Chapter 2 Immunology PDF

Chapter Two- Immunology Outlines  Terminologies in immunology  The immune system Innate and adaptive immunity  Altered /disorder in immunity Hypersensitivity reaction Immune deficiency Auto immunity  Application of immunology: Immunization/vaccination Objectives  Upon comp...

Chapter Two- Immunology Outlines  Terminologies in immunology  The immune system Innate and adaptive immunity  Altered /disorder in immunity Hypersensitivity reaction Immune deficiency Auto immunity  Application of immunology: Immunization/vaccination Objectives  Upon completion of this session and exercises the student will be able to: Define common terms in immunology Describe different forms of immune response Define what is hypersensitivity reaction Describe different forms of hypersensitivity reaction Define immunization/vaccination Describe different forms of immunization/vaccination Definitions  Immunology: study of structure and function of the immune system/ immunity  Immune system: cells, molecules, tissues and organs that mediate protection to infections  Immunity: State of protection from infectious diseases Definitions…  Immune response: collective and coordinated response to the introduction of foreign substances in an individual mediated by the cells and molecules of the immune system  Antigen: foreign substance that recognized by immune system  Antibody: produced by the immune system which recognize foreign substance Functions of antibodies What is the Role of the immune system?  Defense against pathogenic microbes  Defense against the growth of tumor cells  kills the growth of tumor cells  Homeostasis  destruction of abnormal or dead cells
(e.g. dead red or white blood cells, antigen-antibody complex)  Classification of immune system Immune System Innate Adaptive (Nonspecific) (Specific) Soluble factor Cell-Mediated Cells Humoral Complements Phagocytes Th Cells (Ab) Secretions NK Cells Tc Cells B Cell Enzymes Classification of immune system Types of immunity 1. Innate (non-specific) immunity first line of immune response Exist naturally  relies on mechanisms that exist before infection  Based on genetic make-up  Relies on already formed components Rapid response: within minutes of infection ELEMENTS OF HOST PROTECTIVE RESPONSES  We live in a microbial world, and a microbial world lives on and within us.  Our bodies are constantly being exposed to bacteria, fungi, parasites, and viruses  And must restrict the normal f lo ra from entering into sterile tissue sites, discriminate between friend and foe, and defend against invading microbes  Our bodies’ defenses are similar to a military defense Innate (non-specific) immunity  Not specific same molecules / cells respond to a range of pathogens  Has no memory same response after repeated exposure  Does not lead to clonal expansion Major functions of innate immunity  To be a physical and chemical barrier to infectious agents and toxins  Recruit immune cells to the sites of infection through the production of humoral factors called chemokine's and cytokines Major functions of innate immunity  Activate the complement system to mark , e.g., bacteria and promote clearance of dead cells or antibody complexes  Identify and remove foreign substances in the host by specialized white blood cells (neutrophil & Macrophage)  Activate the adaptive immune system through a process known as antigen presentation Components of innate immunity  Surface barriers  Physical or mechanical barriers Skin, cilia and mucus production  Biochemical/ humoral barriers Enzymes, secretions, pH, cytokines, complement, interferons  Biological barriers: Normal flora  Washing mechanisms: tear & urine  Inflammatory reaction  Cellular Barriers: NK cells, neutrophils, macrophages, eosinophil's, dendritic cells 
Components of innate immunity Components of innate immunity… Surface barriers  Physical barrier Skin  epith elial cells compacted, cemen ted togeth er an d impregnated with keratin  effective first-line defense against pathogens Mucous of respiratory, urogenital, eyes and digestive tracts  impedes attachment and entry of microbes Cilia and cough ref lex, sneezing: helps expel microbe containing mucous Biochemical barriers Definition: Chemical secretions produced by the body that inhibit microbial growth  Enzymes secretion  Tear lysozyme against microbes entry  Digestive enzymes  Saliva of the mouth  Keratin of the skin  Antimicrobial peptides of skins  Acidic Ph of skin, vagina & stomach (hydrochloric acid )  bile salt of the liver 
