Week 2 - Immunology + Micro Flashcards
What organs make up the upper respiratory system?
Nasal cavity
Nostril
Oral cavity
Pharynx
What organs make up the lower respiratory system?
Larynx
Trachea
Bronchus (left and right)
Lungs
Diaphragm
What are the main functions of the conducting zone?
Filters, warms and moistens the air going into our body and conducts it to the respiratory zone
What is the main function of the respiratory zone?
Gas exchange
The lower respiratory system is free of _____, while the upper respiratory system (nose, nasal cavity and pharynx) has a diverse ____
resident microbiota
microbiome
Haemophilus spp. is a gram negative anaerobe that is grown on ____ agar and requires ____ and ____ to survive
Chocolate
X Factor (Hemin)
V Factor (NAD+)
_____ is the major cause of sepsis and meningitis
H. influenzae
Veillonella spp. is a gram-negative anaerobe that can break down lactate to produce ____ and break down nitrate into ____
ATP
nitric oxide
Staphylococcus spp. is a gram-positive facultative anaerobe that is responsible for:
pneumonia
meningitis
osteomyelitis
toxic shock syndrome
sepsis
scalded skin syndrome
folliculitis
pimples
Diphtheroids are gram-positive aerobes that live in hair follicles, ferment ____, lower skin ____ and can cause ____
carbohydrates
pH
pimples
Alpha-hemolytic streptococci are gram-positive facultative anaerobes grown on ____ agar and are ____ pathogens
blood
opportunistic
What are some signs and symptoms of strep throat (streptococcal pharyngitis)?
- pain during swallowing
- bad breath
- fever
- malaise
- headache
Strep throat is caused by streptococcus ___ , which are gram-positive, beta-hemolytic, facultative anaerobes
pyogenes
What are the virulence factors of streptococcus pyogenes?
M protein (C3b inhibitor)
- Disrupts opsonization and lysis of foreign materials
Hyaluronic acid capsule
- camouflage system surrounding cell and allowing it to be undetected by phagocytes
Streptokinases
- what S. pyogenes use to break down clots
C5a peptidase
- chemotaxis (attracts WBC’s to site of infection)
Pyrogenic (erythrogenic) toxins
- releases cytokines
Streptolysin O
- lyses all human blood cells
Scarlet fever (strawberry tongue and skin rash) and rheumatic fever (fever, painful joints, involuntary movements) can both result from ____
streptococcal pharyngitis
How is streptococcal pharyngitis treated?
penicillins (G or V) or amoxicillin
A less common bacterial pharyngitis is caused by ____, which presents as a sore throat, localized pain, fever, oozing of fluid and fluid thickening into pseudomembrane
diphtheria
Corynebacterium diptheria is a pleiomorphic ____ bacteria and is ubiquitous (found on skin, respiratory etc.)
gram-positive
What is the virulence factor of diphtheria and how does it work?
diphtheria toxin (AB toxin)
1) B subunit of diphtheria toxin attaches to receptor
2) endocytosis is triggered
3) Subunit A is released
4) Subunit A destroys elongation factor, preventing mRNA transcription in the nucleus of the human cell
How is diphtheria transmitted?
from P2P via respiratory droplets/skin contact
How is diphtheria treated?
antitoxin, erythromycin, vaccination (DTaP vaccine)
What is the process by which rhinoviruses cause the common cold?
1) ICAM-1 (intracellular adhesion molecule-1) binds to receptor on rhinovirus
2) endocytosis is triggered
3) transcription and translation of virus
Binding between ICAM-1 and rhinovirus is optimal as 33 degrees and binds better as the virus is restricted to the ____ tract
upper respiratory
What helps viruses attach to host cell receptors?
spike proteins
Endosomes have a low pH and protective toll receptors that bind to viral proteins being translated triggering an _____ cascade and _____
antiviral
inflammatory mediators
True or false: Production of new viruses kill nasal epithelial cells and infected cells lose ciliary action and slough off when dead
True
True or False: Death of cells releases inflammatory chemicals and stimulates nerve cells
True
Severity relates to serotypes. What are the types of serotypes?
HRV-B: less severe and less frequent
HRV-A/C: more severe, effects vary from country-to-country
How do HRV infections increase susceptibility to bacteria?
