Lectures 11a-11e

Are there more human cells or bacteria in the human body

bacteria

Are most of the bacteria in the body harmful or nonharmful

most do no harm and are symbiotic

What are the bodies primary defenses against pathogens

1) physical barriers like the skin

2) inhospitable environments like in the stomach

3) attachments prevention like mucus

Do most pathogens get past the bodies primary defenses against pathogens

no

What are some hallmarks of a virus

1) they supply their own genome in the form of DNA or RNA

2) hijack the normal cellular machinery

3) not considered alive

4) can insert themselves into the genome and lie dormant for many years

Is COVID RNA or DNA based

RNA based

What is a spike protein

a protein on the outside of a virus that determines which cells the virus can attached to, allowing for the endocytosis of the virus

What is the virus that causes COVID called

SARS-CoV 2

What is the life cycle of a virus

it gets brough into the cell via a vacuole, opened up and the RNA is replicated and turned into proteins. The proteins and RNA gather at the cell wall and make a new virus while the cell stays infected

Where do microbes usually live

they usually live inside the host but outside of the host cells (some do live in the cells tho)

How does the microbes home determine what happens to it

it determines how the immune system interacts with it

What are some types of microbes

1) bacterial prokaryotes

2) Unicellular eukaryotes

3) multicellular eukaryotes like worms

What do antibiotics attack

they all attack different parts of a microbe. Some attack things like the cell membrane or the DNA while others stop protein synthesis

What are three methods of antibiotic resistance

1) Altered Critical enzymes

2) proteins that degrade antibiotics

3) efflux pumps

Why is antibiotic resistance so bad

it means that the cells cannot be killed with medicine and that the antibiotic resistance can spread to other microbes since DNA conferring antibiotic resistance is highly mobile and easily shared

What is the difference between where viruses and microbes live

viruses mostly live in the cell while microbes live outside it

Comparing SARS CoV-2 and E. coli,

which statement is TRUE:

A. E. coli replicates inside of host cells.

B. SARS CoV-2 replicates inside of

host cells.

C. Both can replicate without needing

host proteins.

D. The immune system can clear

E. coli, but not SARS CoV-2.

B

What is the timeline of an immune response

1) Infection at Day 0

2) Innate Immune Response from Day 0-7

3) Adaptive Immune Response from Days 4-7

4) Clearing of Infection from Day 7 on

What is the second (and last) line of defense for the body

the Immune System

What is the innate immune system

the immediate recognition of pathogens using conserved epitopes that contains the infection and activated the adaptive immune system to clear infection

What is the adaptive immune system

the slow recognition of pathogens using specific epitopes made for that pathogen. It tags the pathogen and has a memory function

What is an antigen

a molecule recognized by the immune system

What is an epitope

a specific part of an antigen that is recognized

Is there cross talk between the adaptive and innate immune systems

yes, they active each other

What is the pathway for a pathogen through the innate immune system

1) Detected by an invariant epitope

2) phagocytosis/cell lysis

3) Activation of dendritic cells and adaptive immunity

What is the pathway for a pathogen through the adaptive immune system

1) Pathogen recognized by Unique Epitopes

2) T cell activation

3) Cellular Immunity due to T cells (and activation of cytotoxic t cells to kill pathogen)

4) Activation of helper T cells

5) Humoral Immunity with B cells and antibodies

6) activation of the innate immune system

What are the three parts of innate immunity

1) Complement System

2) Toll-like receptors

3) Cellular Effectors

What are the two parts of Cellular Effectors in the innate immune system

macrophages and dendritic cells

What are Toll-like receptors

a family of receptors that are located on the membrane or endosomes that recognize pathogen structures like RNA and initiate immune system response

What is the complement system

sets of proteins that are made in the liver for use in the blood stream in order to compliment with a bacteria’s membrane to activate the immune system

What are the two parts of a complement system protein and what do they do

1) A Portion: smaller and diffuses away to act like a signaling molecule

2) B Portion: larger and binds to the pathogen to help catalyze more complement proteins to the bacteria

What are the three ways to active the complement proteins

1) Classical: recognize the bound antibody

2) Lectin: recognize the bacterial sugars

3) Alternative: recognize the pathogen surfaces

What happens when the complement system is activated

C3 is cleaved and activates a positive feedback loop of cleavage. C3a then stimulates the innate and adaptive immune systems while C3b tags the pathogen and kills the pathogen

