Innate Immunity Flashcards
Specificity of Innate Immunity
non-specific (preformed)
Kinetics of peak response of innate immunity
immediate to early (hours to a few days)
Cells of innate immunity
phagocytes (macrophages) , neutrophils, natural killer cells
Cell surface receptors of innate immunity
Fc and complement receptors
Lectin (non-polymorphic)
pattern recognition receptors
Circulating molecules of innate immunity
complement (non-polymorphic)
Soluble mediators of innate immunity
macrophage derived cytokines
other acute phase reactants
systemic effects
inflammation
How is innate immunity amplified
recruitment
Does innate immunity have memory
no
Specificity of adaptive immunity
highly specific (develops)
kinetics of peak response of adaptive immunity
later (7-10 days to weeks)
Cells of adaptive immunity
T and B lymphocytes
Cell surface receptors of adaptive immunity
B and T cell receptors
Circulating molecules of adaptive immunity
immunoglobins (diverse)
Soluble mediators of adaptive immunity
lymphocyte-derived factors
Amplification of adaptive immunity
clonal expansion
does adaptive immunity have memory
yes
PRR (pattern recognition receptors)
how the innate immune system recorgnizes molecular structures that are produced by microbial pathogens called PAMPs
pathogen-associated molecule patterns (PAMPs)
ligands for PRR. one of it’s components is lipopolysaccharide
damage associated molecular patterns (DAMPs)
endogenous molecules that are produced by, or released from damaged and dying cells
What does recognition of pathogens via PRR leads to?
activation of innate immunity
leads to signal transduction casacade that results in production of proinflammatory cytokines
What cytokines drive inflammation
TNF, IL-1, IL-6
What is the anti-viral state driven by
interferons
TRL4
a toll like receptor that recognizes LPS, meaning it can see gram-negative bacteria
what does hyperactivation of inflammasome result in
autoinflammatory syndrome, that can be treated with IL-1 antagonist
Mechanical barrier that helps prevent infection
-epithelial cells joined by tight junctions
Chemical barriers that help prevent infection
- defenis and cathelicids which are toxic to microbes
- low pH
- antimicrobial enzymes like lysozyme
Microbiological barrier to help prevent infection
the microbiome (all the bacteria that reside in/on epithelial barriers)
Neutrophils
- short lived
- first cells out to sites of inflammation
- migrate out of vasculature and into tissues
Monocyte/macrophage
- circulate as monocytes in the cell, once they enter the tissue become macrophage
- long lived
- found in all tissues
- tissue resident macrophages may have a different origin than monocyte derived macrophages (yolk sac vs. bone marrow)
Dendritic cell
- immature dentric cells exist in tissues
- highly phagocytic
- after engulfing pathogens, they migrate to lymph nodes where they downregulate phagocytic capacity and upregulate antigen presentation capacity
Opsonins
solbule proteins that recognize phagocytic targets, and are in turn recognized by specific receptors on phagocytic cells
2 major opsonins in blood
complement and antibody
Phagosome
the vesicle that is formed after a phagocyte engulfs a particle
Acidification
acidic phagosome fuses with lysosome, killing bacteria
Toxic oxygen-derived products
superoxide, hydrogen peroxide, singlet oxygen, hydroxyl radial, hypohalite are toxic to microbes
Nitric oxide
produced from activated macrophages especially following macrophage activation with proinflammatory cytokines such as TNF
Lysozyme
produced by macrophages. Breaks down cell wall peptidoglycan of bacteria
cytokines
- can lead to production of NO
- can leads to activation of lymphocytes
Natural Killer Cells
- large, granular
- don’t specifically recognize antigen
- kill virus infected cells and certain tumor cells
When is NK cell killing activity blocked?
when NK cells binds MCH class I on normal cells
Exposure to what causes high activation
IL-2 or interferons
Opsonization
coating of microbes with proteins that facilitate phagocytosis.
Leukocyte migration
chemotaxis stimulated by chemokines
Anaphylatoxins
complement chemokines.
C5a
most potent complement anaphylatoxin
Lysis of pathogens
the terminal components of complement: C5-9 form a pore in the membrane of pathogens (mostly gram neg) resulting in lysis of pathogens
gamma-delta T cells
monospecific populations in skin and mucosa
NKT cells
small subset of lymphocytes that express surface molecules characteristics of both NK cells and T cells
- express TCRs with very little diversity
- produce cytokines
- some recognize lipid antigens
Functions of complement
- pores in cell surface cause death by osmotic lysis
- opsonizes antigen to promote phagocytosis
- produce chemokines to promote inflammation
C3’s relationship to complement pathways
it is central. Cleaved by C3 convertase which creates C3a and C3b.
C3a
chemokine that triggers leukocyte recruitment
C3b
an opsonin that stimulates phagocytosis
Classical Complement Pathway
initiated by antibody antigen complexes. Two molecules of IgG or one of IgM attaches to a microbial surface to activate. Initiation component is C1
Lectin Pathway
Initiated by sugar residues that are found on microbial surfaces.
Alternative Pathway
spontaneous pathway. Low level cleavage of C3 in plasma resulting of generation of C3b that can covalently bind to microbial surface.
Paroxysmal nocturnal hemoglobinuria
caused by a lack of DAF and CD59
Hereditary angioneurotic edema
caused by C1 inhibitor deficiency
C1 inhibitor
restricts the spontaneous activation of C1 in plasma and regulates Hageman factor (which gives rise to HAE)
Immune complex disease caused by what deficiency
C1, C2, C4
What causes bacterial infections, mainly in childhood
deficiency of MBL
What causes infection with pyogenic bacteria and Neisseria spp. but no immune complex disease
Deficiency of Factor D and Factor P
What causes infection with pyogenic bacteria and neisseria spp and sometimes immune complex disease
C3 deficiency
What causes infection with Neisseria spp only
deficiency in C5 thru 9
Biologic actions of type 1 IFNs
inhibit viral replication via a paracrine action
enhance the cytolytic capability of NK cells
increase cellular expression of class I MHC molecules
