BIO 301
Human Physiology


& Body Defenses II

 

Body Defenses

Immunity


Major targets of body defense system:


Bacteria


Bacteria and viruses  



Anti-bacterial defenses

 


The innate immune response functions as the first line of defence against infection. It consists of soluble factors, such as complement proteins, and diverse cellular components including granulocytes (basophils, eosinophils and neutrophils), mast cells, macrophages, dendritic cells and natural killer cells. The adaptive immune response is slower to develop, but manifests as increased antigenic specificity and memory. It consists of antibodies, B cells, and CD4+ and CD8+ T lymphocytes. Natural killer T cells and gamma-delta T cells are cytotoxic lymphocytes that straddle the interface of innate and adaptive immunity (Dranoff 2004). Dendritic cells are leucocytes that get their name from their surface projections that resemble the dendrites of neurons. They are found in most tissues of the body and are particularly abundant in those that are interfaces between the external and internal environments, e.g., skin and the lining of the gastrointestinal tract. Dencritic cells present antigen/self-antigen complexes that activate T-cells. Gamma-delta cells are primarily found in the intestine, the lining of the vagina, and the skin. They encounter antigens at those locations and, therefore, serve as a first line of defense.



Nonspecific Immune Responses



Inflammation  (Check this animation and this one )


Bacterial invasion or tissue damage

Release of histamine by mast cells (plus chemotaxins by damaged cells)

Arterial vasodilation & Increased capillary permeability

Increased blood flow to tissue & accumulation of fluid

Increased numbers of phagocytes & more clotting factors into surrounding tissues

Defense against foreign invader plus 'walling off' of inflamed area


http://www.biologymad.com/Immunology/inflammation.jpg


 
Immunology in the skin

 
Immunology in the gut mucosa


Interferon (check these animations - Antiviral activity of interferon & Interferons):

Virus enters a cell

Cell releases interferon

Interferon binds with receptors on uninvaded cells

Uninvaded cells produce enzymes capable of breaking down viral mRNA

Virus enters previously-uninvaded cell (now with interferon)

Virus-blocking enzymes are activated

Virus unable to multiply in newly invaded cells
 


Source: http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/if.html


Interferon and the immune response


Natural killer cells


Natural killer cells    


The Complement System (check this animation - Activation of complement)

 

The complement cascade after activation by pathogens. Tthe complement cascade is usually activated by antibody complexes (classical pathway) or high-density mannose (lectin pathway) on the surface of pathogens. This activation leads opsonization and phagocytosis, as well as lysis as a result of the formation of the membrane attack complex (MAC). These combined actions of complement lead to the elimination of pathogenic cells (Ricklin and Lambris 2007).


Complement system


Complement system (more detailed!)


Under certain circumstances of infection, bacteria or viruses may become coated with opsonins (C3b, a complement protein, or IgG, an antibody). Such microbes are said to be opsonized (opsonin comes from a Greek word meaning "sauce" or "seasoning"; they make the bacterium or virus more palatable and more easily ingested by a phagocyte.) Opsonins dramatically increase the rate of adherence and ingestion of a pathogen  (Source: http://www.bact.wisc.edu/Bact330/lecturecd2).

 

Specific Immune Responses


Lymphocytes originate as stem cells in the bone marrow. Some migrate to the Thymus & develop into T-cells;
others remain in the Bone marrow & develop into B-cells. Both B- & T-cells then migrate to lymphoid tissue.


Organs and tissues of the immune system
(www.niaid.nih.gov)


B lymphocytes (or B cells) are most effective against bacteria & their toxins plus a few viruses, while T lymphocytes (or T cells) recognize & destroy body cells gone awry, including virus-infected cells & cancer cells.



  Clonal selection and expansion of the vertebrate immune response (Figure from Bergstrom and Antia 2006)

The adaptive immune response of vertebrates works by clonal selection. Independent of exposure to an antigen or pathogen, the immune system generates a repertoire of immune cell lineages or clones (labeled 1–8 in the above Figure), each encoding a receptor with a predetermined shape and specificity. The human immune system creates in excess of 10,000,000 different clones. As a first approximation, those that react with self-antigens (numbers 3, 5, and 8 in Figure I) are deleted shortly after they mature. When the individual is infected with a pathogen, those clones that are specific for the pathogen (number 2 in the above Figure) will proliferate, producing a pathogen-specific immune cell population that is large enough to control that pathogen. This process is known as clonal expansion. After the pathogen is cleared, some of the pathogen-specific immune cells survive and confer immune memory (Bergstrom and Antia 2006).