Humoral barriers/soluble factor  Cytokines: proteins secreted by phagocytes & mediate Inflammatory in response to infection  Complement: proteins in serum that function as a non-specific defense against infection  Lyse bacterial cells  Enhance phagocytosis  Increase in vascular permeability  Recruitment and activation of phagocytic cells  Interferon: small proteins against viral infection Biological Barriers Normal flora  human body is inhabited by a large number of microorganisms, mainly bacteria called body’s normal flora or commensals Means harmless and do not cause disease in immune competent host  Prevent the growth of pathogenic microbes through:  Occupying attachment sites  Competing for essential nutrients for their growth.  Producing substance against pathogenic organism E.g. lactobacilli of the vagina make acidic pH due to breakdown of glycogen Breakdown in Physical & Chemical Barriers Skin/mucous membranes  Eczema, burns  indwelling cannulas  Cough reflex: neurological disease  Mucociliary escalator : Smoking, cystic fibrosis, asthma  Washing mechanisms  Bladder outflow obstruction  Reduced secretions  Acid pH of stomach & skin change  Colonization resistance: Broad spectrum antibiotics Inflammatory reactions Definitions: Any physiological response to exogenous or endogenous stimuli such as infections, injuries or cancer cells involves local inflammation vascular and cellular reaction to the presence of invading microorganisms or injury It is one of the most effective defense mechanism in human and other animals. Inflammatory reactions… stages: Initiation (Damage to tissue) Tissue response Leukocyte response Tissue repair (resolution) & cure  when all harmful agents or substances have been removed or neutralized at the injury site Inflammatory reactions… Tissue response  Damaged tissue release histamines trigger vasodilatation and increased permeability of capillaries  increased fluids & blood flow into the injury site with as redness , heat, swelling & pain at the site Inflammatory reactions…  Leukocyte response Neutrophil (mostly), macrophages and dendritic cells  reach at site of injury & engulf the microbes and damaged tissue through phagocytosis Post capillary vasoconstriction  maintained to keep the pathogen at the site of entry  this lowers the blood flow rate Plus to this it forms, blood clots around the site prevent the microbe or its products from spreading to the other part of the body Inflammatory reactions…  Post capillary vasoconstriction maintained to keep the pathogen at the site of entry this lowers the blood flow rate Optimally, the agent will be removed, leading to restitution and integrum (complete healing). Inflammation process Cellular barriers  Phagocytic cell: Neutrophil, macrophage/monocyte or dendritic cell Produce wide array of chemicals  Release inflammatory cytokines, enzymes Act as scavengers/phagocytosis Act as antigen presenting cells /APC that activate the adaptive immune system Natural Killer cells Kill virus-infected or transformed/tumor cells  Cellular barriers… Natural Killer cells  cytotoxic cells  Surface receptors that recognize Kill virally infected cells or transformed/tumor cells Cellular barriers… Host defense by phagocytosis A process engulf pathogenic particle and digesting  Through neutrophil, macrophage or dendritic cell Phagocytes recognize  pathogen-associated molecular patterns (PAMPs) of pathogens such as Lipoproteins & Proteoglycan  by their pattern recognition receptors (PRRs)  Cellular barriers: Phagocytosis Adherence Engulfment Digestion 2. Acquired (adaptive) immunity Second line of response (if innate fails) Relies on  mechanisms that adapt after infection  genetic events and cellular growth  resistance acquired during life Responds more slowly, over few days  Acquired (adaptive) immunity… Characteristic adaptive immunity  Specific each cell responds to a single epitope on an antigen one cell determines one antigenic determinant  Diversity : Leads to clonal expansion: allowing it to recognize billions of unique structures  C l o n e : A p o p u l a t i o n o f c e l l s o r o r g a n i s m s d e r i v e d
a s e x u a lly f r o m a s in g le p r o g e n it o r. A clo n e is g e n e ra lly a s s u m e d
to be genetically homogeneous  clonal expansion: is a proliferation(multiplying) of antigen specific T cell
