Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
145 Cards in this Set
- Front
- Back
|
CD4+ Cell:
-Cytokines: IFN gamma, IL-12, IL-2 -IgG antibodies -Pro-inflamatory -Cell mediated Immunity |
TH1 response
|
|
|
CD4+ Cell:
-Cytokines: IL-4, 5, 9, 10, 13 -IgG and IgE antibodies -Anti-inflamatory -Humoral Immunity |
TH2 response
|
|
|
CD4+ Cell:
-Improves cell-mediated response -Cytokines influence immune response -cells release interferon gamma (potent activator of macrophages and stimulates expression of MHC II on APCs, which amplifies the Th cell response) -May result in tissue injury |
TH1 response
|
|
|
CD4+ Cell:
-Improves humoral immunity -release interleukin 4, which stimulates B cell responses -activates eosinophils to defend against parasites via IgE antibodies -can also limit tissue damage (anti-inflammatory) |
TH2 response
|
|
|
Parasite:
Host Immune Response: -Toll-like receptors recognize on LPG on parasite surface -activates macrophages -IL-2 and lymphocyte proliferation (Th1) -granulmatous reaction forms ulcer |
Leishmania
|
|
|
Parasite:
Evasion strategy: -hide in immune cell -promastigotes are highly motile, attach and invade macrophages quickly -amastigotes reside in phagolysosome of macrophages -surface molecules activate complement and opsonization into macrophage -GP63 protects degrading proteases -LPG inhibits lysosomal enzymes, formation of MAC, and inhibits IL-12 synthesis |
Leishmania
|
|
|
Parasite:
Vaccine: -immunization with live -highly effective, but not use due to safety -immuinzation results in a lesion that heals -cure accompanied by TH1 response -new DNA and recombinant protein vaccines are in development to reduce primary lesions |
Leishmania
|
|
|
Parasite:
Host Immune Response: -chronic infection/acute serious infection -exclusively extracellular pathogen -antibody+complement -high levels of IgM, eosinophils -B lymphocyte proliferation |
African Sleeping Sickness
|
|
|
Parasite:
Evasion Strategy: -antigenic switching of variant surface glycoprotein (VSG) coat -change coat antigens and antibodies no longer work -waves of fever and parasitemia |
African Sleeping Sickness
|
|
|
Parasite:
Vaccine: -microtubule-associate protein (MAP p15) vaccine (mice) -p15 (native or recombinant protein) generated up to 100% protection from parasite challenge, exhibited strong CD8+ T-cell proliferation |
African Sleeping Sickness
|
|
|
Parasite:
Host Immune Response: -intracellular pathogen with short extracellular phases -macrophages, lysosomal enzymes reactive oxygen species, and NO oxidative burst -IL-12, increases IFN gamma, develop TH1 response -Both CMI and AMI in chronic stage |
Chagas
|
|
|
Parasite:
Evasion Strategy: -primarily intracellular: limited time "exposed" in blood -evade complement, express gp160 (binds C3b and C4b) -escape from killing by macrophage: escape into cytoplasm, avoid digestion in phagolysosome -down-regulates MHC II expression on APCs |
Chagas
|
|
|
Parasite:
Vaccine: -potential autoimmune reactions in natural infection and incomplete knowledge of how the immune system responds have hindered research -no clear agreement if the immune response should be stimulated (to eliminate the parasite) or inhibited (to avoid autoimmunity) -current trend towards DNA vaccines |
Chagas
|
|
|
Parasite:
-alter RBC membranes -develop "sticky" knobs on surface -clogging of cerebral microcirculation -hypoxia and increased lactate production due to anaerobic glycolysis |
Malaria
|
|
|
Parasite:
Evasion Strategy: -primarily intracellular: limited time "exposed" in blood -evade complement, express gp160 (binds C3b and C4b) -escape from killing by macrophage: escape into cytoplasm, avoid digestion in phagolysosome -down-regulates MHC II expression on APCs |
Chagas
|
|
|
Parasite:
Immune Response: -fever spikes -synchornized RBC bursting, release of parasite antigens -TH1 response, rise in serum levels of TNF alpha -IFN gamma, IL-2, IL-12 -hypoglycemia, pulmonary or renal dysfunction, and neurologic changes |
Malaria
|
|
|
Parasite:
Vaccine: -potential autoimmune reactions in natural infection and incomplete knowledge of how the immune system responds have hindered research -no clear agreement if the immune response should be stimulated (to eliminate the parasite) or inhibited (to avoid autoimmunity) -current trend towards DNA vaccines |
Chagas
|
|
|
Parasite:
Host Immune Response: -rupture of RBC releases antigens (acute fevers) -MSP activate toll-like receptors, pro-inflammatory -activate macrophages, prime T cells -inflammatory cytokines, TNF alpha (low levels anti-parasitic, high levels damaging) -NK cells and T cells produce IFN gamma -NO and free radicals kills parasites |
Malaria
|
|
|
Parasite:
-alter RBC membranes -develop "sticky" knobs on surface -clogging of cerebral microcirculation -hypoxia and increased lactate production due to anaerobic glycolysis |
Malaria
|
|
|
Parasie:
Host Immune reponse: -anti-parasitic mechanisms remove antigens (spleen, filters blood, primary site of CMI) -excess T cell activity is reduced, decrease in TNF produced and increase anti-inflammatory cytokines (TGF beta, IL-10) -shifts from TH1 to TH2 -build hemoral immunity -requires continued exposure to parasite and functioning spleen |
Malaria
|
|
|
Parasite:
Immune Response: -fever spikes -synchornized RBC bursting, release of parasite antigens -TH1 response, rise in serum levels of TNF alpha -IFN gamma, IL-2, IL-12 -hypoglycemia, pulmonary or renal dysfunction, and neurologic changes |
Malaria
|
|
|
Parasitic Condition:
-first infection primes the response, second can lead to worst case -liked to IFN gamma -low levels in IFN gamma in primary exposure -T cells produce higher levels on re-exposure -macrophages increase production of TNF, inflammation -NO inhibits neurotransmission -increase risk of severe complications |
Cerebral Malaria
|
|
|
Parasite:
Host Immune Response: -rupture of RBC releases antigens (acute fevers) -MSP activate toll-like receptors, pro-inflammatory -activate macrophages, prime T cells -inflammatory cytokines, TNF alpha (low levels anti-parasitic, high levels damaging) -NK cells and T cells produce IFN gamma -NO and free radicals kills parasites |
Malaria
|
|
|
Parasite:
Parasite Evasion Strategy: Cell Mediated -intracellular pathogen -multiple antigenically distinct stages in life cycle -hide in cells: 1. RBC: no MHC I, not recognized by cytotoxic CD8 T cells 2. Liver Cells: IFN gamma and CD8 T cell activity effective -modulate memory T and B cell response: 1. memory TH1 cells deleted 2. deplete CD4+ parasite-specific cells => no help for B cells -immunosuppression 1. prevent antigen presentation to T cells 2. down-regulation of T cells, prevent long-term immunity |
Malaria
|
|
|
Parasite:
Parasite Evasion Strategy: Antibody Mediated: -alter surface molecules through var genes -antigenic variant switching -antibodies are strain specific, need exposure and time to develop immunity |
Malaria
|
|
|
Parasite:
Host Immune reponse: -anti-parasitic mechanisms remove antigens (spleen, filters blood, primary site of CMI) -excess T cell activity is reduced, decrease in TNF produced and increase anti-inflammatory cytokines (TGF beta, IL-10) -shifts from TH1 to TH2 -build hemoral immunity -requires continued exposure to parasite and functioning spleen |
Malaria
|
|
|
Parasitic Condition:
-first infection primes the response, second can lead to worst case -liked to IFN gamma -low levels in IFN gamma in primary exposure -T cells produce higher levels on re-exposure -macrophages increase production of TNF, inflammation -NO inhibits neurotransmission -increase risk of severe complications |
Cerebral Malaria
|
|
|
Parasite:
Parasite Evasion Strategy: Cell Mediated -intracellular pathogen -multiple antigenically distinct stages in life cycle -hide in cells: 1. RBC: no MHC I, not recognized by cytotoxic CD8 T cells 2. Liver Cells: IFN gamma and CD8 T cell activity effective -modulate memory T and B cell response: 1. memory TH1 cells deleted 2. deplete CD4+ parasite-specific cells => no help for B cells -immunosuppression 1. prevent antigen presentation to T cells 2. down-regulation of T cells, prevent long-term immunity |
Malaria
|
|
|
Parasite:
Parasite Evasion Strategy: Antibody Mediated: -alter surface molecules through var genes -antigenic variant switching -antibodies are strain specific, need exposure and time to develop immunity |
Malaria
|
|
|
-found on RBC membrane
-P. vivax merozoites needs to enter RBCs -people without are resistant to P. vivax -selective advantage |
Duffy Antigen
|
|
|
-alters hemoglobin
-does not give absolute protection or invulnerability to the disease -more likely to survive acute illness from P. falciparum -RBCs at very low oxygen tensions -parasite reduces tensions within RBCs to very low levels as it metabolizes -altered cells is targeted for destruction by phagocytes and removal by the spleen |
Sickle Cell
|
|
|
-multicellular organisms
-complex reproductive systems -life cycles have intermediate hosts, larval stages, and adults |
Helminths
|
|
|
Parasite:
Host Immune Response: -Adults live in lymphatics -Lymphatic damage from inflammatory immune response to adult parasites -Babies migrate to lymph and blood -Response to baby worms is primarily TH2 (IL-2, 5,10, IgE and IgG) -promotes non-inflammatory pathology -pathogenisis: high IgE and high cell-mediated activity |
Filariasis
|
|
|
Parasite:
Evasion Strategy: -TGF beta gene, expressed during molting, which induce regulatory T cell (Tregs) -normally regulate T cell homeostasis and clonal deletion -Tregs down-regulate the immune response to the parasite -prevent protective immunity and co-infections easily established -protease inhbitors block antigen presentation through MHC II pathway -surface glycans interrupt or misdirect inflammatory responses -acquire host serum albumin on cuticle- may act as a disguise |
Filariasis
|
|
|
Parasite:
Vaccine: -DNA vaccine induced partial immunity (rats) -protective immunity linked to larval development of late L3 and L4 |
Filariasis
|
|
|
Parasite:
Host Immune Response: -Early TH1 response switches to TH2 when adults begin to lay eggs -Eggs secrete soluble antigens into tissues, stimulating TH2 response -IL-4, IL-5, IL-13 promote recruitment of eosinophils, B-cells, T cells, macrophages, fibrocytes -Granulomas form around eggs, leave fibrotic plaques -Hepatosplenomegaly, portal hypertension |
Schistosomiasis
|
|
|
Parasite:
Evasion Strategy: -Tegument: unique double lipid bilayer -outer layer rapidly replaced if damaged by immune attack, has few antigens, most proteins on inner layer -molecular mimicry: adsorbs host RBC and serum proteins -blocking antibodies protect new larvae -TNF alpha causes increased egg production -Proteases that cleave host Ig secreted |
Schistosomiasis
|
|
|
Parasite:
Host Immune Response: -TH2, high levels IL-4 and IL-5 -Eosophils and IgE antibodies -Immediate hypersensitivity reactions |
Trichinella spiralis
|
|
|
Parasite:
Evasion Strategies: -lives between muscle cells -macrophage inhibitory factor -nonspecific immunosuppresion |
Trichinella sprialis
|
|
|
Parasite:
Host Immune Response: -variable B and T cell response (not well defined), antibodies not effective -Granulomatous reaction forms hydatid cyst |
Echinococcus granulosus
|
|
|
Parasite:
Evasion Strategy: -develops a hydatid cysts -antigens elicit TH2 response, rather than protective TH1 -complement deletion |
Echinococcus granulosus
|
|
|
-a fibrotic host capsule shelters parasite
-secondary complications due to rupture -release of antigens and infection of other cells -anaphylactic shock |
