(Section B: Immunology) Lecture 11: Innate Immunity II Flashcards
Describe:
Anatomy of the Immune Response
- Infection/Infection
- Innate immunity
- Lymphatic/Blood flow in to lymphoid organ
What is the lymphatic system?
- Parallel to circulatory
- Comprised of lymphatic capillaries, lymph nodes etc.
- Lined with endothelial cells
What is the purpose of the lymphatic system?
“Highway for WBCs”
* Allows white blood cells to travel to and from site of infection/injury
How do lymphatic capillaries run?
- Close to veins and arterioles
- Does not touch them
What are lymph nodes?
- Where lymph vessels come together
What are the major lymph nodes in the body?
- Tonsils
- Groin
- Armpit
- Peyer’s patches (intestines)
Describe:
Structure of a lymph node
- Center is called the medulla
- Surrounding area is called the cortex
Cortex is comprised of:
* Follicle: B-cell zone
* Paracortex: T-cell zone
Describe:
Structure of the Spleen
- Red pulp: Recycle RBCs (dead or dying), prevents iron from being released
- White pulp: Location of WBCs
White pulp comprises of the T-cell zone
Follicles comprises of the B-cell zone
What are the two types of pathogen recognition?
- Adaptive recognition
- Innate recognition
Pathogen
“Sickness generating”
How are pathogen detected?
- Sensed by receptors
- Receptors send signals
Describe:
Intracellular Signaling Pathways
- Reception
- Transduction
- Response
How does reception work?
- Transmembrane protein
- Has intracellular component to send signals inside
How does the transduction work?
Signal-transduction pathway
* Some signals are ON signals, some are OFF signals
* Ex. Normally something is ON, the signal might tell it to turn OFF
How does the response work?
Activation of cellular responses
* Pathways can overlap and “talk” to each other
* Ex. One signal pathway can trigger many others along the way
Define:
PRRs
Pattern Recognition Receptors
* Expressed at surface and within many cell types
* Ex. WBC, some lymphocytes, and some epithelial cells
What do PRRs recognize?
Recognize evolutionarily conserved, invairant regions of pathogens
* Can also recognize damage or infection signals
How is the specificity of PRRs determined?
Germline-encoded
What are PRRs critical for?
Initiating immune responses
List:
4 Families of PRRs
- Toll-like receptors (TLR)
- C-type lectin receptors (CLR)
- Nucleotide oligomerization receptors (NLR)
- RIG-I like receptors (RLR)
Toll-like receptors (TLR)
- “Toll” means “crazy”
- Humans and mammals have many Toll genes
- Can recognize a wide variety of patterns
- Located on cell surface or on endosomes
Where are C-type lectin receptors (CLRs) located?
On cell surface
Where are nucleotide oligomerization receptors (NLRs) located?
Cytosol
Where are RIG-I like receptors (RLRs) located?
Cytosol
What do PRRs recognize?
PAMPs
* Pathogen Associated Molecular Patterns
List:
Examples of PAMPs
- Mannose-rich oligosaccharides
- Peptidoglycans
- Lipopolysaccharides
- Unmethylated CpG DNA (unmethylated cytosine-guanine dinucleotide in DNA)
Examples of PAMPS in bacteria
- Lipoteichoic acid (LTA)
- Peptidoglycan (PGN)
- Lipoproteins
- DNA
- Flagellin
- Lipopolyssacharide (LPS)
Examples of PAMPs in viruses
- Viral nucleic aicds
- Capsid and surface proteins
What is a PAMP in yeast?
Zymosan (beta-glucan)
How can PAMPs be classified?
- Critical for microbe structure
- Viral
- Critical for microbe pathogenicity
List:
PAMPs critical for microbe structure
- Peptidoglycan & Lipoteichoic Acid: In cell walls of Gram-Positive bacteria
- Lipopolysaccharide (LPS): In the cell wall of Gram-Negative bacteria
- Mannan: In the cell wall of yeast
- Glucan: In the cell wall of fungi
List:
PAMP critical for microbe pathogenicity
Bacterial Flagellin
What is the structure of toll-like receptors?
Dimers
* Two protein subunits together
Where are Toll-Like Receptors located?
- On the surface membrane of the cell (allows detection and initiation of phagocytosis)
- On the endosome/lysosomes (tells the cell what is inside the endosome/lysosome based on what signal is activated)
DAMPs
Damage-Associated Molecular Patterns
* Released as a consequence of cellular damage
When are DAMPs released?What are examples of DAMPS?
Released when damage occurs (cuts, scrapes etc.)
* ATP
* Uric acid
* Mitochondrial DNA
* Histones (should only be present in the nucleus during normal conditions)
* Heat shock proteins (HSPs)
* S100
* Hight Mobility Group Proteins (HMGB1)
What form of extracellular communication allows for communication between cells of the immune system?
Cytokines
* “Cell movement”
Do all cells respond to cytokines?
No, only the target cells with receptor for the cytokine will receive it
List:
Cytokine modes of action
- Pleiotropy
- Redundancy
- Cascade induction
Pleiotropy
Same cytokine act on different cells to evoke different responses
Redundancy
Different cytokines evoke same response in cells
Cascade induction
Action of a cytokine on a cell induces production of one or more additional cytokines
What are the 6 major cytokine families?
- Interleukin-1 family
- Class 1 (hematopoietin) cytokine family
- Class 2 (interferon) cytokine family
- Tumor necrosis factor family
- Interleukin-17 family
- Chemokines
Functions of:
Interleukin-1 family cytokines
Includes important inflammatory mediators
Functions of:
Class 1 (hematopoietin) cytokine family
Striking sequence and functional diversity, responsible for many roles in immune system
Functions of:
Class 2 (interferon) cytokine family
Important roles in antiviral responses
Functions of:
Tumor necrosis factor family
Plays roles in inflammation
Functions of:
Interleukin-17 family cytokines
Professor will not teach anything about this family
Functions of:
Chemokines
Serves chemoattractant function
* Tells cells where to go in body
State the receptors for each family of cytokines
- Interleukin-1 family receptors
- Class 1 receptors
- Interferon-type receptors (class 2)
- TNF receptors
- IL-17 receptors
- Chemokine receptors
What are the structures like for cytokine receptors?
- Monomeric
- Dimeric
- Trimeric/Multimeric
Are the two protein subunits for dimeric cytokine receptors the same or different?
Both
* Can be hetero-
* Can be homo-
State:
Relationship between dissociation constant and monomer/dimer/multimer
Multimers have lower dissociation constants (Kd)
* Thus high affinity for their signals
Describe:
IL-2 Signal transduction pathway
- Signal recruits and activates JAK family tyrosine kinases, phosphorylation of receptor
- Also phosphorylates STAT (Single Transduction and Activation of Transcription) Proteins
- Travels into nucleus to turn on/off certain genes
Known as the JAK/STAT pathway
What is IL-2 reponsible for?
Communication between WBCs, tells cells to divide
What are the main responsibilities of chemokines?
Promote cellular migration, tells cells where to go in the body
What are chemokines secreted by?
Immune and Non-immune cells
How do interferon cytokines work?
Virus infected cells secrete Type 1 interferon (IFN-alpha and IFN-beta)
* Initiates immune responses by activating dendritic cells
What cellular responses can be activated by cytokines?
- Changes in gene expression (transcription), turned on/off
- Changes in protein expression (translation), turned on/off
- Cell division
- Cell movement
- Cell differentiation
- Cell survival (life/death)
