MCB3020 UF exam 4

Components of immune system

Blood —> serum

Lymph → lymph systems

-cells, proteins, supporting systems kill/inactivate invadrers, reacts to chemicals/allergens, monister every cell in body

Advantages: kills bacteria,viruses,fungi, parasites; kils infected cells w/intracellular pathogens; neutralize viruses and toxins from bacteria; kills altered human cells(tumour/cancer cells)

disadvantages: cause hypersensitivey, allergic reactions, interferes w/organs and tissue transplants; autioimmune diseases

Organs/tissues of immune system

-bone marrow, thymaus; lymph nodes, spleen, lympatick tissues

—SALT, MALT, BALT

Elements in blood

Red blood cells

white blood cells→ high numbers indicate infection, side effects of medication, autoimmune dieases

platletes

High interferon levels → indicate viral infection

Hematopoiesis: blood elements fromed in red bone marrow stem cells

Basophil; granulocyte

releases histamine; inflammatory

Eosinophil; granulocyte

kills parasite w/oxidative burst

-indicate allergy/ parastic worm infection

Mast cell; granulocyte

antigen-presenting; antibacterial peptides

Neutrophil; granulocyte

phagocytizes bacteria/fungi

-indicate extracellular bacteria infection

Monocyte; agranulocyte

before macrophages, fixed in organs or wanfer, inflammation, phagocytosis

dendritic cell; agranulocyte

skin, respiratriory, intestional mucosa, phagocytizes bacteria, presents antigents to T cells

NK cells; agranular (lymphocyte)

kills cacner cells/virus-infected cells

Plasma cell, B cell; Agranular (lymphocyte)

recognize antigens and produce antibodies

T cells (helper T, Cytotoxic T, T regulatroy) Agranulocyte; lymphocyte

-Helper T: secrete cytokins, CD4 bind to MHC class 2 on antigen presenting cells

-CTLs: recognize/kill nonself cells, CD8 cells bind to MHC class 1

-T regulatory: CD4, destroy cells not correclty showing self

innate/ nonspecific

First line→ surface protection, anatomical/physiological barriers, physical (skin, mucous membrane, microbial antagoism, mucous/mucociliary escalatos, alveolar macrophages), chemical (stomach acid)

second line → cellular/chemical system once pathogen is past 1st line, NK T cells, phagocytosis, inflammation, fever, antimicrobial proteins , phagocytosis, extracellular killing, complement system

Acquired/ specific

third line→ specific identiyt recognition, NK T cells, B cells, T cells, memory cells

Phagocytosis (2nd/3rd line)

-recognize, ingestm digest microbes

-monocytes, macrophagem neutrophils, dendrtic cells

lysosome, organlle full of digestive enzymes/harsh chemicals

-digestive/hyrdolytic enzymes/lipase/nuclease/protease/lysozyme

-harsh chemicals —> toxic reactive, oxidative agents, peroxide, superoxide, hydroxyl radical

Respiratory burst → rxn occurs soon as phagosome formed-toxic o2 products produced which kill invading microbes

phagocytic failure → bactreia may survie killing; prevent fusion of lysosome w/phagosme, possses capsule, neutralize oxidating agents, kill phagocytic cells→ leucodin

Inflammation (2nd line)

• inflammatiory mediatoes, iniatie cascade of events; redness, pain, fever etc.

• cardianla signs: redness, warmth, pain, swelling, altered function

• Acute inflmmatory response: quick, benefical, promotes healing; events eliminatio of pathogens

  • capillary dilation/ increased blood flow, tempertaute rise stimulates inflammatory response, restrict pathogen movement, recruit phagocytes to area

• chronic inflammation: slow; causes permanent damage

Fever

-pyrogens; bacterial toxins, cytoplasmic contents of bacteria releaed by lysis, antibody-antigen complexes (inflammation), interleukins- 1 (IL-1)

muscle contractions, increased metabolic activity, constriction of blood vessles/ reduces blood flow, raises temperature

Complement

• serum proteins destroy extracellular microbes

• function chemostatic signals recruit phagocytes, puncture cell membrane causing cell lysis, complement protein play role in both nonspecific/specific arms of immune system to destroy and remove invading pathogens

• outcomes of activation

  • lyse foreign cells, formation of membrane attack complex, lysis(MAC); attracts phagocytes to area (chemotaxis); aid phagocytes in doing job (opsoinzation

• 3 pathways: classical, alternative, lectin

• Cytolysis, opsonization, inflammation

Antigens

• immune response CB/T cells activated in response to specific antigen

• size restrctions. several antigenic determinant sites (epitopes

• enter body various methods→ breaks skin/ mucous membrane, bite/injection, grafts/organ transplant, autoimmunity

• can be → cell wall, capsule, pili, flagella, proteins of viruses, fungi, protozoa, food/dust,

• haptens: peniclin, small organic molecules-become antigenic binding to another molecule, need larger carrier molecules

• adjuvents: added vaccine make more antigens

Superantigens

stimulate stronger immune respone than normal antigens, no specific T-cells, unrelated t-cells, activated and proliferate nonspecifcally, large fraction T-cells activated, resulting in severe vomiting, shock, TSST by staphyloccouss exotoxins

types of immunity

• Innarte/ natural → buitl in immunity to resist infection, anatomical defenses, inflammation, fever, phagocytois, complemetn proteins

  • barriers: skin, mucous membranes

  • chemicals: complemtn, lacto- and transferrin, antimicrobial peptides

  • cells: granulocytes, mast, monocytes, macrophages, dendritic, innate lymphoid cells

