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Terms in this set (26)
The two principal types of reactions of the innate immune system are ___ and _____ defense
inflammation and antiviral
The innate immune system recognizes structures that are ____ by various classes of microbes and are not present on normal host cells.
Cellular locations of receptors of the innate immune system can be found
Cells of the innate immune system use ____ to sense different microbial products
pattern recognition receptors (PRRs)
What is the function of pattern recognition receptors?
What do they recognize?
recognition of exogenous microbe structures
conserved areas in microbes
Barrier defenses are usually considered part of the innate
Immune system including
mechanical, chemical, and biologic
The normal ___ ____ occupy niches that pathogens may otherwise exploit. Antibiotic treatments disrupt the normal ecology and protective functions of the ___ __.
What are some innate mechanism
goblet cell- mucus
acid producing cells
salivary and GI cells- digestive enzymes
___ and ____ recognize and ingest microbial pathogens for intracellular killing
Neutrophils (A) and monocytes (B)
Function of neutrophils
Most numerous WBC (40-70% of total).
Have a phagocytic function only.
Neutrophils are stored in the bone marrow and move in large numbers to sites of infection.
Respond to bacteria via PRR's
An increase in the number of immature neutrophils = sign of infection (known in hematology as a "left shift").
Stages in the maturation of monocyte/macrophage lineage
Key cell markers:
Key cell surface marker: CD14
What are the differences between monocytes and macrophages?
Where are they found?
How they similar?
Macrophages serve several important roles in immunity:
they produce _____ that induce and regulate _______
they ingest and destroy _____ either by direct contact, or by recognition of opsonized ("flagged") microbes.
What are NK cells?
What is their function?
What marker defines this lymphocyte subset?
Comprise about 5% of total peripheral blood lymphocytes.
Do NOT undergo TcR or Ig gene rearrangement.
Able to kill virus infected cells without prior exposure, unlike T cells.
Able to kill tumor cells, esp. those of hemopoietic lineage.
Have FcR, and so can kill Ig-coated cells via ADCC.
Key cell surface marker: CD56
What is complement (C')?
What is the C' cascade?
What are the three initiating pathways? How are they triggered?
What are the common and distinct components of each pathway?
From the video: How does the alternative C' pathway start?
Complement is a group of serum proteolytic proenzymes that are activated by antigen bound immunoglobulin
OR by membrane components on microbes (alternative and lectin pathways), alternative is spontaneous
The key functions of complement
phagocytosis and killing of microbes
destruction of microbes by leukocytes
What are the acute phase proteins?
What are their functions?
At what point in the infectious process do we see them?
What is the ESR and its clinical relevance?
How do the acute phase proteins affect ESR?
Acute phase proteins, the classic clinical indicators of an acute infection, are also opsonins
Acute phase proteins = C-reactive protein (CRP), MBL, fibrinogen, α1-antitrypsin, and serum amyloid A.
All are markers of inflammation and infection when increased.
Another important clinical marker of inflammation is an increased erythrocyte sedimentation rate ("sed rate"; ESR).
What are cytokines?
What are the most important types?
What are chemokines?
cells of the innate immune system release of inflammatory cytokines after pathogen contact
Cytokines are hormones of the immune system. Actions can be systemic, paracrine or autocrine.
Act by binding to specific receptors on different cell types.
Activate signal transduction cascades.
Most important are interleukins, interferons, tumor necrosis factor (TNF).
Chemokines are a special class of cytokines or chemoattractants that regulate cell movement.
What cytokines are pyrogens (fever inducers)?
What cells and/or tissues do they act upon?
What effects do these cytokines generate?
IL-6. TNF-a, fever
What are the functions of TNF at the micro-and macroscopic levels?
inflammation: biologic actions of TNF
What pathologic events occur when too much TNF is produced?
no enough blood to tissues, very leaky dilated vessels
increased coagulation and low BP
What series of events occur after a pathogen breaches the skin after a puncture wound?
What cells and proteins are involved?
What changes occur at the cellular level?
What changes occur at the histological or tissue level?
Know the signs of an inflammatory response
Infection occurs when barrier defenses are breached or compromised
Innate immune responses are the earliest immune responses
1. macrophage engulf bacteria
2. cytokines are released
3. vasodilation and permeability, fluid, protein, and inflammatory cells come to site of antigen
4. Infected tissue is inflamed
What are the steps involved in leukocyte migration?
What are adhesion molecules?
Define ICAM, adressin, selectin, integrin.
How does inflammation affect their expression?
Leukocytes (and lymphocytes) enter tissues by a four step process
1. Rolling/tethering- E-Selectins (activated endothelium) addressins (leukocytes)
Tight binding (stable adhesion)- ICAMs and integrins (both leukocytes and endothelial cells. ex: LFA-1 and ICAM1)
Diapedesis (extravasation): (migration through endothelium)- chemokines (IL8/CXCL8, RANTES, eotaxin, MIP)
Migration (entry and function Into tissues proper)
Diapedesis and migration are
also mediated by vasodilation
What events can activate a phagocyte?
What key event follows phagocyte activation (esp. with macrophages)?
Phagocytosis and the destruction of microbes
Engulfed bacteria are killed via the respiratory or oxidative burst.
Phagocytes are best at killing opsonized bacteria (C' or antibody-coated).
What are the functions of IFNα and IFNβ?
What pathogens are the specific targets of the type I IFNs?
Anti-viral defense- type I interferons
Type I interferons (IFNα, and IFNβ) inhibit viral replication and activate an antiviral state.
Type I IFNs activate degradation of viral RNA
-inhibition of protein synthesis
-degradation of viral RNA
- inhibition of viral gene expression and virion assembly
- inhibition of viral replication
How do C' components play a role in inflammation?
Which components specifically?
How are they generated?
complement components also have a role in inflammation
C3a and C5a are potent pro-inflammatory mediators (anaphylatoxins)- act on blood vessels to increase vascular permeability
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