Hydatid Cysts
|
|
|
Parasite:
Host Immune Response: -TH2 response -increased # of eosinophils, mast cells -antibody + complement -IL-4, IL-5, activate macrophages/eosinophils |
Soil-Transmitted Helmints
|
|
|
Parasite:
Evasion Strategy: -molecular mimicry-host collagen -high circulating IL-10 is anti-inflammatory -reduced cellular reactivity, lower TH1 and TH2 responses |
Ascaris lumbricoides
|
|
|
Parasite:
Evasion Strategy: -autoinfection leads to chronicity -induce IL-10 secretion, down-regulate IFN gamma, anti-inflammatory |
Strongyloides stercoralis
|
|
|
Parasite:
Evasion Strategy: -shed tegument, migrate around gut to avoid local inflammation |
Hookworms
|
|
|
Parasite:
Vaccine: -larval stage antigens generate protective immunity (in pigs) |
Ascaris lumbricoides
|
|
|
Parasite:
Vaccine: -DNA vaccines created from larval antigen genes resulted in partial protective immunity (mice) |
Strongyloides stercoralis
|
|
|
Parasite:
Vaccine: -protein secreted by infective larvae was purified and injected, inhibited larval migration through the skin (rats) |
Hookworms
|
|
|
Immune Response to Protozoa:
|
-multiply within the host
-antigenically distinct morphological states -innate: PAMPs, Toll-like receptors Extracellular: 1. Complement and phagocytosis 2. TH2 cytokines 3. antibody dependent ADCC, opsonization Intracellular: 1. TH1 cytokines stimulate macrophages and CTLs 2. neutralizing antibodies can prevent entry |
|
|
Immune Response to Helmints:
|
-innate cell-mediated immunity
-usually do not multiply within host -worms are large and usually extracellular -eosinophil mediated -high levels of IgE -granules released onto parasite, histamine -modified Th2 type response (IL-4 high, IFN low) |
|
|
-unicellular eukaryote
-reproduce by budding |
Yeasts
|
|
|
-multicellular hyphae; asexual and/or sexual reproduction
|
Molds
|
|
|
-free living, not obligate
-most infections are mold and self-limiting -opportunistic infections now more common due to immunodeficiency -difficult to treat |
Fungi
|
|
|
Innate Immunity against Fungi
|
-Physical Barriers (skin, mucous membranes)
-Chemical Factors (serum, skin secretions, phagocytosis) |
|
|
Disease caused by Fungi:
-dermatophytes -Candida infection of mucosal surfaces |
Superficial
|
|
|
Disease caused by Fungi:
-puncture wounds, local abscess |
Subcutaneous
|
|
|
Disease caused by Fungi:
-most serious-disseminate infection fatal -immunosuppressed at greatest risk |
Systemic
|
|
|
Pathogenic mycoses:
-inhale spores of free-living fungi -originate in lung, spread to other organs -histoplasmosis, blastomycosis, coccidioimycosis |
Systemic mycoses
|
|
|
Pathogenic Fungi:
-secondary infections to diseases that compromise immune system -candidiases, aspergillosis, cryptococcus, pneumocystosis (PCP) |
Opportunisitic mycoses
|
|
|
Fungal- host innate immune response:
|
-skin, normal flora, complement
-phagocytosis: neutrophils, macrophages, NK cells |
|
|
Fungal- host acquired immune response:
|
-dependent on pathogen specific TH1 cells
-neutrophils produce IL-12, stimulate TH1 cells -TH1 cells activate macrophages -TH2 response and IL-4 reduce TH1 cells and prevent macrophage activation -macrophage and pathogen-specific CD4T cells |
|
|
Fungal type:
-do not invade tissue -antigens are allergens -controlled by strong inflammatory response: 1. delayed-type hypersensitivity response (TH1)- clear infection 2. weak inflammatory or immediate hypersensitivity response (TH2-dependent) leads to chronic infection |
Dermatophytes
|
|
|
Fungi Evasion Strategies:
-complement inhibitor, prevent alternative pathway and C3b -degrades C3 with extracellular protease (less phagocytosis) -hydroltic enzymes invade host cells -secrete enzymes -sheds capsular coat, bind complement receptors -suppress C5a -MSG antigen variation, like VSG in trypanosomes |