What are cytokines

small peptides with signaling functions that act over only short distances to mark infections and control the longevity of activated B and T cells

Are all cytokines interleukins

no, but most are

What are macrophages

Cells that are distributed through the body to digest and dispose of apoptosed cells and microbes

What are dendritic cells

cells that are distributed through the body that match antigens with T cells to activate the adaptive immune response

Which of the following statements about the innate immune system

is FALSE:

A. The innate immune system monitors only extracellular epitopes.

B. The innate immune system can kill bacteria.

C. Complement proteins are activated by proteolysis.

D. Toll-like receptors detect both viral and bacterial pathogens.

A

What is the lymphatic system

The diversion of interstitial fluid from the blood-interstitial fluid pathway into the lymph, then back to the blood

What is a erythrocyte

a red blood cell

What is a leukocyte

a white blood cell (B and T cells)

What is a lymphoid cell

a leukocyte in the lymphatic system

What is a myeloid cell

a leukocyte outside of the lymphatic system (with the exception of dendritic cells)

What are the hallmarks of B cells

1) They act on extracellular epitopes

2) They react with proteins and non-proteins

3) The epitope must be on the outside of the pathogen for it to work

What are the hallmarks of T cells

1) They act on extra or intracellular epitopes

2) They react with protein epitopes only

3) The epitope can be on the outside or inside of the pathogen for it to work

How many types of antibodies do B cells make

only one

What is the structure of an antibody

It looks like a bubble letter Y with the base being a constant region and the arms being variable light and heavy chains. Everything is held together with disulfide bonds

Where does the antigen bind

in the space between the heavy chain and light chain in the antigen binding site

What are the two major requirements for antibody structure

1) Highly variable to detect as many epitopes as possible

2) Conserved to be recognized as an antibody always

What is the problem with encoding antibody diversity

we would need so much more space in the nucleus

What are the four ways of creating antibody diversity

1) V-Region Assembly

2) Junctional Diversity

3) Class Switching

4) Somatic Hypermutation

What two methods create an assembly of a functional antibody locus

1) V-Region Assembly

2) Junctional Diversity

What two methods of Somatic DNA recombination are used during an immune response

Class Switching and Somatic Hypermutation

What is V-Region Assembly

combinatorial use of DNA segments encoding variable regions

What is Junctional Diversity

addition of random nucleotides to joints between DNA segments

What is Class Switching

the use of different constant chains to generate different classes of antibodies

What is somatic hypermutation

mutate hypervariable region to obtain higher affinity antibodies

What happens during antibody locus rearrangement

a recombination reaction occurs where there are double stranded breaks that permanently alter the genome with every daughter cell getting the same whack genome

What happens during junctional diversity

during recombination, the DNA ends are processed to add and remove nucleotides at random

How many heavy and light chain loci are there

1 heavy chain and 2 light chains

What are the pluses of the way that we make antibodies

there is a lot of variety, it is encoded in the DNA, and it can be remembered

What are the cons of how we make antibodies

most rearrangements are non-productive since not all heavy and light chains can pair and some react with host proteins

Why do 2/3 of all additions cause issues

they change the reading frame

Explain the process of B cell Rearrangements

1) 1st chromosome tries to make heavy chain (if works moves onto 3, if not it moves to 2)

2) 2nd chromosome tried to make heavy chain (if works moves onto 3, if not it dies)

3) 1st chromosome tried to make the k light chain (if works, antibody made, if not it moves to 4)

4) 2nd chromosome tried to make the k light chain (if works, antibody made, if not it moves to 5)

5) 1st chromosome tried to make the gamma light chain (if works, antibody made, if not it moves to 6)

^) 2nd chromosome tried to make the gamma light chain (if works, antibody made, if not it died )

What are the steps for testing for productive rearrangements

1) Is the heavy chain productive

2) Is the light chain productive

3) Are the heavy and light chain compatible

4) Does the antibody attack self proteins

What do B cells need to activate and proliferate

co-stimulation

What happens if you get antibody stimulation without co-stimulation

the B cell is inactivated

Which statement is TRUE:

A. The DNA of all B Cells is identical.

B. Each antibody molecule can bind two identical

antigen molecules.

C. The light chain locus rearranges before the

heavy chain locus does.

