Innate Immunity Flashcards
The innate immune system consists of all the immune defenses that lack _________
The innate immune system consists of all the immune defenses that lack IMMUNOLOGIC MEMORY.
A characteristic of innate responses is that they remain ________ however often the antigen is encountered.
A characteristic of innate responses is that they remain UNCHANGED however often the antigen is encountered.
Innate (also called natural or native) immunity is ______ working/present in healthy people.
Innate (also called natural or native) immunity is ALWAYS working/present in healthy people.
Components of innate immunity:
- Host barriers,
- Enzymes in epithelial and phagocytic cells (e.g. lysozyme),
- Inflammation-related serum proteins (e.g. complement components, C-reactive protein, and lectins)
- antimicrobial peptides, AMPs, (e.g. defensins) on the surface of cells and within phagocyte granules,
- Phagocytic cells,
- cell receptors that sense micro-organisms and signal defensive response
- complement
- acute inflammation
- pro-inflammatory cytokines
- NK cells
- mast cells and other granulocytic cells
Phagocytic cells (macrophages, dendritic cells, and neutrophils) identify pathogens by recognizing ________ and ________
Phagocytic cells (macrophages, dendritic cells, and neutrophils) identify pathogens by recognizing PATHOGEN-ASSOCIATED MOLECULAR PATTERNS (PAMPs) and DAMAGE-ASSOCIATED MOLECULAR PATTERNS (DAMPs)
What is the human microbiome?
The human microbiome is the collection of bacteria, fungi, and viruses that live in and on the human body
The microbiome protects against pathogen overgrowth, and modulates the balance between ________ and _________
Protects against pathogen overgrowth, and modulates the balance between INFLAMMATION and IMMUNE HOMEOSTASIS
Coagulase-negative staphylococci on the skin produce ________ that can inhibit growth of _________
coagulase-negative staphylococci on the skin produce AN ANTIMICROBIAL PEPTIDE that can inhibit growth of STAPHYLOCOCCUS AUREUS.
Neutrophil - type and function
- Type: WBC granulocyte,
- Function: engulf bacteria and fungi; oxidative burst
Monocyte/Macrophage - type and function:
- Type: WBC mononuclear,
- Function: engulf bacteria, fungi, and cellular debris; produce cytokines; antigen processing
Eosinophil type and function:
- Type: WBC granulocyte
- Function: Associated with allergic response and parasitic infection
Basophil type and function:
- Type: WBC granulocyte,
- Function: Associated with hypersensitivity and release histamine
Mast cell type and function:
- Type: Bone marrow derived cell,
- Function: Granules contain vasoactive amines like histamine, proteases kill bacteria
NK cells type and function:
- Type: WBC lymphocyte,
- Function: recognizes stressed or infected cells and kills them by secreting macrophage-activating cytokine INF-gamma
Dendritic cell type and function:
- Type: bone marrow derived cell,
- Function: Phagocytosis, APC, initiation of T-cell responses
PMNs develop in the _______
PMNs develop in the BONE MARROW
PMNs kill engulfed substances in vesicles called a _______ where the microbe is killed and degraded
PMNs kill engulfed substances in vesicles called a PHAGOLYSOSOME where the microbe is killed and degraded
_______ cells have a potent respiratory burst of reactive oxygen species to kill engulfed bacteria
PMN/Neutrophil cells have a potent respiratory burst of reactive oxygen species to kill engulfed bacteria
What is the lifetime of Neutrophils?
<2 days
When monocytes migrate into ________, they further differentiate into macrophages.
When monocytes migrate into TISSUE SPACES, they further differentiate into macrophages.
Macrophages are phagocytic and create __________
Macrophages are phagocytic and create PHAGOLYSOSOMES
Macrophages serve to ___ and to ______ antigens and also to ‘______’ peptides from those antigens.
Macrophages serve to KILL and to DEGRADE antigens and also to ‘PRESENT’ peptides from those antigens.
