
‭➢‬ ‭Defenses present at birth‬
‭➢‬ ‭Does not involve specific recognition by a microbe and does not have a memory‬
‭response‬
‭➢‬ ‭Includes first and second line of defense‬

‭ADAPTIVE IMMUNITY‬
‭➢‬ ‭Based on a specific response to a specific microbe once microbe has reached the‬
‭innate immunity defenses‬
‭➢‬ ‭Slower to respond but does have a memory component‬
‭○‬ ‭The body could remember the microbe and would specifically produce such‬
‭reaction once the microbe enters the body‬
‭➢‬ ‭Third line of defense‬

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‭ YPES OF IMMUNITY‬
T
‭FIRST LINE OF DEFENSE‬
‭➢‬ ‭Chiefly composed of external physical barriers to pathogens specially the skin and‬
‭mucous membrane‬
‭➢‬ ‭Made up of structures, chemicals, and processes that work together to prevent‬
‭pathogens from entering the body in the first place‬
‭➢‬ ‭Once broken or damaged, like the skin, can be a portal of entry for pathogens‬

‭FACTORS‬
‭a.‬ ‭Mechanical factors‬
‭➢‬ ‭Skin: composed primarily of the epidermis which has keratin on top‬
‭○‬ ‭Keratin: protective layer‬
‭○‬ ‭Epidermis: tightly packed cells with little or no material between the cells‬
‭➢‬ ‭Mucous membrane: slipper‬
‭○‬ ‭Epithelial layer and underlying connective tissue layer which secretes mucous‬
‭composed of glycoprotein produced by goblet cells‬
‭➢‬ ‭Ciliary escalator: microbes trapped in mucous are transported away in the lungs‬
‭➢‬ ‭Lacrimal apparatus: washes eyes through the tears‬
‭➢‬ ‭Saliva: washes microbes‬
‭➢‬ ‭Nose: hair inside which filters air entering our body‬
‭➢‬ ‭Epiglottis: prevents entry into the digestive system which is not part of normal flora‬
‭➢‬ ‭Urine: flushes the microbes into our body‬
‭➢‬ ‭Vaginal secretions‬

‭ .‬ C
b ‭ hemical factors‬
‭➢‬ ‭Sebum or oil glands: from sebaceous glands which provide protective film over the‬
‭surface of the skin‬
‭○‬ ‭Sebum has unsaturated fatty acids‬
‭➢‬ ‭pH: between 3-5 (acidic) discourages growth of microbes‬
‭➢‬ ‭Lysozymes: enzyme capable of breaking down cell walls or gram-positive bacteria‬
‭➢‬ ‭Gastric juices: mixture of hydrochloric acid (HCl), enzymes, and mucous‬
‭➢‬ ‭Vaginal secretion: has lactic acid that inhibits microbes‬

‭‬ N
● ‭ ormal microbiota: normal flora‬
‭●‬ ‭Microbial antagonism: a normal microbiota competes with pathogens and produces‬
‭compounds that are inhibitory or kill other bacteria and fungi‬
‭○‬ ‭If there is foreign organism entering the body, there is immediate reaction‬
‭which is the normal flora fighting the foreign microorganism‬

‭SECOND LINE OF DEFENSE‬

‭➢‬ ‭Internal and composed of protective cells‬
‭➢‬ ‭Composed of blood-born chemicals and processes that inactivate or kill invaders‬

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 ‭➢‬ B ‭ oth first and second line of defense are nonspecific, that is they respond against a‬
‭wide variety of pathogens including parasitic worms, protozoa, fungi, bacteria, and‬
‭viruses‬
‭○‬ ‭Operate in a generalized way independent of the nature of the intruder‬
‭➢‬ ‭Formed elements in the blood, means these are cells and cell fragments suspended‬
‭in plasma consisting of erythrocytes, leukocytes, and platelets‬
‭○‬ ‭Erythrocytes: red blood cells‬
‭■‬ ‭Transport oxygen and carbon dioxide‬
‭○‬ ‭Leukocytes: granulocytes and agranulocytes‬

‭ ATURAL AND NON-SPECIFIC RESISTANCE‬

N
‭BODY’S FIRST LINE OF DEFENSE‬

‭ROLES OF SKIN IN NON-SPECIFIC DEFENSE‬

‭➢‬ ‭Skin is the largest part of the body being the organ with the greatest surface‬
‭➢‬ ‭Outer epidermis and inner dermis‬
‭➢‬ ‭Epidermis: contains phagocytic cells called the epidermal dendritic cells‬
‭○‬ ‭Also known as the Langerhans cells‬
‭○‬ ‭Slender finger-like processes of dendritic cells extend among the surrounding‬
‭cells, forming an almost continuous network to intercept invaders‬
‭○‬ ‭These cells won’t phagocytize pathogens nonspecifically and play a role in‬
‭specific immunity‬
‭○‬ ‭The combination of the barrier function of the epidermis is that its continual‬
‭replacement and the presence of the phagocytic dendritic cell or Langerhans‬
‭cells which provide specific significant defense against colonization and‬
‭infection by pathogens or foreign microorganisms‬
‭➢‬ ‭Dermis: also defends nonspecifically‬
‭○‬ ‭Contains top fibers of a protein called collagen which gives the skin the‬
‭strength and pliability to prevent jabs and scrapes from penetrating the‬
‭dermis and introducing microorganisms‬
‭○‬ ‭The blood vessels in the dermis defensive cells and chemicals‬
‭➢‬ ‭The skin has several substances that nonspecifically defend against pathogens‬
‭➢‬ ‭Sweat glands: secrete perspiration which contains salt and lysozyme‬
‭○‬ ‭Salt: draws water osmotically from invading cells which inhibits their growth‬
‭and kills them‬
‭○‬ ‭Lysozyme: enzyme that destroys the cell walls of bacteria by cleaving the‬
‭bonds between the sugar‬
‭■‬ ‭If cell walls are destroyed, the bacteria is more susceptible to osmotic‬
‭shock and digestion by other enzymes within phagocytes‬
‭○‬ ‭Sebaceous glands which secrete sebum‬
‭■‬ ‭Fatty acids lower the pH of the skin surface to about pH 4 which is‬
‭inhibitory to most bacteria.‬
‭○‬ ‭Both physical and chemical structure of the skin enables it to act as an‬
‭effective defense‬