1 - makes host more prone to infection by secondary bacteria
2 - promotes staph into pneumocytes (increased release of IL-6 and IL-8)
3 - Virus more likely to be internalized
4 - HRV stimulates S. pneumonia allowing for adhesion to tracheal epithelial cells by inducing surface expression of PAFR
5 - Macrophages activation
What is the pathogenesis of adenoviruses?
1) attachment and entry (endocytosis): binds to CAR (coxsackie B/adenovirus) membrane receptors
2) receptors expressed in many/most tissues
3) virus inhibits DNA/mRNA/protein synthesis
4) host cell lysis
Most coronaviruses belong to the ____ and ____ variants
alpha
beta
____ and ___ coronavirus variants mostly affect bird species
delta
gamma
What is the structure of coronavirus?
- spike glycoproteins
- nucleoprotein and RNA genome
- membrane protein
- envelope small membrane protein pentamer
What is the pathogenesis of coronavirus?
1) cleavage of SARS-CoV2 S protein
2) activation of S2 domain
3) fusion of viral and host membranes
What is the causative agent of mononucleosis?
human herpesvirus 4 (Epstein-Barr virus) - enveloped, dsDNA, icosahedral capsid
Mononucleosis infects ____, can become latent and prevents apoptosis in these cells
B lymphocytes
Symptoms of mononucleosis include:
sore throat, fever, enlarged lymph nodes, and extreme fatigue
What are the infection stages of epstein-barr virus?
1 - virus gets out into blood
2 - enters B cells and becomes lysogenic
3 - incorporated into host cell DNA (circulates in body for rest of life)
4 - virus is shed out into mucus and out of body through mucus tract
5 - trigger of immune response
What diseases are associated with EBV?
- oral hairy leukoplakia
- burkitt’s lymphoma
- chronic fatigue syndrome
- nasopharyngeal cancer
True or false: EBV is ubiquitous in humans and thus prevention is impossible
True
Antigens must be presented to a ___ in order for them to recognize them
T-cell
Antigens are presented by being bound to particular ___ found on other cells, known as ___ in mice and rats or ____ in humans
proteins
MHC (major histocompatibility) proteins
HLA (human leukocyte antigen) proteins
The ___ protein can help a T-cell distinguish between foreign and self antigen
HLA
True or false: Antigens are not bound tightly to HLA proteins
True
HLA proteins can present a wide variety of antigens to a wide variety of ____
lymphocytes
HLA class I proteins interact with _____ and binds ____ antigens, while HLA class II proteins interacts with _____ and binds ____ antigens
cytotoxic T-cells
intracellular
T-helper cells
extracellular
What is the co-receptor for HLA class I and II?
CD8
CD4
Alpha 1, 2 and 3 subunits form the ____ heavy chain in the HLA-I structure
glycoprotein
The antigen binding site for MHC class I is found between the ___ and ___ subunits, and binds antigens 8-10 amino acids long
alpha 1
alpha 2
The CD8 co-receptor on the cytotoxic T cells binds to the ___ subunit in MHC class I
alpha 3
The ___ microglobulin subunit is not covalently bound to the heavy chain and is needed for proper folding
beta 2
The HLA-II structure is composed of two ____ of similar sizes which are ____ and ____
glycoproteins
beta 1- beta 2
alpha 1 - alpha 2
The antigen binding site for MHC class II is found between the ___ and ___ subunits, and binds antigens 13-18 amino acids long
beta 1
alpha 1
The CD4 co-receptor on the T-helper cells binds to the ___ and ___ subunit
beta 2
alpha 2
HLA type I molecules subtypes are indicated by the designation:
A, B or C
HLA type II molecules subtypes are all indicated by the designation:
D
True or False: Differing allelic variants of class I and II HLA proteins is the main reason we usually reject organs from randomly-matched organ donors
true
True or false: The presence of particular allelic variants have been associated with increased risk of some autoimmune diseases
true
HLA-1 types are expressed on almost all _____, with the highest expression level found on ____
nucleated cells
lymphocytes
HLA-1 proteins typically bind intracellular antigens via the ____ pathway, and most of the time these are _____
endogenous
self-antigens
True or false: During viral infection, some HLA-1 molecules on a cell will express viral peptides, while some will express host peptides
true
What is the endogenous pathway of HLA-I expression?
