Patho week 2 Physical and Mechanical barriers- When pathogens attempt to penetrate this physical barrier they may

be removed by mechanical means. The physical barriers that cover the external parts of the human body offer considerable protection from damage and invasion by pathogens These barriers are composed of tightly associated epithelial cells of the skin and of the membranes lining the GI, GU and resp tracts. They do this through sloughing off of cells, coughing and sneezing, flushing, vomiting, raising body temperature, and mucus and cilia Biochemical barrier- Epithelial surfaces also secrete substances meant to trap or destroy pathogens. Mucus, perspiration, saliva, tears are all examples of biochemical secretions that can trap potential invaders and contain substances that will kill microorganisms. It is composed by the synthesized and secreted saliva, tears, earwax, sweat, and sebum, antimicrobial peptides, normal bacterial flora Inflammation: A response to tissue injury, infection, or allergic reaction at a vascurlized site. It is a biochemical and cellular process. The classic symptoms of inflammation include redness, heat, swelling, pain and loss of function. Heat and redness are the result of vasodilation and increased bld flow through the injured site, swelling occurs as exudate accumulates in the tissues, swelling is usually accompanied by pain caused by pressure exerted by exudate accumulation. Caused by exogenous and endogenous pyrogens, act directly on the hypothalamus. The characteristic of inflammation are: -Vasodilation: increased size of the bld vessels which causes slower blood velocity and increases bld flow to the injured site -Increased vascular permeability and leakage of fld out of the vessel causing swelling at the site of injury; as plasma moves outward, bld in the microcirculation becomes more viscous and flows more slowly, and the increased bld flow and increasing concentration of red cells at the site of inflammation cause locally increased warmth and redness -WBC adherence to the inner wall of vessels and their migration through enlarged junctions between the endothelial cells lining the vessels into the surrounding tissue The benefits and goals are: Limits and controls damage through the influx of plasma protein systems Prevents infections from contaminating microorganisms Inititates the adaptive immune response Initiates healing Limit and control the inflammatory process Prevent and limit infection and further damage Interact with components of the adaptive immune system Prepare the area of injury for healing

Plasma protein systems are mediation by- complement, clotting & kinin, activated in cascade, and cause inhibitory enzyme control The Plasma Protein Systems contain inactive enzymes and are sequentially activated. Each system has a unique role in inflammation, each system consists of multiple proteins in the blood, each system contains a few proteins that can be activated by products of tissue damage or infection, activation of the first component results in sequential activation of other components of the system, leading to a biologic function that helps to protect the individual and involves: -Complement system: consists of a large number of proteins (sometimes called complement components) that together constitute about 10% of the total circulating serum protein, can destroy pathogens directly , can actively collaborate with other components of the inflammatory process. The system can be activated by: -Classical: activated by proteins of the acquired immune system antibodies -Lectin: activated by certain bacterial carbohydrates -Alternative pathway: activated by gram negative bacterial and fungal cell wall polysaccharides -Coagulation (clotting) system: Forms a fibrous mesh work at an injured or inflamed site. Prevents the spread of infection, keeps microorganisms and foreign bodies at the site of greatest inflammatory cell activity, forms a clot that stops bleeding, provides a framework for repair and healing, main substance is an insoluble protein called fibrin -Kinin system: interacts closely with the coagulation system, the final product of the kinin system is a small molecular called bradykinin, which at low doses causes dilation of bld vessels, induces pain (acting with prostaglandins), causes smooth muscle contraction and increases vascular permeability. Causes dilation of blood vessels, pain, smooth muscle contraction, vascular permeability, and leukocyte chemotaxis. Functions to activate and assist inflammatory cells Mast Cells are a granulocyte,cellular bags of granules located in the loose connective tissues close to blood vessels, skin, digestive lining, and respiratory tract. They are activated through physical injury, chemical agents, immunologic processes, and toll-like receptors. They are released through degranulation and synthesis of lipid-derived chemical mediators. -Histamine: is a vasoactive amine that causes temporary, rapid constriction of the large blood vessels and the dilation of the postcapillary venules, retraction of endothelial cells lining the capillaries. The histamine receptors are: -H1 receptor (proinflammatory) located in smooth muscle of the bronchi