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‭ROLES OF MUCOUS MEMBRANES IN NON-SPECIFIC DEFENSE‬
‭➢‬ ‭Mucous-secreting membrane is the second part of the first line of defense (skin) and‬
‭lines all body cavities that are open to the outside environment‬
‭○‬ ‭Lumens of respiratory, urinary, digestive, and reproductive tracts‬
‭➢‬ ‭Contains mucous and slippery‬
‭➢‬ ‭Act nonspecifically to limit the inspection both physically and chemically‬
‭➢‬ ‭Two distinct layers‬
‭○‬ ‭Epithelium: outer covering of superficial cells‬
‭■‬ ‭Deeper connective tissue layer that provides mechanical and nutritive‬
‭support for the epithelium‬
‭■‬ ‭The epithelial cells are packed closely together, but forms only a thin‬
‭tissue‬
‭○‬ ‭Surface of mucous membranes are alive and play roles in the diffusion or‬
‭distribution of nutrients and oxygen, and in the elimination of wastes‬
‭■‬ ‭The thin epithelium on the surface of mucous membrane provides less‬
‭efficient barrier to entrance of pathogens than multiple layers of dead‬
‭cells found at the skin surface which is why some mucous membranes,‬
‭specially those of the respiratory and reproductive systems can be‬
‭common portals of entry‬
‭■‬ ‭However, these epithelial cells of mucous membrane are tightly‬
‭packed to prevent entry of pathogens‬
‭■‬ ‭Epithelial cells are continually shed and replaced via the cytokinesis of‬
‭stem cells‬
‭■‬ ‭The epithelia of some mucous membranes has still other means of‬
‭removing pathogens such as in trachea, stem cells produce both goblet‬
‭cells which secrete a sticky mucous which traps bacteria and‬
‭pathogens, and ciliated columnar cells whose cilia propel the mucous,‬
‭particles, and pathogens trapped within it from the lungs‬
‭■‬ ‭Some mucous membranes produce chemicals that defend against‬
‭pathogen such as nasal mucous containing lysozyme which chemically‬
‭destroys bacterial cell wall‬

‭ROLES OF NORMAL MICROBIOTA IN NON-SPECIFIC DEFENSE‬

‭➢‬ ‭The skin and mucous membrane of the body are normally home to a variety of‬
‭protozoa, fungi, bacteria and viruses‬
‭➢‬ ‭These normal microbiota plays a role in protecting the body by competing with‬
‭potential pathogen (microbial antagonism)‬
‭○‬ ‭When a foreign organism enters the body, the normal flora kills the foreign‬
‭microorganism‬
‭➢‬ ‭Some microbiota secrete antimicrobial substances that limit the growth of potential‬
‭pathogens‬
‭➢‬ ‭Microbiota also consume nutrients making them unavailable to pathogens‬
‭➢‬ ‭They can change the pH creating an environment favorable to themselves, but‬
‭unfavorable to foreign microorganisms‬
‭➢‬ ‭Presence of microbiota stimulates the body’s second line of defense‬

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‭ ormal microbiota of the intestines improve overall health by providing several‬
‭vitamins including biotin and pantothenic acid which are important in glucose‬
‭metabolism‬
‭○‬ ‭Folic acid: essential for production of urine and pyrimidine-bases of nucleic‬
‭acid‬
‭○‬ ‭Vitamin K: important role in blood-clotting‬
‭■‬ ‭If blood clots faster, the open wounds heal faster‬

‭OTHER FIRST LINE OF DEFENSE‬

‭➢‬ ‭Secretions and activities that contribute to the first line of defense‬
‭➢‬ ‭Digestive system: the saliva washes microbe from teeth, gums, tongue and palate‬
‭○‬ ‭Contains lysozyme‬
‭➢‬ ‭Stomach acid: digest or inhibit microorganism‬
‭➢‬ ‭Gastroferrin: sequesters iron during its absorption‬
‭➢‬ ‭Bile: inhibits most microorganism‬
‭➢‬ ‭Intestinal secretions: digest and inhibits microorganisms‬
‭➢‬ ‭Peristalsis: movement in digestive system‬
‭○‬ ‭Moves the gastrointestinal contents through the gastrointestinal tract‬
‭○‬ ‭Constantly eliminates pathogens‬
‭➢‬ ‭Defecation: eliminates pathogen which is also similar to vomiting‬
‭➢‬ ‭Nervous system: tears wash eyes; also containing lysozyme‬
‭➢‬ ‭Urinary system: contains lysozyme; acidity inhibits microorganisms and washes‬
‭microbes from ureters and urethra during urination‬
‭➢‬ ‭Reproductive system: vaginal secretion; acidity inhibits microorganism‬
‭○‬ ‭Contains iron-binding proteins that sequester iron making it unavailable for‬
‭microbial use‬
‭➢‬ ‭Menstrual flow: cleanses ureters and vagina‬
‭➢‬ ‭Prostate secretion: contains iron-binding proteins that sequester iron making it‬
‭unavailable for microbial use‬
‭➢‬ ‭Cardiovascular system: acts as first line of defense by blood removing‬
‭microorganisms from wounds‬
‭➢‬ ‭Coagulation: prevents entrance of many pathogens‬
‭➢‬ ‭Transferrin: binds iron for transport making it unavailable for microbial use‬

