Unit 2 - Lecture 9 Overview of the Immune System (Innate Immunity) Flashcards
What are sites of viral entry?
So in order for a virus to cause disease what must occur?
In order for a virus to cause disease:
- Gain access to a susceptible host
- Target tissue/tropism
- Evade the host’s immune defenses
- Innate immune system
- Adaptive immune system
- Cause damage/death to the host in which it replicates
What is the innate immunity?
What does it include?
Innate immunity: non-specific defenses against infection that are ready for immediate action prior to attack by a pathogen
Includes:
- Anatomical barriers (skin and mucous membranes)
- Chemical barriers such as stomach acid and anti-microbial molecules
- Cells with receptors able to recognize a variety of pathogens (viral, bacterial, fungal)
–Most ancient form of defense in vertebrates
– Co-evolved to interact with, and even activate, specific host defenses (adaptive immune system)
What is involved in the external barrier Skin?
- Desquamation of skin removes bacteria (transient) that have adhered to epithelial surfaces
- Skin also secretes a number of peptides and proteins with potent anti-microbial activity (i.e., psoriasin)
Chart:
- Keratin = “waterproof” protein
- Tightly packed epithelial cells
- Specialized innate cells
- Connective tissue
- Blood Vessels
What are Mucous Membranes?
Where are they located?
What is the purpose of them?
- Gastrointestinal, respiratory, and urogenital tracts.
- Saliva, tears, and mucous secretions wash away microbes.
- Antibacterial and antiviral substances (lysozyme, defensins, surfactants)
- Cilia in respiratory tract propel mucus-entrapped microbes from body.
- Stomach contains acid and digestive enzymes.
- Normal flora colonize mucosal surfaces to out-compete pathogenic microbes for space and nutrients.
What is involved in the Respiratory Tract?
What type of cells and structures are involved?
What are the anti-microbial compounds in the saliva?
- Mucus secreted epithelial cells lining the airways entraps foreign microorganisms
- Cilia (hair-like protrusions) propels mucus-entrapped microbes from the respiratory tract
- Anti-microbial compounds in saliva and in the epithelia of the mouth
****Surfactant A
****Lactoferrin (repels viral particles)
*****Lysozyme (nasal secretions)
****Defensins
What are defensins in Innate Antiviral immunity?
- Defensins inctivate enveloped virus particles
- Defensins can block fusion of viral membranes with endosomes
A. Effects on the virion
B. Effect on the HIV infected cell
C. Effect on influenza-virus-infected cell
Describe the Gastrointestinal Tract
- Epithelial cell barrier
- Surface area of GI tract is approx. the surface area of football field
- Low pH (1-4)
- Mucus
- Digestive enzymes
- Health-enhancing intestinal bacteria
- Inductive immune sites
- Specialized cells (M cells) that capture antigens and microbes
What is the Urogenital Tract?
- Epithelial cell barrier
- Urine
********Slightly acidic
********Flushing action
- Mucous lining
- Antimicrobial peptides
- Specialized cells (M cells) that capture antigens and microbes
What is involved in Inflammation?
What are acute and chronic inflammation?
Name the 5 Clinical signs that are included in inflammation.
- *Inflammation:** Complex cascade of biological events initiated by a breach of the outer anatomical barriers (skin, mucous membranes) by infection or tissue damage.
- *Acute=** initial response of the body to harmful stimuli involving the increased movement of leukocytes from the blood to the injured tissue(s).
- *Chronic**= prolonged inflammation characterized by simultaneous destruction and healing of the tissue; arthritis and cancer
Five Clinical signs:
- Swelling caused by accumulation of fluid (edema)
2&3. Redness and heat caused by increased blood flow
- Pain due to release of chemicals that stimulate nerve endings
- Loss of Function
What is the Inflammatory Response?
- Tissue damage causes release of vasoactive and chemotactic factors that trigger a local increase in blood flow and capillary permeability.
- Permeable capillaries allow an influx of fluid (exudate) and cells
- Phagocytes migrate to site of inflammation (chemotaxis)
- Phagocytes and antibacterial exudate destroy bacteria.