• Acquired/ adaptive → established to adapt to infection, specificty, tolerance, momery

  • Cell mediated immunitu: effector T cell and Memory T cells

  • anti-body mediated immunity: B effector cells and B memory cels

Humoral/ Antibody mediated immunity

• B cells

• neutralization of toxins and viruses

• marks invaders for attakcs b y immune system componests

• activate complement system

• aids phagocytosis (opsoinzation)

• stimulatie inflammation

Cellular/ cell mediated immunity

• T helper cells, cytotoxic T cells, NK cells

• alterd self cells, infected cells, intracellualr, pathogens, tumoru/cancer cells

Cytokines

• soluble proteins/glycoproteins act as mediators

  • released by 1 cell population acts as intercellular medicators/ singnalin molecules

  • used for cell-to-cell communicaton'

• Autovrine function → attacks self

• Paracrine → attacks nearby cells

• endocrine → affect is sytemic

• tumour necrosis factor(TNF), Interleukins, Colony-stimulating facotes (CSFs), interferons (INFs)

Immunoglobin

• fab binds antigen specifaclly; marks antigen for immunoloigcal attack, activates nonspecific defense mechanims that can destroy antigens

  • opsonization for enhanced phagocytosis

• Fc mediates binding —> host tissues, various cells of immune system, first component of complement system

• importance of antibody binding: neutrlizes toxins/viruses, marks invaders of attakcs by other immune system componenets, activate complement system, aids phagocyotosis, stimulate inflammation

• Consequences: formation og Ag-AB complex, immune response, tissue damage, autoimmune diseases

• IgG→ major circulating antibody

• IgM→ firs to appear after infection

• IgA→ major antboy in secretions

• IgE→ allergic reactions

Major Histocompatibility complex (MHC)

• membrane proteins → gluycoproteins

• Class 1 → almost all nucleasted cells, present endogenous molevules

• class 2 → only on APCs, B cells, macrophages, dendritic cells, presents endogenous molecules

• Antigen processing → t-independent antigens: large molecules/ bind to B cells, resulted in B cell activation and AB production, no need to APC

• T-dependent antigens: small, molecules, APC needed, proccess them and presen to T helper cells

Antibody titer: primary and secondary immune responses

• first exposue to antigen IgM is realsed, takes several days, long altent periodns

• slowlu developed, weats off quickly

• secondary exposure B cells mount a heighnted/ anamnesitc respones

  • charactrs as having shorter lag, more rapid log phase, persistent, higher IgG titer, production of antibodies w/ higher affinity for antigens

Types of aquired immunity

• naturally: infection/breastmilk

  • active: antigens enter body naturally, body induces antibodies and speaclaizes lympocytes; develop humoral and CMI make own B/T antibodies

  • passive: antibodies pass from mother to fetus via placenta/breastmilk; prefromed antibodies

• artifically: vaccination

  • active: via vaccines, body produces antibodies, and specaized lymphocytes, not formed, reaction to vaccine

  • passive: preformed antibodies in immune serum introduced by injection, alreadu formed via medication

principled of effective vaccination/immunization

• provokes primary immune response → leads to formation of antibodies/ memory cells

• produces rapid, intense secondayr response

• herd immunity: immunity in most of population → outbreaks sporadic due to lack of susceptible individiuals

list of bacterial/viral vaccine from CDC

• meningitis, Penumonia, tatnus, diptheria, pertussis, chickenpos, hepatitis A and B, HPV (genital), Flu, polio, MMR, Rabies

Types of vaccines

• Live attenuated: weakened pathogen, closley mimic actual infection, confers lifelong cellular/humorla immunity

• Inactivated killed: safer than live, required repeasted boosters, inducne mostly humoral immunity

• subunit: antigenic fragments stimulare immune response

  • recombinant: subunit vaccines produced by genetic modification

  • toxoids: inactivated toxins

  • Virus-like particle vaccine: resemble intact viruses bud don’t contain viral genetic material

• Polysaccharide: moleculed in pathogens capsule, not very immunogenic

• conjucated: disease in children w/poor immune response to capsular polysacchardies

• recombiant: avirulent viruses/bacteria genetically modified to deliver genes coding antigens

• mRNA: Covid-19

• Nucleic acid (DNA): dna direclty introduced into host cell via air pressure/gene gun.=, dna taken into nuc/pathogens dna fragments is expressed, host immune system responsed to foreign proteions, stimulare hormonal cellular immunity

vaccine production/ delivery, formulations

• develop vaccines w/o use of animal hose, plamnts as source', more oral safer'

• dry vaccines→ skin pathc, nanopatch: delivers dry formulation of vaccine to skin, skin contains high numbers of APC, no fridge

• multiple-combination vaccones, vaccines for chonic diseases

• reverse vaccionology: developmet of cellular immunity → predicting best epitotes, analyzing genome for best possibele surface protein

• Adjuvants: chemical additives added to vaccines to improve effectivness

  • alums and monophosphorly lipid A → only apporvded adjuvants in US

  • improve innate immune response

Vaccine-preventable diseases

• health immunization campaigns saved millions of lives ex.Diptheria vaccin, polio

• almost eradictated diseases but came back due to lack of immunizations

Disorders associated with Immune system

• Dysbiosis: imbalance causes adverse effects in humans

  • antibiotics kills normal gur microbiota, C.DIff prolierate

  • possibe cause of IBD ulcerative colitis and crohn’s diseases

• Allergies/astham: less allergy complication in tribal populations and children growing up on farms, due to wider range of microbial exposures in farm settings, led to lower asthma rates