‭BODY’S SECOND LINE OF DEFENSE‬

‭➢‬ ‭When pathogens succeed in penetrating the skin or mucous membrane, the body’s‬
‭second line of defense comes into play‬
‭➢‬ ‭Also nonspecific, but this does not have barriers; instead, it is composed of cells‬
‭specially phagocytes‬
‭➢‬ ‭Has antimicrobial chemicals like the complement and interferons‬
‭➢‬ ‭Processes like inflammation and fever‬
‭○‬ ‭Inflammation: first and natural reaction of the body when there are‬
‭pathogens or foreign microorganisms‬

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‭PLASMA‬
‭➢‬ ‭Mostly water-containing electrolytes, ions, dissolved gases, nutrients, and variety of‬
‭proteins‬
‭➢‬ ‭Some plasma proteins are involved in blood clotting‬
‭○‬ ‭Blood-clotting: defense mechanism that both reduces blood loss and risk of‬
‭infection‬
‭■‬ ‭s blood loss and risk of infection When clotting factors have been‬
‭removed from the plasma, the remaining liquid is called serum‬

‭FORMED ELEMENTS‬
‭➢‬ ‭Cells and cell fragments suspended in plasma‬
‭➢‬ ‭Hematopoiesis: the blood stem cells located principally in the bone marrow‬
‭within the hallow cavities of the large bones produce three types:‬
‭erythrocytes, platelets, and leukocytes‬

‭A.‬ ‭ERYTHROCYTES‬
‭➢‬ ‭Most numerous and carries oxygen and carbon dioxide‬
‭B.‬ ‭PLATELETS‬
‭➢‬ ‭Pieces of large cells called megakaryocytes‬
‭○‬ ‭Split into small portions of cytoplasm surrounded by cytoplasmic‬
‭membranes and are involved in blood clotting‬
‭C.‬ ‭LEUKOCYTES‬
‭●‬ ‭White blood cells‬
‭●‬ ‭Directly involved in defending the body against invaders‬
‭●‬ ‭Increased infection = increased leukocytes‬

‭GRANULOCYTES‬
‭➢‬ ‭Has large granules in their cytoplasm‬
‭○‬ ‭Seen after staining and differentiated into basophils, eosinophils and‬
‭neutrophils‬
‭■‬ ‭Both eosinophils and neutrophils can phagocytize pathogens‬
‭and both can exit the blood to attack invading microbes in the‬
‭tissues by squeezing in between the cell lining in the capillaries‬
‭in a process called diapedesis‬
‭■‬ ‭Basophils release histamine during inflammation‬
‭AGRANULOCYTES‬
‭➢‬ ‭Have granules in their cytoplasm but is not visible after staining‬
‭○‬ ‭Lymphocytes: smallest leukocytes and have nuclei that nearly fill the‬
‭cell‬
‭■‬ ‭Lymphocytes are found in blood, spleen, lymph nodes and bone‬
‭marrow‬
‭■‬ ‭They have the ability to kill a wide variety of infected body cells‬
‭that display a usual or abnormal plasma‬
‭■‬ ‭If with proteins, they are known as perforin‬
‭■‬ ‭The enzymes known are granzyme‬

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 ‭○‬ ‭Monocytes: matures into macrophages which function for phagocytosis‬
‭■‬ ‭Initial function is to devour foreign objects including bacteria,‬
‭fungi, spores, dust, and dead cell‬

‭ ONOCYTES‬
M
‭WANDERING MACROPHAGES‬
‭➢‬ ‭Leave the blood via diapedesis‬
‭○‬ ‭Phagocytize pathogens and can exit the blood to attack microbes squeezing‬
‭through cell linings and capillaries‬
‭➢‬ ‭Perform scavenger function white traveling throughout the body, including‬
‭extracellular spaces‬

‭FIXED MACROPHAGES‬
‭➢‬ ‭Fixed and do not wander‬
‭➢‬ ‭Generally phagocytize within a specific organ where they associate with a reticulum‬
‭(network) of fibers that join the organ’s cells together‬
‭➢‬ ‭Also known as histiocytes which are residents of certain organs in the body‬

‭RETICULOENDOTHELIAL SYSTEM OR THE MONONUCLEAR PHAGOCYTIC SYSTEM‬

‭➢‬ ‭Composed of macrophages of all types and monocytes attached to endothelial cells‬
‭➢‬ ‭T-Cell: cell-mediated immunity‬
‭➢‬ ‭B-Cell: produces antibody like immunoglobulin which prevents growth of antigen‬

‭ HAGOCYTOSIS‬
P
‭CHEMOTAXIS‬
‭➢‬ ‭A movement of a cell toward a chemical stimulus (positive) or away from a‬
‭chemical stimulus (negative)‬
‭➢‬ ‭In case of phagocytes, positive chemotaxis involves the use of pseudopodia to‬
‭move microorganisms at the site of infection‬
‭➢‬ ‭Chemicals that attract phagocytic leukocytes include microbial waste product‬
‭and secretions components of damaged tissues and white blood cells, and‬
‭also chemotactic factors‬
‭○‬ ‭Include peptides derived from complement and chemicals called‬
‭cytokines or chemokines‬
‭○‬ ‭Released by leukocytes at the site of infection‬

