EXSC2530 Lecture 18: Immune System I

Does not include slides on specific immunity (humoral and cell-mediated)

Immune system functions

defends the body against pathogens, removes dead or damaged cells, and contributes to the homeostasis of all organ systems

Virus

typically consists of a nucleic acid molecule (RNA) in a protein coat that is able to multiply only inside of cells

Bacterium

unicellular microorganisms that have cell walls and are able to multiply in the extracellular fluid

Non-specific immunity

* defend the body against all microorganisms (i.e. is not specific to a microorganism)
* same arsenal used to eliminate microorganisms
* first line of defense

Innate immunity

defenses that you were born with (i.e. you don’t develop/acquire them)

Non-specific or innate immunity have no __ __

immunological memory

Immunological memory

capacity to “remember” prior exposure to a microorganism (i.e. virus), which allows for a more rapid and effective elimination when re-exposed to the organism

Specific immunity

* targeted assault on specific microorganisms
* arsenal to eliminate microorganism is specific to microorganism

Acquired immunity

defenses that you develop over time

Specific or acquired/adaptive immunity have an __ __

immunological memory

Specific or acquired immunity have two components; __ __, and __ __

humoral immunity; cell-mediated immunity

Effector cells of the immune system are __

leukocytes (WBC)

What are the two categories of leukocytes?

granulocytes and agranulocytes

Granulocyte have several __

granules

There are __ types of granulocytes

3 (neutrophils, eosinophils, and basophils)

What is the primary type of leukocyte found circulating in blood?

neutrophils

Neutrophils

make up approximately 60% of all circulating leukocytes

Eosinophils

make up approximately 3%-5% of all circulating leukocytes

Basophils

make up approximately less than 3% of all circulating leukocytes

Agranulocytes have only a couple of __

granuoles

There are __ types of agranulocytes

2 (monocyte, lymphocyte)

Monocytes

make up approximately 10% of all circulating leukocytes

Lymphocytes

make up approximately 30% of all circulating leukocytes

Lymphocytes include __ and __ __

T-lymphocytes; B cells

There are __ different types of T-lymphocytes

2 (cytotoxic T cells, helper T cells)

Leukocytes are made in __ __ and stored in bone marrow, lymph nodes, spleen, and lungs

bone marrow

Concentrations of leukocytes in blood __ after infection, injury or other stressors

increase

Process in which leukocytes can leave the bloodstream and enter into infected or injured tissue

diapedesis

What are the primary effector cells of non-specific immunity

Phagocytic cells: Granulocytes (primarily neutrophils), monocytes, and macrophages

What are the primary effector cells of specific immunity

Lymphocytes (T helper,, T cytotoxic, and B cells)

Phagocytic cells

ingest and destory bacteria, cellular debris, denatured proteins, and toxins

Complement proteins

promote destruction of bacteria; enhance inflammatory response

T/F: Mast cells are not leukocytes

true

Phagocytosis

internalization and subsequent degradation of microorganisms and/or components of injured cells/tissue

Pseudopods

outward finger-like projections on the surface of phagocytic cells that grab hold of bacteria and internalize it

What are the arsenals of phagocytosis

free radicals and proteases

Free radicals

highly reactive chemicals (e.g. bleach)

Proteases

enzymes found in lysosomes/granules that degrade proteins

“Frustrated” phagocytosis

the release of arsenal kills the microorganisms but could also cause injury to healthy cells that reside in the tissue

as a result of phagocytosis, the phagocytic cell will __

die

Your body will produce over a __ __ of neutrophils every day because phagocytosis is constantly occuring

quarter pound

Phagocytic cells consist of…

neutrophils, monocytes and macrophages

Neutrophils perform phagocytosis in…

the blood and tissues

Monocytes perform phagocytosis only in…

the blood

macrophages perform phagocytosis only in…

tissues

Upon the monocyte’s entry into tissues, they mature and become __

macrophages

The efficiency of phagocytosis can be enhanced in other components of the immune system __ a pathogen

mark/flag

Opsonization

“coating the surface”: the process in which targets for phagocytosis are marked/flagged

Factors that serve as opsonins

antibodies/immunoglobulins of the igG category, and proteins if the complement system

What is the primary opsonin for phagocytosi?

antibodies/immunoglobulins

All antibodies are produced by __ __

B lymphocytes

Antibodies bind to __ on pathogens

structures (antigens)

Antigens are __ to the body

foreign

Uniqueness of an antibody is related to the __ region

Fab

__ region is identical for the most common antibody found in blood

Fc

IgG

main form of antibodies in circulation: production increased after immunization; secreted during secondary response

Antibody-mediated enhanced phagocytosis

1. antibodies circulating in blood will enter infected/injured tissue
2. antibodies bind to an antigen on the surface of bacteria via opsonization
3. phagocytes bind to the Fc region of the antibody which triggers phagocytosis

In antibody mediated enhanced phagocytosis, the production of arsenal will __ many fold greater than “standard” phagocytosis

increase

Inflammation

body’s response to a local infection or injury in which a part of the body becomes reddened, swollen, hot, painful, and dysfunctional

