- The cells proliferate when they encounter their respective antigen, and this is what creates clonal selection in T and B cells (and B-cell antibodies)

- These can specialize into cytotoxic, helper, and memory cells in the clones

- If faulty cells are produced, they are checked and deleted

- The entire activation of the immune adaptive response takes about 5-6 days

Lymphatic System

- Lymph nodes: where immune system vessels and blood vessels meet

- They also serve as a “checkpoint” for the bloodstream checking for pathogens

Inflammation

- Immune system maintains homeostasis in the body as well as fighting disease

- Inflammation alerts the body that the area needs more nutrients, blood, etc.

- Tumor Promoting Inflammation: mimics this effect through immune editing so that it gets more resources to continue growth

Hypersensitivity Disorders

- Allergies

- Autoimmune disease

Hyposensitivity Disorders

- Immune deficiency (due to malnutrition, or on the other extreme hygiene)

- Immune imbalance

Book Notes

Immunity – means state of protection from infection and disease

Earliest recorded attempt at reducing immunity

- 15^th century Chinese and Turks used variolation technique to gain smallpox immunity

- Small dried crusts were either inhaled or inserted into cut skin

- 1798 – Edward Jenner discovers that cowpox inoculation could cause resistance to the more dangerous smallpox

Later history

- Louis Pasteur accidentally discovered cholera immunity by using some “old” bacteria in his chicken injections

- The “old” or attenuated strain bacteria were weaker and could be used in a vaccine

- He was able to extend this to many other diseases, including anthrax and even rabies

(Note: see book for more detailed historical information)

Vaccination

- Herd immunity: when a disease cannot spread due to the population being immune

Antigen – anything that causes a response by b or t cells

- Clonal selection: when antigens attach one of the many receptors in the membrane, it activates the cell and causes it to proliferate into many more daughter cells

Pathogens – organisms that cause disease

- The process of inducing disease is called pathogenesis

- Four major categories: Bacteria, Viruses, Fungi, Parasites

- Immune Response is how we deal with these, and varies greatly depending on a lot of factors

- Often cytotoxic t cells are a major part of this process

Generation of Diversity

- Randomness in development of b and t cells from stem cells creates a theoretical population of cells that can respond to any antigen

- This is increased by their ability to proliferate upon recognition of a specific antigen and replicate the same receptors

- The recognition molecules are called B-cell receptors (found on surface and on antibodies) and T-cell receptors for the larger cells that are insoluble

Tolerance

- It is essentially the self recognition of certain antigens that protects tissues from self-attack by the immune system

- Burnet and Medawar proved tolerance by exposing mouse embryos to certain antigens and proving their tolerance to these antigens later in life

- B and T cells are checked after being produced and having their random mutations occur to ensure that they haven’t evolved any receptors that would attack “good” antigens and are destroyed if they do

- This ensures that self and “nonself” (or foreign) are kept distinguishable

- The Damage Model refers to the ability of cells to recognize “good” versus “bad” cell death (ex. apoptosis versus viral infection) and respond accordingly

Cytokines: messenger proteins secreted that can stimulate immune response

- Chemokines are like molecular flags that induce other cells

Immunologic Memory – adaptive arm of the immune system allowing for quicker response (as opposed to innate response which is the same no matter the exposure number)

- Primary Response: clonal selection and specialization slowly selects and produces the necessary lymphocytes to fight the pathogen

- Secondary Response: much faster than primary response due to previous exposure

- Facilitated by memory cells produced in the primary response which are essentially the last step skipping other previous selection steps

Immune Dysfunction

Hypersensitivity: allergy (attacks on common benign foreign antigens)

- Anaphylaxis: sudden extreme and potentially lethal overreaction to something the immune system has seen before

- Examples: allergies, asthma

Autoimmune disease: bad targeting of self-proteins or tissues

- Autoimmunity: breakdown in self-tolerance, causing attack on host tissues

- Examples: Crohn’s disease, rheumatoid arthritis, multiple sclerosis

Immune deficiency: insufficiency of immune response

- Immunodeficiency: a component of innate or adaptive immunity is absent or defective

- Primary immunodeficiencies: result from genetic factors

- Secondary immunodeficiencies: result from disruption/damage (ex. chemical, physical, biological, etc.)

- Examples: selective immunodeficiency, severe combined immunodeficiency (SCID), malnutrition, AIDS, HIV

Immune imbalance: dysregulation of immune system leading to incorrect activity, in particular increased inflammation or reduced inflammation

- Can think of it as a balance between brake and gas pedal, partially controlled by the inhibitory arm of the immune response (brake)

- Most noncommunicable diseases have been linked to uncontrolled inflammation (stuck gas pedal)

- Absence of some commensal organisms in the gut is like losing the brakes