‭ADHERENCE‬
‭➢‬ ‭After arriving at the site of infection, phagocytes attach to microorganisms‬
‭through the binding of complementary chemicals such as glycoproteins found‬
‭on the membranes of cells, a process called adherence‬

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 ‭INGESTION‬
‭➢‬ ‭After phagocytes adhere to pathogens, they extend pseudopods to surround‬
‭the microbe‬
‭➢‬ ‭The encompassed microbe is internalized as the pseudopodia fuse to form a‬
‭sac called a phagosome‬

‭DIGESTION‬
‭➢‬ ‭Begins when lysosomes within the phagocytes fuse with the newly formed‬
‭phagosomes to form phagosomes or digestive vesicles‬
‭➢‬ ‭Lysosomes contain digestive enzymes and other antimicrobial substances in‬
‭an environment with a pH of about 4.0 due to the presence of lactic acid‬
‭○‬ ‭Among 30 or so different digestive enzymes within lysosomes are‬
‭lipases, proteases, nucleases, and a variety of others‬
‭○‬ ‭These digestive enzymes are most active at acidic pH‬
‭➢‬ ‭Digestion of most pathogens is complete within 30 minutes, though some‬
‭bacteria contain virulence factor that resist digestion‬
‭➢‬ ‭After digestion, a phagolysosome is known as a residual body‬

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 ‭ELIMINATION‬
‭➢‬ ‭Digestion is not always complete, and phagocytes eliminate undigested‬
‭remnants of microorganisms via exocytosis, a process that is essentially the‬
‭reverse of ingestion‬
‭➢‬ ‭Some microbial components may remain attached to the cytoplasmic‬
‭membranes of some phagocytes, a phenomenon that plays a role in the‬
‭specific immune response‬

‭EXTRACELLULAR KILLING BY LEUKOCYTES‬

‭➢‬ ‭NATURAL KILLER CELLS (NK CELLS): another type of nonspecific, defensive‬
‭leukocyte that works by secreting toxins onto the surfaces of virally infected‬
‭cells and neoplasms (tumors)‬
‭○‬ ‭NK cells identify and spare normal body cells because the latter‬
‭expresses membrane proteins like those on the NK cells‬
‭➢‬ ‭Phagocytosis involves killing a pathogen once it has been ingested‬
‭➢‬ ‭In contrast, eosinophils and natural killer cells can accomplish extracellular‬
‭killing‬
‭○‬ ‭Eosinophils can phagocytize, however, this is not their usual mode of‬
‭attack‬
‭○‬ ‭Eosinophils primarily attack parasitic helminths or worms by attaching‬
‭to the worm’s surface often binding to antibodies that themselves have‬
‭bound to chemicals that are specific to worms‬
‭○‬ ‭Once bound, eosinophils secrete extracellular proteins toxins into the‬
‭surface of the parasite which weakens the helminth‬
‭○‬ ‭Eosinophilia: abnormally high number of eosinophils in the blood and‬
‭is often indicative of helminth infection‬

‭NON-SPECIFIC CHEMICAL DEFENSES AGAINST PATHOGENS‬

‭➢‬ ‭The chemical defenses augment phagocytosis in the second line of defense‬
‭➢‬ ‭The chemicals involved assist phagocytic cells either by directly attacking‬
‭pathogens, or enhancing other features of nonspecific resistance‬

‭COMPLEMENT/THE COMPLEMENT SYSTEM‬

‭➢‬ ‭Set of serum proteins designated numerically according to the order of‬
‭discovery‬
‭➢‬ ‭Act as opsonins and chemotactic factors that trigger inflammation and fever‬

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 ‭➢‬ C
‭ LASSIC PATHWAY-‬‭binding of antibodies to foreign antigens activates‬
‭complement‬
‭➢‬ ‭Various complement protein acts nonspecifically to complement or act‬
‭in conjunction with the action of antibodies‬
‭➢‬ ‭The complement fragments cleave other complement molecules to‬
‭form fragments‬
‭➢‬ ‭Most fragments have specific and important roles in achieving the‬
‭functions of the complement system‬
‭➢‬ ‭The end-product of the entire complement system cascade are‬
‭membrane attack complexes (MAC) which, from clearly circular roles in‬
‭a pathogen’s membrane‬
‭➢‬ ‭The production of numerous membrane attack complexes lead to lysis‬
‭in a wide variety of bacterial and eukaryotic pathogens‬
‭➢‬ ‭Gram-negative bacteria are particularly sensitive to production of MAC‬
‭via complement cascade because outer membranes are exposed‬
‭➢‬ ‭C3b: acts as opsonin and fragment C3a‬
‭➢‬ ‭C5b: functions as chemotactic factors attracting phagocytes to the site‬
‭of infection‬
‭○‬ ‭Both C3a and C5b are inflammatory agents that trigger‬
‭increased vascular permeability and dilation‬

‭➢‬ ‭ALTERNATE PATHWAY-‬‭also known as Properdin Pathway‬

‭➢‬ ‭Pathogens or pathogenic products activate the complement system‬
‭➢‬ ‭Occurs independent of antibodies; initiated by interaction between‬
‭three proteins, properdin factors (B, D, P), and endotoxins and‬
‭lipopolysaccharides from bacteria and fungi.‬
‭➢‬ ‭Molecules from microorganisms stabilize molecules of the C3b, which‬
‭are always found in small quantities in the blood‬
‭○‬ ‭Cleave: makes holes which will serve as pathway to release‬
‭more C3b molecules‬
‭➢‬ ‭Even though this is less efficient than classical pathway, it is useful in‬
‭early stages of infections caused by fungi and gram-negative bacteria‬
‭➢‬ ‭Complement proteins, once activated, react with one another in an amplifying‬
‭sequence of chemical reactions in which the product of reaction becomes an‬
‭enzyme that catalyzes the next reaction (cascade) many times‬
‭➢‬ ‭When there is inactivation of complement, the membrane-bound proteins on‬
‭many cells can bind with and break down activated complement proteins‬
‭which interrupt the complement cascade before damage can occur‬
‭○‬ ‭Human cells replace their cell membrane at a very high rate‬
‭○‬ ‭Old membrane and any membrane attack complexes within it and are‬
‭shed or taken via endocytosis, then digested‬