Acquired (adaptive) immunity… Characteristic adaptive immunity  Memory  Has anamnestic memory repeated exposure leads to faster, stronger response Longer lasting response  Self/non-self recognition Acquired (adaptive) immunity…  Primary response production of specific clones of effector T cells and memory clones develops in several days does not limit the infection  Secondary response more pronounced, faster more effective at limiting the infection Example - cytotoxic reactions against intracellular parasites, delayed hypersensitivity (e.g., Tuberculin test) Acquired (adaptive) immunity… Adaptive Active Immunity Passive Immunity immunity Natural Clinical or via breast milk sub-clinical infection placenta Artificial Vaccination: immune serum Live immune cells Killed/inactivated purified antigen vaccine Acquired (adaptive) immunity… Acquired (adaptive) immunity… Components of adaptive immunity  Humoral mediated immunity: B-lymphocyte mediated by antibodies & eliminate extra-cellular
microbes and their toxins B-Cells  Plasma Cells  Antibodies  Cells (Cell mediated) immunity T-lymphocytes (T- lymphocytes): TH & T cytotoxic cells Eliminate microbes that survive within phagocytes or other infected cells Acquired (adaptive) immunity…  Effective immune response involves Cellular Immunity (T lymphocytes) Humoral Immunity (B cells) Accessory cells (antigen-presenting cells). Acquired (adaptive) immunity… Humoral immune response  immunity mediated by B-cells  recognize specific antigens proliferate and differentiate into antibody-secreting plasma cells  Antibodies bind to specif ic antigens on microbes; destroy microbes  Are APCs & recognize the whole pathogen without any need for Ag processing  With antigen specific receptors  Some B lymphocytes evolve into the resting state - memory cells 
Humoral immune response & activation of Th cells Humoral Mediated Immunity Cytokines T-Cell Plasma Cell B-Cell 2/12/2025 Introduction to Immunology 47 Cell mediated immune response  Immune response with antigen specific T cells (T – lymphocyte)f Tells  Major types  Cytotoxic T cells (CTLs)  Helper T cells (HTLs)  Other sub types: Regulatory T cells recognizes antigen processed by macrophage (APC) in association with major histo-compatibility complex (MHC) class I/II  identifies molecules on cell surfaces  helps body distinguish self from non-self  able to kill infected cells Cell mediated immune response… Cytotoxic T cells (CTLs) (CD8cells) Role:  Kills cells that are  Infected with viruses or other intracellular pathogen  Damaged or dysfunctional Recognition and activation:  When their T cell receptor (TCR) bind to specific antigen in combination with class I MHC molecule of another cell APC & activation of T cytotoxic cells  CD8+ T-Cell APCs & CD8 T- + Cytotoxins Cells T-Cell Fas ligand Receptor APC Fas Protein Protease Peptides MHC-Class I 2/12/2025 Introduction to Immunology 51  Cell mediated immune response Helper T cells (HTLs) (CD4+) Role: Regulate both innate and adaptive immune response Help to determine which immune response the body makes to a particular pathogen Recognition and activation:  do not kill infected cells or directly destroy pathogen Rather control the Immune response by directing other cells that perform this tasks recognize antigen bound to class II MHC molecule of other cells  CD4+ Th1-Cell APCsCD4+ Th1-Cells IL-2 Protein IFN-gamma Macrophage 2/12/2025 Introduction to Immunology TNF-alpha 53 Professional APC
CD4+ Th2-Cells IL-5, IL-6, IL-10 IL-4 Th2-Cell Plasma Cell B-Cell 2/12/2025 Introduction to Immunology 54 Summary of innate and adaptive immunity Summary of innate and adaptive immunity  Summary of innate and adaptive immunity Adaptive and Innate - Interactions Infectious Innate Immunity No Exposure holds Disease Innate Immunity Fails Adaptive Immunity Specific memory Disease Adaptive Second Infectious Recovery Exposure Immune system Same organism 


Altered/ disorder immune response

Hypersensitivity reaction Immune deficiency Autoimmune disease  Objectives Upon completion of this session the student will be able to: Define hypersensitivity Describe the classification (types) of hypersensitivity reaction. Describe diseases and the mechanism of damage associated with hypersensitivity reactions Explain what mean by immune deficiency Define autoimmune disease and describe different types of autoimmune disease Hypersensitivity reaction In normal condition an immune response eliminates antigen without extensively damaging the host’s tissue Under certain circumstances, however, this response can have excessive or inappropriate activation of the immune system deleterious effects, resulting in significant tissue damage or even death This inappropriate immune response is termed hypersensitivity or allergy Hypersensitivity reaction… Mediated by pre existing immunity to self or foreign antigen require pre-sensitized (immune) state of the host an increased response inappropriate immune response to an antigen. may develop in the course of either humoral or cell-mediated responses Classification of hypersensitivity