Lecture 3: Physiology of the Immune System

What is the innate immune system?

- present at birth (you are born with this system)

- responds at the location of the pathogen

- involves mechanical and chemical barriers (such as skin and secretion such as sebum), inflammation, complement and immune cells

What does the innate immune system lack?

specificity (could cause death of cell for the greater good of killing pathogens) (it is very generalized)

What are neutrophils? (what is there function)

white blood cells that eat bacterial or fungal infections (phagocytosis). These are the most common first responders to microbial infection.

What are eosinophils?

White blood cells that fight parasitic infections and allergic reactions (inflammatory)

What are basophils?

White blood cells that promote the inflammatory response against allergic and antigen response (by releasing histamine causing vasodilation)

What are monocytes? What do they become outside of the bloodstream?

Number one thing that eat up bacteria in the interstitial spaces. Outside of the bloodstream, they become a macrophage (they can eat a lot of bacteria)

In what system are natural killer cells apart of?

innate immune system

What are the first lines of defense?

skin, mucous membranes (respiratory: cilia, phlegm, cough flex, GI: host bacteria, and GU), and chemical barriers (hydrochloric acid of stomach, lysozymes in sweat and tears, and lactic acid in vagina)

Any tissue damage that initiates a set of vascular, cellular, and molecular processes that assists in cleaning out debris and initiated the healing process is __________________

inflammation

What are the 5 cardinal signs of inflammation?

- heat

- erythema

- pain

- edema

- joint immobility

What is an antigen?

a foreign protein (something that is not self) (could even be part bacteria)

Antigen binds to __________ and they release _____________, __________, __________, ____________

mast cells, they release histamines, leukotrienes, prostaglandins, and serotonin

which cells are secretors ?

mast cells

The release of molecules from mast cells and cell membranes all cause endothelial cells to become more _________ (_________) and express P selectins that trap neutrophils and monocytes in blood and lead to _____________ and ___________

permeable (edema), margination and diapedesis

What is margination?

cells rolling over P selectins on endothelia lining getting flagged down

What is diapedesis?

neutrophils and monocytes "wiggle" through vessel wall to site of tissue injury

Monocytes outside of blood become ____________

macrophages

Neutrophils and macrophages ingest pathogens and secret ______________ and ________________ to recruit more neutrophils and monocytes from the blood stream. This is a ____________ response as these molecules need to be produced by these cells days later.

interleukin 1, tumor necrosis factor-alpha (TNF), secondary

________________: chemical mediators released by cells to guide other cells to infection in interstitial tissues

positive chemotaxis

What are effects of interleukin 1 and TNF on the body? (3)

- hypothalamus of brain causes a fever

- liver promotes acute phase reactant proteins that act as opsonins

- bone marrow causes leukocytosis (makes more neutrophils, monocytes, and eosinophils)

_____________: process by which neutrophils and macrocytes engulf and destroy bacteria.

phagocytosis

Macrophages are much _________ than neutrophils.

larger (they can take in ~100 bacteria compared to neutrophils that take up 5-10 bacteria)

What is the complement cascade?

20 different proteins produced by the liver. They are in your blood from birth. There is a pattern that they follow and the end result is three things: opsonization, membrane attack complexes, and enhancing inflammatory response and chemotaxis

What is opsonization?

process of coating a bacterium with complement particles to be more easily recognized by phagocytes (think of sprinkling powdered sugar on french toast: makes it more delicious)

What is the membrane attack complex? What is the result?

Combination of 5 proteins to create a semi-permeable structure that can create a hole in the bacterium where sodium and water can enter.

- results in cell lysis (cell explosion)

What is the adaptive immune system?

- develops after birth

- develops in response to an infection

- VERY specific response

- First response is muted

- Second response in future markedly AMPLIFIED due to memory cells

What are the two major cells of the adaptive immune system?

- T lymphocytes (cell-mediated response)

- B lymphocytes (humoral response - related to antibodies in fluid of the body)

Precursor cells from bone marrow migrate to ___________, during fetal life and soon after birth, where they become ______________.