• inflammatory bowel diseases: possible link lack normal microbiota metabolic products leading to chronic inflammaory state

  • treating crohn’s diease w/worms, whipworm eggs supress T helper cell pathways

• fecal transplant C.Diff infections —> taking gut microbiota from healthy people and transplanting it into patient

Hypersensitvity

• antigenic resposnse beyondnormal, senstitzed previpois exposure to antigen/allergen, 4 types of hypersensitive: anaphylactic, cytotoxic, immune complex, delayed cell-mediated

• immunopathology: study of hypersensityvt reactions

• hygein hypotheise: limiting exposure to pathogens, lower immune tolerance and ability to cope w/ harmless antigens

Type 1/ Anaphylactic

• less than 30 mins; IgE bind to mast cell/basophil, cause degreanulation of cell and release reactive substance like histamine

• minuts afterbeing reexposed to antigen

• combine with IgE antibboides

• IgE: attaches to mast cells and basophils

  • mast ce;;s/basophils undergo degranulation, releases mediatios

    • histamines: increase permeability of blood capillaires

    • leukotrienees: cause prolonged contractio of smootjh muscles

    • prostaglandis: affect smooth muscle and increase mucus secretion

• systemic anaphlxis: exposed again, circulatroy collapse and death, epinephrine

• localized anaphylaxis: ingest/inhaled antigens, sympms differ on route of entry, hives, hay fever, asthma

• prevenoting: antigens inoculated beneaht epidermis test for rapid inflammaroy rxn

  • desentization: increase dosages of antigen injected beneasth skin; produces IgG acts as blocking antibodies to intercept and neutralize antigens; ALLERGY SHOT

• common allergens: plant pollen, peniclon, sulfa drugs, nuts, seafood, eggs,milk, insect venom, ant, bee, wasp, dust mite, latex gloves,

• commone treatments: antihistamines, cortiosnes, epinerpherines, cromolyn sodium

Hypersensityvyt/ Cytotoxic Type 2

• 5-12 hrs; antigen causing formation of IgM and IgG antibodies that bind to target cell, whencombined with action of complmeent, destroys target cell

• of complemetn by combination of IgG or IgM w/ antigenic cells, causes cell lysis/damage byc=macrophages

• ABO blood group: antibodied form against certain carb amntigen on RBS, A, b antgens or both, type ORBCs no antigens

• Rh blood group: Rh antigen found on RBCS of 85% of population, rh= given to Rh- stimulare anti-Rh antibodies inrecipekint

• Hemolytic diseases of Newborn: mother w/ Rh+ feuts uaes mother to produce anti-Rh; second Rh+ fetus recieve anti-Rh, damaging fetal RBC

Immune complex-mediated hypersensitivty/ Type 3

• 3-8 hrs; antibodies/antigens form complexes that cause damaging inflammation

• antiboides from agaisnt soluble antigens in serum

• immune complexes lodhge basment membranes beneath cells, Activate complement causing inflammation

• Arthus rxn: rare side-effect of toxoid-containing vaccines, occurs glomeruli and othes, due to complement activation in patient w/already ciru=culaing IgG to injected antigen

• Serum sickness: swelling and inflammation due to injection of foreign serum

Delyaed cell-mediated/ Type 4

• 24-48 hrs; Antigens activate CTLs that kills target cells

• CMI response by T cells delyaed Hypersensitiviry

• antigens are phagocytized and presented to receptos on T cells, sensitization

• re-exposure to antigen causes memory cells to release destructive cytokines

• allergic contact dermatitis: haptens combine w/proteins in skin, producing immune response, allergic response to poisin ivy, cosmectics, metals, latex

• Donore recipent matching: MHC compatobility betwen both parties hard to achieve, high degree of MHC variability among individuals

• Host T helper cells: recognize foreign MHC molecules on transplanted tissue (graft), aid cytotoxic T cells, destroying graft, OR, T-helper cells release cytokines stimulating destruction of graft by macrophages

• Grafts

  • Autograft: own slef

  • Isograft: indentical twins tissue

  • Allografts: tissue from another person

  • Xenotranplantion product: nonhuman tissues; must overcome hyeracute rejection→ respone to nonhuman antigens

bone marrow transplant aka Hematopoietic stem cell transplants

• enable reciepent to produce healthy blood cells

  • Graft versus Host disease": result from transplanted bone marrow that contains immunocompetent cells

    prevented: treating donor w/ immunosuppressive drugs to deplete marrow of mature T cells

Privleges sites/ tissues

• transplant may be attacke by T cells,macrophages, complements fixing antibodies

• transplant to privles area do not cause immune resposse —> corena transplants, heart valve transplants

• explains why: fetus arent reejected. fetux not privleged site but not rejected

• rejection is prevent by many different immunosuppressive mechanims

• early embroys dont express MHC class I and II on placental layer that is in contact w/maternal tissues

• cytokines → enhances MHC expression have no effect on placental cells

• T cells → prevented from function in placenta to reject fetus

Stem cells

• master cells, renweing self, differeentitatinf into organ-specific specalized cells

• Embryonic stem cells: hasrvested from blactocyts used to regenerate tissues and organs; pluripotent-can generate all types of cells

• Adult stem cells: stem cells in adult tissues have differenetiated, become induced pluripotent stem cells by introducing genes

Autoimmune diseases

• immune system attacking self, causing damage

• serum antibodies against self-antigens (autoantibodies)

• benign/natural consequences of agin/induced by infectious organims drugs. etc.’