-H2 receptor (anti-inflammatory) located in the parietal cells of the stomach mucosa and induces the secretion of gastric acid. - (H3) receptor: The H3 receptor is still not fully understood but appears to modulate the release of neurotransmitters in the central nervous system. -(H4) receptor: The H4 receptor is on mast cells, histamine results in chemotaxis of more mast cells to the area of allergen exposure. The release of histamine from the mast cell sends a message that attracts neutrophils (NCF), the predominant cell needed to kill bacteria in the early stages of inflammation, and eosinophils (ECF-A) help regulate the inflammatory response. Phagocytosis is the process by which a cell ingests and disposes of foreign material, including microorganisms. There are 5 steps to phagocyotsis: -Opsonization, recognition, and adherence phagocyte to its target - engulfment (ingestion or endocytosis) -formation of a phagosome -fusion of the phagosome with lysomal granules within the phagocyte - destruction of the target Cells that perform this are called phagocytes: -neutrophils: Also referred to as polymorphonuclear neutrophils (PMNs) predominant phagocytes in the early inflammatory response, they arrive within 6-12 hours after the initial injury It is a mature cell, not capable of division and sensitive to acidic environments, it is short lived, and becomes part of the exudate or pus. Ingest bacteria, dead cells, and cellular debris -Monocytes and macrophages: produced in the bone marrow, enter the circulation, and migrate to the inflammatory site, where they develop into macrophages, arrive at the inflammatory site 24 hours or later after neutrophils, activation results in increased size, plasma membrane area, glucose metabolism, number of lysosomes, and secretory products, better suited than neutrophils to long term defense because they can survive and divide in the acidic inflammatory site -Eosinophils: are only mildly phagocytic, they serve as the bodys primary defense against parasites and they help regulate vascular mediators released from mast cells -Natural killer (NK) cells: Function is to recognize and eliminate cells infected with viruses and some function in eliminating cancer cells.

-Platelets: Activation results in degranulation and interaction with components of the coagulation system. Platelets circulate in the bld stream until injury occurs after injury once activated they serve to interact the coagulation cascade to stop bleeding, and they release biochemical mediators which assist with degranulation Cytokines: molecule produced by cells of acquired immune system, mediates interactions between cells during inflammatory response, they can be either pro inflammatory or antiinflammatory in nature -Interleukins (IL): Messengers produced primarily by macrophages and lymphocytes in response to a pathogen or stimulation by other products of inflammation. Effects: alteration of adhesion of molecules on many cells, induction of leukocyte chemotaxis, induction of proliferation and maturation of leukocytes in bone marrow, general enhancement or suppression of inflammation - Interferon (INF): Protects against viral infections, do not kill viruses directly but prevent them from infecting additional healthy cells but have no effect on cells that have already been infected, enhances inflammatory response by increasing activity of macrophages -Tumor Necrosis Factor: Secreted by macrophages, induces fever by acting as an endogenous pyrogen, increases synthesis of inflammatory serum proteins, causes muscle wasting (ataxia) and intravascular thrombosis as a consequence of prolonged exposure in cases of severe infection Cytokines trigger the production of white blood cells as well as a coagulating response that seeks to heal the damaged area. This process accelerates the healing process for wounds inside or outside the body. A chemokine is a special type of cytokine whose main objective is to guide the white blood cells to the affected area, a process which is known as chemotaxis.