‭INTERFERONS‬
‭➢‬ ‭Protein molecules released by host cells to nonspecifically inhibit the spread of viral‬
‭infection‬

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 ‭➢‬ I‭ ts lack of specificity means that interferon produced against one viral invader‬
‭protects somewhat against the infection by other types of viruses as well‬
‭➢‬ ‭Viruses use a host metabolic machinery to produce new viruses and for this reason,‬
‭it is often difficult to interfere with virus replication without also producing effects to‬
‭the host‬
‭➢‬ ‭Particularly effective against viruses with RNA genome and are often crucial in‬
‭reducing their effects‬
‭➢‬ ‭Also cause body malaise, muscle aches, chills, and fever typically associated with‬
‭viral infections‬
‭➢‬ ‭It has three types: alpha, beta, gamma‬
‭○‬ ‭In general, alpha and beta interferons are present in early viral infections‬
‭○‬ ‭Gamma interferon appears in the later course of infection‬
‭➢‬ ‭Interferons do not protect the cells that secrete them, instead, they trigger‬
‭protective steps in neighboring uninfected cells‬
‭○‬ ‭Alpha and beta interferons bind to interferon receptors in the cytoplasmic‬
‭membranes of neighboring cells‬
‭■‬ ‭Such binding triggers the production of antiviral proteins (AVP) which‬
‭remains inactive within the cells until the AVP binds to double-stranded‬
‭RNA‬
‭■‬ ‭Common among viruses, but generally absent in eukaryotic cells‬
‭■‬ ‭AVP enzymes essentially destroy protein production system of a cell,‬
‭preventing viruses from being replicated‬
‭■‬ ‭Cellular metabolism is also affected‬
‭■‬ ‭The antiviral state lasts for 3-4 days which is long enough for the cell‬
‭to get rid of itself of the virus, and still short enough for the cell to‬
‭survive without protein production‬
‭○‬ ‭Gamma interferon is produced by activated P-lymphocytes and NK cells‬
‭■‬ ‭Because T-lymphocytes are usually produced as part of the specific‬
‭immune response‬
‭■‬ ‭After infection has occurred, gamma interferon occurs later than alpha‬
‭and beta‬
‭■‬ ‭Its action in stimulating the activity of macrophages gives its other‬
‭name macrophage activating factor‬

‭INFLAMMATION‬
‭➢‬ ‭In general, is nonspecific response to tissue damage resulting from a wide variety of‬
‭causes including heat, chemicals, ultraviolet light, abrasions, cuts, and pathogens‬
‭➢‬ ‭Acute inflammation:‬‭develops quickly and is short-lived‬
‭○‬ ‭Typically beneficial and results in elimination or resolution of whatever‬
‭condition precipitated it‬
‭➢‬ ‭Chronic inflammation: develops slowly and lasts a long time, and cause damage or‬
‭death of tissue causing the disease‬
‭➢‬ ‭Both types of inflammation exhibit similar signs and symptoms such as rubor‬
‭(redness), calor (localized heat), tumor or edema (swelling), dolor (pain), and also‬
‭loss of function‬

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‭Acute inflammation results in:‬
‭●‬ ‭Dilation and increased permeability of blood vessels‬
‭●‬ ‭Migration of phagocytes‬
‭●‬ ‭Tissue repair‬

‭DILATION AND INCREASED PERMEABILITY OF BLOOD VESSELS‬

‭➢‬ ‭Damaged cells release various chemicals, including histamine, prostaglandins, and‬
‭leukotrienes‬
‭➢‬ ‭MAST CELLS:‬‭release histamine when they are exposed to complement fragments‬
‭C3a and C5a‬
‭➢‬ ‭Prostaglandins, leukotrienes, and histamine also make blood vessels more‬
‭permeable, that is, they cause cell lining the vessel to contract and pull apart,‬
‭leaving gaps in the vessel’s wall through which macrophages and neutrophils can‬
‭move into the damaged tissue and fight invaders‬
‭➢‬ ‭Increased permeability also allows delivery of more blood-born antimicrobial‬
‭chemicals into the site‬
‭➢‬ ‭Dilation of blood vessels in response to histamine results to redness (rubor) and‬
‭localized heat (calor)‬
‭➢‬ ‭Fibrinogen:‬‭the blood’s clotting protein‬
‭○‬ ‭Clots form at the site of injury or infection to wall off area and help prevent‬
‭pathogens and their toxins from spreading‬
‭➢‬ ‭One result of formation of pus is the fluid containing dead tissue cells and dead‬
‭leukocytes in the walled off area of tissue destruction‬
‭○‬ ‭May push up toward the surface and rubbed, or may remain isolated in the‬
‭body where it is slowly absorbed over a period of days‬
‭○‬ ‭Such isolated site of infection is called abscess‬