• Loss of self-tolerance; ability to discriminate self v. nonself

• cytotoxic, immune complex, cell-mediated

• results from ctivation of self-reactive T and B cells/leads to tissue damage

• Multiple sclerosis: autoantiboides, T cells, macrophages, attack mylein sheath of nerves, expose nerve cells and compromise nerve impulse transduction

• graves disease: abnormal antibodies in thyroid produce excessive amts of hormones

• myathenia gravis: antibodies coats acetylcholine receptos; muscle fail to receive nerve signals

• Systemic lupus erythematosus: immune complexes form in kidney glomeruli

• rheumatoid arthris: immune complese form in joints

• Insulin-depenedent diabetes mellitus: T cell destruction of insulin-secreting cells

• psoriasis/psoriatic arthrisis: autoimmune disorders of skin

• chronss disease, IBD

Immunodeficiency

• conditions resulting from defective immune mechanims; failure to recognise and/or response properly to forign antigens; opportunisitc infections play importan t part of these diseases’

• primary/congenital: defective/missing genes, result from genetic/developmental defect→ infants/ young children

• Acquired immunodefiecney: later in life; direct consequence of some other cause, drugs, cancer, infection,Sever stress → xs corticosteriods supress CMI; Malnutrtion → inhibit b and t cell development

• Acquireed immunodef syndrome (aids) → CD$ t cells affected

• Severe combined immunodef -. B and T cells affected

• Thymic Aplasia/ DiGerorge → defective thymus, T cell affected

• X-linked infantile (bruton’s) → b cells affected, low antibody, agammaglobulinema

Cancer and immune system

• cancer cells removed by immune survelliance

• tumore-associated antigens mark as non-self

• CTLs activated cytotoxic T cels and macrophage lyse cancer cells

• Limiataiton: no antigenic epitope for immune system to targer, tumor cells, reproduce too rapidly, tumour becomes vascularized and invisible to immune system

Diagnostic immunology

• sensitivity: probabilyt test is reactive if specimen is true positive

• specifitcytL probaboloty positive test will not be reactive is specimen is true negative

• Immunologic-based: interaction of humor antibodies w/antigens, known antibody can be identify an unknow pathogen, known pathogen can id unknow antibody

• antibody-antigen interactions → in vivo, be under control in lab condtions for in vitro testing

• detection of antigens/antibodies → useful when culutre wont grow

• serological: easy, rapid, sensitive, specific, monoclonal antibodies to ID infectious agents

Interactions between antige/antibodies

• precipitation→ rxn of solube antigens w/antibodies to from large, interlocking aggreagtes called lattices, detect souble antigens, toxins from bacteria

  • antigen-antibody complex —. forms, followe =d gy formation of lattice precipate from solution

  • Preciptin ring test: clpudy line forms where optimal ratio of antigen and antibody

• neutralization→ antigen/antibody rnx, harmful effects of exotoxin/virus blocked antibodies to toxn (antitoxin),

  • viral hemagglutination inhibition test: ID vituses

    • detects mupms, measles, flu

    • Toxin + cell → cell damaged by toxin

    • Toxin + antitoxin + cell → antitoxin neutrialize toxin, leave undamaged cell

    • RBC + Antiviral antibpides from serum + viruses → viruses neturalized and hemaggluination inhibited

• complement fixation

• aggluttination → particulate antigens binding to antibodies to form visible aggregtes

  • hemagglutination: blood typing

  • direct aggluntination tests: detect antibody, measure concetratio of serum antibody

• opsonization

monoclonal antibdoeis

• hybridoma: immortal, cancerosu B cell, myeloma, w/ antibody-producing normal B cell

  • Hybridoma → monoclonal antiboidies (Mabs)

  • antibody-producing B cell turnd into cancer cells

• Mabs: uniform, hughly specific, produced in large quantites, diagnostic tool, human therpay, mouse cells, leading to side effects

  • neutralize TNF block progessuon of R..Arthrisits

  • treat allergic astham preventing binding of IgE on mast cells and basophils

• Pregnancy test: free monoclonal antibody specific for hCG → captuer monoclonal antibody bound to substrate → sandwich formed by combination of capture antibody and free antibody when hCG is present, creating color change

Fluroescent-Antibody( AB) technique

• combine fluorescent dye w/antibodies

• Direct FA tests → ID microorganims in clinical specimen

• Indirect FA tests → detect specific antibody in serum

  • anti-human immune serum globulin: added an react with any antibody inseroum if result is positive

• Fluprescene-activated cell sorter: laser beam strikes droplet containing cell, detector determine size and fluorescnee of surface moleucles; imparts charge to cell, seperating cell

Ensyme -linked immunosorbent assay (ELISA)

-Direct ELISA: detects antigens, detects infectious agents in pateintes specimens, both qualitative and quantitiatve tsts, meausre titer and ID antigen

-Indirect ELISA: both qualitative and quantitative test, measure titer and ID antibody; detect antibodies in blood, detects if somone produced ab againsts infection

Future of diagnostic and therapeurtic immunology

• increase automation of tests

• PCR and DNA probes

• inexpesinse and simple tests for developing countries

• disease prevention and therapy

Human microbiome

• symbiosis: living in close association, commensalim, mutalism, antagonism

• normal microbioata: permanetly colozine host and dont cause diease

• human microbiome prj: analyzes relationship between microbioal communites on body and human health; distribution and composition of normal microbiota, determined by nutroients, barriers, immune system etc.