Local

Systematic

Acute inflammation( swelling, pain, heat, redness)

Leukocytosis- increase number of circulating white blood cells

Exudate

Plasma protein synthesis in liver

Plasma protein system

Fever

Sed rate, or erythrocyte sedimentation rate (ESR), is a blood test that can reveal inflammatory activity in your body. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly. The sed rate test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response of your immune system. Chronic inflammation: inflammation that lasts more than two weeks and can occurs when the invader or injury cannot be eliminated such that there is ongoing stimulation of the innate and adaptive immune responses. It can occur because of an unsuccessful acute inflammatory response such as when there is a persistent foreign body or infection. Macrophages may differentiate into epithelioid cells (which are inefficient phagocytes) or fuse into giant cells (which are excellent phagocytes and can envelop large particles) and form a granuloma that consists of a wall of epithelioid cells surrounding the nidus (focal point) of persistent inflammation, often with necrotic tissue at its core. Fibrin deposition and calcification of the lesion may also occur. Tissue damage is followed by a period of healing that begins during acute inflammation and may last for as long as 2 years -Resolution: Returning injured tissue to the original structure and function -Repair: Replacement of destroyed tissue with scar tissue, scar tissue composed primarily of collagen to restore the tensile strength of the tissue Dysfunctional wound healing may occur during any phase of the process and may involve insufficient repair, excessive repair, or infection. The cause can be related to a predisposing disorder, such as diabetes, to an acquired condition, such as hypoxemia (insufficient oxygen in arterial blood) or to numerous drugs and nutrients. Healing is prolonged if bleeding is not stopped during acute inflammation. Large clots increase the amount of space that granulation tissue must fill and serve as mechanical barriers to oxygen diffusion Dysfunction during inflammatory response Hemorrhage Fibrous adhesion Infection Dysfunctional during reconstructive phase Impaired collagen matrix assembly Keloid scar Hypertrophic scar Impaired epithelialization

 Excess scar formation Wound sepsis Hypovolemia Hypoproteinemia

Anti-inflammatory steroids, hypoxemia, and nutritional deficiencies Impaired contraction Anti-inflammatory steroids

Wound disruption: Dehiscence, wound pulls apart at the suture line, excessive strain and obesity are causes, increases risk of wound sepsis. Dehiscence generally occurs 5-12 days after suturing, when collagen synthesis is at its peak. About half are associated with infection Natural immunity is aquried by birth via the placenta and breast milk (IgG) Aquired immunity is either active or passive. Active acquired produced by the individual after either natural exposure or after immunization. Passive acquired does not involve hosts immune response at all. Passive occurs when T cells are transferred to the donor can occur naturally pregnancy when maternal antibodies cross the placenta to the fetus or artificially through immune globulins Humoral immunity: Antibodies circulate in the blood and binds to antigens on infectious agents. This interaction results in direct inactivation of the microorganism or activation of a variety of inflammatory mediators that will destroy the pathogen Primary Response Initial Exposure IgM dominated Catabolized Immune system primed Secondary Response memory cells IgM, IgG, confer active acquired immunity Molecular Structure of Immunoglobulin (antibody) Antigen binding fragments (fab) Recognition sites (receptors) and specificity (antigen)

Crystalline fragment (FC) Activates components of inflammation : phagocytosis and complement cascade transport & binding to surface Antibody protect host by neutralizing bacterial toxins, viruses (direct effect) promoting phagocytosis (opsonization) (indirect effect) activation of inflammatory response (indirect effect) Complement Cascade System Mediator of inflammatory response Circulating proteins Causes Inflammation by :Vascular permeability, chemostasis, phagocytosis, lysis of foreign cell Cell-mediated immunity: T cells undergo differentiation during an immune response and develop into several subpopulations of effector T cells that react directly with antigen on the surface of cells or infectious agents. Some develop into cytotoxic T cells that attack and kill targets directly T cells respond directly to antigens (bacteria/virus), Produces antibodies that will attack an antigen. Involves destruction of target cells such as virus infected cells through the secretion of lymphokines (lymph proteins).T Lymphocytes originate from stem cell in bone marrow & thymus gland controls their maturity. T killer, helper or suppressor cells. Natural killer: recognize chemical changes. T Killer cells bind to the surface of the invading cell, disrupt the membrane and destroy it by altering its internal environment. T Helper cells stimulate B cells to mature into plasma cells which begin to synthesize and secrete immunoglobulin. T Suppressor cells reduce the humoral response. An antigen is a molecule that can react with antibodies or antigen receptors on B and T cells. Most, but not all antigens are also immunogens. An antigen that is immunigenic will induce an immune response resulting in the production of antibodies or functional T cells. Certain criteria influence the degree to which an antigen is immunogenic: -Foreigness to the host -Adequate size

