Immune System APSBI4UP

• Phagocytic Cells

• Antimicrobial proteins

• Inflammatory Response

• Natural Killer Cells

• Skin

• Mucus layer

TYPES OF IMMUNITY

INNATE IMMUNITY ACQUIRED IMMUNITY

EXTERNAL DEFENCES INTERNAL DEFENCES HUMORAL

RESPONSE

CELL- MEDIATED

RESPONSE

Human Physiology - Introduction to the Immune Systemhttps://www.youtube.com/watch?v=CG931UYMbN0

• Phagocytic Cells

• Antimicrobial proteins

• Inflammatory Response

• Natural Killer Cells

• Skin

• Mucus layer

TYPES OF IMMUNITY

INNATE IMMUNITY ACQUIRED IMMUNITY

EXTERNAL DEFENCES INTERNAL DEFENCES HUMORAL

RESPONSE

CELL- MEDIATED

RESPONSE

Human Physiology - Innate Immune System

https://www.youtube.com/watch?v=sYjtMP67vyk

Innate Immunity

External Defences: the pathogen must first enter through the external barriers in order to penetrate the host. This is the first line of defense exhibited by organisms

1) Intact skin: ◦ Low pH, hostile for pathogenic bacteria

◦ Has good flora bacteria, overcrowds the skin

◦ if there is a tiny abrasion the pathogen may enter the body

2) Mucus Lining:

◦ secreted by the epithelial cells of the respiratory and digestive tract

◦ Trap anything foreign and remove it from the body

Innate Immunity

Internal Cellular and Chemical Defenses:

If the pathogen manages to enter the human body, it must now fight against internal defense mechanisms.

- Most of these defenses involve ‘phagocytosis’

- Phagocytic cells have receptors that can bind to the

pathogen and engulf the pathogen.

Some viruses and bacteria have developed mechanisms that have enabled them to either not be recognized by the receptors or be resistant against the enzymes in the lysosomes.

Internal Defenses

1) white blood cells (a.k.a leukocytes). Each will differ in its life span and phagocytic ability.

Neutrophils: approximately 60-70% of all WBCs. They go to the site of infection and engulf any pathogen. But they will also self-destroy themselves in the process and thus only live for a few days.

Monocytes: give rise to macrophages and make up 5% of the blood. Some macrophages will reside in the tissue in which they differentiated and others will circulate the blood and patrol for pathogens. When they come in contact with a pathogen and engulf them, a series of pathways are activated which gives it its function.

Eosinophils: have a low phagocytic activity. They release toxins/chemicals that help to destroy any parasite that has entered the body.

Basophil: secrete histamine.

Lymphocytes. They create antibodies to defend against bacteria, viruses, and other potentially harmful invaders

Dendritic Cells: not a WBC. They process antigen material and present it on the cell surface to the T cells of the immune system

2) Antimicrobial Proteins:

Belong to the complement system. Proteins are only activated in the presence of a pathogen.

Interferon alpha and beta:

virus-infected cells will release these proteins to neighbouring cells so that they can either burst or stop the process of transcription/translation so that no viral proteins are made

Interferon gamma:

stimulates macrophage and activates them

Internal Defences

3) Inflammatory Response: Chemicals are released by cells to initiate an inflammatory response when tissues are damaged.

•Mast cells • located in the connective tissues

• will release histamine when pathogen destroys nearby tissue

• Other chemicals released by the mast cells and macrophages will help dilate the blood vessels and increase blood flow → redness and heat associated with an inflammation

•Delivers the appropriate antimicrobial proteins and clotting factors to heal the tissues

•The chemokines released throughout this process also help to signal more WBC to the injured site.

Internal Defences

Internal Defenses: Inflammatory Response

The Inflammatory Response HD Animation

https://www.youtube.com/watch?v=fcAAnj4czzo

Acquired Immunity

When the macrophages and dendritic cells have engulfed the pathogen, they release proteins (cytokines) that help attract and activate lymphocytes to the site of infection.