Macrophages are called professional _________
Macrophages are called professional ANTIGEN PRESENTING CELLS
Conventional dendritic cells are important in ___________
Conventional dendritic cells are important in IMMUNOSURVEILLENCE
Dendritic cells present antigens to ____ cells
Dendritic cells present antigens to T cells
Dendritic cells pick up antigens by _______
Dendritic cells pick up antigens by ENDOCYTOSIS (less phagocytic than neutrophils and macrophages)
_________ cells are specialized stromal cells in lymph nodes and spleen. They are adept at trapping antigen and presenting antigen to B cells
FOLLICULAR DENDRITIC cells are specialized stromal cells in lymph nodes and spleen. They are adept at trapping antigen and presenting antigen to B cells
Where do NK cells arise and mature?
The bone marrow
NK cells contain granules (_____ and _____), and cell surface receptors for ___
NK cells contain granules (GRANZYME and PERFORIN), and cell surface receptors for IgG
NK cells destroy ____-infected and _____ cells
NK cells destroy VIRALLY-infected and MALIGNANT cells
Pattern Recognition Receptors (PRRs):
Receptors/components specific to the innate immune system that can recognize and interact with components specific to microbes
-innate system recognizes structures that are shared by various classes of microbes and are not present on normal host cells
PAMPS:
Pathogen-associated molecular patterns; these are microbial molecules that stimulate the innate immune response
Pattern recognition receptors are divided into two groups:
- Secreted and circulating proteins and peptides;
- transmembrane and intracellular signal transducing receptors (more traditional receptors)
Describe what types of microbial molecules PRRs might recognize:
•Each component of innate immunity may recognize many bacteria, viruses, or fungi:
- bacterial endotoxin, also called lipopolysaccharide (LPS),
- terminal mannose residues of bacterial glycoproteins,
- double-stranded ribonucleic acid (dsRNA) in many viruses,
- unmethylated CG-rich oligonucleotides in microbial DNA.
TLRs specific for _______, ______, and ______ are located on cell surfaces
TLRs specific for MICROBIAL PROTEINS, LIPIDS, and POLYSACCHARIDES are located on cell surfaces
TLRs that recognize _______ are in endosomes, where _______ are ingested
TLRs that recognize NUCLEIC ACID are in endosomes, where MICROBES are ingested
TLR 2:
Recognizes several bacterial and parasitic glycolipids and peptidoglycans
What TLRs are specific for viral single-stranded and double-stranded RNAs?
TLR 3, 7, 8
TLR 4:
specific for bacterial LPS (endotoxin)
TLR 5:
specific for a bacterial flagellar protein called flagellin
TLR 9:
recognizes unmethylated CpG DNA that is abundant in microbial genomes
Why have microbes not adapted to avoid the motifs recognized by innate immunity?
Innate immunity targets motifs that are indispensable to the microbes.
Primary reactions of the innate immune system are _________ and ___________
Primary reactions of the innate immune system are ACUTE INFLAMMATION and ANTIVIRAL DEFENSE
Acute inflammation is:
Acute inflammation is the recruitment and activation of leukocytes and plasma proteins at sites of infection or tissue injury.
Innate immune defense against intracellular viruses is mediated mainly by the help of the ________ system
Innate immune defense against intracellular viruses is mediated mainly by the help of the INTERFERON system
- Type I interferons (IFN-a and IFN-B)
- Type II interferon (IFN-y)
Describe the relationship between the interferon system of innate immunity and virus infections:
-Pattern recognition receptors on plasmacytoid dendritic cells (pDC) and macrophages detect a virus attack, they make “warning proteins” named interferon-a and interferon-b, they are Type I interferons. If a “warned” cell become infected, it knows to undergo suicide to prevent spreading.
NK cells are a key source of ______, which is used to activate _______
NK cells are a key source of IFN-gamma, which is used to activate macrophages
Acute phase response cytokines:
Key players are TNF, IL-1, IFN-y, and IL-6; these help establish a bigger systemic change both at the site of injury and throughout the body
An increase in the concentration of plasma proteins that are referred to as ___________ accompanies inflammation and tissue injury.
An increase in the concentration of plasma proteins that are referred to as ACUTE PHASE REACTANTS (APR) accompanies inflammation and tissue injury.