-Adequate chemical complexity -Being present in a sufficient quantity -Foremost among the criteria for immunogenicity is the antigens foreigness Immunogloblin- general term for antibodies. Used for short infections or disease such as alloimmnue and rabies bite. They are specific for a disease and is usual not from the host body Most individuals are tolerant to their own antigens. Size also influences an antigens immunogenicity for example haptens are antigens that are too small to be immunogens by themselves, but become immunogenic after combining with large molecules that function as carriers. High or low extremes of antigen quantities may induce a state of tolerance and are unable to elicit an immune response. Antibody is made in response to an antigen. IgG 80% of plasma antibodies Major antibacterial & antiviral antibody IgM 1st produced during immune response.Present only in vascular system

IgA Saliva, sweat, tears, mucus, bile. Defends against pathogens on body surfaces IgD Present only in plasma, easily broken down. Predominant antibody on surface of B cells (antigen receptor) IgE Immediate hypersensitivity reactions, develop within minutes of exposure to antigen, release of mast cells (histamine & heparin)

Antigen-Presenting Cells (APCs): Macrophages, Dendritic Cells, B cells -Antigen presenting cell takes up a foreign antigen -Processes and presents part (peptide) on its cell surface -presents the processed antigen to the T cell -T cell recognizes the peptide by T cell receptor (TCR) -Specific recognition only made within the context of MHC -T cell can now starts activation Major Histocompatibility Complex (MHC): Group of membrane glycoproteins that bind/ recognize antigens, Genetically coded in chromosome 6, Differs among individuals, 2 Classes: -Class I: all nucleated cells -Class II: antigen-presenting cells (APCs) Direct rolesThe direct effect requires the antigen-specific Fab portion of the antibodies to bind to the target antigens, forming antigen-antibody (immune) complexes. This process is effective for the neutralization of viruses and neutralization of bacterial toxins as direct effects of

antibodies. This usually result in the effective removal of the antigens from the blood, but immune complex deposition in tissues can cause damage to those tissues. Indirect rolesIndirect effects of antibodies occur through the stimulation of other cells, especially phagocytes such as the polymorphonucleocyte (neutrophil) or the macrophage. The two indirect effects of antibodies are opsonization and activation of complement. Secretory immune system: the primary function of the secretory immune system is to halt viral and bacterial invasion before local or systemic disease can develop and to prevent a carrier state IgA is the primary immunoglobulin produced by these B cells and is secreted onto mucosal surfaces and into tears, saliva, breast milk, and sweat. T cells travel to the thymus gland for completion of their maturation process under the influence of thymic hormones. -Helper T Cells (CD4, TH) TCRs: Recognize antigens and MHC II. TH1: Activate cells related to cell-mediated immunity. TH2: Activate B cells to produce Ab. -Cytotoxic T Cells (CTL=CD8, TC) Recognize Ag Ag + MHC I. Induce apoptosis in target cell. -Regulatory T Cells (Treg) (CD4 & CD25 ) Suppress other T cells Suppress T cells against self Previously named T supressor (Ts) Clonal diversity describes the process in which antigen specificity develops before the lymphocyte leaves the primary (or central) lymphoid organs, the thymus (T cells), or the bone marrow (B cells). Through this process, lymphocytes have the capacity to recognize an estimated 1018different antigens that might be encountered in the life of an individual Clonal selection is the process of antigen-activation of a lymphocyte with the subsequent generation of more cells with the same antigen specificity. Once foreign antigen is encountered by a lymphocyte, that lymphocyte is stimulated to proliferate in order to provide more cells with that same antigen specificity to help remove the antigen and to create a group of long-lived memory cells that can provide immunologic memory for that antigen. Primary immune Response (First exposure): Takes time to develop (sensitization, activation of B cell), Peak at 1-2 weeks, declines rapidly, Antibody class is IgM: produced faster than IgG, less effective Secondary Immune Response (Second exposure): Memory B cell responds immediately, Antibody levels higher and more sustained, Antibody class is IgG: stays longer than IgM, more effective, Basis of immunization

