2. Immunology of Infectious Disease

Question 1

mutliple outside of host cells, staph strep neisseria ecoli costridium, tissue destruction through two mechanisms, induce inflammation by destruction due to inflammatory mediators, toxins that kill host cells. kill extracellular bacteria and neutralize the toxins

Answer 1

general principles of extracellular bacteria

Question 2

uses phagocytic cells like macrophages and neutrophils, phagocytes recognize bacterial structures like polysaccharides and peptides which contain an RGD sequence, they express Fc receptors and C3b receptors to bidn IgG and C3b, phagocytic cells in the lymph nodes and spleen remove bacteria in the lymphatic system and blood respectively, bacterial DNA contains abundant unmethylated CpG dinucleotide motifs that can activate macrophages, neutropgils release lactoferrin during degraenulation to lower local iron concentrations, bacterial products can induce release of histamine from tissue mast cells which enhances inflammatory process by upregulating proteins to aid extravasation, peptidoglycan and lipopolysacharide activate the alternative complement pathway leading to lysis or opsonization, deficiences in C5-C9 lead to neisseria meningitis infections, also lyses gram negative bacteria, opsonizes gram positive bacteria

Answer 2

innate immunity principles

Question 3

Fc receptors, complement receptors, scavenger receptors, other integrins, lectins, toll-like receptors

Answer 3

phagocyte receptors

Question 4

humoral immunity is the principal protective response, IgG opsonizes and enhances phagocytosis, toxin specific antibodies neutralize bacterial toxins, IgM and IgG activate classical complement to lyse bacteria

Answer 4

adaptive immunity

Question 5

in neonates maternal antibodies disappear between 3-6 months predisposing the child to infections with s pneumoniae, neisseria, and haemophilus influenzae type B, s pyogenes and s pneumoniae have many forms of m protein and polysaccharide capsules so antibodies to one serotype won’t protect against others, IgA antibody can opsonize bacteria at mucosal sites, aggregates bacteria to facilitate expulsion, prevents invasion of bacteria through the mucosal epithelium, fixes complement, IgA deficienct individuals IgM may compensate , T helper cells that activate B cells and secrete interferon gamma which is the most potent activator of macrophages

Answer 5

adaptive immunity

Question 6

bacteria with polysaccharide capsules resist phagocytosis and may inhibit complement activation via the alternative pathway, variation of surface antigens by e coli, neisseria, and haemophilus, neisseria genes have 10^6 different forms of adhesion proteins, strep pneumo and some neisseria/hemophilus produce IgA 1 protease and can hamper mucosal immunity, s pyogenes produces strain specific M proteins, s pneumoniae makes C3 protease, s typhy is a type III secretion system which is acts like a syringe allowing secretion of proteases across macrophage plasma membranes to inhibit the NFkB mediated siglaning pathway and secretion of TNFa

Answer 6

evasion of immunity

Question 7

septic shock presents with hypotension and DIC that can result in death, many gram negative due to LPS and some gram negative bacteria induce macrophages to release TNF-a and IL-1, some bacterial toxins are superantigens which bind to class II MHC proteins on APCs and to certain Vb chains on T cells which activates T cells, septic shock like reaction due to T cells and macrophages producing TNF-a, disease causing antibodies include rhematic fever from cross reactive antibodies produced by streptococcal M protein during pharyngeal infection which binds to sarcolemma proteins in the heart leading to carditis, and poststreptococcocal glomerulonephritis which is an infection with streptotocci with antibodies forming immune complexes with bacterial antigens lodged in the kidney leading to nephritis

Answer 7

deleterious effect of the immune response

Question 8

spirochetes are motile organisms that use corkscrew movement, treponema pallidum leads to syphilis, borrelia leads to lyme disease, not able to penetrate unbroken skin, enter through breaks in skin or via arthropod vectors like ticks, local multiplication leads to dissemination through the body and can affect the skin, CNS system, and heart, disease can be interrupted by periods of latency

Answer 8

general principles

Question 9

innate involves neutrophils with phagocytosis and killing, role of macrophages is unclear in controlling organisms, treponema pallidum can activate alternative complement cascade, organism is not readily killed, adaptive immunity involves treponema pallidum which elicits a strong cell mediated and humoral immunity, Th1 immunity is most effective in clearing organisms, antibodies lead to opsonization and protective immunity is after latent syphilis, classical complement activation is by anti-Borrelia antibodies which is critical for the activation of borellia burgdoferi, interferon gamma is released by Th1 cells activating macrophages for better killing

