Unit 2 - Lecture 9 Overview of the Immune System (Innate Immunity) Flashcards
(36 cards)
1
Q
What are sites of viral entry?
So in order for a virus to cause disease what must occur?
A
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
2
Q
What are Anaphylatoxins?
A
- Fragments C3a and C5a function as anaphylatoxins to bind on receptors found on innate immune cells.
- Induce degranulation, smooth muscle contraction, increased vascular permeability.
- Induce monocytes and neutrophils to adhere to endothelial cells and extravasate to sites of inflammation.
3
Q
A
4
Q
What are Cytokines?
A
Cytokines: Hormone-like proteins tha tcommunicate via cell-receptors to induce cell activities.
5
Q
The second part of the Innate immune system is called:
Complement System
A
- First identified in 1890 as a component of serum that works with antibodies to destroy bacteria.
- Later discovered to be a complex group of proteins in serum that interact to facilitate a number of immune activities.
- Synthesized mainly by liver hepatocytes and constitute 5% of the serum globulin fraction.
- Linked to adaptive immunity through its interactions with antibodies.
- Also linked to innate immunity due to its recognition of pathogen-associated moleculat patterns (PAMPs).
6
Q
What is involved in the external barrier Skin?
A
- 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
7
Q
The fever response is initiated by what?
A
Fever Response:
- Pyrogens
- Cytokines
8
Q
How are Viruses Detected?
A
- 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
9
Q
What are Natural Killer (NK) cells?
A
- 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
10
Q
What is the Urogenital Tract?
A
- Epithelial cell barrier
- Urine
********Slightly acidic
********Flushing action
- Mucous lining
- Antimicrobial peptides
- Specialized cells (M cells) that capture antigens and microbes
11
Q
What is the Coagulation System?
A
- Coagulation system (clotting process) activated upon severe tissue injury
- Coagulation can physically trap microbes in blood clots
- Some products are directly antimicrobial.
12
Q
Describe the Gastrointestinal Tract
A
- 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
13
Q
In the Nonspecific Immunity what is involved with the Natural Killer Cells?
A
- 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
14
Q
What are Chemokines?
A
Chemokines: Subgroup of cytokines that cause cells to move towards the site of injury or infection.
15
Q
Alick Isaacs and Jean Lindenmann performed what type of experiment?
A
Interference Experiement
Substance secreted by cells “interfered” with viral infection.
Interferons were first discovered.
16
Q
What are TLR family Members?
A
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
17
Q
What is Viral Neutralization?
A
- C3b can aggregate viral particles, reducing their infectivity.
- Antibody+ complement further neutralizes the virus and facilitates phagocytosis and intracellular destruction via binding to complement receptors on phagocytes.
- Complement itself can lyse most enveloped viruses.
18
Q
What is involved in Inflammation?
What are acute and chronic inflammation?
Name the 5 Clinical signs that are included in inflammation.
A
- *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
19
Q
What is the innate immunity?
What does it include?
A
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)
20
Q
What is involved in the Respiratory Tract?
What type of cells and structures are involved?
What are the anti-microbial compounds in the saliva?
A
- 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
21
Q
What is the Inflammatory Response?
A
- 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.
22
Q
What is involved in the generation of antimicrobial Speicies in Phagocytes?
A
- 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.
23
Q
What are Dendritic Cells (DC)?
A
- 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
24
Q
What is the interferon response?
A
- See History of Interferon: The Magic Bullet
- IFNs are cytokines
- Three types of IFNs
—- Share amino acid similarities
- Induce an antiviral state in host cells
- –PKR activated by dsRNA
- —2′5′-oligo(A) synthetase
- –RNase L
- More than 300 IFN-stimulated genes
- Some viruses are resistant to the effects of IFN
25
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)
26
What is the cellular localization of TLRs?
**_Extracellular:_** TLRs that recognize extracellular microbial ligands; dimers
**_Intracellular:_** TLRs that recognize intracellular microbial ligans (RNA, DNA)
27
Describe the summary of Innate Immunity:
What are the different Pathways?
What are the different things involved?
**Pathways:**
**1. Classical**
**2. Alternative**
**3. Lechin**
* Complement system comprises a group of serum proteins, many of which circulate in an inactive form.
* Complement activation occurs through the classical, alternative, and lectin pathways.
* Classical pathway is “adaptive” in that it requires antibody binding.
* Alternative and lectin pathways are “innate” in that they are activated by recognition of PAMPS.
* Three pathways converge at the generation of a molecular complex that causes cell lysis.
* Complement system also mediates opsonization of bacteria, activation of inflammation, and clearance of immune complexes.
* Innate immunity is found in many organisms- vertebrates, invertebrates, and even plants
28
What are the activities of the complement system?
1. Lysis
2. Opsonization: more tasty
3. Activation of inflammatory response
4. Clearance of immune complexes
29
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
30
What is Apoptosis with viral infections?
**Apoptosis:**
* Programmed dell death (PCD)
- morphological changes
* Viruses can trigger PCD, counteract PCD, or do both
--- activation of **caspases**
-- apoptosis and disease severity
* Halt virus spread
* Viral dissemination
31
What is the clearance of Immune Complexes?
* Antibody-antigen complexes become coated with C3b.
* C3b facilitates binding to CR1 on red blood cells.
* Red blood cells carry complexes to spleen and liver.
* Phagocytes remove immune complexes from red blood cells and destroy them.
* Deficiencies in this process leads to deposition of immune complexes in tissues and tissue damage (i.e., lupus).
32
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.
33
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.
34
What else is involved in Dendritic Cells?
* Act as scouts that are very efficient at identifying foreign invaders such as viruses and bacteria.
* Dendritic cells internalize the pathogen, digest it, and display or present the foreign peptides on their surface through the MHC II molecules to T helper (TH) cells.
35
What is Phagocytosis?
Phagocytosis:
1. Bacterium becomes attached to membrane evaginations called pseudopodia
2. BActerium is ingested, forming phagosome
3. Phagosome fuses with lysosome
4. Lysosomal enzymes digest captured material
5. Digestion products are released from cell
* Many of the cells attracted to the inflamed site work to engulf and kill pathogens (termed “phagocytosis”).
36
What is Opsonization?
* C3b (and C4b) fragments coat immune complexes, antigens, and pathogens.
* Phagocytic cells express complement receptors (CR) that bind C3b and C4b, allowing enhanced phagocytosis of coated particles.
* C5a anaphylatoxin increases the expression of CR on phagocytes to further faciliatate phagocytosis of opsonized particles.
