17: Infectious Diseases and Vaccines Flashcards
Which type of response controls mucosal or barrier infections?
T(H) 2 type
Especially anti-helminth immunity
Activation of ILC2s, T(H)2 specific cytokines (i.e. IL-4 and IL-13), and IgE capable of recognizing surface epitopes of the pathogen.
Extracellular response:
Controlled by a combination of innate and adaptive effector mechanisms: - Phagocytosis and pAPC activation (via PRR binding and cytokines) - Complement activation - Antibody binding
T(H)2 and T(H)17
Against bacteria, helminths and fungi.
B cells
mIgA, IgM, IgG
Phagocytic cells
Antimicrobial compounds.
Intracellular infections
Most difficult to detect
Membrane-bound or cytosolic:
Different immune response mediators
In vesicles:
Most effective eradicated via macrophages activated by the cytokines secreted by T(H)1 cells.
Cytosol:
Requires host cell lysis by CTLs (generated with DC-licencing help from T(H)1 cells), cytotoxic T(H)1 cells, or NK cells.
Example:
T(H)1 cells can recruit and activate macrophages, which surround dead and dying infected cells that harbor the bacteria, walling off the bacteria from spreading further and, in some cases, clearing the debris.
Intracellular infections
Most difficult to detect
Membrane-bound or cytosolic:
Different immune response mediators
In vesicles:
Most effective eradicated via macrophages activated by the cytokines secreted by T(H)1 cells.
Cytosol:
Requires host cell lysis by CTLs (generated with DC-licencing help from T(H)1 cells), cytotoxic T(H)1 cells, or NK cells.
Example:
T(H)1 cells can recruit and activate macrophages, which surround dead and dying infected cells that harbor the bacteria, walling off the bacteria from spreading further and, in some cases, clearing the debris.
Antiviral innate response
Encounter with viral PAMPs
=>
Secretion of type 1 interferons, inflammasome and NK-cell activation, IL-12 production
Humoral response: viruses
Antibody (especially IgA)
- Blocks binding of virus to cells
IgG, IgM (and IgA) - Block fusion of viral envelope with host cell's plasma memb. - Enhance phagocytosis (opsonization)
IgM
- Agglutinate viral particles
Complement activated by IgM or IgG - Mediates opsonization by C3b and lysis of enveloped viral particles (and infected cells) by membrane-attack complex
Cell-mediated response: viruses
IFNγ secreted by T(H) or T(C) cells
- Direct antiviral activity
Cytotoxic T-lymphocytes
- Kill virus-infected self-cells
NK + macrophages
- Kill virus-infected cells by Ab-dependent cell-mediated cytotoxicity (ADCC)
Evasion strategies of viruses
Expression of immune-blocking or -inhibiting compounds
Suppression of MHC class I expression
Regularly changing surface Ag’s (Ag drift)
Delivery of instructions that misdirect the host immune response
Immunotoxins
Induces local inflammatory response by extracellular bacteria.
Endotoxins:
Integral components of the bacterial cell wall, i.e., lipopolysaccharide (LPS)
Exotoxins:
Secreted toxic proteins
Antibody-mediated mechanisms for combating infection by extracellular bacteria (Figure 17-5, p. 652)
- Antibody neutralization of
bacterial exo- or endotoxins - Complement-mediated lysis
- Opsonization (by C3b) and
phagocytosis - Anaphylatoxins (complement
peptides: C3a, C5a) mediate
mast cell degranulation. - Recruitment of neutrophils and
macrophages.
Bacterial evasion mechanisms
Attachment to host cells
Block IgA
Inhibit complement
Change antigenic structure
Inhibit phagocytosis or phagosome lysosome fusion => avoid intracellular degradation
Parasite infections
Includes:
- Unicellular protozoans
- Metazoans (helminths or worms)
Immune response depends on:
- Mode of immune detection
- Parasitic stage
- Location
Typically generate weak immune responses
Helminths
Enter hosts intestinal tracts
Exclusively extracellular
Weak immune response
- T(H)2-type responses, incl. ILC2s, IL-4 and IgE production
Evasion:
- Decrease external Ag expression
- Wrap themselves in host proteins to limit immunity
Fungal infections
Innate immunity: - PRR recognition of common surface structures - Neutrophils - Complement
Adaptive immunity may be acquired
- Ab’s
- T(H)1, (T(H)17)
Evasion:
- Capsules => prevent PRR binding
- Fungi-induced expulsion from
macrophages.
Emerging and reemerging infectious diseases
Reasons:
- Crowding in cities
- International travel (i.e., West Nile virus)
- Improper antibiotic use (resistant strains)
- Laxity in vaccination program adherence
- Combinations of diseases (i.e., HIV and tuberculosis)
- Zoonotic pathogens (Ebola primary host is fruit bat)