epidemiology

• study of where/when/who dieases occur and how transmitted in populations

• Hisotry development

  • john snow: cholera in london

  • semmelweis: hand washing

• epidemiologists: determine etiology of disease, id other important factors concerining spread of diseases, develop methods controlling disease, assemble data and graphs to outline incidnece of disease

• Descriptive: collection and analusis of data - John snow

• analytical: analyzes particular disease to determine probable cause→ nightingale

• experimental: hypotheis and controlled experiment → semmeweis

Incidence

# of people who develop disease during time period

Prevalence

# of people who develop disease during time period, regarless when first appeared

• both old and new cases

Endemic disease

disesae constantly present in population

epidemic

disease acquired by many people in area in short time

Pandemic

worldwide disease

Emerging infectious disease

new, increasing incidnece, having potential to increase near future

• new strainfs of flu, cholera, ARB

• contributing factors

  • modern transportaion: chikungunya and West nile virus

  • ecological disaster, war, expaninf human settlement coccidiomycosis

  • animal control measures: lyme disease

  • public health failute: diptheria

CDC

• collects and analyzes epidemiological info in US

• Morbity and Mortality Weekly report

  • Morbitiy: specific notibfale disease incidences

  • Mortality: deaths from notifiable disease

• Notifiable infectious disease: must be reported to CDC

  • HIV, Hepatitve, LYme, Malarea, Gonohrreha, etc.

Transmission of diseases

• Resevoirs of infection; concstne presecn of source infection

  • Humna: carries may have inapparent infectetion or latent

  • Animal: zoonoses, animals to humans

  • nonliving: soil and water

• Contact transmssion:

  • direct: close association between infected and susceptible host

  • Indirecrt contact transmission: spread host by non-living object called FORMITE

  • Droplet: airborne droled less than 1 meter distance

• vehivle transmission: water and food

• vector: arthropods, fleas,ticks, mosquiteos

  • transmit diease by 2 general methods

  • Mechanical: arthropod carried pathogen on feet

  • Biological: pathogen reproduced in vector, transmited via bites/feces

Healthcare-associared infections aka NOSOCOMIAL infections

• got when getting treated in healtcare setting

• common 1/25 patients, 2 million/ year, 20k deaths

• from Microorganism in envrioment, wekaned status of host, chain of transmission in hospital

• compromised host: individual resistance to infection impared by disease, therapy, burns

• control univerdsal precautions:

  • stanard precaustions: basic, minimum practices,

  • transmission-based: supplemental standard precautions, designed for known/suspected infections, contact, droplet airborne

• reduce number of pathoges

  • handwashing, disinfection, cleaning instruments, disposable bandages

• infection control

Koch’s postulates-cause of diease

• same pathogen must be present in every case

• pathogen must be isolated from diseases host and grown in pure culutre

• pathogen in pure culture must cause disease when inpculateed into healthy animal

• must be isolated from inoculatd andimal and shown to be orignal organims

• prove cause of infection

  • some pathogens can cause several disease conditions, multiple disease, microbes have never been culutred

Pathology, infection, disease

• Pathogen: causes disease

• disease: abnromale state of body not functioning normaly

• opportunistic pathogen: cause disease when host is immunocompromised

• pathogenicity: abiility to cause disease

• virulence: degre of harm infliced on host

  • pathogen must contact host and survive w/in to cause disease

• acute disease: symptoms develop rapidly, doesnt last long

• chronic diseae: symptoms develop slowly

• latent disease: causative agent inactive for time then activate and produces symptoms

Host involvment

• local infection: pathogens limited to small area of body

• systemic infection: throughout body

• sepsis: toxic inflmmatroy constion, spread of microbes, bacteris/ toxins from focus of infections

• septicemia: blood poisoning, growth of bacteria in blood

• Gram-negative sepsis: endotoxin shock; lps cause sever drop in BP, antibiotics worsen conditon by killing bacteria, treatment involved neutralizing LPS compoents and inflammatory causing cytokines

Signs, symptoms, syndrome

symptoms: chanes in body FELT by patients

signs: changes measures or SEEN by others

syndrome: specific group of signs/symptoms accompaning disease

contagious disease: easily/ rapidly spread from 1 host to another

Development of disease

• incubation period: interval between inital infection and first sign/symptom

• prodromal: short period after incubation, early, mild symptoms

• period of illness: disease most severe

• period of decline: signs/symptoms subside

• period of convalescene: body returns to pre-diseases state

agent of infectious disease

• bacteris: G-, G+; fungi, protozoa, viruses, acellular infectious agents,

  • intracellular pathogen: faculatieve intracellular pathogens

    • live w/in host cells/environment —> Myobacteria Salmonella

    • obligate intracellular pathogens: incapable of growth and multiplication outside of host → Rickettsia, chlamydia

portals of enrty/exist

• portals of entry: skin, mucosu membranes, parenteral routes, deposited directly skin/mucous membrane, preferred portal of entry

• ID50: infectious dose for 50% of smaple population; measure virulence of microbe

• LD50: lethal dose for 50% of sample population; measures potency of toxin

Virulence factors

• Adherence: manhy pathogens attach to host stisseu,

  • adhesins→ lignands on pathogens bind to receptos on host cells, capsule (glycocalyx), pili, fimbriae

  • biofilms formation: communites that chare nutrients

• m Protein: resist phagocytosis → streptococcus pyogenes

• Capsule: glycocalyx around cell wall-impair phagocytosis → Streptoccus pneumonia, Haemophilus influenzae → pneumonia, meningitis