Allergy defined as hypersensitivity to environmental antigens resulting in an exaggerated immune response and deleterious effects on tissues Autoimmunity a disturbance in tolerance of self-antigens to a degree that host tissues are damaged by alloantibodies or autoreactive T cells Alloimmunity an immunologic reaction to tissues from another individual such as those seen in transfusion, transplantation, and pregnancy

Diseases caused by hypersensitivity reactions can be characterized also by the particular immune mechanism that results in the disease. Hypersensitivity reactions are immediate or delayed immediate is a reaction that occurs within minutes to a few hours, delayed may take several hours and at maximum severity days after re-exposure to the antigen.The most severe and rapid is anaphylaxis -Type I (IgE -mediated allergic reactions): IgE mediated. Against environmental antigens (allergens). IgE binds to Fc receptors on surface of mast cells (cytotropic antibody) in connective tissues and basophils (leukocyte). Caused by predispositing factors, genetics. Histamine release. Itching, Urticaria, Conjunctivitis, Rhinitis Anaphylaxis: Acute Type I reaction (IgE-mediated), Causes: systemic exposure to sensitizing drugs or antigens, Serums (vaccines), pollen, enzymes, hormones, Antibiotics *penicillin, foods (nuts, seafood), contrast medium, insect venom. Vasodilation - histamine effects (smooth muscle, edema, vascular permeability, dilation), Feelings of impending doom, Hives, urticaria, wheals, Cyanotic, pallor, dyspnea, diaphoresis -Type II (tissue specific [cytotoxic] reactions): Tissue specific, Specific cell or tissue (tissuespecific antigens) is the target of an immune response. Cells express a variety of antigens on their surfaces, some of which are called tissue-specific antigens because they are expressed on the plasma membranes of only certain cells. Hemolytic anmeia Five mechanisms: Cell is destroyed by antibodies and complement Cell destruction through phagocytosis Soluble antigen may enter the circulation and deposit on tissues Antibody-dependent cell-mediated cytotoxicity Causes target cell malfunction

-Type III (immune complex reactions): Immune Complex Mediated Injury, Antigenantibody complexes formed in circulation & deposited in vessel walls, Antibody binds to soluble antigen and the complex is deposited in the tissues, Harmful effects caused by activation of complement activation, Attraction of neutrophils and release of lysosmal

enzymes cause most of resulting tissue damage, Kidney (glomerulonephritis), vasculitis (vessels) and arthritis (DJD) -Type IV (cell-mediated): mediated by specific sensitized T lymphocytes, no antibody, Occurs through cytotoxic T lymphocytes (Tc cells) or lympokine producing Th1 cells attack & destroy cell targets directly or by release lysosomal enzymes and toxic reactive oxygen from activated macrophages Delayed hypersensitivity: Slow onset - 24 to 72 hours, T lymphocyte & macrophage infiltration, May be transferred to an unreactive recipient by cells but not by serum, Contact dermatitis carrier protein in skin of host, Delayed - poison ivy Autoimmune disease: Breakdown of immunologic homeostasis, Begins to recognize selfantigens as foreign, Responds against self, Causes: Exposure of previously sequestered antigen, Complication of infectious disease, Alteration of suppressor T cell function, Original insult, genetic factors. Lupus is the most comon, complex and serious autoimmune disorders, Characterized by the production of a lg variety of autoantibodies against self-antigens, Excessive levels of autoantibodies react with the circulating antigen and form circulating immune complexes these complexes then get deposited kidneys, brain, heart, spleen, lung, GI tract, peritoneum and skin, causing the body to attack these regions. Alloimmune disease: Immune response against antigens on tissues of same species graft rejection, pregnancy. Primary reaction is Type IV cell mediated. Rbcs express several important surface antigens, known collectively as the blood group antigens, which can be targets of alloimmune reactions -Transplant rejection: major histocompatibility complex (MHC) are major targets of transplant rejections these are also called human leukocyte antigens (HLA). Hyperacute is immediate and rare, Acute is cell mediated response that occurs days to months after transplantation, Chronic can occur after a period of months or years of normal function slow progressive organ failure. MHC antigens (sometimes called HLA, or human leukocyte antigens) allow the immune system to distinguish between self and nonself. The immune system is tolerant of an individual's own tissues because it recognizes the presence of glycoprotein molecules on the surface of all cells The ABO blood group describes two antigens, A and B. Individuals with type A blood have the A antigen on their red cells, those with type B blood have the B antigen, those with type AB blood have both, and those with type O blood have neither antigen. The Rh blood group is very complex and contains at least 5 antigens and numerous variants on RBCs

