Innate Immune System Flashcards
What components of the immune system would be beneficial in fighting an infection of bacteria or worms/helminths in epithelial surfaces (mucosa)?
- antibodies
- intraepithelial polymorphonuclear cells (PMNs) (e.g. neutrophils, phagocytes)
What components of the immune system would be beneficial in fighting an infection of bacteria, protozoa, viruses, fungi, or worms/helminths in the blood or lymphatics?
- antibodies
- PMNs
- complement system
What components of the immune system would be beneficial in fighting an infection of bacteria or mycobacteria in the vesicular part of the cell?
- T cells
- NK cells
- macrophages (phagocytes)
What components of the immune system would be beneficial in fighting an infection of bacteria, protozoa, or viruses in the cytoplasmic part of the cell?
- cytotoxic T cells (CTLs)
- NK cells
- T cells
- macrophages (phagocytes)
What are the 4 main functions of the innate immunity?
- prevents/controls/eliminates infection before engagement of adaptive immunity
- if the pathogen load is significant, the innate immunity keeps infection in check until adaptive immunity can kick it
- directs adaptive immunity toward either Ab-mediated or cell-mediated response
- eliminates host damaged cells and initiates tissue repair through: recognition (host cells that are stressed/damaged/dead), phagocytosis of cell debris, and stimulation of tissue remodeling
What are the circulating effector cells and their roles within innate immunity? (3)
- neutrophils: early phagocytosis and killing of microbes
- macrophages: effecient phagocytosis and killing, secretion of cytokines that (+) inflammation
- NK cells: lysis of infected cells, activation of macrophages
What are the circulating effector proteins and their roles within innate immunity? (3)
- complement proteins: kill microbes, opsonize microbes, activate leukocytes
- mannose-binding lectin (collectin): opsonize microbes, activates complement (lectin pw)
- C-reactive protein (pentraxin): opsonize microbes, actives complement
What are the cytokines and what are their roles within innate immunity? (6ish)
- TNF, IL-1, chemokines: inflammation
- IFN-α, -β: resistance to viral infection
- IFN-γ: macrophage activation
- IL-12: IFN-γ production by NK cells and T cells
- IL-15: proliferation of NK cells
- IL-10, TGF-β: control inflammation
What happens within the innate immunity when a host cell is infected by an extracellular pathogen?
- the host cell is activated to possibly release cytokines and/or chemokines that causes systemic effects (e.g. fever), inflammation (recruitment of immune cells and complement to infection site), and trigger adaptive immune response
- the host cell can also release anti-microbial substances (e.g. peptides, interferons)
- the host cell signals to macrophages and dendritic cells that it is infected, triggering phagocytosis and degradation by macrophage
- the dendritic cell will trigger adaptive immune response
What is the innate immune repsonse to viral infection? (2)
- type I IFN (IFN-α/β) render antiviral resistance to host cells
- NK cells kill virus infected host cells
Where do natural killer (NK) cells originate from?
- lymphoid lineage: have a T-cell precursor (different from all other cellular components of innate immunity)
How do NK cells function?
- recognize ligands on infected/stressed host cells
- kill infected/stressed host cells by inducing apoptosis
- release intracellular pathogens for phagocytosis by macrophages
- must act in concert w/ macrophages, b/c they can kill infected host cells but CANNOT produce harm to viruses
- IFN-γ primed macrophages phagocytose pathogens that have been released
How does the IFN-γ/IL-12 amplification loop work?
- macrophage with phagocytosed microbe produces IL-12
- IL-12 is pontent inducer of IFN-γ synthesis in NK cells
- the NK cell “goes off” and produces the IFN-γ that activates phagocytosis and killing of microbs by other macrophages
How do macrophages respond to IFN-γ produced by NK cells?
- the IFN-γ activates classical pathway within macrophages:
- activates phagocytosis
- increased syn of proinflammatory cytokines
- increased prod of ROS and syn of NOS
- increased prod of lysosomal enzymes
- enchanged Ag presenting properties
What 2 types of receptors do NK cells have on their surface?