What are Cytokines?
Cytokines: Hormone-like proteins tha tcommunicate via cell-receptors to induce cell activities.
What are Chemokines?
Chemokines: Subgroup of cytokines that cause cells to move towards the site of injury or infection.
The fever response is initiated by what?
Fever Response:
- Pyrogens
- Cytokines
What is the Coagulation System?
- Coagulation system (clotting process) activated upon severe tissue injury
- Coagulation can physically trap microbes in blood clots
- Some products are directly antimicrobial.
How are Viruses Detected?
- PAMPS: pathogen-associated molecular patterns
–-Essential for viral replication
—Not expressed in the host
- PRR: pattern recognition receptor expressed by host to detect “nonself” molecules
- —Expressed by immune cells
- –Recognize PAMPS
- –Activate innate immune responses
What are TLR family Members?
Toll-like Receptors (TLR)
- 11 TLRS in humans
- 12 TLRs in mice
- Distinct TLRs between mammals and non-mammals.
- All recognize indispensible components of pathogens
What is the cellular localization of TLRs?
Extracellular: TLRs that recognize extracellular microbial ligands; dimers
Intracellular: TLRs that recognize intracellular microbial ligans (RNA, DNA)
What are neutrophils?
Cells of the Innate Immune System:
- First cells to migrate from blood to site of infection.
- Capable of ingesting microbes or particles (phagocytosis).
- Express several TLRs to recognize bacteria & viruses.
- Secrete anti-microbial enzymes and peptides (i.e., defensins)
What is Phagocytosis?
Phagocytosis:
- Bacterium becomes attached to membrane evaginations called pseudopodia
- BActerium is ingested, forming phagosome
- Phagosome fuses with lysosome
- Lysosomal enzymes digest captured material
- Digestion products are released from cell
* Many of the cells attracted to the inflamed site work to engulf and kill pathogens (termed “phagocytosis”).
What is involved in the generation of antimicrobial Speicies in Phagocytes?
- Respiratory burst: O2 consumed by phagocytes (neutrophils, macrophages) is converted within phagosomes to toxic reactive oxygen species (ROS)
- Occurs via action of the enzyme NADPH phagosome oxidase.
- Some pathogens possess non-oxidant defenses to mediate survival when in the phagosome.
- Inducible nitric oxide synthetase (iNOS): oxidizes L-arginine to nitric oxide
- Nitric oxide (NO) by itself has antimicrobial activity.
- NO can also combine with superoxide to from even more potent antimicrobial compounds.
What are Macrophages?
Cells of the Innate Immune System
- Express several TLRS to recognize microbes.
- Great phagocytic activity upon activation.
- Express high levels of MHC class I and II to present antigens to T cells.
- Secrete a variety of cytokines involved in inflammation (IL-1, TNF-a, IL-6).
- Activated macrophages also secrete complement proteins.
What are Natural Killer (NK) cells?
- First line of defense against viruses.
- Target and kill virally-infected cells and tumor cells.
- Produce cytokines that regulate immune responses (i.e., IFN-g and TNF-a):
–Stimulate dendritic cell maturation
—Activate macrophages
—-Initiate T cell responses
In the Nonspecific Immunity what is involved with the Natural Killer Cells?
- NK cells recognize
Cells that undergo a declined expression of MHC molecules or
Cells that contain surface antigens displayed by some tumor cells or
Virally infected cells
- Once activated, NK cells release pore-releasing proteins
***Perforins
***Granzymes (proteases)
***Chemokines
- NK cells can bind to cells containing bound antibodies through recognition of Fc region of antibodies
What are Dendritic Cells (DC)?
- Provide a broad link between innate and adaptive immunity.
- Engulf and kill microbes through phagocytosis.
- Express MHC class I and class II.
- Use a variety of TLRs to recognize pathogens.
- Recognition causes DC maturation and increased production of MHC class II.
- Secrete cytokines involved in inflammation (IL-12, TNF-a, and IL-6).
- Subset secretes type I interferons that block viral replication