How do B & T cells recognize unwanted cells & other material?


B-cells: Antibody-mediated immunity

 



Source: National Cancer Institute
Activation of B Cells to Make Antibody

The B cell uses its receptor to bind a matching antigen, which it proceeds to engulf and process. Then it combines a fragment of antigen with its special marker, the class II protein. This combination of antigen and marker is recognized and bound by a T cell carrying a matching receptor. The binding activates the T cell, which then releases lymphokines—interleukins—that transform the B cell into an antibody- secreting plasma cell.
 
 


Plasma Cell


Humoral immunity  

 
Humeral response

 
Antibody production


 

 

Antibodies



Source: NIAID

 
Understanding allergies


Source: Check (2007).


Source: National Cancer Institute
IgA and IgM

IgA -- a doublet -- concentrates in body fluids such as tears, saliva, and the secretions of the respiratory and gastrointestinal tracts. It is, thus, in a position to guard the entrances to the body. 

IgM usually combines in star-shaped clusters. It tends to remain in the bloodstream, where it is very effective in killing bacteria.



Source: http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/exo.html


The different biological effects of antibodies (Casadevall et al. 2004).


Plasma cells vs. Memory cells


(a) Development of memory B cells and effector B cells (plasma cells) occurs in two phases. Short-lived plasma cells that make mostly IgM (but some IgG) are generated during the primary response and occupy sites, such as lymph nodes. The second phase involves the formation of the memory B-cell pool and seeding of long-lived plasma cells to the bone marrow. Plasma cells do not give rise to memory cells. All arrows are driven by antigen and T-cell help. (b) Development of memory T cells. After activation, cells differentiate into effector T cells. Memory T cells might be generated by divergence from this pathway or directly from effector T cells. There might be two subsets of memory cells: quiescent, central memory cells that recirculate from blood to secondary lymphoid organs, and effector memory cells that migrate through tissues and deliver a very rapid response on reactivation with antigen (Gray 2002).

Plasma cells:


Memory cells:


Primary response vs. Secondary response:


Active immunity vs. Passive immunity



As long ago as the 5th century B.C., Greek physicians noted that people who had recovered from the plague would never get it again - they had acquired immunity. This is because, whenever T cells and B cells are activated, some of the cells become "memory" cells. Then, the next time that an individual encounters that same antigen, the immune system is primed to destroy it quickly. The degree and duration of immunity depend on the kind of antigen, its amount, and how it enters the body. An immune response is also dictated by heredity; some individuals respond strongly to a given antigen, others weakly, and some not at all.

Infants are born with relatively weak immune responses. They have, however, a natural "passive" immunity; they are protected during the first months of life by means of antibodies they receive from their mothers. The antibody IgG, which travels across the placenta, makes them immune to the same microbes to which their mothers are immune. Children who are nursed also receive IgA from breast milk; it protects the digestive tract. Passive immunity can also be conveyed by antibody-containing serum obtained from individuals who are immune to a specific infectious agent. Immune serum globulin or "gamma globulin" is sometimes given to protect travelers to countries where hepatitis is widespread. Passive immunity typically lasts only a few weeks.

"Active" immunity (mounting an immune response) can be triggered by both infection and vaccination. Vaccines contain microorganisms that have been altered so they will produce an immune response but will not be able to induce full-blown disease. Some vaccines are made from microbes that have been killed. Others use microbes that have been changed slightly so they can no longer produce infection. They may, for instance, be unable to multiply. Some vaccines are made from a live virus that has been weakened, or attenuated, by growing it for many cycles in animals or cell cultures.


T Lymphocytes: Cell-mediated Immunity


Cytotoxic T cells: (check this animation)


Source: National Cancer Institute


Figure slightly modified from Iwasaki and Medzhitov 2010


Cytotoxic T cell attacking cancer cell

Helper T cells (check this animation)


Source: National Cancer Institute

 

Suppressor T cells (also called Regulatory T cells):

 

The various regulatory T (TReg)-cell mechanisms.