Based on mechanism involved and time taken for the reactions Type I (anaphylactic) reactions Type II (cytotoxic) reactions Type III (immune complex) reactions Type IV (T-cell-mediated) reactions Type I, II & III occur within the humoral branch and are mediated by antibody or antigen-antibody complexes Type IV within the cell-mediated branch & termed delayed-type hypersensitivity, or DTH  Hypersensitivity reaction… Type I (anaphylactic) reactions known as immediate hypersensitivity Occur within minutes (15-30 minutes) of exposure to antigen mediated by IgE Cross-linking of cell-bound IgE antibodies to antigen degranulation of mast cells or basophils and release d/t mediators such as histamine Dilates and increases permeability of blood vessels (swelling and redness), increases mucus secretion (runny nose), smooth muscle contraction (bronchi) Type I (anaphylactic) reactions… Type I hypersensitive reaction… Type I (anaphylactic) reactions… It can be systemic : shock-like and often fatal state localized: Limited to a specific target tissue or organ and Allergic rhinitis (hay fever): reaction of airborne allergens with sensitized mast cells of nasal mucosa to induce the release of inflammatory active chemicals Asthma: D/t allergens trigger an asthmatic attack (allergic asthma) Atopic dermatitis: inflammatory disease of skin Food allergies: IgE on mast cells of GIT for vomiting or diarrhea  Type II (Cytotoxic) Reactions AKA cytotoxic responses Mediated by IgG or IgM binding to an antigenic cell activation complement system, or  results in the activation of cytotoxic immune cells The reaction time is minutes to hours Type II (Cytotoxic) reactions… Cytolytic or cytotoxic effect d/t organs and tissue e.g Transfusion reaction ABO Blood group system (IgM) Inc o mpatible do no r c e lls are lyse d as the y e nte r bloodstream massive intravascular hemolysis of the transfused red blood cells by antibody plus complement Hemolytic disease: Rh incompatibility Rh negative can be sensitized to destroy Rh positive blood cells Type II (Cytotoxic) reactions… Hemolytic disease of the newborn: Ab to Rh antigen (IgG)/ Rh incompatibility maternal IgG AB specif ic for fetal blood- group antigens cross the placenta and destroy fetal red blood cells  Type III (immune complex) reactions Usually involves IgA antibodies bind to soluble antigen large antibody-Antigen immune complexes formed Deposited and not easily cleared by the phagocytic cells initiates a recruitment of neutrophils and release granular activate complement developed localized reaction & can inflammatory tissue- damaging e.g. Serum sickness: formation of immune complexes & inflammation blood-vessel walls , synovial membrane of joints or glomerular basement membrane of the kidney or Lung Glomerulonephritis inflammatory kidney damage Type III (immune complex) reactions… Formation of circulating immune complexes contributes to the pathogenesis of a number of conditions other than serum sickness  Autoimmune diseases:  Systemic lupus erythematous  Rheumatoid arthritis: joint  Infectious diseases  Post-streptococcal glomerulonephritis  Meningitis  Hepatitis Type III (immune complex) reactions…  Type IV (Cell-Mediated) reactions Called delayed-type hypersensitivity delayed by one or more days delay in time required for the reaction to develop & cytokines to induce localized influxes of macrophages and their activation Involved by sensitized lymphocytes by intracellular pathogens Not induced by circulating Ab sensitized lymphocytes release lymphokines which activate leucocytes, macrophages Type IV (Cell-Mediated) reactions…  Reactions are frequently displayed on the skin:  dermatitis- itching, redness, swelling, pain. e.g. Mycobacterium tuberculosis developed a localized inflammatory response when injected intra-dermally cause granulomatous reaction Tuberculosis skin test Agent: Poison, cosmetics, topical medication Latex in gloves and condoms Phases of the DTH(Type IV) response Sensitization phase initial sensitization phase of 1–2 weeks after primary contact with an antigen TH cells are activated and clonally expanded by antigen presented together with the requisite class II MHC molecule on an appropriate antigen presenting cell Type IV (Cell-Mediated) Reactions Effector phase A subsequent exposure to the antigen induces the effector phase of the DTH response response generally peaks 48–72hr after second contact TH1 cells secrete a variety of cytokines that recruit and activate macrophages and other nonspecif ic inflammatory cells Overview of the DTH response Summary of hypersensitive reaction Summary of hypersensitive reaction  Review questions Define