• Toxins: posions substances produced by microorganisms

  • toxemia: presence of toxins in host’s blood

  • Intoxications: presence of toxin w/o microbial growth

• Enzymes: coagulase: coagulate fibrinogen; kinases: digest fibrin clots; Hyaluronidase: digest polysacchrais that hold cells together, Collagenase: breakse down collagen; IgA: proteases: destroys IgA antibodies

• exotoxins: proteins inside bacteris, G+ some G-, sectreted intp surounding medium during log phase, soluble in bodilu fluids, destroy host cells, inhibit metabolic functions; botulism, Gangrene, Diptheria, Travlers diarrhea

  • high toxicity, no fever, affect cell functions, nerves, GI tract

  • antitoxins: antibodies agaisnt specific exotoxins

  • toxoids: inactivated exotoxins used in vaccines

  • A-B toxin: contains enzyme component (A) and binding part (B),diptheria toxin

  • Membrane-disrupting toxins: lyse host cells distrupting plasma membrane, Hemolysins -. kill RBC

  • Superantigens: cause intesne immune response due to release of cytokines from host t cells. cause fever, naseua, vomiting, diaherrea, shock, death

• Endotoxins: G-, lps, LIpid A, bacteria dies, cell wall lyses break apart, release in death and bacterial multplication

  • fever, weakness, aches, shock, low toxicity

  • stimulates macrophages releasing cytokines, cause disseminated intravascular coagulation

factors contribtuting to diseae

• triangle infection: microbe, host, enviroment

• genetics: host/infectious agents

• immunity: immunocompromised hosts

• vaccine

• climate change: spread vector-borne diseases, mosquito-born diseases, dengue viruse, zika virus, etc. disease limited to africa and asia now spreading to americas and others

• natural disasters: flood, earthquake,etc, cholera →WBD

Plasmids and viruses in bacterial Pathogenesis

• plasmids carry genes for toxins, production of antibiotics and enzymes, antibiotic resistance, exchanged among bacteria through conjucation

• lysogenic (viral) infection: result in virus carrying genes from one bacteroum to next

• lysogenic conversion: genes coding for A.R. or exotoxins production are exchnaged among bacteria during lysogenic infections, conversion chnages characteristis of microbe due to incorporation of prophage

Skin and mucous membrane, physical barrier

• Epidermis→ tight layer of cell w/ constant shedding, layer of dead cell onsurface,

• sweat, lyszyome, sebum, other antimicrobial peptides,

• sebum secreted by oild glands contains fatty acids inhbiting pathogens

• mucous membrane: line body cavioty open to exterior; epithelium: tight layer of cell w/constant shedding

• normal flora-compete w/pathogens and prevent from extabliished presence → bacteria, yeast, no know virus

• Skin rashed/ lesions

  • Exanthem: skin rash from disease

  • vesicles: small flat fluid filled lesions

  • macules: flat reddended lesions

  • papules:raised lesions

  • pustules: raised lesions w/pus

Infection caused by Staphylococci

• Staphylococcus aureus: G+, cocci clusters, part of normal flora

  • MRSA strain are A.R.

  • Virulence factors: coagulase: clots fibrin in blood; capsuke, hyaluroindase, leucocidin, exotonixs- exfoliatve, tsst, etc.,

  • folliculitis: infections of hair folleices

  • sty: folliculitis of eyelasy

  • furuncle (boil): tyoe of abscess; localized region of pus surrounded by inflamed tissue

  • \carbuncle: damage and inflammation of deep tissue from spreading duruncle

  • impetigo: crusting sores, spread by autoinoculation

  • Scaled skin syndrom: toxin B causes exfoliation

  • Toxic shock syndrome: fever, vomiting, shock, organ failure, strep aureaus

Group A Streptococci (GAS)

• streptococcus pyogenes: G+, cocci in chains, normal flora

  • M-protein: allow adherence and immune system avoidance, stop phagocytosis

  • capsule-anti-phagocytic, hyaluriondiase

  • TSST-1: toxic shock toxien

  • Hemolysin: beta hemolytic → lyse RBC

  • Exotoxins: streptolysin

  • Diseases: soar throat, respiratory infections, skin infections→ erysipelas, impetigo, Necrotizing fasclitis → flesh-eating bacteria

Skin infection

• bacterial

  • pseudomonas infection: opportunistic infection in burn victims, ear infections in swimmers, ubiquitious, resisatant to many antibiotics, forms biofilms

  • Propionibacterium: acne, most common skin disease, skin cells shed in hair follices and combine w/sebum→ causes blockages, sebum formation → affected by hromones, not diet; Mild acne → easily treated w/ topical formations; sever acne → inflmed lesions w/pus deep in skin

• Viral

  • Chickenpox: varicella-zoster; virus becomes altent in central nerve ganglia, prevented by live attentuated vaccine

  • Shingles: herpes zoster; reactivtion of latent VZV due to stree and lower immunity

  • HSV: cold sore, fever blister, genital lesions, Oral → HSV-!, genital-. HSV-2,

    • genital wart- not rash, caused by HPV → cervical cancer;

    • measles: red spots in mouth, kopliks spot, MMR vaccine

Skin and nail infection caused by fungi

• Mycosis: fungal infection of body

• dermatomycoses: cutaneous mycoses-ring worm, hair nails, scalp, jock itch, athletes foot

• Candidiasis: yeast infection, opportunistic inffection, occurs in skin, mucous membrane of genitourinary tract/ mouth