D. A single B Cell may make several antibodies,

recognizing different epitopes.

E. Statements A – D are ALL FALSE.

B

How does antibody signaling happen

an antibody is complexed with kinase proteins and when an antigen attached the BCR activates a signaling pathway

How does CO-stimulation happen

while the BCR is bound, a complement binding protein must also be bound and start a signaling pathway in order to fully activate the B cell

How does T Cell dependent activation happen

the co-stimulatory signal comes from binding to a Helper T cell instead of a antigen

What does T Cell dependent activation activate

1) The B Cell

2) Class switching

3) Somatic Hypermutation

4) Memory functions

5) Proliferation

6) antibody secretion

What does T cell independent activation activate

1) proliferation

2) antibody secretion

How does class switching work

multiple molecular processes like alternative splicing or DNA recombination help to change the heavy chain’s invariable region

What can alternative splicing produce

secreted and membrane bound antibodies with the same constant region

How do co-stimulatory signals and co-activating cells direct class switching

via cytokines

What is somatic hypermutation

the site-directed mutation of the variable region

What can B cells do

1) inactivate bacterial toxins

2) flag pathogens for clearance

3) Present antigens to T cells

4) Form a memory

Which of the following statements is TRUE:

a) Antibodies can directly lyse a bacterium.

b) All antibodies are secreted.

c) Engaging the BCR is sufficient

to initiate somatic hypermutation.

d) Antibodies can neutralize small toxins.

e) ALL statements a) through d) are TRUE

D

What does TCR stand for

T Cell Receptor

How are TCRs similar and different from antibodies

1) There are only 2 chains (similar to one arm of the antibody)

2) There is a constant and variable region on each chain

3) They associate with kinases to make a receptor

What forms of diversity do T cells have

only V-region assembly and junctional diversity

What are the two major classes of T cells

Cytotoxic and helper

What do cytotoxic t cells do

directly kill viruses and infected cells

What do helper T cells do

active B, T and effector cells

Is MCH Class 1 on all cells

yes

Is MCH Class 2 on all cells

no, only antigen presenting cells

What do the MCH molecules do

present peptides to other cells

What types of cells do MHC Class 1 associate with

B and Helper T

What types of cells do NCH Class 2 associate with

Cytotoxic T

How do the TCR and MHC interact

the TCR sits on top of the MHC and detects the peptide

How do you load MHC 1 molecules

let a virus in and when the protean is sent to a proteosome the viral peptides go into the ER and are detected by and MHC 1 and sent to the membrane to be detected

How do you load MCH 2 molecules

A MHC 2 is added into an endosome and detects the antigen and then is moved to the membrane

How does T cell development work

the T cell must be created successfully, then it circulates in the blood until needed as naive. It must make the TCR and weakly recognize MHC molecules with self peptides for survival, but must acitvate and differentiate after co-stimulation

How do T cells bind

they bind to both the MHC and the foreign peptides

Which immune cells are most likely to interact with the

following pathogens/antigens?

Antigens on the outside of an extracellular bacterium

Answer Options:

A) B Cells (antibodies) alone D) T H Cells alone

B) TH Cells and B Cells (antibodies) E) T C Cells alone

C) TC Cells and B Cells (antibodies)

B

Which immune cells are most likely to interact with the

following pathogens/antigens?

Antigens on the inside of an extracellular bacterium.

Answer Options:

A) B Cells (antibodies) alone D) T H Cells alone

B) TH Cells and B Cells (antibodies) E) T C Cells alone

C) TC Cells and B Cells (antibodies)

D

Which immune cells are most likely to interact with the

following pathogens/antigens?

Viral proteins from inside a host cell

Answer Options:

A) B Cells (antibodies) alone D) T H Cells alone

B) TH Cells and B Cells (antibodies) E) T C Cells alone

C) TC Cells and B Cells (antibodies)

E

Which immune cells are most likely to interact with the

following pathogens/antigens?

Coat proteins from extracellular viral particles

before infecting host cells.

Answer Options:

A) B Cells (antibodies) alone D) T H Cells alone

B) TH Cells and B Cells (antibodies) E) T C Cells alone

C) TC Cells and B Cells (antibodies)

B

T Cells recognize ________and _______portions of

_________and _________proteins.

external, internal, extracellular, intracellular