Thymus, T lymphocyte cells

First, each T lymphocyte develops specifically on its receptor to ______________. Second, the thymus selects out and kills ____% of these to ensure T cells are not reactive to ______

ONE antigen, 90%, self

T cells are activated for foreign attack only when it is on the surface of a cell that carries foreign and self antigens. They learn to recognize foreign antigens only in combination with a person's own self-antigens know as the ______________________ (molecule that present antigen to T cells)

major histocompatibility complex (MHC)

After the thymus, where do the T lymphocytes migrate to?

lymph nodes, lymph-associated tissue, and blood

What is a cluster of differentiation (CD)? What are two major types with distinct roles in immunity?

(little proteins that stick out of the cell) system for identifying molecules on the surface of cells, like antigens. Different CD markers help classify and distinguish different types of immune cells and their function.

- CD4 and CD8 T cells are two major types with distinct roles in immunity

What is MHC-1? What do they interact with?

- MHC-1 are in all of our nucleated cells

- collection of peptides from cytosol (endogenous: inside the cell)

- viral antigens

- they interact with CD8 T cells (Cytotoxic T cells)

(It kills the cell)

What is MHC-II? What does it interact with?

- present on antigen-presenting cells (such as macrophages)

- collection of peptides from intracellular vesicles (exogenous)

- bacterial from outside that are phagocytized antigen

- interact with CD4 cells (helper T cells)

What are the two types of T cells?

Helper T cells (CD4) and Cytotoxic T cells (CD8)

What are cytotoxic T cells?

Killer rT cells or CD 8 cells

- direct role in killing viruses or cancers that are INSIDE host cells

- host cells present antigen on surface of cell with MHC-1

Killer T cells are cloned to make ____________. During the cloning process, _______________ are made.

effector T cells, memory T cells

What are helper T cells?

CD4 cells

- they bind to antigen presenting cells APCs (dendritic cells, macrophages, and B lymphocytes)

- Antigen presented via MHC II to cell surface which helper cell binds

- more clones of helper cells are made including memory cells

What do Helper T cells produce and recognize?

- produces cytokines

- recognizes pathogens

B lymphocytes mature initially in the ________ in mid-fetal development.

liver

B lymphocytes eventually migrate to the ______________ where final development occurs

bone marrow

After B cell development, B cells are made to be very specific to ...

ONE antigen

The majority of B cells and T cells lie dormant in ____________ and _________________ awaiting signaling from other cells of immune system

lymph nodes and lymph-related tissue

What are the functions of antibodies?

- can physically hinder antigens

- enhance activity of other defense systems

How can antibodies physically hinder antigens? How can they bind to foreign cells?

- Neutralization: they combine with toxins and prevent harmful chemicals from interacting with susceptible cells

- can bind to foreign cells by agglutination

How do antibodies enhance activity of other defense systems?

- activating complement system (tail of antibody will bind with and activate system)

- enhancing phagocytosis by opsonization

- stimulating killer (NK) cells

NK cells have receptors for the tail portion of antibodies. When target is coated with antibodies, NK cells can bind. This is known as _________________________________

Antibody-dependent cellular cytotoxicity (ADCC)

What are the 5 types of antibodies?

IgA, IgD, IgE, IgG, IgM

Which antibody is the most common?

IgG

Which antibody gets called first?

IgM (has lots of areas to fix antigens)

Which antibody is the least called for?

IgD

What is IgA?

secreted into mucous, saliva, tears, and colostrum. Tags pathogens for destruction

What is IgD?

B-cell receptor. Stimulates release of IgM

What is IgE?

(ALLERGY) Binds to mast cells and basophils. Allergy and anti-parasitic activity

What is IgG?

Binds to phagocytes. Main blood antibody for secondary responses. Crosses placenta

What is IgM?

Fixes complement. Main antibody of primary responses. B-cell receptor. Immune system memory

Patient with G6PD deficiency often will exhibit a hemolytic crisis when faced with a stressor such as an antibiotic, due or fava beans. What makes RBCs so susceptible to an enzyme deficiency that effects all cells?

Lack of a nucleus

Patient with multiple myeloma have cancer that have large increases in plasma cells. Given where B cells have early development, where would you expect damage from these tumors?

Bones