Part I - 01 Basic Concepts in Immunobiology

Question 1

What is immunology and who invented it?

Answer 1

Immunology is the study of the body’s defense against infection.

The beginning of immunology as a science is usually attributed to Edward Jenner for his work on vaccination in the late 18th century.

Question 2

What is vaccination?

Answer 2

Term is still used to describe the inoculation of healthy individuals with weakened or attenuated strains of disease-causing agents in order to provide protection from disease.

Question 3

What is variolation?

Answer 3

The inhalation or transfer into superficial skin wounds of material from smallpox pustules—had been practiced since at least the 1400s in the Middle East and China as a form of protection against that disease.

Question 4

What two types of diseases does the immune system protect us from?

Answer 4

The immune system protects from two types of disease:

1. caused by infection with a pathogen
2. cancer

Question 5

Give 4 examples when the immune system is not always protective.

Answer 5

The immune system is not always protective

• tissue damage in severe inflammation
• allergy
• autoimmunity
• organ transplant rejection

Question 6

What is a pathogen?

Answer 6

Pathogen: A pathogen is any organism that has the potential to cause disease to the host.

– usually a microorganism or parasite (Fig. 1.3, 1.4).

– Review: bacteria vs. virus vs. fungi vs. protozoa.

– Some are called “opportunistic pathogens” since they only cause disease in immunologically weakened or compromised hosts, e.g. HIV-infected or patients undergoing immunosuppressive therapy.

– most pathogens don’t kill the host; best to allow host to survive and transmit disease. Even severe diseases like influenza usually don’t kill the patient, as the immune system eventually eliminates the virus.

Question 7

Term for normal gut flora?

Answer 7

Many microorganisms are not pathogens though they co-exist in the body. e.g. the normal “flora” of the gut. Term for normal gut flora is commensal species. Some of these have essential “symbiotic” functions.

Question 8

What are opportunistic pathogens?

Answer 8

Some are called “opportunistic pathogens” since they only cause disease in immunologically weakened or compromised hosts, e.g. HIV-infected or patients undergoing immunosuppressive therapy. Many microorganisms are not pathogens though they co-exist in the body. e.g. the normal “flora” of the gut.

Question 9

What is an antigen?

Answer 9

Antigen: a substance that induces an immune response

– usually a macromolecule derived from a pathogen

– can be any molecule not normally found in the host

Question 10

Innate Immunity

Answer 10

Mechanisms that recognize and control/eliminate pathogens without requiring prior exposure. A first line of defense that is “pre-existing” in the host but relatively non-specific.

Question 11

Adaptive Immunity

Answer 11

Mechanisms that are not pre-existing but develop over time after exposure to a pathogen. The adaptive immune response is mediated by lymphocytes (T cells and B cells), is antigen-specific and provides lifelong immunity to re-infection.

Question 12

Leukocyte

Answer 12

white blood cell

Question 13

Lymphocyte

Answer 13

A subtype of leukocyte that includes T cells and B cells. Also includes Natural Killer (NK) cells that are part of innate immunity.

Question 14

Antibody

Answer 14

Antigen-binding protein in plasma and other body fluids

Question 15

Plasma

Answer 15

The liquid component of the blood. Plasma leaks out of the blood vessels into tissues and mixes with extracellular fluids. Together this material is called lymph. Blood plasma can be obtained from blood by removal of the cells (leukocytes, red blood cells and platelets) using centrifugation, without clotting (blood collection tube has to contain an anti-clotting agent).

Question 16

Serum

Answer 16

The liquid component of the blood when clotting occurs before separation of the cells.

Question 17

Why is the protein composition of serum different than plasma?

Answer 17

This is because clotting causes cleavage of some plasma proteins, and secretion of additional proteins by activated platelets.

Question 18

For innate immunity, name 4 anatomic barriers and 1 physiological barrer.