1) source of antigenic peptide is from the cytosol
2) peptide is derived from proteasomal degradation of foreign/altered proteins
3) peptide is transported into the RER and loaded onto the HLA-1 protein
4) HLA-1 is expressed on the cell surface
Proteins destined for degradation by proteosomes get tagged via a process known as ____
ubiquitylation
Cells that are very good at presenting HLA-1 bound peptides to T-cells have specialized proteosomes called _____
immunoproteosomes
Immunoproteosomes have slightly different subunits that are substituted into the regular proteosome and this can be induced by _____
cytokines (IFN-gamma and TNF-alpha)
The peptides that are produced by immunoproteosomes bind with better affinity to ____
HLA-1
The protein that translates the peptide fragment into the RER for loading onto the HLA-1 is called:
TAP
Some viruses have the ability to block ____, preventing their viral peptides from being expressed on HLA-1
TAP
The presence of intracellular invaders will trigger an increase in transcription of _____, which occurs via binding to NOD-like receptors
HLA-1 proteins
Binding of NOD-like receptors ____ the expression of HLA-1, and NODs activate ___
upregulate
NFkB
What are the steps of the NFkB pathway?
1) Upon activation of the pathway, an inhibitory protein (IkB) is phosphorylated and degraded
2) NFkB is free to travel to the nucleus
3) Promotion of transcription of NFkB target gene
Which cytokines increase the expression of HLA-1 molecules?
- Both type 1 and type 2 interferons (IFN)
- Tumor necrosis factor alpha (TNF-alpha)
The source of the type 1 and 2 interferons and TNF-alpha results from:
he activation or infection (or both) of a cell nearby
Local antigen-presenting cells are the first to produce ____ and ____, and later activated T-helper cells will contribute to ____ production
TNF-alpha
type-1 interferons
IFN-gamma
Once a peptide-bound HLA-1 is expressed on the surface of a cell, it can bind a ______ and activate it, which will kill infected cells by inducing apoptosis
CD8 cytotoxic T-cell
HLA-2 types are expressed exclusively on ____
antigen-presenting cells
- professional: dendritic cells, macrophages, B-cells
- non-professional: fibroblasts (skin), glial cells, pancreatic beta cells, thymic epithelial cells, intraepithelial lymphocytes, vascular endothelial cells
Dendritic cells always express high levels of ___ and are very good at co-stimulating _____
HLA-2
helper T-cells
Macrophages need to be activated before they express ___, and are good at co-stimulating ___
HLA-2
helper T-cells
B-cells always express ____ at low levels and are good at co-stimulating ____
HLA-2
helper T-cells
Non-professional APCs will only express ____ under particular conditions such as sustained ____
HLA-2
inflammation
HLA-2 proteins bind extracellular antigens via the _____ pathway
exogenous
In B-cells, IFN-gamma ____ HLA-2, however IL-4 ___ HLA-2
downregulates
upregulates
HLA-2 expression is upregulated by the _____ cytokine
interferon-gamma
What are the steps involved in HLA-2 expression via the exogenous pathway?
1) Phagocytosis is upregulated and is the source of the peptides that are loaded on HLA-2 (can occur through regular pathway or antibody mediated in B-cells)
2) The phagocytosed antigen is processed in a phagosome and merges with a vesicle containing the HLA-2
3) The antigen is loaded onto HLA-2 and expressed on the surface of the cell
How can phagocytosis by B-cells be antibody-mediated?
1 - antigen binds to specific antibody on the surface of the B-cell
2 - antigen and antibody are phagocytosed together (receptor-mediated endocytosis)
3 - antibody is recycled back to the surface of the cell and antigen is processed in an endosome
How do we ensure a cytosolic antigen isn’t loaded onto a HLA-2 in the RER?
- In the RER, the HLA-2 protein associates with the invariant chain which prevents this
- blocks the HLA-2 from being accessible to the intracellular antigen so has nowhere else to go except HLA-1
When a peptide binds with sufficient affinity to HLA-2, ____ is displaced
CLIP
As the HLA-2 containing vesicle merges with the phagosome/endosome containing the antigen, the invariant chain known as ____ is chopped up, and it will remain bound to the HLA-2 peptide binding region until displaced
CLIP
HLA-2 with the bound extracellular antigen gets expressed on the ____
surface of the cell
_____ helps with loading the antigen onto HLA-2
HLA-DM
Under what exceptions can exogenous antigens be presented by HLA-1 and endogenous antigens presented by HLA-2?
