W o r k b o o kLessons 5.1,2 1

Review the physical, chemical, and cellular barriers of the immune system.

Before proceeding with a discussion about how immune responses work, we need to refresh our memory about the immune barriers that we discussed in Unit 1.5. Use your knowledge of these barriers to answer the questions to the right, but if you need to return to Unit 1.5 to refresh your memory.

Our body’s barriers – the innate im-mune system

LESSONS 5.1 & 5.2 WORKBOOK

What do the physical barriers of the immune system include? __________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________What do the chemical barriers of the immune system include?

_______________________________________________________________________________________________________________________________________________________________________________________________________________________________________What do the cellular barriers of the immune system include? _________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

DEFINITIONS OF TERMS

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For a complete list of defined terms, see the Glossary.

In Unit 5 we are going to explore how the body responds to infection and how pathogens bypass these responses. In this lesson we will review the structures / barriers of the immune system that we learned in Unit 1. We will then fo-cus on cellular responses to microbes that enter the sterile areas of the host. This discussion will begin by defining in-nate and adaptive immunity. Then we will focuses on how cells of the innate immune system recognize and respond to pathogens. These cells ‘see’ the world as ‘self’ and ‘non-self’ with receptors that recognize structures in microbes that do not exist in humans. Once they recognize a non-self entity, innate immune cells respond by removing the threat and sounding the alarm. Most infec-tions are stopped by these innate immune responses!

MacrophageMacrophage  

W o r k b o o kLessons 5.1,2 2

Immune responses are generally broken into two classes; innate and adap-tive.Once a pathogen gains access to the sterile parts of the body, like the bloodstream, it will meet im-mune cells. These cells come in two main class-es: innate and adaptive. As the names suggest, we are born with innate responses and they don’t change in respond to different pathogens. Because they are pre-made they can respond quickly when a foreign entity is encountered. In contrast, adaptive responses need to learn to fit individual pathogens. This process takes time so adaptive responses are delayed when a pathogen is encountered for the first time, but the response is remembered so if the same pathogen is encountered again the response will be swift.

There are numerous types of innate cells but only two types of adaptive cells.

As we learned before, innate and adaptive immune cells are found in the sterile interior of the body. They are only called into play when a microbe breaches other immune barriers to gain access to the sterile interior. There are many types of innate cells but we will focus on the functions of the three most important: macro-phages, dendritic cells, and neutrophils. All of these cells are specialized to remove pathogens by eating them (phagocytosis). They also call for help by releasing cytokines. The cytokines can stimulate or inhibit cells or in some cases they can physically attract them. When the cytokines attract other cells to the site of infection or host damage this is called chemotaxis.

If innate cells are not able to control an infec-tion they will activate adaptive immune cells. As mentioned above, there are only two types of adaptive cells: B cells and T cells. We all have a single B and T cell specific for every imagin-able pathogen already, but one is not enough! in order to respond to an infection this single cell needs to multiply. Thus there is a delay after the pathogen has been recognized while the B and T cells expand to generate a large enough army to fight the invader.

DEFINITIONS OF TERMS

Innate respnses are the first line of defense. We are born

with innate immunity encoded in our DNA. Innate responses

provide general pathogen recognition, they are not

pathogen specific.

Adaptive responses add another line of defense when they are called into action by

the cells of the innate immune system. Recognition by adaptive

cells is learned rather than pre-made at birth and responses

are tailored to fit specific pathogens.

LESSON MATERIALSCan the receptors that innate cells use to recognize pathogens change to better recognize pathogens?

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Why are adaptive immune responses delayed?