The primary effector cells of inflammation are:

neutrophils, monocytes, and macrophages

There are __ phases of inflammation

two

Vascular phase of inflammation

events that enhance the delivery of phagocytic cells into infected or injured tissue

Cellular phase of inflammation

process by which phagocytic cells enter infected/injured tissue, migrate to infected/injured area, and remove pathogen or components of injured tissue/cells

Mast cells reside in connective tissue, and release __ during the inflammation response to a bacterial infection

histamine

The vascular phase of inflammation is initiated by the release of __ from pathogens, injured cells, and/or other cells residing in the infected or injured area.

products

Histamines produced by mast cells, which reside in connective tissue is an example of which phase of inflammation?

vascular phase

Fragments of complement proteins contribute to the initiation of the __ phase of inflammation

vascular

Numerous __ contribute to the initiation of the vascular phase of inflammation

cytokines/chemokines

Lots of __ are capable of initiation the vascular phase of initiation

products/molecules

When the vascular phase is initiated, the diameter of arterioles __

increases

When the vascular phase is initiated, the permeability of capillaries __

increases

Cells that make up capillaries

endothelial cells

Endothelial cells are…

a barrier that restricts fluid accumulation within tissue

Increased permeability of capillaries due to the initiation of the vascular phase facilitates entry of __ and __ into infected/injured area

leukocytes; proteins

Due to the initiation of the vascular phase, the __ are to be released from the bone marrow into the blood

phagocytes

The increased diameter of arterioles due to the vascular phase causes an increased blood flow and hence, the delivery of __ and __ to infected/injured area

neutrophils; monocytes

The increased permeability of blood vessels due to the vascular phase makes it easier for __ to enter the interstitium (i.e. leave blood vessel), and allows __ that function as opsonins to enter the interstitium

phagocytes; proteins

What are the consequences of the vascular phase?

local redness and edema (increased interstitial fluid volume)

Diapedesis of the cellular phase of inflammation

movement of a leukocyte from the blood vessel (leaving) into tissue

Migration of the cellular phase of inflammation

movement of a leukocyte in the tissue to the injured cell

Chemotaxis

the movement of cells toward a chemical attractant (chemoattractant)

Chemoattractants are…

complement proteins or proteins released from infected or injured tissue

The source(s) of chemoattractant are…

bacteria and injured cells

Complement system

component of innate immunity that contributes to the elimination of bacteria by enhancing phagocytosis and direct killing

The complement system has a large number of __ __

complement proteins

complement proteins are…

synthesized by the liver and circulate in the blood in an inactive state

Classical pathway

specific immunity of the complement system

Alternative pathway

non-specific immunity of the complement system

In the classical pathway of the complement system, complement proteins are cut into different pieces by __

enzymes

Activation of the compliment system results in the cleavage of complement proteins, and results in the formation of the…

membrane attack complex (MAC)

During the activation of the complement system, complement proteins become inserted into the plasma membrane of bacteria or other cells, flagging/marking the target, which enhances __

phagocytosis

complement fixation (opsonization)

complement proteins become inserted into the plasma membrane of bacteria or other cells

Complement-mediated enhanced phagocytosis

When phagocytic cell binds to complement proteins on a bacteria, it enhances the elimination of the bacteria. it serves as a mean through which phagocytic cells can recognize the bacteria and remove it.

Complement-mediated enhanced phagocytosis is solely the result of __ __

complement fixation

During the activation of the complement system, complement proteins group together to form a pore cared __ __ __ in the membrane of bacteria or other cells

membrane attack complex (MAC)

What are the main functions of the complement system?

enhancing phagocytosis (through complement-mediated enhanced phagocytosis) and direct killing

What are the minor functions of the complement system?

chemotaxis of phagocytes and increased capillary permeability

C3a, C4a, and C5a serves as chemoattractants and __ in the complement system

anaphlylatoxins

Sequential stages of inflammatory response to bacteria infection

1\. Cut in skin and entry of bacteria \n 2. Mast cells and other cells release factors that initiate the vascular phase which causes: dilation of arterioles (which increases blood flow and delivery of phagocytes to infected area) and increase vascular permeability (which allows fluid, phagocytes, antibodies, complement proteins to accumulate in infected/injured area) \n 3. Phagocytes enter into infected/injured tissue via diapedesis \n 4. Neutrophils/macrophages migrate to infected area via chemotaxis \n 5. Antibodies and complement proteins "mark/flag" bacteria for phagocytosis via opsonization \n 6. Neutrophils and macrophages bind to the Fc region of antibodies (via Fc receptors on their surface) and fragments of complement proteins (e.g. C3b) via complement receptors on their surface. \n 7. Elimination of bacteria via phagocytosis and formation of membrane attack complex (MAC)

Four methods of killing bacteria

1\. Phagocytosis \n 2. Antibody-mediated enhanced phagocytosis \n 3. Complement-mediated enhanced phagocytosis \n 4. Formation of a membrane attack complex (MAC)