Module 9: The Immune System

Function of the immune system

Provides protection against infection and disease. Classified into innate and adaptive defenses

Difference between innate immune system and adaptive immune system

Innate has General defense strategies, is present at birth, and fast acting, ex. inflammation

Adaptive has specific strategies, acquired over time, slow but powerful, cell mediated and humoral mediated, has memory

Immune system defenses on the surface barriers

Skin and mucous membranes

Function of the epidermis

Mechanical barrier to harmful pathogens and other substances

Feature of the epidermis and it's function

Contains keratin which makes it resistant to most weak acids and bases and bacterial enzymes

What are the integumentary system secretions and what is their function

Sweat and sebum. They are slightly acidic substances that inhibit bacterial growth. EX. Dermcidin (antimicrobial)

What do intact mucous membrane secrete and why

Lysozyme - inside that breaks down bacterial cell wall

Feature of the intact mucous membranes and it's function

Contains mucin which is the thick sticky mucus that traps microorganisms.

Where is mucin

Lines that Digestive and respiratory passageways

Function of acids in skin and mucous membranes

Inhibit bacterial growth

Where are protective acidic secretions secreted

In the skin (sebum), stomach and vagina

What are defensins

Broad spectrum antimicrobial peptides

Internal innate differences of the immune system

Phagocytes (macrophages neutrophils dendritic cells), natural killer cells, inflammation, antimicrobial proteins, fever

Function of the immune system internal innate defenses

Identify potentially harmful substances then recognize and find molecules that are part of infections organisms but not part of normal cells

What are General molecules

Types of molecules that are found on lots of different types of viruses and bacteria

What are PAMPs

Pathogen-associated molecular patterns recognize General molecules common to many pathogens

What are DAMPs?

Damage-associated molecular patterns that recognize General molecules come into many damaged or disease cells

What do DAMPs do?

Mainly signals for phagocytosis to occur

Examples of DAMPs

Nucleotides, alarm ends, stress proteins, calcium binding protein

What are PAMPs and DAMPs recognised by

Immune cell receptors

What are TLRs?

Toll Like Receptors are proteins that are able to identify pathogenic molecules

How do toll-like receptors work

When molecular patterns bind to a TLR, and alarms the immune system, which triggers an immune response, leading to inflammation

Neutrophils

Most abundant white blood cell. Phagocytic

Macrophage

Largest white blood cell that removes bacteria, foreign particles, and dead cells

How are macrophages produced

Monocytes found in the blood migrate to tissues and become macrophages

Where are the different types of macrophages found

Microglia - Brain

Alveolar macrophage - alveoli

Langerhans - skin

What are natural killer cells

Large granular lymphocytes that kill cancerous cells and virus infected cells before the adaptive immune system is activated

What are the two ways natural killer cells work

Not phagocytic. They attach to cells inject chemicals and induce apoptosis. They also secrete cytokines to call other immune cells and initiate information

What are cytokines

Any molecules secreted by a body cell that induces an immune response

Paracrine signaling

Acts by signaling nearby cells

Endocrine signaling

Act by secreting into the blood

What is inflammation

A condition in which the body reacts to injury, irritation, or infection.

What can induce inflammation

Trauma, heat, irritating chemicals, or infections by microorganisms

What are the four purposes of inflammation

Protects spread of damaging agents, disposes of cell debris and pathogens, alerts adaptive immune system, set stages for repair

What are the stages of inflammation

1. Inflammatory chemical release

2. Vasodilation and increased vascular permeability

3. Phagocyte mobilization

Stage one of inflammation

Chemical alarm set off by cells at the site of injury. Mast Cells secrete histamine, kinins, prostaglandins, cytokines

Stage 2 of inflammation

Inflammatory chemicals cause local arterial dilation and increased permeability of blood vessels. Can lead to swelling

Hyperemia and it's function

redness of the skin due to increased blood flow. Leads to more blood and immune cells to the site of injury

Why does a person experience heat during inflammation

Increased blood and immune to the site of injury

Why does a person experience swelling during inflammation

Increased fluid to the site of injury

Why does a person experience PAIN during inflammation

Increased fluid to the site creates pressure which is painful

Exudate

fluid, such as pus, that leaks out of an infected wound. Contains important proteins and clotting factors, which are important for walling off the injury site.