Opportunistic Mycoses
|
|
|
Fungi Evasion Strategies:
-forms tissue cyst (protected), no inflammation -proliferates intracellularly in alveolar macrophages -BAD1 antigen uses complement receptor to bind to other host cells and tissues -change surface antigens |
Systemic Mycoses
|
|
|
Type of Bacteria:
Cell Wall: basic peptidoglycan Flagellae fimbriae: +/- Capsule: +/- Breakdown: lysosomal enzymes phagocytosis |
Gram +
|
|
|
Type of Bacteria:
Cell Wall: Lipopolysaccharide coat Flagellae fimbriae: +/- Capsule: +/- Breakdown: complement cytotoxic cells |
Gram -
|
|
|
Type of Bacteria:
Cell Wall: Complex-glycolipids, mycolic acids Capsule: +/- Breakdown: complex |
Mycobacteria
|
|
|
Type of Bacteria:
Cell Wall: Complex-lipoprotein, outer envelope Flagellae fimbriae: +/- Breakdown: complex |
Spirochaetes
|
|
|
Primary defense against bacteria:
|
-intact skin
-fatty acids produced by skin -cilliary action on epithelial surfaces -pH changes |
|
|
Secondary non-antibody defense against bacteria:
|
-activation of complement by alternative pathway (antibody independent)
-chemotaxis -cytokines from macrophages, NK cells -adjuvant effects of some bacterial cell wall components -LPS neutralized by LPS binding protein -activation of endothelial cells (increase vascular permeability can lead to hypertension and shock) -increased release of TNF alpha, IL-1, IL-12 |
|
|
Secondary antibody defense against bacteria:
|
-neutralize bacterial toxin
-neutralize bacterial enzymes that increase invasiveness -prevent binding to epithelial surfaces (IgA) -block transport mechanisms and receptors -more efficient targeting of complement |
|
|
Defense by Bacteria:
|
-avoidance of complement-mediated damage
-bacteria secrete: toxins that inhibit chemotaxis, blocks activation of cells by IFN -avoidance of death by phagocytosis -infected cells do not act as APC -lysis of cell when killed releases many infectious bacteria with invade other cells |
|
|
-secretions from bacteria which causes illness, without invading host tissue
|
Exotoxin
|
|
|
-lipopolysaccharide = toxin is part of LPS that is a component of the cell wall of gram negative bacteria and is released when they are lysed
|
Endotoxin
|
|
|
-contains unique sugars and phosphate groups that confer stability within the cell wall
-genus specific -common among different endotoxins |
Middle segment: Core Polysaccharide
|
|
|
-integral with cell wall-fatty acid substituted diglucosamine- hydrophobic
-very little diversity -variable toxicity |
Inner segment: Lipid A
|
|
|
-species specific structure
-outermost segment |
Outermost segment: O antigen
|
|
|
Toxin:
-secreted actively from viable microbes -heat labile; protein -very toxic -toxoidable (can be denatured to remove toxicity and retain antigenicity) (Tetanus) |
Exotoxin
|
|
|
Toxin:
-part of bacterial structure -heat stable; lipid/sugar -variable toxicity -non-toxoidal (chemical composition prohibits molecular modification) (cannot make a vaccine) |
Endotoxin
|
|
|
Bacteria:
-gram positive, spore forming, non-motile bacillus -spore germinates in macrophage and is transported to regional lymph nodes from where toxins spread through lymphatic and circulatory system -toxins coded by large plasmids in the bacterium |
Anthrax
|
|
|
requires 2 separate proteins for activity
|
Binary Toxin
|
|
|
Toxin's activity for Anthrax:
|
-Protective Antigen (PA) binds to receptor on eukaryotic cell (primarily macrophage) and is cleaved
-PA then binds the Lethal Factor (LF) or Edema Factor (EF) toxins and is transported into the cytoplasm -EF is activated and produces cAMP which block cells from sending out cytokines indicative of bacterial infection -LF also inhibits cytokine production |
|
|
Genetic Factors for Infectious Diseases:
|
-HLA, cytokines, chemokines, receptors, complement, MBP, adhesion molecules, etc.