• Thrush: oral candidiasis

• Fluminating diseases: immunocompromiesed

• Vulvovaginal candidiasiis: vagointis, yeasty, thick, yellow discharge

bacterial Eye infections

• opthalamia neonatorum: nesisseria gonorrheoaese, large amts of pus forms, ulcerations of corneas results → blindness

• Inclusion conjunctivitis: chlamydia trachomatis

• Trachoma: clyamydies tachomatis; leading caused of blindness, transmission → hand contact/flies; infection causes permament scaring, scars abrade cornea, leading to blindness

Bacterial meninitis

• meniges protect CNS; provided blood-brain barrier, Menginiteis: inflamtion of mengeisis, encephalitis: inflammation of brain

• fever, headachem stiff neck then naseaa and vomiting then convulsions and oma

• death→ shcok, inflammation, due to endotoxins release

• Hemophilus influenzar Megigits: notmal flora of throat, capsule type B major virulense factors, prevented by Hib vaccins, atypical Penumonia- mycoplasma

• Neisseria Meningitidis Meningitis: meningoccocal meningitis; G-, cocci w/capsule, 40% carry bactris in nose and pharynx, poutbreaks commin in dorms and military barracks, vaccination protects against some types

• streptococcus Penumonia meningitis: Pneumonococcal menginitis; G+ w/ capsule cocci; 70% carry bacteria resperiatroy tract, most common in children 1month- 4 years

  • Mortality: 85 in children, 22% in elderly

  • prevented by conjugated vaccine

• Viral meningitis: more common but milder;

  • diagnosis/ treatment: sample CSP, spinal tap/lumbar puncture, latex agglutination tests, chemotheapy intiated before diagnosis

Infections of Nervous system

• Polio: poliomyelitis, poliovirus, transmitted thru fecal-oral-route later enters CNS, 1% of cases becaome paralytic destruction of motor neurons;

  • post-polio syndrome: muscl weakness occuring decades after infection

  • Vaccines: almost eradicated virus worldwide, except few places

• Rabies: rabies virus; salvia of animal bite; bats most commone cause, long incubation period, muscle spasms of moth and pharynx, hydrophoboa

  • post-exposure prophylaxis: vaccine plus immune globulin, antibody, raccon in eastern state, skunk dominates central plains

• Arboviral encephalitis: arthorpod-born viruse mosquioe born viruses

  • west nile virus: mosquito borne

• Cryptococcal meningitis: Fungal, soil fungus associated w/pigeon and chicekn droppins, respiratroy route thru drie bird dropings, immunocomprimsed spread to CNS can be fatal

• Prions: protein particles, creutzfeldt-Jakob diseae in humans, mad cow disease

Respiratroy tract infection

• streptococcal pharyngitis: strep throat; Group A streptocci (Gas), fever, tonsilities, enlarged lymph nodes

• Scarlet fever: RBC toxin produced by lysogenized S.Pyogense’

• Diptheriea: Corynebacterium diptheria; tough grayish membrane in throat, blocks passage of air to lungs, diptheria toxin does damage, vaccine

Tuberculosis

• mycobacterium tuberuclosis, acid-fast rod, thic waxy cell walls, resistant to drying and antimicrobials, transmising by inhaling bacteria

• inhaed orgamnims phagocytized by alverolar macrophages but resist killing

• progression of diease → bacter enter thru alveoli, engulfed by macrophages → survie killing→ multiply → more macrophages contain

• causes: inflam ation, may go away, become dormant (latent TB) → caseous forms

• caseous center w/live bacteria inside may break → latent TB cause reinfection and spread to other organs,

• Miliatry TB: disseminated infection

• TB skin test: positive rxn current/previous infection

  • rapid blood test -. IFN-y and PCR, transtional methods: X-ray/ CT exam

  • Acid-fast staining of sputum and culturing;

  • @0 mill develop tb yearly, 2 mil dies, 1/3 has latent TB, leading cause of death with TB is HIV

  • BOG vaccine: live culture avirulent strian, 1st/2nd line-drugs: isoniazid, rifampn, etc.

  • Multi-drug-resistenat striand: resistnt to 1st line of drugs

  • Extensively drug resistatnt: XDR, resistant to 2 line drugs

Pneumonia

• Bacterial: S. pneumonia; pneumococcal pneumonis, preventwed w/ vaccine; has capsule resists phagocytosis

  • haemophiles influenzae pneumonia: similar symptoms to above pneumonis, Hib vaccine, very young and oil people at risk

  • Atypical penumoina: mycoplasma; mild symptoms, young adults

  • viral pneumonia: complicateons of flue, measleas, covid 19, less sever than bacterial Pneumonia

• viral: enveloped RNAvirus w/spikes, chil;s, fever, headache, muscle aches

  • Hemaggluints spikes: attack host

  • Neuramindiase spikes: help virus spread

  • vaccone avaliable

  • treatment w/ tamifluy/ relenza → inhibit neuraminidase'

  • antigenic drift: minor antigenic chages H and N→ allow virus to eldie some host immunity

  • Antigenic shifts: major changes; lead to pandemics

fungal diseases of lower respirartoy system

• histoplasmosis: lung infection caused by fungi, spread bat droppingsm limited geograhpical range in US

• Pneumocytis pneumonia: lung ifection caused byfungi, affects immunocomprimised individuals, primary indicator of AIDS

• Aspergillosis: lung infection associated fungi grows in compost piles

Lymphatic system

• plasma leaves capillaries to become interstitial fluid; lymph capillaires transport interstitli fluiid, to lymph vessles and nodes; picks up microorganism and infectious agents; lymph nodes contain fixed macrophages, Band T cells,

