Human Physiology: Adaptive Immune System

Front 1

What is the difference between innate and adaptive immune responses?

Back 1

- Innate: Non-specific immunity is a rapid response that brings about inflammation. It promotes wound healing and defense against infection.
- Adaptive: Specific immunity is a slower process (takes several days) that requires that a foreign molecule (an antigen) be recognized by specific cells of the immune system.

Front 2

__________ are the essential cells in adaptive immune responses.

Back 2

LYMPHOCYTES. Unlike the innate response mechanisms, lymphocytes must recognize the specific foreign material to be attacked.

Front 3

What is an antigen?

Back 3

- Any molecule that can trigger an adaptive immune response against itself or the cell bearing it.
- Any molecule that the host does not recognize as self.
- Examples: Proteins or Large Polysaccharides

Front 4

True or False:
There are more lymphocytes circulating in the the blood than in the organs and tissues.

Back 4

FALSE.

The great majority of lymphocytes are found in a group of organs and tissues collectively called LYMPHOID ORGANS.

Front 5

True or False:
Lymphoid Organs are subdivided into primary and secondary lymphoid organs.

Back 5

TRUE

Front 6

Identify the primary lymphoid organs and describe their function(s).

Back 6

Primary Lymphoid Organs: Bone Marrow and Thymus
- Initial sites of lymphocyte development.
- Supplies the secondary lymphoid organs with mature but "naive" lymphocytes; not yet been activated by antigens.

Front 7

Identify the secondary lymphoid organs.

Back 7

Secondary Lymphoid Organs:
- Lymph Nodes
- Spleen
- Tonsils
- Lymphocyte Accumulations in the linings of the intestinal, respiratory, genital, and urinary tract.

Front 8

Describe the function of secondary lymphoid organs; LYMPH NODES.

Back 8

- Oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach and linked by lymphatic vessels.
- A site of lymphocyte cell division and initiation of adaptive immune response.
- Each node is a honeycomb of lymph-filled sinuses with large clusters of lymphocytes between the sinuses.
- Also contains many macrophages and dendritic cells.
- Road block for pathogens in lymphatic system.

Front 9

Describe the function of secondary lymphoid organs; SPLEEN.

Back 9

- The second largest lymphoid organ.
- Lies in the left part of the abdominal cavity between the stomach and the diaphragm.
- Blood circulates through the vascular meshwork of the spleen's interior where large collections of lymphocytes, macrophages, and dendritic cells are found.
- Road block for pathogens in systemic circulation.

Front 10

Describe the function of secondary lymphoid organs; TONSILS.

Back 10

- Tonsils and adenoids are a group of small, rounded lymphoid organs in the pharynx.
- Tonsils are in the back of your throat.
- Adenoids are higher up, behind your nose.
- Filled with lymphocytes, macrophages, and dendritic cells.
- Have openings called crypts to the surface of the pharynx.
-Both help protect you from infection by trapping germs coming in through your mouth and nose.

Front 11

What are the cells of adaptive immune responses?

Back 11

1. Macrophages
2. T Cells
3. B Cells
4. Natural Killer Cells
5. Mast Cells

Front 12

Explain the function of cells involved in adaptive immune responses; MACROPHAGES.

Back 12

- This is a link between the innate immune response and the adaptive immune response.
- When activated secrete cytokines, which activates T and B cells and causes them to divide.
- Present foreign antigen to helper T cells.

Front 13

Explain the function of cells involved in adaptive immune responses; T CELLS (T Lymphocytes).

Back 13

- Separated into three major functional subsets; cytotoxic T cells, helper T cells, and regulatory T cells.
- Cyctoxic T Cells = upon activation by specific antigen, directly attacks a cell bearing that type of antigen and destroys it. (MAJOR KILLER OF VIRUS INFECTED and CANCER CELLS).
- Helper T Cells = do not themselves function as attack cells but, rather, assist in the activation and function of B cells, macrophages, and cytotoxic cells via its secretion of cytokines.
- Regulatory T Cells = believed to suppress the ability of certain B and cytotoxic T cells to attack a person's own proteins (which can occur in diseases known as autoimmune diseases).

Front 14

Explain the function of cells involved in adaptive immune responses; B CELLS (B Lymphocytes).

Back 14

Make antibodies.

Front 15

What is an antibody?

Back 15

- Proteins that travel all over the body to reach antigens identical to those that stimulated their production.
- Combine with these antigens and guide an attack that eliminates the antigens or the cells bearing them.

Front 16

Explain the function of cells involved in adaptive immune responses; NATURAL KILLERS.

Back 16

- Another distinct type of lymphocytes.
- Cells arise in the bone marrow.
- Similar to cytoxic T cells but are nonspecific.

Front 17

Explain the function of cells involved in adaptive immune responses; MAST CELLS.

Back 17

Release histamine.

Front 18

What are the two types of responses by the adaptive immune system? Define each and identify which immune system cells mediate each response.