-many polymorphisms -differ by race/ethnic group |
|
|
Type of Bacteria:
-bacilli -acid fast stain -complex cell wall -unique fatty acid cell wall components -cultivation difficult-growth slow -infection leads to a cell mediated (delayed type) hypersensitivity reaction (type IV granulomatous) |
Mycobacteria
|
|
|
-concentration of high molecular weight lipids in cell wall
-makes organisms resistant to drying and to aqueous bacteriocidal agents -one properly stained, staining is not removed -many types can appear on sputum smear yielding "smear positive" result |
Acid-Fast Bacilli (AFB)
|
|
|
Bacteria:
-aerobic, gram positive rod, slightly curved -slow-growing (24 hour generation time, 4-6 weeks for colonies) |
Mycobacterium tuberculosis
|
|
|
Bacteria:
Transmission: -spread by aerosolized droplet nuclei produced by infected individual -introduced into environment by coughing, sneezing, laughing, talking -infection usually from prolonged exposure |
Mycobacterium tuberculosis
|
|
|
In healthy individuals, pulmonary tuberculosis can be diagnosed and treated with a ___% cure rate
|
95
|
|
|
Bacteria:
Course of Infection: site of primary infection is usually alveoli of lung where macrophages ingest inhaled bacilli -some bacilli killed; others multiply in the macrophages and are transported to lymph nodes -lymphocytes and macrophages infiltrate area and granulomas develop |
Mycobacterium tuberculosis
|
|
|
Bacteria:
Infection: -T lymphocytes and macrophages form granuloma -granuloma walls of bacillus -interaction between IFN gamma secreting CD4+ and CD8+ T cells within granuloma acts to contain bacillus -may eventually kill the bacteria => granuloma calcification and healed infection -surrounding tissue: necrosis and scarring -bacilli may spread to other sites of the body: skeletal, genital, urinary tract, CNS, gastrointestinal, adrenal cardiac |
Mycobacterium tuberculosis
|
|
|
-"reactivation" Tuberculosis
-dormant infection in granulomata, usually with extensive tissue necrosis -develop into tubercules, areas with central caseous necrosis -may erode into bronchi and drain infectious material, extremely contagious |
Secondary Tuberculosis
|
|
|
TB testing:
|
-Culture (slow)
-PCR -Chest X-ray -Skin Test (tuberculin test) -Blood assay for TB induced IFN secretion |
|
|
Tuberculin testing:
-useful in areas with low incidence of TB -5 tuberculin units are injected dermally to form a small wheel -antigen specific T cells secrete TNF alpha and TNF beta => induce endothelial cells to produce adhesion molecules 1. recruits neutrophils, monocytes and T cells 2. an infiltrate 3. an area of red induration in 48-72 hours Positive after vaccine |
Purified Protein Derivative (PPD)
|
|
|
-absence of PPD reactivity in persons infected with TB
-immunocompromised -newly infected |
Anergy
|
|
|
PPD:
-it is the _______ that determines the size, not there area of ______ |
induration, redness
|
|
|
PPD positive test:
>5mm |
-HIV-infected patients
-close contacts of active cases -persons with fibrotic chest x-ray films |
|
|
Screening Assay:
-diagnosis latent TB and TB disease -no reaction if BCG vaccinated ELISA assay for IFN gamma release -mix heparinized whole blood from patient with synthetic peptides simulating 2 M. tb. proteins -TH cells in blood sample produce IFN gamma if they react to the peptides |
QuantiFERON-Gold
|
|
|
MTB induces progression of HIV via:
|
1. inducing replication of HIV in cells of the monocyte lineage and in acutely infected primary macrophages
2. activating transcriptionally latent HIV in alveolar macrophages or in monocytes newly recruited to sites of MTB infection 3. induces TNF alpha which accelerates HIV replication |
|
|
-one of the most common complications in AIDS patients
-often causes disseminated disease |
Mycobacterium avium Complex (MAC)
|
|
|
Bacteria:
-Hansen's disease -person to person via droplets -mainly affects the skin, peripheral nerves, mucosa of the upper respiratory tract, eyes |
Leprosy
|
|
|
Bacteria:
-infects macrophages -loss or impairment of sensation -nerve thickening -only known human bacterial pathogen that attacks the Schwann cell of the peripheral nervous system -testing for antibody may not be useful, check for lesions |