- activating (KAR)
- inhibitory (KIR)
How do NK cells recognize infected/stressed cells?
- infected/stressed cells have MICA/MICB “kill me” signals on their surface
- when NK cell KAR binds with the MICA/MICB, protein tyrosine kinase (PKT) is activated
- all cells (except erythrocytes) have MHC I molecules that binds NK cells KIR and activates tyrosine phosphatase (PTP), negating the activation signal by KAR
- any disbalance in expression of MICA/MICB or MHC I molecules trigger activation in NK cells
*NK cells are not activated by antigens
How does NK cell kill infected host cells? (4 steps)
- NK releases perforins, make holes in infected cell wall
- release granzymes into hole, degrades infected cell enzymes
- infected cell dies by apoptosis
- macrophage engulfs and digests dying cell
How do viruses usually infect host cells?
receptor-mediated endocytosis
What type of cytokines do viral infected host cells release?
type I IFNs (IFN-α/β)
What occurs in the IFN-α/β autocrine feedback loop?
- viral infected host cell releases cytokines (IFN-α/β)
- IFN-α/β inhibit viral gene replication
- IFN-α/β increases expression of MHC I receptors
- viral peptides ub MHC I binding groove allow for recognition of infected cell by CTLs
- CTLs induce apoptosis
What are PAMPs and DAMPs role in a viral infection?
- PAMPs (e.g. ss-RNA) and DAMPs locally activate tissue macrophages and dendritic cells
- activated macrophages release cytokines/chemokines to create acute inflammation
- DCs engulf viruses and transport viral antigen to local lymph nodes (to activate T cells)
- viral antigens transported to lymph nodes (to activate B cells)
What is the role of cytokines and chemokines in a viral infection?
- cytokines ( TNF-α > IL-1) produ by tissue macrophages and mast cells up-regulate endothelial expression of adhesion molecules (P/E selectin, ICAM-1/VCAM-1)
- chemokines (e.g. IL-8 to neutrophils, MCP-1 to monocytes) attract cells through endothelium to site of infection
- IL-1, TNF-α, and IL-6 prod by tissue macros enter blood stream to prod systemic effects:
- fever (IL-1 > TNF-α > IL-6)
- acute phase proteins (CRP in liver) (IL-6 > IL-1 > TNF-α)
- arthralgia/myalgia (TNF-α)
What happens when dendritic cells enter the lymph node with the viral antigen?
- DCs present viral antigen to CD4+ and CD8+ T cells
- T cells that have complementary receptors to viral peptide are activated
- CD4+ cells become Th1 or Th2, CD8+ cells become CTLs
What happens when viral antigen particles are brought (via lymphatic system) back to lymph nodes?
- naive B cells are activated
- they produce low affinity/high avidity IgM antibodies
- mature B cells (by Th 2 cells) differntiate and switch prod of antibodies to high affinity IgG or IgA, with same specificity
What happens once CD8+ T lymphocytes are activated to cytotoxic T cells (CTLs)?
- CTLs leave LN and find host cells infected with virus
- they are able to find the infected cells, as they are producing the viral antigen on their surface
- CTLs kill the infected host cell by inducing apoptosis
- Th 1 cells produce IL-2 which create strong proliferation of virus-specific CTLs
- IFN-γ and IL-2 increase CTLs resistance to apoptosis (so they can keep killing ;))
Why must CTLs act in concert with macrophages?
- CTLs only kill infected cells, but do not produce harm to viruses
- macrophages prompty phagocytose released viruses from CTL killed cells, preventing infection of new host cells
What is the main cytokine that triggers macrophage phagocytosis? What cells produce it?
IFN-γ
Produced by lots of cells! NK cells, infected host cells, Th 1 cells, and CTLs
How do B cells participate in innate immunity?
- complementary activation of B cells leads to production of anti-viral antibodies that neutralize viruses, binding to their surface, and tagging them for phagocytosis