• byboes: swollen lymph nodes

Cardiovascular and systemic infections

• Rheumatic fever: autoimmune complications of S.Pyogense, inflammation of heart valves, immune rxn against streptococcal M-protein

• Gangreene: necrois, dead tissue- myonercrosis, cut blood supply to tissue (ischemia), treated w/ antibiotics, and surgical removal of dead tissue (amputation)

• lyme disease: bacterial infection transmitted thru tick bite, cause CNS/jheart complications, arthritis

• Plaque: bacterial infection transmitted thru flea dfrom rodents, infect lung(pneymonic) and lymph nodes (bubonic)

• protooan dieases

  • toxoplasmosis: primary danger → congenital infection, stillbirth, neurological damage, cat feces

  • leishmaniasis: transmitted via sanflies, invade internal organs’Malaria: mosquire bites, grows in mosquoioes and live in rbc in humnas, ruoture of rbc → fever/chills every 2-3 days, vaccines underway, treated w/ chloroquine

Enterobacteriaceae

• short G- rods, faculiatative, ferment flucose w/acid ± gas, normal flora,

• classification based on: biochemical tests; antigenic characteris

  • O- somatic

  • H- flagella

  • K-capsule

• virulence:

  • endotoxin: lipid A

  • exotoxin, enterotoxins (food posining), cyototoxins → bloody v. watery diarpehas

  • invasiveness

  • type 3 secretion: enables bacteria to inject toxins direclty into host cytoplasm, bypassing extracellular environment

• members: escehrchia, shigella, salmonella, yersinia’

• disease:

  • gastroenterists, mild/sever

  • septicemia

  • enteric fevers

  • pneumonia

  • UTI

Diarrheal infecion caused by bacteria

• shihellpsis: bacillary dysentery → low ID50 about 200

• shiga toxin: simialr to Enterohemorrhagic e.coli

• salmonellosis: mild, can become extra-intestinal infection, very serious complication, results in typocid enteric fever sever-life thereatneing

• enterotoxigenic e. coli: travelers diarrehra → produce Lt, St toxins, oral rehydration therapy

• UT: e coli, staphylocci, psudomonas, most common in females

• enterohemorrhagic e.coli: 0157:H7; produces shiga-like toxin; causes hemorrhagic colitis, hemolytic uremic syndrome

C. Diff- associated diarrhea

• G+, endospore forming anaerobe, cause more deaths in all other intestinal ifnections combined, mostly in healthcare settings, ;ife threating colitis→ ulceration and perforation of intestinal wall; precipated by extended use of antibiotics → elimnated competing intestinal bacteria

Hepatits

• A virus: HAV; acute infection- entry via oral route, spreads to liver, kidneys, spleen, anorexia, nasuea, diarrhea, fever chills, jaudice, dark urine, vaccine

• b virus: HBV, serum hepatitis-transmitted via blood, bloodily fluids, prevented by vaccine, no specific tratment, ultumtli require liver transplant, acute hepB→ fulminant hepaitied → sudden massive liver damage, fatal, may lead to liver cirrhosis, cause chronic infection/liver cancer

• C voirus: HCV, transmitted via 4 drug use and blood transfussion, destroy liver, kills kopre in use than Aids, cause chroic infection/cancer, no vaccine, no vaccine, effective drugs to treat and cure

Gastroenteritis

• Viral

  • rotavirus: diarrhea/vomiting- commin inc hildren; prevented w/live oral vaccine\norovirus: diarrheas/vomiting-fecal-oral-transmission, low infectious dose; asscoicated w/outbreaks in cruise ships

• Protozoa

  • giardiasia: prolong diarrhea asscoaited w/ outdoor activites

  • cryptosporidioais: diarehers municipality outbreaks

  • ambeiasis: blood diarrhea, may spread to other organs

Gonorrhea

• neisseria gonorrhoeae, G- cocci; 300k cases yearly

• attaches to epitherlial mucous bu fimbraie; causees inflammation, pus formation, affect throat, larynx, anus

• symptoms: men: painful urination, discharge of pus, epiditymitis; women: fewer sympmts, PID

• left untreated -. disseminate and become systemic, spread to heart, menignes, joints

• Oplthalmia neonatroum: infacnt blindness due to gonorrheal infection of eyes, treat with antibitoics, Ceftrixone, azithromycin, can’t devlop immunity due to antigenitc variations,

• men: less chnace og getting infected after 1st exposure, higher chnace of developing sympomts

Pelvic inflamtoruy disease

• extensive bacteial infection of female pelvic organs

• polymicroial infection → N.gonorrhoeae, C.trachomatis

• chornic abdominal pain

• salpingits: infection of uterine tubes; most serous form of PID, scaring, infertlity/ ectopic pregnancy

• treatment: doxyclycline and cefoxitin

Chlamydia infection

• bacterial infection, most common STI

• Intracellular parasie- energy parasite: enters via abrasion/lacerations in conjuctiva/ mucus membrane; limited non-ciliated epithelia cells: uroenital, respiraory conjunctiva

• increased infection risk of cervical caner

• chlamidia infection: mostly asymtomatic infections

  • lymphogranuloma ver=nereum, infection of lymphoid tissues

    • regional lympj nodes become enlarged and tender, dischagre of pus and scarring

    • PID, trachoma, conjunctivtis

• Epidemiology: age: perons 15-24, teenage girls higher risk

  • affects both male and female, 1:1

  • urogential infections: men→ onfection of urtehra, prostate gland; women → cervical infection, inflammation of flaoppian tubes