Reference: http://bcs.whfreeman.com/thelifewire/content/chp18/1802001.html

Back 18

ANTIBODY MEDIATED RESPONSE (Humoral) - mediated by circulating antibodies; major defense against microbes and toxins in the extracellular fluids. (Helper T Cells and B Cells)

CELL MEDIATED RESPONSE - cells of the immune system kill cells of the body that has been infected; mediated by Cytotoxic T Cells.

Front 19

Provide a brief overview of the Antibody Mediated (Humoral) Response.

Note: Occurs in two phases; Activation Phase and Effector Phase.

Back 19

ACTIVATION PHASE:
1. Begins when a cell of the immune system (macrophages, B Cells, or dendritic cells) engulfs an antigen.
2. Inside the cell a phagosome is formed and fuses with a lysosome (which contains digestive enzymes).
3. The enzymes break down the engulfed antigen into fragments; antigen processing.
4. Processed antigens combine with Class II MHC proteins and is then displayed on the cell's plasma membrane; antigen presentation.
5. Helper T Cells have receptors that can bind to both the Class II MHC proteins and the particular presented antigen.
6. Binding triggers the cell to release interleukin-1 and tumor necrosis factor alpha, which activates the Helper T Cells.
7. The activated Helper T Cells now secretes its own various cytokines (ex. interleukin-2) that stimulate proliferation of cloned Helper T Cells and and has paracrine effects on adjacent B Cells and any nearby cells.
EFFECTOR PHASE:
1. Once activated Helper T Cells migrate to lymph nodes where they interact with Antigen Presenting B Cells (B Cells become antigen presenting in the same manner as described in the Activation Phase).
2. Helper T Cells help activate B Cells.
3. Once B Cells are activated, the B Cell differentiates into a plasma cell or a memory cell.

Front 20

Provide a brief overview of the Cellular Mediated Response.

Note: Occurs in two phases; Activation Phase and Effector Phase.

Back 20

ACTIVATION PHASE:
1. Beings when an antigen enters a body cell.
2. Body cell becomes infected and the antigen uses the cell's own machinery to replicate its genetic material and produce new antigen particles.
3. During the infection, some of the antigen particles are broken down by the cell and attached to Class I MHC proteins then presented not the cell's surface.
4. Cytotoxic T Cells that has T Cell receptors specific to the displayed antigen, binds to the complexes of antigens; Activation of Cytotoxic T Cells.
5. Activated Cytotoxic T Cells proliferates to form clones, each with T Cell receptors specific for the same antigenic determinant.
EFFECTOR PHASE:
1. Activated Cytotoxic T Cells can now encounter and eliminate other cells of the body that are infected with the antigen.
2. Upon binding, a Cytotoxic T Cell is stimulated to release molecules called perforin. Perforin kills the target cell by poking holes in its plasma membrane and causing the cell to lyse.

Front 21

Briefly explain the stages of a typical adaptive immune response.

Back 21

1. Encounter and recognition of an antigen by lymphocytes.
2. Lymphocyte activation.
3. Attack launched by the activated lymphocytes and their secretion.

Front 22

How do lymphocytes distinguish one antigen from another?

Back 22

Lymphocytes' Receptors.

-Both B and T cells express receptors on their plasma membrane.

Front 23

Describe B-Cell Receptors.

Back 23

- Each B cell always displays on its plasma membrane copies of the particular antibody its plasma cell progeny can produce; this surface protein acts as the receptor for the antigen specific to it.
- B cell receptors and plasma cell antibodies constitute the family of protein known as IMMUNOGLOBULINS.

Front 24

Explain the structure and function of an IMMUNOGLOBULIN.

Back 24

- Composed of four interlinked polypeptide chains.
- Two long chains; HEAVY chains.
- Two short chains; LIGHT chains.
- All Fc ("Stem") region of the heavy chains are the same for all immunoglobulins of a particular class.
- A small portion of the light chains are the same for a given immunoglobulin class.
- Upper part of each heavy chain and its associated light chain form an ANTIGEN BINDING SITE and is variable from one immunoglobulin to the next.
- The particular immunoglobulin that any B cell displays as a receptor on its plasma membrane is determined during the cell's maturation in the bone marrow.

Front 25

Describe T-Cell Receptors.

Back 25

- Receptors are two chained proteins that have specific regions that differ from one T cell clone to another.
- Remain embedded in the T cell membrane and are not secreted like antibodies.
- The particular receptor that a T cell has is determined during the cell's maturation in the thymus.
- T CELL RECEPTORS CANNOT COMBINE WITH ANTIGEN UNLESS THE ANTIGEN IS FIRST COMPLEXED WITH THE BODY'S OWN PLASMA MEMBRANE PROTEINS KNOWN AS MAJOR HISTOCOMPATIBILITY COMPLEX (MHC).

Front 26

What are MHC proteins?