Regulatory T (TReg) cells are essential for maintaining peripheral tolerance, preventing autoimmune diseases and limiting chronic inflammatory diseases. However, they also limit beneficial responses by suppressing sterilizing immunity and limiting antitumor immunity. Thus, TReg cells can have both beneficial and deleterious effects (Vignali et al. 2008).

 



Autoimmunity may arise in several ways:


Major autoimmune diseases (Source: www.cdc.gov)



Blood typing

Red Blood Cells:


ABO system:

Blood type Antigen present
A
A
B
B
AB
A & B
O
neither A nor B


Source: ghr.nlm.nih.gov

Antibodies:

Blood type
Antigen
Antibody
A
A
anti-B
B
B
anti-A
AB
A & B
neither
O
neither
both anti-A & anti-B

If you mix anti-A antibodies with blood cells that have the A antigen OR mix anti-B antibodies with blood cells that have the B antigen, the results will be AGGLUTINATION (or clumping of red blood cells). This reaction can be used to type blood. You simply take two drops of 'unknown' blood and place a drop of anti-A antibody solution on one blood drop & a drop of anti-B antibody solution on the other blood drop. Then, look closely to see if any clumping occurs. If clumping occurs in the drop of blood where you added the anti-A antibodies, then you know that the A antigen is present (and, of course, if there is no clumping, then the A antigen is not present). If clumping occurs in the drop of blood where you added the anti-B antibodies, then you know that the B antigen is present (and, of course, if there is no clumping, then the B antigen is not present). Using this information, you can determine the blood type:
 

Drop of blood in which 
anti-A antibody was added
Drop of blood in which
anti-B antibody was added
Blood type
Clumping
No clumping
A
No clumping
Clumping
B
Clumping
Clumping
AB
No clumping
No clumping
O

Type O blood is the most common blood type, followed by type A, type B, and, the least common blood type, AB.


O+ 37%, O- 6%, A+ 34%, A- 6%,
     B+ 10%, B- 2%, AB+ 4%, AB- 1%

In the above chart, the blood types are listed with either a + or -. The + or - refers to the presence or absence of the Rh factor.

Type O:

Type AB:

Rh system:


Erythroblastosis fetalis (also called Rh disease):

RhoGAM:
 
Rh factor

Literature cited:

Bergstrom, C. T. and R. Antia. 2006. How do adaptive immune systems control pathogens while avoiding autoimmunity? Trends in Ecology and Evolution 21:22-28.

Iwasaki, A., and R. Medzhitov. 2010. Regulation of adaptive immunity by the innate immune system. Science 327:291-295.


Related links:

Lifeblood

Acute Inflammation

Lymphatic System & Immunity

General Immunology

Introduction to Immunology

Cell Mediated and Humoral Immunity

Understanding the Immune System

Humoral Immunity

Immuno Biology Animations

Blood Types Tutorial


Back to 301 syllabus
 

Lecture Notes 1 - Cell Structure & Metabolism

Lecture Notes 2 - Neurons & the Nervous System I

Lecture Notes 2b - Neurons & the Nervous System II

Lecture Notes 3 - Muscle

Lecture Notes 4 - Blood and Body Defenses I

Lecture Notes 5 - Cardiovascular System

Lecture Notes 6 - Respiratory System


Literature cited:

Casadevall, A., E. Dadachova, and L.-a. Pirofski. 2004. Passive antibody therapy for infectious diseases. Nature Reviews Microbiology 2: 695-703.

Check, E. 2007. Immunology: pimp my antibody. Nature 446: 964-966.

Dranoff, G. 2004. Cytokines in cancer pathogenesis and cancer therapy. Nature Reviews Cancer 4: 11-22.

Gray, D. 2002. A role for antigen in the maintenance of immunological memory. Nature Reviews Immunology 2: 60-65.

Ricklin, D. and J. D. Lambris. 2007. Complement-targeted therapeutics. Nature Biotechnology 25: 1265-1275.

Vignali, D. A. A., L. W. Collison, and C. J. Workman. 2008. How regulatory T cells work. Nature Reviews Immunology 8: 523-532.