Infection by a pathogen influenced by: -Mechanism of action direct damage of cells, interference with cellular metabolism, and rendering of cell dysfunction due to acculmulation of pathogenic substances and toxin production -Infectivity- ability of the pathogen to invade and multiply in the individual -Pathogenicity- ability of an agent to produce disease -Virulence- potency of a pathigen measured in terms of the # of microorganisms required to kill a host -Immunogenicity ability of the pathogen to induce an immune response -Toxigenicity- a factor important in determining a pathogens virulence, such as production of soluble toxins or endotoxin -Portal of entry direct contact, inhalation, ingestion, bite (animal or insect) Antigenic drift emergence of new strains of organisms, in viruses is most often the result of random mutations that occur during rapid viral replication. Some of these mutations confer a selective advantage such that increased infectivity, invasiveness, and resistance to both host immune defenses and antimicrobials Antigenic shift recombination of genes from one strain of pathogen to another, antigenic shift occurs, different strains of influenza are exposed to one another when they infect the same host (human, swine, bird). Segments of the viruses' genomes undergo recombination such that a new hybrid virus is formed. The bodies counter measures against pathogens: -Physical barriers: Skin Mucosa of internal passageways Tears Saliva Urine Vaginal secretions -Chemical barriers Fungistatic fatty acid in sebum Low pH (35) of skin Low pH (1.23.0) of gastric juice Low pH (35) of vaginal secretions Lysozyme in sweat, tears, saliva, and urine Normal Flora (commensals): competing with pathogens -Systematic Immune response

Bacterial Pentration of the host Capsules: Help resist phagocytosis E.g Polysaccharide capsule in S. pneumoniae Cell wall components: M protein in S. pyogenes Waxy lipids (mycolic acid) in M. tuberclosis Enzymes: Coagulase: Coagulate blood Hyaluronidase: Hydrolyses hyaluronic acid Collagenase: Hydrolyzes collagen IgA proteases: Destroy IgA antibodies Endo and exotoxins Viruses: are intracellular microorganisms that take over the metabolic machinery of host cells and use it for their own survival and replication, frequently resulting in destruction of the infected cell. Bacteria: are prokaryocytes (lack a nucleus) and can be aerobic (require oxygen) or anaerobic (do not require oxygen), motile or immotile. They can take many forms; the most common bacterial forms are spherical (cocci), rodlike (bacilli), or spiral (spirochetes). Bacteria also take up common stains differently, depending on the structure of their cell walls Fungi: take the form of yeasts (single-celled spheres) or molds (multicelled filaments or hyphae), or both (dimorphic). They are not motile and have thick polysaccharide cell walls that render them resistant to most antibacterial drugs Clinical manifestation of infection: Result from the hosts inflammatory & immune responses fever: Pyrogens, Systemic fatigue, malaise, uneasiness, weakness, headache, anorexia, weight loss, loss of concentration, generalized aching, tachycardia local inflammation, hypotension and decreased peripheral vascular resistance, jaundice, changes in mental status, Laboratory markers: leukocytosis or leukopenia, anemia with chronic infection, acute phase response ( elevated ESR), DIC A live vaccine is a vaccine with active microbe (virus or bacteria), meant to proliferate in the person to vaccine