Lymphocytes: - the primary WBC involved in the secondary response

- release antibodies that recognize the epitope of the antigen.

Antibodies: - proteins that are released by lymphocytes

- can recognize the epitope of different antigens

Antigens: - any pathogen that can elicit a response from a lymphocyte

- proteins that are either on the surface of the pathogen or the

toxins released by the pathogen.

Epitope: - the surface of the antigen

Lymphocytes

•reside in the spleen, lymphatic tissues, lymph vessels

•circulate in the blood and are activated when needed

•two main type of lymphocytes:

1) B lymphocytes (B cells):

- able to recognize the antigen in an intact state and will bind to its epitope to destroy it

- contain antibodies (antigen binding receptors) on its surface that help bind and recognize specific epitopes

2) T lymphocytes (T cells):

- only recognize fragments of the pathogen that are presented by the macrophages

Both lymphocytes contain approximately

100 000 antigen receptors on their cell

membrane that recognize the antigens.

B Cells

• Y-shaped and contains 4 polypeptide chains: 2 heavy chains and 2 light chains.

•Each B cell will have two identical antigen-binding sites.

•When antigen binds, it is held by non covalent bonds to the V-region of the receptor

•The variable region, will vary between B-cells in its amino acid sequence

•→ allows it to recognize a variety of cells/antigens

•The constant regions will be similar between all B-cells

•B-cells may also secrete antibodies into the blood stream (free floating) These are known as immunoglobins.

B Cells

T Cells

The receptor: alpha and beta chain are connected by disulfide bridges

T cells are able to recognize fragments of antigens that are presented on MHC molecules.

What are MHC molecules?

Cells infected by the pathogen or cells responsible for killing the pathogen will present fragments of the pathogen onto its cell surface through the MHC molecules (major histocompatibility complex).

Phagocytic WBCs phagocytose antigens and display them on their surface.

MHC molecules/receptors are made within the cell and transported to the cell surface along with the antigen.

Infected cell

Antigen

fragment

Class I MHC

molecule

T cell

receptor

(a) Cytotoxic T cell

A fragment of

foreign protein

(antigen) inside the

cell associates with

an MHC molecule

and is transported

to the cell surface.

1

The combination of

MHC molecule and

antigen is recognized

by a T cell, alerting it

to the infection.

2

Microbe Antigen-

presenting

cell

Antigen

fragment

Class II MHC

molecule

T cell

receptor

Helper T cell

A fragment of

foreign protein

(antigen) inside the

cell associates with

an MHC molecule

and is transported

to the cell surface.

1

The combination of

MHC molecule and

antigen is recognized

by a T cell, alerting it

to the infection.

2

(b)

T Cells

dendritic cells, macrophages or B cells Cells infected by pathogen

Human Physiology - The Specific Immune Response: Characteristics of B and T Cells

https://www.youtube.com/watch?v=J0Y1MlanzCk

Lymphocyte Development

Lymphocytes are made by stem cells in the bone marrow.

Some are delivered to the thymus and will develop into a T cell.

Lymphocytes that remain in the bone marrow develop into a B cell.

The development of lymphocytes happen in three main steps:

1) Lymphocyte diversity

2) Removal of self-reactive lymphocytes

3) Clonal Selection of Lymphocytes

occur before the cells contact an antigen

occurs when it encounters an antigen

•specific enzymes rearrange and make sure that there is always a J segment associated with a V segment.

•The gene segments undergo random rearrangements which increase diversity.

•The V regions of the antigen receptor will vary between lymphocytes. The amino acids determine its specificity.

•The C region codes for the constant region which is never rearranged.

•This occurs for the light and heavy chains separately, increasing variability even more.

1) Lymphocyte Diversity 1) LYMPH. DIVERSITY

2) Removal of Self-reactive Lymph.3) Clonal Selection of Lymph.

•Due to the random rearrangements, some lymphocytes may recognize antigens on the cell surface of host cells.

•Thus, they are tested in their site of maturation for potential of any self-reactivity.