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‭MIGRATION OF PHAGOCYTES‬
‭➢‬ ‭Increased blood flow due to vasodilation delivers monocytes and neutrophils to the‬
‭site of infection‬
‭○‬ ‭As they arrive, these leukocytes stick to the walls of blood vessels in a‬
‭process called margination and they squeeze between the cells of the vessel’s‬
‭wall and be eliminated through the blood‬
‭○‬ ‭After diapedesis, they will enter the site of infection usually within an hour of‬
‭tissue damage‬
‭➢‬ ‭Phagocytes are attracted to the site of infection by chemotactic factors, including‬
‭leukotrienes, microbial components, and toxins and C3a and C5a‬
‭➢‬ ‭Neutrophils → monocytes‬
‭○‬ ‭Once monocytes leave the blood, they change and become wandering‬
‭macrophages‬

‭TISSUE REPAIR‬
‭➢‬ ‭The final stage of inflammation which in part involves the delivery of extra nutrients‬
‭and oxygen to the site‬
‭➢‬ ‭If the damaged tissue contains undifferentiated stem cells, tissues can be fully‬
‭restored‬
‭➢‬ ‭If fibroblasts are involved to a significant extent, scar tissue is formed, inhibiting‬
‭normal function‬

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‭FEVER‬
‭➢‬ ‭Body temperature above 37°C‬
‭➢‬ ‭Fever augments the beneficial effects of inflammation‬
‭➢‬ ‭HYPOTHALAMUS:‬‭controls the body’s internal (core) temperature‬
‭➢‬ ‭PYROGENS:‬‭trigger hypothalamic thermostat to reset at a higher temperature‬
‭○‬ ‭Include bacterial toxins‬
‭○‬ ‭Cytoplasmic contents of bacteria that are released upon lysis, the antibody‬
‭antigen complexes and interleukin-1 which is a pyrogen released by‬
‭phagocytes, that have a phagocytized bacteria‬
‭➢‬ ‭If the fever is too high, critical proteins are denatured; additionally, nerve impulses‬
‭are inhibited, resulting in hallucinations, coma, and even death‬
‭○‬ ‭Can produce convulsion which can affect how the mind works‬
‭➢‬ ‭Increased temperature of fever enhances the effect of interferons‬
‭○‬ ‭Inhibits the growth of some microorganisms and is thought to enhance the‬
‭performance of phagocytes‬
‭➢‬ ‭The activity of cells of specific immunity and the process of tissue repair‬

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 ‭UNIT 4 CHAPTER 2: IMMUNOLOGY‬

‭I.‬ ‭INTRODUCTION‬

‭SPECIFIC DEFENSE‬
‭➢‬ ‭The Third Line of Defense‬
‭➢‬ ‭“Smart” System that has “memory” about specific pathogens, so that when it‬
‭encounters them a second time, it responds rapidly and effectively. This response is‬
‭called Specific Immunity.‬

‭SPECIFIC IMMUNITY‬
‭➢‬ ‭The body’s ability to recognize and defend itself against distinct invaders and‬
‭their products, whether they are protozoa, fungi, bacteria, viruses, or toxins.‬

‭II.‬ ‭ELEMENTS OF SPECIFIC IMMUNITY‬

‭ANTIGENS‬
‭➢‬ ‭Molecules which triggers specific immune responses followed by a brief description of‬
‭cells, tissues, and organs of specific immunity.‬
‭➢‬ ‭The body does not direct specific defense against whole bacteria, fungi, protozoa, or‬
‭virus. Instead, it is directed against parts of cells or single molecules that the body‬
‭recognizes as foreign and worthy of attack.‬

‭PROPERTIES‬
‭➢‬ ‭Not every molecule is an effective antigen‬
‭➢‬ ‭The body only recognizes an antigen by the 3d shapes of region called‬
‭Antigenic Determinants aka Epitopes‬
‭➢‬ ‭“Haptens” – small molecules that can become antigenic when bound to larger‬
‭carrier molecules (often proteins)‬
‭➢‬ ‭Complex molecules make better antigens than simple ones.‬

‭TYPES‬
‭➢‬ ‭Exogenous Antigens are produced by microbes outside the cells of the body.‬
‭➢‬ ‭Endogenous Antigens are produced by protozoa, fungi, bacteria, and viruses‬
‭inside a body’s cells‬

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‭LYMPHATIC SYSTEM‬
‭➢‬ ‭Composed of the lymphatic vessels, which conduct the flow of a liquid (lymph),‬
‭lymphatic cells, tissues, and organs, which are directly involved in specific immunity.‬
‭➢‬ ‭Together = SURVEILLANCE SYSTEM that screens tissues of the body and of the body‬
‭for foreign antigens.‬

‭LYMPHATIC VESSELS‬
‭➢‬ ‭Form a one-way system (flows toward the heart) that conducts lymph from‬
‭local tissues and returns it to the circulatory system.‬
‭LYMPH‬
‭➢‬ ‭is first conducted by remarkably permeable lymphatic capillaries, are in most‬
‭parts of the body and collect fluid from intercellular spaces.‬
‭RED BONE MARROW‬
‭➢‬ ‭site of production of cells of a specific immune system.‬
‭➢‬ ‭Contains stem cells.‬

‭MALT‬
‭➢‬ ‭aka Mucosa Associated Lymphatic Tissue‬
‭➢‬ ‭contains leukocytes that defend against foreign antigens entering the blood, the‬
‭respiratory, and digestive tracts.‬
‭LYMPHOCYTES‬
‭➢‬ ‭After lymphocytes are produced in the bone marrow, they must undergo a‬
‭maturation process.‬

‭B-LYMPHOCYTES (B Cells)‬
‭➢‬ ‭Lymphocytes that mature within the bone marrow‬
‭➢‬ ‭Plasma Cells - B cells that actively fight against exogenous antigens. They‬
‭secrete soluble proteinaceous antigen binding molecules called antibodies or‬
‭immunoglobulins‬
‭➢‬ ‭Humoral Immune Response or Humors‬
‭➢‬ ‭Has heavy chains and two identical lighter chains.‬

