Immunity to Pathogens Flashcards
Infection
Harmful relationship between pathogen and host organism
Pathogen must overcome innate immunity and adaptive immunity
Innate immunity
Surface/mechanical defences, phagocytic/inflammatory demesnes
Natural resistance that involves pattern recognition receptors not specific for any particular pathogen
Can be through induction of type 1 interferons (IFNalpha and beta) via TLR
Pathogenesis
Usually caused by host’s immune response to pathogen rather than direct tissue damage caused by pathogen or its toxins
IFNalpha/beta
Made by stimulation of TLR by viral dsRNA
Bind receptor on infected cells and nearby uninfected cells
Induces transcription Mx proteins, Rnase and dsRNA-dependent protein kinase R
IFNalpha/beta NK cells
Bind receptor
Inducing lytic activity
Enhanced by IL12 produced by innate immunity dendritic cells
Increase cytotoxic activity of NK cells
(IL12 induces IFNgamma production in NK cells)
Mx proteins
Inhibit virus transcription and assembly
Rnase L
Degrades vial mRNA
dsRNA-dependent protein kinase R
Blocks protein translation
Antibodies block spread of viruses by (4)
- Blocking viral attachment to host cells (secretory IgA)
- Preventing fusion of viral envelope with host cell membranes
- Agglutination and opsonization of viral particles for removal by phagocytes
- Activation of classical complement pathway, causing opsonization of viral particles by C3b and lysis of enveloped virus by membrane attack complex
Viral clearance (4)
- IFNgamma secreted by CD4+ Th1 cells and CD8+ CTL has direct antiviral activity
- CTL (activated by Th1 cell produced IL2) target and kill virus-infected cells
- NK cells (activated by IFNgamma and IL2) are directly lytic for infected cells and kill by ADCC
4) Macrophages (activated by IFNgamma) can kill infected cells by ADCC
Viral evasion of immune response (7)
- Blocking dsRNA-dependent protein kinase R
- Down regulating class I MHC or TAP molecule for antigen processing
- Reduce class II MHC expression by APC
- Alterations in viral antigens by drift/shift
- Shedding or capping of viral antigen on surface of infected cells following antigen interaction with antibody
- Interfering with complement function
- Suppressing antivirus immune responses by activating Treg, altering Th1/Th2 cytokine balance, or destroying lymphoid tissues
TAP
Transporter molecule needed for antigen processing
Interfering with complement function
Ie. Binding proteins
Immunity to extracellular bacteria through antibody (4)
- Prevent attachment/colonization (IgA)
- Neutralize bacterial exotoxins /endotoxins
- Act as opsonin to enhance phagocytosis
- Activate complement classical pathway
Classical pathway
Results in lysis of gram-negative bacteria by MAC
Production of C3b (opsonin)
Production of C3a and C5a (anaphylatoxins) that cause mast cell degranulation
Vasodilation and extravasation of leukocytes into infected tissue
Chemotactic factors produced by mast cells and by complement degradation that are chemotactic for macrophages and neutrophils
Bacterial evasion of immune responses (6)
- Production of pili or adhesion molecules (enhance ability to attach to mucosal epithelium)
- Secrete proteases that cleave IgA at hinge region to reduce half-life
- Changes in aa sequence of surface structures
- Express surface structures such as polysaccharide capsule or M proteins that inhibit phagocytosis
- Bacterial toxins
- Interfering with complement system
Bacteria interfering with complement system (4)
- Poor activation of alternative complement pathway due to synthesis of capsules that do not stabilize C3bBb
- Resistance to MAC due to presence of capsules (gram neg) or peptidoglycan (gram pos) that prevent insertion of terminal complement components
- Complement activation site deviation by secreted decoy proteins or bacterial surface proteins
- Acceleration of complement breakdown by secreted enzymes
Elastase
Secreted by Pseudonyms aeruginosa
attacks C3a and C5a
Immune response to extracellular bacteria increasing pathogenesis by (2)
- Overproduction of septic shock inducing IL1
2. TNFalpha in repose to cell wall endotoxins of gram neg bacteria
Intracellular bacteria colonize phagocytic cells by (3)
- Inhibiting lysosome fusion (mycobacteria sp)
- Resisting oxidative/lysosomal attack (mycobacteria sp)
- Excaping phagosome before fusion with lysosome (listeria)
Cell medicated immunity against intracellular bacterial infections
Delayed type hypersensitivity response
Th1 cells (+CTL, NK) release IFNgamma to activate macrophages and enhance class II MHC expression
CTL (activated by IL2 from Th1) ill infected macrophages to release bacteria which is phagocytosed by uninfected macrophages
Chronic cell-mediated immune response if infection persists
Granuloma
Isolation of site of infection
Can lead to tissue necrosis due to accumulation of high local concentration of lysosomal enzymes secreted by activated macrophages
Protozoa
Unicellular eukaryotic organisms
Often have multistage growth cycles
Some stages are extracellular and others are intracellular
Humoran and cell-mediated immune responses are only effective at certain times
Malaria
Caused by Plasmodium species introduced into humans by mosquito bites
Surface antigens change as going through cycle and shed
Sporozoites
From mosquito
Pass through blood to liver cells
Merozoites are produced
Only in blood for 30 minutes
Merozoites
Leave liver to infect RBC
Infected RBC rupture releasing attritional merozoites
Become male and female gametocytes that are injected by mosquitos and spread
Trypanosome parasite
African sleeping sickness
Large repertoire of genes coding for variable glycoprotein
Sequential expression allows evasion of antibody responses
Helminths
Large, multicellular parasitic worms that are extracellular
Protection through humeral and cell-mediated immunity
Th2 and IgE synthesis
Schistosoma species
Have protective mechanisms that decrease expression of antigens on its outer membrane and antigen masking with host ABO blood group and histocompatibility agents
IgE in helminth infection
Worm antigens cause IgE-sensitized mast cells in the gut to degranulate
Increased vascular permeability and secretion of eosinophil chemotactic factor
Eosinophil chemotactic factor
Calls eosinophils to lumen in gut
Eosinophils bind IgG coated work via Fc receptors and release major basic proteins hat kills worm
Smooth muscle contraction caused by histamine and other mast cell mediators expels worms
Anaphylatoxins in helminthic infections
Induction and maintenance of acute inflammatory responses