During the acute phase response, the usual levels of various proteins maintained by homeostatic mechanisms can change substantially. These changes are thought to contribute to:
Host defense and other adaptive capabilities
________ is the chief stimulator of the production of most acute-phase proteins, whereas the other implicated cytokines influence subgroups of acute-phase proteins
INTERLEUKIN-6 is the chief stimulator of the production of most acute-phase proteins, whereas the other implicated cytokines influence subgroups of acute-phase proteins
Conditions that commonly lead to substantial changes in the plasma concentrations of acute-phase proteins include:
infection, trauma, surgery, burns, tissue infarction, various immunologically mediated inflammatory conditions, and advanced cancer
An acute-phase protein is one whose plasma concentration increases (positive acute-phase proteins) or decreases (negative acute-phase proteins) by at least ___ percent during inflammatory disorders.
An acute-phase protein is one whose plasma concentration increases (positive acute-phase proteins) or decreases (negative acute-phase proteins) by at least 25 percent during inflammatory disorders.
The changes in the concentrations of acute-phase proteins are due largely to changes in their production by ________.
The changes in the concentrations of acute-phase proteins are due largely to changes in their production by HEPATOCYTES.
___________ can promote the recognition and elimination of pathogens and enhance the clearance of necrotic and apoptotic cells during the acute phase response
C-REACTIVE PROTEIN (CRP) can promote the recognition and elimination of pathogens and enhance the clearance of necrotic and apoptotic cells during the acute phase response
Pro-inflammatory effects of CRP include:
- activation of the complement system,
- the induction in monocytes of inflammatory cytokines
The assumption that APR are largely beneficial is based upon the known functions of the __________, but is also influenced by speculation as to how they may serve useful purposes in ______ or ______.
The assumption that APR are largely beneficial is based upon the known functions of the INDIVIDUAL, but is also influenced by speculation as to how they may serve useful purposes in INFLAMMATION or HEALING.
Serum amyloid A (SAA) proteins influence _________ during inflammatory states.
Serum amyloid A (SAA) proteins influence CHOLESTEROL METABOLISM during inflammatory states.
Complement components serve pro-inflammatory roles, including:
chemotaxis, plasma protein exudation at sites of inflammation, and opsonization of infectious agents and damaged cells
_______ and _______ are antioxidants that protect against reactive oxygen species by removing iron-containing cell-free hemoglobin and heme, respectively, from the circulation.
HAPTOGLOBIN and HEMOPLEXIN are antioxidants that protect against reactive oxygen species by removing iron-containing cell-free hemoglobin and heme, respectively, from the circulation.
Hepcidin can contribute to decreases in serum iron by:
reducing intestinal iron absorption and impairing the release of iron from macrophages
Fibrinogen influences wound healing. Fibrinogen causes:
endothelial cell adhesion, spreading, and proliferation, which is critical to tissue repair.
The measurement of serum acute phase reactant (APR) levels is useful because:
Abnormalities generally reflect the presence and intensity of an inflammatory process. However, APR measurements cannot distinguish infection from other causes of acute and chronic inflammation.
Bacterial infections are targeted by which components of innate immunity?
- Complement,
- Neutrophils,
- Macrophages,
- Dendritic cells
Parasitic infections are targeted by which components of innate immunity?
-Eosinophils
Fungal infections are targeted by which components of innate immunity?
- Neutrophils
- Macrophages
Viral infections are targeted by which components of innate immunity?
- Complement,
- Interferons,
- NK cells,
- Dendritic cells,
- Macrophages
Infections is initially contained by the _______ responses
Infections is initially contained by the INNATE IMMUNE responses
A person lacking the innate immune response shows:
uncontrolled infection
A person lacking the adaptive immune response shows:
initial containment but not effective clearing from the body
How might the innate immune system both sense trouble and also possibly cause trouble?
- TLRs sense trouble, but out of control phagocytosis would cause trouble by killing the tissue.
- Complement proteins respond and sense trouble, but inappropriate activation could cause autoimmune diseases, etc.
Synthesis of local inflammatory cytokines, led by ______, leads to the acute phase response
Synthesis of local inflammatory cytokines, led by INTERLEUKIN-6, leads to the acute phase response