1) an infected cell dies and is phagocytosed
- viral particles in the cytosol of infected cell will be presented on the HLA-2 of phagocyte (intracellular antigens become extracellular)
2) autophagy can result in peptides from cytosol being presented on HLA-2
3) cross-presentation
- blend of exogenous and endogenous pathways (i.e., dendritic cells and all APCs)
- allows APCs to either sequentially or simultaneously activate both T-helper and cytotoxic T cells
4) antigens can leak out of endosome after phagocytosis into the cytosol and be presented to HLA-1
Once a peptide-bound HLA-2 is expressed on the surface of a cell, it can bind a ____ and activate it
CD4+ T-cell (helper T-cell)
CD4 is the major co-receptor that distinguishes a _____ from a ____
T-helper cell
cytotoxic T-cell
T-cells need a co-stimulatory activation, which is best represented by ___ on the T-cell with ___ on the APC
CD28
CD80/98
What are the steps of T-cell activation with HLA-2?
1) T-cell receptor interacts with HLA-2
2) CD4 co-receptor interacts with HLA-2
3) CD28 interacts with CD80/86
True or false: although most T-cells express CD28, most cells in the body do not express its ligands (CD80/86)
true
Only professional APCs have the capacity to express ____
CD80/86
What cells are the best activators of naive T-cells, and always express CD80/86s:
Mature dendritic cells
Macrophages and B-cells have the capacity to ____ CD80/86, after they are activated by an encounter with a pathogen
upregulate
How does CD28 signaling add to the effects of TCR signaling?
1) enhances the strength of signal between the T-cell and APC
2) initiates a cell-signaling cascade to promote T-cell survival and proliferation
- CD28 recruits PI3 kinase
The two categories that the interactions between the T-cell and APC can be divided into are:
1) cSMAC (central supramolecular activation complex)
- TCR and HLA-2 (with co-activator CD4)
- Co-stimulator interaction (CD28 & CD80/86)
2) pSMAC (peripheral supramolecular activation complex)
- includes other receptor-ligand interactions that help strengthen the connection between the T-cell and APC to sustain the signal
What else is involved in TCR and HLA-2 interactions and co-stimulatory interactions?
paracrine signaling between the APC and the T-cell
Paracrine signaling between the APC and the T-cell help to polarize the helper T-cells, and this polarization depends on 2 factors:
1) the type of APC interacting with the T-helper cell
2) the cytokines present during the time of activation
True or false: Co-stimulators are usually expressed at high levels on APCs
False
- Co-stimulators are usually NOT expressed at high levels on APCs
HLA-2 and costimulatory expression increase only when the APC recognizes a ___ or a ___
DAMP
PAMP
- prevents unnecessary inflammation
How does IL-2 serve as a growth factor for T-cells and B-cells?
1) proliferation and differentiation of activated naive T-cells
2) Proliferation and differentiation of B-cells
Once activated, naive T-cells begin to synthesize IL-2 and the high-affinity forms the ____
IL-2 receptor
IL-2 binding to the Th IL-2 receptor acts in an ____ fashion, and activates the Th cell and causes it to enter the cell cycle and avoid ____
autocrine
apoptosis
True or false: Synthesis of both IL-2 and the high affinity IL-2 receptor is induced after CD28-CD80/88 binding and recognition of the antigen by the ___
TCR (via HLA-2)
Ag recognition in absence of co-stimulation causes T cell ____
anergy
True or false: Anergic T-cells cannot produce IL-2, which means they cannot proliferate and differentiate into effector cells when they encounter Ag
true
What is the process of T-cell activation with IL-2?
1) naive T cells express the low affinity IL-2 receptor
2) activated T-cells express the high affinity IL-2 receptor and secrete IL-2
3) Binding of IL-2 to the high-affinity receptor sends a signal to the T-cell
4) The signal sent from the IL-2 receptor induces T-cell proliferation
True or false: CD4 helper T-lymphocytes never kill pathogens or other “foreign-looking” entities directly
true
How do helper T-cells aid immunity?
1) activate or inhibit other cells through direct contact (i.e., the immunologic synapse)
- CD8 cytotoxic T-cells, B-cells, macrophages
2) activate or inhibit other cells through the secretion of cytokines (influences a range of effectors)
Helper T-lymphocytes that cause cells to differentiate after activation is known as ____
T-cell polarization
Polarization is a specialized Th phenotype and the Th secretes a profile of ___ that mediate distinct effector cell functions
cytokines
True or false: Th type is determined by the environment is it found in
true