Function of exudate

Contains important proteins and clotting factors, which are important for walling off the injury site and preventing infection spread

What types of vessels pick up the fluid from the interstitial space

Lymphatic vessels, which goes to lymph nodes (why lymph nodes get swollen when there's infection)

Stage 3 of inflammation

Phagocyte mobilization. leukocytosis, margination, diapedesis, chemotaxis

Stage 3 of inflammation - a. leukocytosis

Injured cells secrete leukocytosis inducing factors. Neutrophils enter blood from bone marrow

Stage 3 of inflammation - b. margination

Phagocytes cling briefly to inner walls of inflamed endothelial cells, which leads to a slow rolling movement

Stage 3 of inflammation - c. diapedesis

Inflammatory chemicals called neutrophils to flatten and squeeze between the endothelial cells of the blood vessel

Stage 3 of inflammation - d. chemotaxis

Breadcrumb Trail of inflammatory chemicals cause the neutrophils to the site of injury. Monocytes follow behind and become macrophages once in tissues

How do antimicrobial proteins enhance innate immunity

By attacking microorganisms directly. By hindering their ability to reproduce

What are the two important antimicrobial molecules

Interferon and complement

What is a virus

Infectious substance that contains genetic material encased in a protein capsule. It uses a host cell to replicate

What are interferons

Molecules that help protect cells that aren't yet infected with a virus

What are the three ways interferons work

prevent viral replication to other cells by:

inhibiting viral protein synthesis

Signals neighboring cells to undergo apoptosis

Activate immune cells

What are complement proteins?

A group of plasma proteins in the blood that, when activated, trigger reactions to destroy pathogens.

What 3 actions do complement proteins trigger?

Lysis of bacteria, destruction of foreign substances including viruses, amplification and activation of immune system

What are the three main initiators of complement proteins

Classic pathway-antibodies

Lectin pathway-bacteria

alternative pathway-spontaneous

What are the three primary outcomes of complement proteins

Opsonization - protein-coated pathogen tagged for fake cytosis

Enhancing inflammation - histamine release, but vessel permeability, chemotaxis attracts phagocytes

Membrane Attack Complex - Hole in bacterium leading to cell lysis

What is a fever

Abnormally high body temperature

Difference between inflammation and fever

Inflammation is a local response to injury, and fever is more widespread/systemic

What are pyrogens

fever producing substances

Body's internal thermostat

hypothalamus

What are the four benefits of fever

Increased metabolism, liver and spleen sequester iron and zinc, increase neutrophil and monocyte function, potential to cook the bacteria to death

Potential cost of fever

Too high temperature can cause denaturing of proteins, leading to tissue damage

What does the adaptive immune system rely on

Relies on antigens to function

What are antigens

Anything that evokes an immune response

Antigenic determinant (epitope)

Part of the antigen that antibody or immune cell receptors bind to

Glycoproteins

Carbohydrates that dot the extracellular surface of cells

Self-marker

labels the body's cells as a "friend" and are tolerated by the immune system

Major Histocompatibility Complex (MHC)

Group of genes that code for proteins found on the surfaces of cells that help the immune system recognize foreign substances.

MHC1 molecules function

Informs other cells/immune system that this is self

Which cell type would not display MHC1 molcules

erythrocytes

How do MHC1 molecules inform the immune system

They contain a peptide-binding groove that displays amino acids of normal healthy proteins

What are the 3 cell types of adaptive immunity

1. Antigen-presenting cells (APCs)

2. B-cells

3. T-cells

Function of antigen-presenting cells (APCs)

engulf antigens and present fragments of antigens to T cells for recognition

How do antigen-presenting cells (APCs) work

They engulf pathogens then fuse with a lysosome which breaks down the pathogen

Cell-mediated immunity

type of adaptive immunity produced by T cells that attack infected or abnormal body cells

Humoral immunity

Specific adaptive immunity that produces antibodies to deactivate and tag antigens

Where do T cells come from and where do they mature

bone marrow, mature in thymus

Where do B cells come from

bone marrow, mature in bone marrow

Cell-mediated immunity receptors

T-cell receptors (TCR) and cluster of

differentiation (CD)

Humoral immunity receptors

Antibodies and B cell receptors (BCR)

At the end of the B and T cell maturation process, they become either

Effector cells which fight immediate infection, and memory cells that respond to the same antigen at a later date

Where do antibodies circulate?

Freely in body fluids.

What type of targets does humoral immunity have?

Extracellular targets.

2 B cells populations

Plasma B cells (effector cells) and memory B cells

Types of antibodies

IgG, IgM, IgA, IgD, IgE

IgM

Type of antibody that elicits early primary immune response.

If IgM found, indicates:

current infection

IgA

Antibody found in secretions that stops pathogen attachment to epithelia

IgD

B cell receptor that detects antigens for activation

IgE

Antibody that binds to basophils to release histamine, for allergic reactions

Where is IgE found

Skin, mucosa of GI, respiratory and tonsils

Most abundant antibody type

IgG

IgG

Main antibody of late primary and secondary immune responses

Function of IgG

Protects against bacteria, viruses,

ant toxins (blood and lymph)

Primary immune response

Cell proliferation and differentiation upon exposure to antigen for the first time

Which types of B cells respond to primary immune response

Plasma (effector) cells

How long does the primary immune response take and why?

3-6 days because it takes time for the cells to proliferate

What is the role of Memory B cells upon re-exposure to the same antigen?

They provide a faster, more prolonged, and more effective immune response.