‭B-CELL RECEPTORS(BCR)‬
‭➢‬ ‭They are in the surfaces of each b lymphocytes.‬
‭➢‬ ‭surface of lymphocytes is covered with 250,000 to 500,000 identical copies‬
‭of B cell receptor‬
‭➢‬ ‭An antibody that remains integral to the cytoplasmic membrane. Like a‬
‭secreted antibody molecule, each has two (2) antigen binding sites.‬
‭➢‬ ‭Do not form in response to antigens‬
‭➢‬ ‭is complementary in shape to an antigenic determinant‬
‭➢‬ ‭B cells do not mount a humoral immune response directly. Instead, they‬
‭respond to most antigens only with the assistance of T Lymphocytes or T cells‬

‭T LYMPHOCYTES (T Cells)‬
‭➢‬ ‭Lymphocytes that travel to and mature in the thymus‬

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 ‭➢‬ ‭act directly against endogenous invaders‬

‭TYPES OF T CELLS‬
‭➢‬ ‭Cytotoxic T (TC) cell - Distinguished by hundreds of copies of its unique TCR.‬
‭T Cells that directly kills other cells.‬
‭➢‬ ‭Helper T Lymphocytes (TH cells) - Distinguished by the presence of CD4‬
‭glycoprotein. Their function is to “help” in regulating the activity of B cells and‬
‭cytotoxic T cells.‬
‭SUBTYPES OF HELPER T LYMPHOCYTES‬
‭➢‬ ‭Type 1 Helper T Cells (TH1) - Assist Cytotoxic T cells. Produces cytokines,‬
‭specifically interferon Y.‬
‭➢‬ ‭Type 2 Helper T Cells (TH2) - Function in conjunction with B cells. Important‬
‭in the activation of eosinophils.‬
‭➢‬ ‭T regulatory cells (Treg) - Functions to combat autoimmunity by suppressing‬
‭T cells that escape deletion in the thymus.‬

‭T CELL RECEPTOR (TCR)‬

‭➢‬ ‭Composed of two (2) different polypeptide chains with a groove between‬
‭them that acts as an antigen binding site‬
‭➢‬ ‭TCR recognizes and binds to a complementary antigenic determinant, and‬
‭there are at least 10 different TCRs.‬

‭ANTIBODIES‬
‭➢‬ ‭soluble proteinaceous antigen binding molecules‬

‭FUNCTIONS OF ANTIBODIES‬

‭AGGLUTINATION‬ ‭NEUTRALIZATION‬ ‭OPSONIZATION‬

‭ inders the activity of‬

h ‭ ntibodies can block‬
A ‭ nhanced phagocytosis is‬
E
‭pathogenic organisms and‬ ‭attachment molecules on‬ ‭known as opsonization.‬
‭increases the chance that‬ ‭the surfaces of bacteria and‬ ‭Antibodies act as opsonin‬
‭they will be phagocytized‬ ‭viruses such that they‬ ‭molecules that stimulate‬
‭cannot adhere to target cells‬ ‭phagocytosis.‬

‭ LASSES OF ANTIBODIES (IMMUNOGLOBULINS)‬

C
‭IgG‬
‭➢‬ ‭most common class of antibody in the blood‬
‭➢‬ ‭85% of serum of antibodies‬
‭➢‬ ‭very small in size‬
‭➢‬ ‭the only type of antibody that can cross the placenta to protect a developing child‬
‭➢‬ ‭Plays a major role in antibody mediated defense mechanisms, including complement‬
‭activation, agglutination, opsonization, and neutralization.‬
‭IgM‬
‭➢‬ ‭second most common class of antibody in the blood‬
‭➢‬ ‭5x larger than IgG‬

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 ‭➢‬ i‭s more efficient than IgG at complement activation, neutralization of virions and‬
‭agglutination because of its numerous antigen binding sites.‬

‭IgA‬
‭➢‬ ‭Most closely associated with various body secretions, including tears and milk.‬

‭IgE‬
‭➢‬ m ‭ ediates between specific and non-specific response because histamine, which‬
‭causes inflammation, is part of the body's nonspecific defense.‬
‭➢‬ ‭important in allergic diseases infections.‬
‭➢‬ ‭acts as signal molecules which attach to receptors found on certain WBCs to trigger‬
‭the rapid release of histamine.‬

‭IgD‬
‭➢‬ c ‭ an participate in the generation and maintenance of Bcell memory.‬
‭➢‬ ‭Enhances mucosal homeostasis and immune surveillance‬

‭IMMUNE SYSTEM CYTOKINES‬

‭➢‬ ‭CYTOKINES - are soluble regulatory proteins that act as intercellular signals when‬
‭released by certain body cells. These are proteins that regulate the intensity and‬
‭duration of immune responses‬
‭➢‬ ‭Cytokines of the Immune System includes:‬
‭○‬ ‭Interleukins (Ils)‬
‭○‬ ‭Interferons (IFNs)‬
‭○‬ ‭Growth Factors‬
‭○‬ ‭Tumor Necrosis Factors (TNFs)‬
‭○‬ ‭Chemokines‬

‭III.‬ ‭THE BODY’S PREPARATION FOR A SPECIFIC IMMUNE RESPONSE‬

‭LYMPHOCYTE EDITING BY CLONAL DELETION‬

‭➢‬ ‭Lymphocytes randomly generate the shape of their receptor.‬

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 ➢
‭ ‬ m‭ ake a clone and delete it so that they eliminate the antigen.‬
‭➢‬ ‭Apoptosis - is the critical feature in the development of self-tolerance because‬
‭lymphocytes with receptors for autoantigens die before they can reproduce, and their‬
‭potential daughter cells (clones) are deleted.‬