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Dendritic cell

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All cells in the blood, including immune cells, are made in the bone marrow through a process called hematopoiesisLike most cells in the body, blood cells are constantly dying and being replaced (this is called turning over), and both in-nate and adaptive cells behave in the same way. All cells in the blood are generated from stem cells in the bone marrow. The stem cells can either di-vide, which keeps the number of stem cells constant, or they can acquire the specialized characteristics of all the cell types in the blood (this is called differen-tiation). Immune cells differentiate from stem cells in stages:First, a stem cell differentiates into a my-eloid or lymphoid progenitor cells (it is not important to remember these specific names, but you should remember that the first stage does not pro-duce fully mature cells). Then, these immature blood cells further differentiate. The immature myeloid progenitor cells become blood cells, platelets, and innate immune cells. The lymphocyte progenitor cells then become mature adaptive immune cells (either B or T cells). It is important to understand this process because combating infection often requires certain immune cells to expand considerably in number. As we will see later, this rapid expansion requires a considerable amount of energy. In fact, when a person has an infection their metabolic needs may increase by 1,000 calories a day.

The rest of this unit focuses on the cellular responses to an infection.

Macrophages, dendritic cells, and neutro-philes reside in the blood and tissues of the body, constantly patrolling for foreign invad-ers. They use their innate receptors to recog-nize these invaders. The picture on the right shows a neutrophil (yellow) attached to a for-eign cell (pink).

DEFINITIONS OF TERMS

Stem cell: is a cell that can divide into more stem cells or

change (differentiate) into other cell types.

Differentiation: is the process of a cell changing to become another cell type or subtype. For example, a stem cell can

turn into a lymphocyte.

For a complete list of defined terms, see the Glossary.

LESSON MATERIALSHow are stem cells involved in hema-topoiesis?

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How does cellular differentiation play a role in hematopoiesis?

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How might the process of hemato-poiesis relate to the phrase: feed a cold?

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Neutrophil

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Innate receptors ‘see’ targets that are not found in the hostTo fight infection, immune cells need to be able to distinguish between a pathogen and a self cell. This ability to distinguish between self and non-self is the foundation of the immune response, and re-quires specific receptors that can recognize non-self molecules. This is why many patho-gens adapt ways to camouflage them selves from immune cells. After all, if immune cells can’t ‘see’ the pathogen they won’t respond.The receptors innate cells use to recognize pathogens are inherited and don’t change, so they need to recognize parts of pathogens that are highly conserved. These targets of recognition are called Pathogen Associated Molecular Patterns (PAMP). As you can see in the slide to the right, most PAMPs are structures that are required for a pathogen’s life cycle, so mutating the PAMP to try to avoid immune recognition is likely to put the pathogen at a selective disadvantage. Because of this the innate immune system can clear about 99% of all infections. However, if the pathogen does mutate, the innate receptors can’t adapt in response, so the innate cells may become blind to the pathogen!

After innate cells recognize a PAMP they neutralize the threat in two main ways: Phagocytosis and Chemotaxis

Phagocytosis: When an innate cell recog-nizes a pathogen it will engulf it. Once inside, the innate cell digests (kills) the pathogen us-ing an endosome that acts like the stomach of an innate cell.

Chemotaxis: Innate cells also sound the alarm by releasing molicules (cytokines and chemokines) that recruit other immune cells. Cytokine release also increases blood flow at the site of infection causing swell-ing and heat (inflammation). For example, a mosquito bite becomes red and hot because innate cells move to the site.

Most infections stop here!!!

DEFINITIONS OF TERMS

Conserved: A structure or sequence that is unchanging or similar across species, cells, or

microbes.

Endosome: a compartment inside of a cell contained within

a membrane.

Chemokines: These molecules are a type of cytokines that are

used to attract other cells by chemotaxis.

For a complete list of defined terms, see the Glossary.

LESSON MATERIALSPAMPS that innate cells recognize are generally conserved structures. Why might this be the case?

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Define phagocytosis:

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Define chemotaxis:

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W o r k b o o kLessons 5.1,2 5

If innate responses can’t clear an infection they will prime adaptive im-mune cells.

Innate cells activate adaptive cells in three ways:

One, they release cytokines that stimulate B and T cells. Two, they release chemokines to attract adaptive cells to the site of infection. Three, they display the peptides from the digested invader on their cell surface for patrolling T cells to see. These molecules are called PAMPS and the process of displaying them is called antigen pre- sentation and it is required to activate T cells. Antigen presentation is shown in the figure above, and we will describe how antigen presentation occurs in subsequent lessons.

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