Leprosy
|
|
|
Leprosy Classification:
-lack effective cell-mediate immune response (macrophage not activated) (granuloma) -antibodies present, TH2 immune response -multibacillary, multiple lesions- massive numbers of macrophages containing large number bacilli -facial skin thickening and corrugation- leonine appearance; nodules on ears and nose -Bacilli in nasal smears -lack of activation is an antigen specific response of T cells by non-responders -exogenous IL2 reverses unresponsiveness and causes expansion of already sensitized cells |
Lepromatous (LL)
|
|
|
Leprosy Classification:
-TH1 type response with delayed hypersensitivity (macrophage activated) -antibodies absent -localized skin lesions single or multiple, well defined (Paucibacillary, lesions organized into granulomas) -intense lymphocyte and epitheloid granulomatous infiltrate around nerves cause thickening, function loss, sensation loss -Lepromin -Lymphocyte Transformation |
Tuberculoid (TT)
|
|
|
Leprosy Classification:
-intermediate types between lepromatous and tuberculoid -delayed type hypersensitivity reaction -can develop either LL or TT |
Borderline Leprosy
|
|
|
~tubercuoloid but more lesions, edges less well defined, lesions larger, peripheral nerve involvement
|
Borderline Tuberculoid (BT)
|
|
|
~lepromatous but lesions not all anesthetic and borders vary in distinctness
|
Borderline Lepromatous (BL)
|
|
|
Leprosy Classification:
-variable course -75% spontaneous healing -may progress to other forms -few lesions, hypopigmented -little sensory loss |
Indetermine
|
|
|
Pathology for Lepromatous (LL):
|
no CMI, no CD4/CD8 in lesion, high # of bacteria
|
|
|
Pathology for Tuberculoid (TL)
|
high CMI, few or no bacteria in lesion
|
|
|
Leprosy and HIV
|
-co-infection do not reinforce each other
-IRIS = Immune Reconstitution Inflammatory Syndrome -after anti-retroviral treatment for HIV, CD4 count increases and leprosy lesions from dormant infections develop in some individuals |
|
|
Bacteria:
-patients develop antibodies against extracts of normal tissues (cardiolipin) -lipoidal material is released from host early in infection -treponeme cell wall contains lipids |
Syphilis
|
|
|
Syphilis- disease stage:
-chancre at inoculation site 21 days -endothelial thickening -lymphocytes, macrophages, plasma cells aggregate -last 1-6 weeks and heals spontaneously |
Primary
|
|
|
Syphilis- disease stage:
-25% if left untreated -4-10 weeks after initial chancre forms -generalized rash, lyphadenopathy, fever, malaise, headache, nausea, anorexia, joint pain -last 9 weeks; spontaneous healing with relapses |
Secondary
|
|
|
Syphilis- disease stage:
-no clinical symptoms: noninfectious (except for pregnant women who can transmit to fetus) -early, up to 1 year after initial infection -late, after one year -most untreated cases stay in this stage |
Latent
|
|
|
Syphilis- disease stage:
-30% of untreated cases -10-30 years after infection -benign- gumma (granulomas in skin, mucous membranes, eye) -cardiovascular (involve coronary arteries or aorta) -neurosyphylis (CNS involvement) |
Tertiary
|
|
|
Syphilis:
-women with early or early latent syphilis infect ____ or _____ trimester fetus |
2nd, 3rd
|
|
|
Bacteria:
Immune Response: -T lymphocytes and macrophages key role -antibody damages membrane; opsonization |
Syphilis
|
|
|
Syphilis Assays:
-Sensitivity test depends on ________ |
stage of disease
|
|
|
Syphilis Assays:
-non treponemal (VDRL, RPR) measure IgG and IgM antibody to ______ |
reagin (cardiolipin)
|
|
|
Syphilis Assays:
-measure IgG to antigen -reactive for life, even if no longer infected |
Treponemal
|
|
|
False Positive for Syphilis in VDRL/RPR test:
Why? |
may have antibody that cross reacts with other infections
|
|
|
Negative Test for Syphilis in RPR:
Why? |
-w/o clinical evidence, no current infection or an effectively treated infection
-w/ clinical evidence, 1. early primary syphilis, secondary syphilis, prozone reaction, late syphilis -incubating syphilis infection must have clinical evidence |
|
|
Syphilis Testing:
If: -labor costs an issue -high number of assay |
Screen by EIA
