Innate Immune system

Describe the three lines of defense of our immune system.

first line: physical and chemical barriers

• skin, mucous membranes, secretions, microbiome

• how body is built; “walls” that keep you safe

second line: innate immunity

• phagocytes, interferon, complement, inflammation, fever

• part of immune system that is always turned on, active, and monitoring for things that don’t belong; starts as soon as microbe passes first line

• covers you for 7-10 days as the adaptive response turns on

third line: adaptive immunity

• specialized lymphocytes (T cells and B cells), antibodies

• much stronger response; not always on—needs to be turned on/induced

• takes about 7-10 days to ramp up adaptive response

What are the goals of the first line of defense?

prevent

inhibit

kill (potentially) microbes

Where are mucous membranes located? What are the opposing functions of the mucous membranes?

located: respiratory, digestive, urinary, and reproductive tracts

function: acts as a barrier to microbes to not be able to get to the thin tissues; many cell layers thick

Explain why mucous membranes are a more vulnerable portal of entry than the skin.

they are more susceptible to infections because they are very thin tissues and moist

Give some examples of secretions and their chemical components that protect the skin and mucosal surfaces. Explain how the normal microbiota serves a protective role against microbial invasion.

secretion: mucous—protects tissues from pathogens; more mucous will develop when we are sick for this very reason

secretion: tears—contains lysozymes which target PG in bacteria

secretion: sweat—contains salt that targets PG

normal microbiota: microbial antagonism

• microbes that live in /on our bodies have an advantage over those who want to invade; they take up space and resources that makes it harder for the pathogens to get into our system

What are the goals of the second line of defense?

• eliminate/kill/restrict growth of invading pathogen

  • if possible, will get rid of pathogen right then and there

  • if it can’t kill, it will do everything it can to control the spread/growth of it

• contact adaptive immune system to get third line of defense started (does this via cytokines)

How does the second line of defense distinguish “self” from “non-self”?

Pathogen Associated Molecular Pattern (PAMP):

• structures found on many different microbes

• Toll like receptors (TLR):

  • how a macrophage recognizes a PAMP

  • TLR on surface of host cell that look for pathogens on exogenous pathogens

Explain how the innate immune cells can detect extracellular pathogens (that live outside of host cells) and intracellular pathogens (those that are inside host cells).

What are the phagocytic cells that participate in the second line of defense?

neutrophils

• WBC

• most prominent

• roams around the body to phagocytize pathogens

• turns into pus after they die

macrophages

• phagocyte

• antigen presentation

• migrate to lymph nodes

dendritic cells (DC)

• phagocyte

• antigen presentation

• migrate to lymph nodes

B cells

• adaptive immune cells

• antigen presentation, migration

• antibody production; produce antibodies when activated (via plasma cells)

What is chemotaxis and why is it important in an innate immune response?

chemo= chemical

taxis= movement

moves toward cytokine

other immune cells will move toward the cytokines to help out with infection; will INDUCE a BIGGER response

How do phagocytes recognize pathogens?

PAMPS

phagocytes get activated when their TLR bind to PAMP on antigen, leading to phagocytosis and cytokine release

Describe the mechanism of phagocytosis.

cell extends cellular arms and brings microbes in

traps microbe in a vesicle

• once vesicle forms it breaks down the pathogen, leaving it in pieces

• if its a macrophage or DC, the proteins (usually) from pathogen will get displayed via MHC Class II

Describe some strategies that some microbes use to evade phagocytosis.

Describe how phagocytic cells process and present antigen on their surface.

once the pathogen is digested, the protein particles from that pathogen in the vesicle will fuse with the phagocyte’s outer membrane via MHC class II so that they can present the antigen to other cells

What is MHC class II?

MHC class II is a protein in the phagocytes that allow for protein particles from the pathogen to stick to it, and present it to other cells in the lymph nodes

After dendritic cells process and present pathogen, they travel to the lymph nodes. Why is this an important part of the immune response?

Its important because once the DC is in the lymph nodes, it needs to present the pathogen to the correct helper T cell to start clonal expansion and differentiation.

Describe, in general terms, how the complement system tags microbial cells and products as foreign.

Factors B, P, and D bind to the microbe.

after this occurs, C3 binds to B, P, D on the microbial surface

This leads to fragmentation of C3, and activation of the complement pathway

SPECIFICALLY ANSWERING THE QUESTION

C3 splits into C3a and C3b

C3b activates:

• opsonization: coats/covers outside of cell

  • putting proteins on surface of a pathogen

  • taking half of C3b and put on surface of microbe so that its easier for phagocytes to see

• Membrane attack complex

  • attacks the membrane of a microbe

  • triggers combination of other complement proteins

How does fragmentation of C3 lead to the activation of complement? What are the function of C3a, C3b, C5a and C5b?

What are the three outcomes of complement activation? Describe how the alternative pathway activates complement. Under what conditions does this happen? Describe how the lectin pathway activates complement. Under what conditions does this happen?

Describe how the classical pathway activates complement. Under what conditions does this happen? There are three ways to activate complement. Which one happens first, second and third during a response to a pathogen?

Explain the difference between intracellular TLRs and TLRs in the membrane of the cell. What purpose do each of them serve?

Describe how viruses and intracellular bacteria trigger the production of interferons.

How do interferons help to defend the host against the spread of the infection.

What are the targets of natural killer cells? How do they kill their target cells?

Describe how cells process and present endogenous antigen on their surfaces.

Only professional antigen presenting cells can present on MHC class II, but all cells can present on MHC class I. Why is that an important part of the immune response?

What are the four signs and symptoms of inflammation? What are the functions of inflammation?

Describe the steps of inflammation: Be sure to use the terms vasodilation, phagocyte migration, histamines, cytokines, margination, and diapedesis

What are the first types of phagocytes that migrate to the site of infection? Which come later?