‭MHC ANTIGENS‬
‭➢‬ ‭are molecules which are important in determining the compatibility of‬
‭transplanted tissues in successful grafting.‬
‭➢‬ ‭glycoproteins found in the membranes of most cells of vertebrate animals.‬
‭➢‬ ‭Human Leukocyte Antigens (HLA)‬
‭➢‬ ‭When HLA is clustered, Major Histocompatibility Complex (MHC) - functions to‬
‭hold and position antigenic determinants for presentation to T cells.‬
‭THE ROLES OF MHC‬
‭➢‬ ‭Class I MHC molecules are found on the cytoplasmic membranes of nucleated cells.‬
‭Thus red blood cells, which do not have nuclei, do not express MHC class I molecules‬
‭➢‬ ‭Class II MHC proteins are found only on B lymphocytes and special cells called‬
‭antigen presenting cells (APCs). APCs include monocytes, macrophages, and their‬
‭functional relatives.‬

‭ANTIGEN PROCESSING‬
‭➢‬ ‭Antigen’s processing occurs via somewhat different processes according to whether‬
‭the antigen is exogenous or endogenous.‬
‭➢‬ ‭For exogenous antigens such as extracellular pathogens, an APC internalizes the‬
‭invading pathogen and enzymatically catabolizes the pathogen’s antigenic molecules,‬
‭producing fragments or antigenic determinants which are contained in a‬
‭phagolysosome.‬

‭IV.‬ ‭HUMORAL IMMUNE SYSTEM‬

‭B CELL ACTIVATION AND CLONAL SELECTION‬

‭a.‬ ‭Antigen presentation‬
‭b.‬ ‭Differentiation of TH into TH2 cells. In a humoral immune response, APCs signal the‬
‭TH cell with IL-1 to become a TH2 cell.‬
‭c.‬ ‭Clonal Selection‬
‭d.‬ ‭Activation of B cell.‬

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‭MEMORY B CELLS AND THE ESTABLISHMENT OF IMMUNOLOGICAL MEMORY‬
‭➢‬ ‭Memory B cells – survived cells produced by B cell proliferation but do not secrete‬
‭antibodies.‬
‭➢‬ ‭Memory Cells - They have BCRs and persist in the lymphoid tissues. They can survive‬
‭for months or even years, ready to initiate antibody production is the same antigen‬
‭is encountered again.‬

‭V. CELL-MEDIATED IMMUNE RESPONSE‬

‭➢‬ ‭used by the body to fight intracellular pathogens and abnormal body cells. Given that‬
‭the most common intracellular invaders are viruses.‬

‭THE PERFORIN-GRANZYME CYTOTOXIC‬

‭➢‬ ‭The cytoplasm of cytotoxic T cells has vesicles containing two key protein‬
‭molecules called cytotoxins- perforins and granzymes.‬
‭THE CD95 CYTOTOXIC PATHWAY‬
‭➢‬ ‭involves an integral glycoprotein called CD95 that is present in the‬
‭cytoplasmic membranes of most body cells; its receptor, CD95L, is present on‬
‭activated TC cells.‬
‭➢‬ ‭when an activated TC cell encounters its target, which then activates enzymes‬
‭that trigger apoptosis.‬

‭MEMORY T CELLS‬
‭➢‬ ‭When stimulated by endogenous antigen and cytokines from TH1 cells, T cells‬
‭undergo repeated division and differentiation‬
‭➢‬ ‭The number of memory T cells is greater than the number of T cells that‬
‭recognize the antigen during initial exposure, a secondary cell-mediated‬
‭immune response is much more effective than a primary response.‬

‭T CELL REGULATION‬
‭➢‬ ‭The body carefully regulates cell-mediated immune responses so that T cells‬
‭do not respond to autoantigens‬
‭➢‬ ‭Immunological Synapse - If a cell does not receive the signals required for its‬
‭activation, it will “shut down” as a precaution against autoimmune responses.‬

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‭VI. TYPES OF ACQUIRED IMMUNITY‬

‭ ATURALLY-ACQUIRED‬
N
‭ACTIVE IMMUNITY‬
‭➢‬ ‭Occurs when the body responds to exposure to pathogens and environmental‬
‭antigens by mounting specific immune responses.‬
‭➢‬ ‭Once an immune response occurs, immunological memory persists, on subsequent‬
‭exposure to the same antigen, the immune response will be rapid and powerful and‬
‭often provides complete protection‬
‭PASSIVE IMMUNITY‬
‭➢‬ ‭Via these two processes, a mother provides her child with antibodies that protect it‬
‭during its early months because the child is not actively producing its own‬
‭antibodies, this type of protection is known as naturally acquired passive immunity.‬

‭ RTIFICIALLY-ACQUIRED‬
A
‭ACTIVE IMMUNITY‬
‭➢‬ ‭Physicians induce immunity in their patients by introducing antigens in the form of‬
‭vaccines. The patient’s own immune systems then mount active responses against‬
‭the foreign antigens, just as if the antigens were part of a naturally acquired‬
‭pathogen‬
‭PASSIVE IMMUNITY‬
‭➢‬ ‭Active immunity usually requires days to weeks to develop fully, and in some cases‬
‭such a delay can prove detrimental or even fatal.‬
‭➢‬ ‭They can acquire these antibodies from the blood of immune humans or animals,‬
‭typically a horse or other large animal. Physicians then inject such Abs.‬

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