Attenuated (weakened) viruses illicit a vigorous immune response but can cause disease in some individuals (e.g., measles, mumps, varicella) Advantages: Activates all phases of the immune system (for instance IgA local antibodies are produced) Provides more durable immunity; boosters are required less frequently Low cost Quick immunity Easy to transport/administer

Disadvantages:

Secondary mutation can cause a reversion to virulence. Can cause severe complications in immuno-compromised patients. Can be difficult to transport due to requirement to maintain conditions (e.g. temperature)

Killed virus gives somewhat less protection than attenuated viruses but cannot cause disease (e.g., hepatitis A) They cannot revert back to the pathogenic form if they are killed properly. Although safer than attenuated vaccines, killed vaccines are less effective. Killed whole cell (whole organism) vaccines generally retain the full spectrum of antigens of the pathogen, although some of these antigens are damaged by the killing process. In addition, because the agent is not alive and cannot replicate it is quickly cleared from the body and does not activate the immune response as well as a live organism. Although killed vaccines are not as effective as live attenuated vaccines they may give better protection than isolated component (sub-unit) vaccines because they present a wider spectrum of antigens and activate a greater inflammatory response which induces more effective antigen presentation by dendritic cells. However, because of this, such vaccines have more side effects such as local pain, fever, allergic and hypersensitivity reactions. A variety of mutations can lead to antibiotic resistance. -Mechanisms of antibiotic resistance Enzymatic destruction of drug. -Prevention of penetration of drug. -Alteration of drug's target site. -Rapid ejection of the drug. -Resistance genes are often on plasmids that can be transferred between bacteria -Misuse of antibiotics Primary immunodeficiencys can be classified into 5 major categories of defects, including deficiencies of:

B lymphocytes T lymphocytes Combined T and B lymphocytes Complement Phagocytes

Any of these defects leads to a reduction in the ability of the host to respond to invasion by microorganisms, as well as other types of organ dysfunction. Secondary immune deficiency: Also referred to as acquired deficiencies, far more common than primary deficiencies. Normal physiologic conditions pregnancy, infancy, aging Psychological stress emotional trauma, eating disorder Dietary- malnutrition, vitamin deficiency, infections, AIDs Malignancies

Physical trauma burns Medical tx surgery, anesthesia, cytotoxic drugs Other disease: diabetes, alcoholic cirrhosis, sickle cell disease, Chromosome abnormalities downs syndrome

Acquired immune deficiency syndrome (AIDS): Syndrome caused by a viral disease (Human immunodeficiency virus (HIV)), Depletes the bodys immune system (Th cells) making individual susceptible to life threatening infections and malignancies HIV suppresses the immune response against itself and causes a generalized immune deficiency by suppressing the development of immune responses against other pathogens and opportunistic infections leading to the development of acquired immunodeficiency syndrome HIV ribonucleic acid virus (RNA) HIV gp 120 binds to CD4 cells known as helper T cells that regulate normal immune response Once bound viral genetic material enters CD4 cell Virus replicates within the CD4 cell nucleus using an enzyme called integrase becoming a permanent part of cells genetic make up Virus may remain latent If infected cell activated translation of viral information may be initiated leading to shedding of infectious HIV particles Retroviruses use a viral enzyme reverse transcriptase to convert RNA into a double stranded DNA the new DNA in inserted into the infected cells genetic material may remain dormant but when activated results in formation of new virions lysis and death of the cell, and shedding of infected particles

Clinical manifestations: Serologically negative, serologically positive but asymptomatic, early stages of HIV, or AIDS Window period is the period between infection and appearance of antibody Diagnosis of AIDS is made in association with various clinical conditions (box 72) Th cells <200 cells/mm3 Atypical or opportunistic infections, and cancer

Depletion of CD4 cells has a profound effect on the immune system causes a diminished response to a number of infectious pathogens and malignant tumours