Answer 9

immunity

Question 10

treponema pallidum lacks virulence factors and is resistant to normal host immune mechanisms, borrelia burgdorferi coats itself with amorpgous host materal preventing phagocytosis and complement mediated lysis and evades adapative immunity, effective to nearly all exposed organisms productively infected

Answer 10

evasion of immunity

Question 11

secondary syphilis has immune complexes which play a role in pathogenesis, anti-treponemal antibodies can cross react with host fibronectin and possibly collagen, a treponemal antigen shares a 6 amino acid sequence with human fibronectin, antibodies though to play some role in the pathogenesis of disseminated disease, it is likely that T cells are responsible for inducing lyme arthritis

Answer 11

deleterious effects of the immune response

Question 12

important causes of morbidity or mortality include an increase in opportunistic fungal infections due to increased immunodeficiency patients like AIDS patients, cancer patients on chemo, transplant patients on immunosuppresive drugs, fungi can live in extracellular tissue and inside phagocytic cells, immunity involves humoral and cell mediated immunity

Answer 12

general principles of fungal immunity

Question 13

neutrophils and to a lesser degree macrophages are the principle mediators of innate immunity, phagocytosis leads to killing of many fungi, neutropenic individuals are highly susceptible to opportunistic fungal infections such as candida albicans, unlike other fungal pathogens, innate immunity is the dominant protective mechanism against disseminated candidiasis

Answer 13

fungal innate immunity

Question 14

Th1 mediated immunity is the most important form of immunity for most fungi, cryptococcus neoformans is eliminated by CTL’s, intracellular fungus histoplasma capsulatum is controlled by granulomas, importance of antibody in eliminating fungal infections not established, the exception is candida albicans infections, higher antibody titers are correlated with improved clinical outcomes

Answer 14

fungal adaptive immunity

Question 15

parasitic infestation are diseases causd by protozoa and helminths

Answer 15

parasitic immunity general principles

Question 16

not very effective, macrophages can phagocytize protozoa, but many organisms are resistant to killing and may even replicate, outer layer of helmints activates alternative complement but is resistant, also resistant to granule contents of neutrophils and macrophages because of thick teguments

Answer 16

parasitic innate immunity

Question 17

IgE production for some parasites, mast cells release mediators which are mainly histamine and increase the flow of lymph flushing antigen into lymph nodes, also triggers muscular contraction to expel pathogens from the gut, usually involves TH1 or TH2 mediated immune response, Th1 uses CTLs, macrophage mediated killing and/or IgG, TH2 uses IgE and infiltrates by neutrophils, remember cyotkines downregulate the opposing response, protozoa like leishmania and trypanozoma cruzi survive within macrophages that stimulate TH1 immunity, CD4+ t lymphocytes secrete interferon gamma to activate macrophages which are more efficienct at killing intracellular macrophages, nitric oxide is produced by macrophages exposed to interferon gamma, plasmodium uses Th1 immunity and cytotoxic lymphocytes against the intrahepatic stage of the parasite, antibodies are generated against sporozoite and erythrocytic stages but not as effective as CTL’s, helminthic infestations use IgE which is used by eosinophils for ADCC, IgE is recognized through Fc receptors, eosinophilia and elevated IgE are associated with the worst worm infections

Answer 17

parasitic adaptive immunity

Question 18

conceals self in intestinal lumen or forms of protective cysts, coats self with host proteins not seen as foreign, more but don’t memorize

Answer 18

parasitic evasion of immunity

Question 19

dysregulated Th1 response in children with cerebral malaria by p falciparum due to increased TNF a production which is prognostic of death, chronic activation of adaptive immune responses to schistosoma mansoni eggs leads to severe liver fibrosis, disruption of venous flow, which disturbs the normal architecture of the liver, chronic parasitic infections form immune complexes which leads to vasculitis and nephritis. filaria can lodge in lymphatic channels leading to chronic Thq immunity with severe fibrosis which restricts lymph flow leading to severe lymphedema, chronic infections induce strong Th2 immunity and inhibit development of Th1 immunity to vaccine antigens which is a problem in developing nations where many are parasitized

Answer 19

parasitic deleterious effects of immune response