Back 26

Major Histocompatibility Complex Proteins:
- Each individual has his/her own set of MHC genes, and therefore, MHC proteins.
- Genetic markers of self.
- Classified into Class I MHC Proteins and Class II MHC Proteins.

Front 27

True or False, and explain:

Different subsets of T-Cells do NOT have the same MHC requirements.

Back 27

TRUE.

Cytotoxic T Cells - Requires antigens to be associated with Class I MHC proteins.

Helper T Cells - Requires antigens to be associated with Class II MHC proteins.

Note:
* B-Cells; Do not interact with MHC proteins.
* NK Cells; Interaction with MHC proteins not require for activation.

Front 28

Where can you find Class I MHC proteins?

Back 28

Found on all nucleated cells of the body.

Front 29

Where can you find Class II MHC Proteins?

Back 29

Found only on macrophages, dendritic cells, and B cells.

Front 30

When can T Cells bind to antigens?

Back 30

T cells can only bing antigen only when the antigen appears on the plasma membrane of a host cell complexed with the cell's MHC proteins; antigen presenting cells (APCs).

Front 31

Explain the attack launched by the activated cytotoxic T Cells.

Back 31

Activated cytotoxic T Cells destroy infected host cells by releasing perforin or by triggering the infected cell to undergo apoptosis (programmed cell death).

Front 32

Explain the attack launched by the activated B Cells.

Back 32

Activated B Cells differentiate into…
- PLASMA CELLS; secretes antibodies that recognize the specific antigen.
- MEMORY CELLS; these cells live for years, and are able to mobilize quickly to produce more of the specific antibody should the antigen reappear in the future.

Front 33

Explain the attack launched by the Natural Killer (NK) Cells.

Back 33

- They attack and kill antigens directly after binding with them.
- Not antigen specific.

Front 34

What are the effects of antibodies?

Back 34

Antibodies bound to the antigen on the microbial surface do not directly kill the microbe but instead link the microbe physically to the actual killing mechanism.
- Direct Enhancement of Phagocytosis; antibodies can act as opsonins.
- Activation of the Complement System; occurs only with IgG and IgM.
- Link target cells to NK cells which then kills the targets directly by secreting toxic chemicals; antibody dependent cellular cytotoxicity (ADCC).

Front 35

Define immune tolerance and how it is essential for healthy life.

Back 35

The lack of immune response to self components.

It is virtually certain that in each person, clones of lymphocytes would have emerged with receptors tat could king to that person's own protein. The existence and functioning of such lymphocytes would be disastrous because such binding would launch an immune attack against the cells expressing these proteins.

Front 36

What two mechanisms that aid in immune tolerance?

Back 36

1. Clonal Deletion - destruction by apoptosis in the thymus of those T Cells that have receptors capable of binding to self proteins.
2. Clonal Inactivation - process occurring in the periphery that causes self reacting T cells to become non responsive.

Front 37

What are the two primary functions of vaccines?

Back 37

1. Maximize Memory B and T Cell Response.
2. Limit Inflammation.

Front 38

What are the three types of vaccines?

Back 38

1. Live – Live vaccines may be of live modified or non-human microbes which carry antigens similar, or identical, to pathogens known to infect humans. Alternatively vaccines may be attenuated, that is made much less pathogenic. This is often the most successful type of vaccination.

2. Killed – Killed pathogens are used similarly to live vaccines but carry no risk of infection. Their disadvantage is killing pathogens may decrease their immunogenicity.

3. Subunit – Subunit vaccines most commonly use purified components of the pathogen – thereby reducing the chance of infection drastically – but not losing the original immunogenicity of the subunit. However, many of these types of vaccines must be administered along with an agent which will cause limited inflammation to initiate the response.

Front 39

What is the term used to identify the undesirable reactions produced by the normal immune system?

Back 39

HYPERSENSITIVITY.

Front 40

Explain a Type I Hypersensitivity.

Back 40

- Immediate Hypersensitivity
- Most Common Example: Allergies.
- The term is deceptive however, as most allergic reactions do not happen during the first exposure, but rather exposures afterwards.
- Upon second exposure, Plasma cells recognize the antigen and through stimulation by activated helper T cells promote the production of IgE.
- IgE binds to Mast Cells promoting degranulation and a potent immune response.
- Responses include sneezing, urticaria (itchy swelling), angioedema (non-itchy swelling), and runny nose.

Front 41

Explain a Type IV Hypersensitivity.

Back 41

- Autoimmunity; delayed type hypersensitivity.
- Result of an inappropriate attach triggered by body's own proteins acting as antigens.
- In a normal state the body is immune tolerant towards its own cells, unfortunately in this situation tolerance breaks down.
- Immune cells begin to recognize cell components occurring naturally within the host body and the immune system begins to attack cells bearing antigen causing a variety of disease states such as rheumatoid arthritis and multiple sclerosis.