Answer 18

Anatomic barriers (Skin, mucous, cilia, epithelium)

Physiological barriers (low pH of stomach)

Question 19

For innate immunity, what are two main polypeptide mediators classes?

Answer 19

• lysozyme is an enzyme in saliva and tears, breaks bacterial cell walls;
• defensins are anti-bacterial peptides in GI tract and other epithelial surfaces

Question 20

Phagocytosis

Answer 20

Phagocytosis: cells internalize and break down foreign cells and macromolecules

Question 21

Inflammation

Answer 21

Inflammation: tissue damage and infection induce leakage of vascular fluid and cells that help fight infection.

Question 22

How does normal flora work as part of the innate immune system?

Answer 22

Normal flora protect against infection by pathogens by competing for resources/niches.

Question 23

What is the role of the innate immune system with regards to the adaptive immune system

Answer 23

The innate immune response plays a critical role in the initiation and direction of the adaptive response through secretion of cytokines (general term for secreted small protein with biological activity on other cells) and chemokines (proteins that attract and activate other leukocytes), along with processing and presenting pieces of the pathogen (antigens) to lymphocytes.

Question 24

Cytokines

Answer 24

Cytokines - general term for secreted small protein with biological activity on other cells

Question 25

**Chemokines**

Answer 25

**Chemokines** - proteins that attract and activate other leukocytes

Question 26

What is **inflammation**, how does it happen?

Answer 26

heat, pain, redness, swelling Cells of the innate immune system recognize pathogens (see below) and secrete cytokines that cause local dilation of capillaries * Increased blood flow causes local warming and redness * gaps in vessel walls allow leakage of fluid from bloodstream into infected tissue site; causes swelling and pressure on local nerve endings --\> pain * cells are attracted by chemokines and cross openings in vessel walls to enter infected tissue; these release further inflammatory substances

Question 27

What are PAMPs, what do they do?

Answer 27

PAMPs - “pathogen-associated molecular patterns” Cells of the innate immune system can also directly recognize pathogen surfaces that have common invariant structures that are not present in the host.

Question 28

How does the **complement system** protect during innate immunity?

Answer 28

Plasma proteins (e.g. components of the **complement** system) bind to pathogen surfaces and mark them as dangerous. Cells of the innate immune system have surface receptors that recognizes complement-coated pathogens and mediate uptake and destruction.

Question 29

Describe **adaptive immunity**

Answer 29

Adaptive immunity Is antigen-specific (i.e. can distinguish one strain of bacteria or virus from another) Requires a delayed period of induction (4-10 days) Provides long-lasting immunological **memory**; second encounter with antigen induces a much stronger and faster response. This is the basis for vaccination. The memory is specific. Is mediated by lymphocytes and antibodies enhances effector mechanisms of innate immunity by focusing the effective elements to the site of invasion and by enhancing responses such as phagocytosis

Question 30

What mediates adaptive immunity

Answer 30

Lymphocytes ( specifically **T cells** and **B cells**) and antibodies

Question 31

What is **antigen specificity of lymphocytes**?

Answer 31

Each lymphocyte has a single antigen receptor---but the sequence is unique for each cell. This sequence diversity is unprecedented in biology and is generated by random cutting, splicing and modification of small gene segments. Therefore, each lymphocyte has a different antigen **specificity**.

Question 32

What is **clonal selection** of the adaptive immune system?

Answer 32

**Clonal selection** refers to the proliferation of antigen-specific clones that are useful in combating an infection. In other words, the immune system is prepared to respond to an almost infinite array of antigens, but each pathogen selects only a few cells that then make many copies of themselves. The reason that adaptive immunity requires time to develop is because it takes time for selected cells to proliferate and make enough copies of themselves to carry out their immune function.

Question 33

Compare loss of components of innate immune system vs adaptive immune system?

Answer 33

Loss of components of the innate immune system generally leads to more rapid death by infection than loss of adaptive immune system (e.g. burn victims, radiation ablation of bone marrow vs. HIV)