Confirm by RPR |
|
|
Syphilis Testing:
If: -test cost is an issue -number of assay is low to moderate -need to quickly confirm recent infection |
Screen by RPR
Confirm by EIA |
|
|
Bacteria:
-antigenically complex- over 200 known pathogenic serologic variants -no universal antigen -ingestion or contact with mucus membranes of water contaminated by urine of infected animals (usually rats) -no effective test to cover many serotypes |
Leptospiroris
|
|
|
Leptospirosis Assays:
|
-Microagglutination Assay (MAT)
-ELISA -Dipstick IFA -Latex agglutination |
|
|
Leptospirosis Assay
-Human type "O" erythrocytes are coated with genus-specific leptospiral antigens -incubation with antibody positive serum causes agglutination of these RBCs -determine antibody titer -also assay serum with control cells to detect non-specific reactivity |
Indirect Humagglutination Assay (IHA)
|
|
|
Bacteria:
-genes encoding outer membrane are extrachromosomal, on a linear plasmid -determine the adaptive antigenic variation of the organisms -different genotypes may cause different disease syndromes -transplacental transmission: if mother becomes infected during 1st trimester, fetal death may result |
Lyme Disease
|
|
|
Lyme Disease Stage:
-incubation period 7-14 days (range 3-30 days) -non-specific flu-like illness (fever, headache, fatigue, myalgia) -60-80% develop localized bulls-eye rash (erythema migrans) |
Acute
|
|
|
Lyme Disease Stage:
-occurs days to weeks later -10-15% develop multiple secondary erythema migrans lesions -neurologic: meningitis, Bell's palsy, radiculoneuritis -musculoskeletal: migratory joint pain, muscle pain -cardiac (rare): myocarditis |
Disseminated
|
|
|
Lyme Disease Stage:
-weeks to months PI -50-60% arthritis, 10% chronic (HLA-DR4) -chronic encephalopathy -spontaneous remission |
Late Disseminated
|
|
|
Bacteria:
Immune Response: -initial T cell suppression of antibody response -4-6 weeks after erythema migrans, or as late as 3 months after infection -IgG to flagella antigen |
Lyme Disease
|
|
|
Bacteria:
Immune Response: antibodies: -are not protective -peak during arthritis phase -antibiotic treatment in early localized disease may prevent or reduce antibody response -persist for months or yeras following successfully treated or untreated infection -patients with early disseminated or late-stage disease usually have strong serological reactivity -seropositivity alone is not a marker for active disease (antibodies does not mean currently infected) |
Lyme Disease
|
|
|
Bacteria:
Diagnosis: -clinical: characteristic rash (missing in 40% cases) -antibodies appear late -seroactivity is a marker of infection at an undetermined time in the past, not necessarily active infection -presence of antibody does not indicate protective immunity |
Lyme Disease
|
|
|
Bacteria:
-lonestar tick, Amblyoma americanum in SE and South Central US -unculturable spirochaete named Borrelia lonestari -serologic assays for antibody to Borrelia burgdorferi are negative in cases |
Southern Tick-Associated Rash Illness (STARI)
|
|
|
Type of Hypersensitivity:
-start within seconds, resolve within 2 hours -Antigen cross-linking of IgE on surface of mast cells induces release of vasoactive mediators -manifestations: systemic anaphyltaxis or local anaphylaxis, such as hay fever, asthma, hives, food allergies, and eczema |
Immediate Hypersensitivity
|
|
|
Type of Hypersensitivity:
-start within hours, may resolve within 24 hours -involve IgG immune complex formation and cell damage through complement activation and either NK cells (type II) or neutrophils (type III) |
Intermediate Hypersensitivity
|
|
|
Type of Hypersensitivity:
-start ~48 hours after antigen exposure -T cells release cytokines that activate macrophages, resulting in cell damage |
Delayed Hypersensitivity
|
|
|
% of no TB infection after exposure
|
70%
|
|
|
% of TB infection after exposure
|
30%
|
|
|
% of TB disease after infection
|
primary TB 5%
(if HIV+ ~40%) |
|
|
% of TB infection with no disease
|
PPD+ 95%
(if HIV+ ~60%) |
|
|
% of TB infection with no disease with lifelong containment
|
95%
|
|
|
% of TB infection with reactivated disease
|
5%
(if HIV+ 2-10%) |