•They are tested again MHC I and MHC II cells that are located in the area

•The cells that contain receptors recognizing self are destroyed by apoptosis

1) Lymph. Diversity2) REMOVAL OF SELF-REACTIVE LYMPH.3) Clonal Selection of Lymph.

2) Removal of Self-Reactive Lymphocytes

•When the pathogen comes in contact with the various lymphocytes, it will only bind to the one that have the specific receptor.

•Once bound to the antigen, that lymphocyte will divide and clone itself into short lived effector cells that will combat the pathogen immediately.

3) Clonal Selection of Lymphocytes1) Lymph. Diversity2) Removal of Self-reactive Lymph.3) CLONAL SELECTION OF LYMPH.

It will also clone memory cells which will circulate in the body from now on and help fight the same pathogen if infected again

Primary vs. Secondary Immune Response

Humoral and Cell Mediated Immunity

Acquire immunity can be subdivided into two branches:

1)Humoral Immunity: Clonal selection of B cells which help secrete antibodies into the blood stream. The memory B-cells are used later on during the secondary immune response.

2) Mediated Immunity: Clonal selection of cytotoxic T cells which help to destroy target cells

Helper T cells

• have surface proteins known as CD4 which allow it to bind to Class II MHC cells.

• Dendritic cells are required to trigger a primary immune response.

• When it binds to the CD 4 receptors of the helper T cell, both the dendritic cells and the helper t-cells will release cytokines to activate other lymphocytes to attack the pathogen.

Cytotoxic T cells (Cell Mediated Response)

• have a CD8 receptor which help to recognize Class I MHC.

• The binding of the MHC molecules and the CD8 helps to activate and differentiate the cytotoxic T-cell.

• The helper T-cells that were previously activated by MHC class II cells release their cytokine and help further activate this process.

• The activated cytotoxic T-cell will release proteins that will then bind to the infected cell and cause it to die from apoptosis.

Human Physiology - Cell Mediated Immunity

Human Physiology - Cell Mediated Immunity, Part 1

https://www.youtube.com/watch?v=fBIEwoWz1So

Human Physiology - Cell Mediated Immunity, Part 2

https://www.youtube.com/watch?v=RzGf7GccEAg

B cells (Humoral Response)

• a response to extracellular pathogens

• When B-cell comes in contact with a pathogen, it is bond to its antibody’s variable region on its cell surface.

• Earlier, a Helper T-cell would have bound to a class II MHC dendritic cell which would have presented a fragments of that same pathogen.

• The helper T-cell will in turn bind to the B-cell with the same antigen and activate the B-cell through the release of cytokines.

• The activated B-cell will then divide and make more B-cells for secondary immune response or release antibodies which will circulate the body looking for more of the same pathogen.

B cells (Humoral Response)

• Similar to the other dendritic cells, it is able to engulf an antigen, break it into fragments and present it on its cell surface receptors.

• However, unlike the dendritic cells, the B-cells are highly specific and can only bind to one type of antigen.

• Most antigens contain a variety of different epitopes on its cell surface. Thus it is able to activate a variety of different B-cells. Each one of them proliferating and giving rise to many different memory cells and antibodies.

Human Physiology - Humoral Immunity

https://www.youtube.com/watch?v=y0-BaWcU-SE

Antibody Mediated Disposal of Antigens

Agglutination: clumps the bacteria or viruses so that they can be easily ingested by phagocytic cells.

Complement system activation: Causes the protein to activate a channel that allows ions and water to flow into the cell, causing cell lysis.

Active vs. Passive Immunity

Passive response: • transferring antibodies from a

person who has been infected by the pathogen to a person who has not been exposed

• will only last the lifespan of that particular antibody (about a week)

• the person will not become permanently immune to the pathogen

Active Immunity: • depends on a person’s own lymphocytes and their development• can also be triggered by vaccinations• Activating lymphocytes so that they can have a good secondary response when exposed

to the pathogen.

Human Physiology - Naturally and Artificially Acquired Immunity

https://www.youtube.com/watch?v=UP4voM92r3k