hypersensitivity Describe the types of hypersensitivity reaction Explain diseases associated with hypersensitivity reactions  Immunodeficiency Loss or inadequate function of various components of the immune system/ body’s defensive mechanisms Or an abnormality of the immune system that renders a person susceptible to diseases normally prevented by a normal functioning immune system  Immunodeficiency… Can occur in any part or state of the immune system Physical barrier, phagocytes, B lymphocytes, T lymphocytes, complement, natural killer cells Or other homeostatic systems in the body will be disrupted by the defect The immune-compromised host has an impaired function of immune system is at high risk of infection Immunodeficiency…. It can be: Congenital (primary) immunodeficiency genetic abnormality defect in lymphocyte maturation Acquired (secondary) immunodeficiency Results from infections, nutritional deficiencies or treatments AIDS, chronic leukemia E.g. problem with T lymphocytes (both CD4 helper cells ) + Immunodeficiency….  Bad… Autoimmunity n th e Good Turn s Wh e Definition: Autoimmunity: failure of an organism in recognizing its own constituent parts as self  immune system response to self component causes localized or systemic injury  Autoimmune disease: any disease that results from aberrant immune response to recognizing self-cells  E.g Grave’s disease: antibodies attach to TSH receptors on thyroid gland and stimulate production of thyroid hormone cause Goiter (enlarged thyroid)  Mechanisms of Autoimmunity  Breakdown of immunological homeostasis or  Breakd own in regulation because of genetic predisposition permits Immune stimulation activation of self-reactive clones of T-cells or B-cells Organ function stimulated, or blocked by auto Ab’s resulting in localized /systemic autoimmune disease Molecular mimicry: Cross reacting foreign Ags epitopes between an infectious agent and its host e.g Rheumatic fever  Sequestered Ags: some deep tissue may not exposed to  Autoimmunity… Self Ag are found in hidden location : Sequestered Ags organ damage Hidden Ag released Reaches blood stream Encounter Ag sensitive cells Stimulate autoimmunity e.g Rheumatoid Arthritis Autoimmunity… Autoimmunity… Autoimmunity… Rheumatic fever/heart disease 
Applications of Immunology  Immunization/vaccination Immunization/vaccination Immunity to infectious microorganisms can be ac hi ev e d by ac ti v e o r passi v e immunization/vaccination Can be acquired either by natural processes (usually by transfer from mother to fetus or by previous infection by the organism) or artif ic ial means such as injection of antibodies or vaccines  Immunization/ vaccination… Vaccines A biological substances that stimulate the immune system Prepared from pathogens that can raise a protective immune response, without causing illness as immunotherapy will stimulate the immune cells & help to create memory cells that can later mount a vigorous immune response to an encounter with the real pathogen to produce an immune response identical to that produced by the natural infection. 
Vaccines… It can Prevent the debilitating and & fatal infectious diseases. Help to eliminate the illness and disability protect the vaccinated individual or protect society  Immunization/ vaccination… Aim of an ideal vaccine: To produce the same immune protection which usually follows natural infection but without causing disease Or prepare the immune system for future exposure to a virulent pathogen for immediate clearance To generate long-lasting immunity To interrupt spread of infection Immunization Acquired through Effect Passive Natural maternal immunity Elicits Natural short-term Immune globin/antibody artificial protection immunity Antitoxin Active Natural infection Elicits Natural Vaccines long-term artificial Whole organism protection immunity Live attenuated: Tuberculosis Whole Killed/Inactivated: Anthrax Purified microbial macromolecules (toxins) Toxoids, microbial antigen or polysaccharide capsules DAN vaccine  Immunization/ vaccination… common vaccines use Inactivated (killed) but still antigenic Live/altered: attenuated microorganisms Lose ability to cause significant disease (pathogenicity) Purified macromolecules from pathogen, capable of producing an immune response inactivated toxins capsular polysaccharides recombinant microbial antigens Immunization/ vaccination… Immunization/ vaccination… Immunization/ vaccination…  Review question  Explain the important of vaccination  List various vaccine type  Differentiate between passive and active immunity  D e sc ribe the d iffe re nc e be twe e n atte nuate d and inactivated vaccines