BIOL 2512 - Ch. 17 Study Points

Why is immunology important to study and to understand?

Pathogens enter our body everyday

Microbiome - autoimmune disorders and microbiome dysbiosis

Immune system disorders

Cytokine storm

Understand how vaccines work - train immune system

Detect and investigate bacteria and viruses

Educate patients and discredit pseudo-science

First line of defense

Innate, non-specific

Present at birth

External barriers

Second line of defense

Adaptive, specific

Develops as body is exposed to antigens throughout life

Innate immunity

Non-specific

Always ready to go

Doesn’t remember infectious agents

Act immediately after exposure to foreign substance

Anatomic, physiologic, phagocytic, and inflammatory

Adaptive immunity

Highly specific

Doesn’t come to play until there’s an antigenic challenge

Remembers the infectious agent

Require some time before it can act on foreign substances

Humoral and cell mediated

Physical barriers

Skin

Mucous membranes

Endothelia

Blood-brain barrier

Skin

Physical barrier

Difficult for microbes to penetrate

Composed of dermis and epidermis

Epidermis

Physical barrier

Many layers of epithelial cells

Outermost are dead, filled with keratin - repels water, maintains dry environment

Continually flake off along with any
attached microbes

Dermis

Physical barrier

Tightly woven fibrous connective tissue

Endothelia

Physical barrier

Tightly packed epithelial cells lining blood vessels,
lymphatic vessels, urogenital tract

Microbes cannot pass through these tight cell to cell junctions

Blood-brain barrier

Physical barrier

Protects CNS from microbial invasion

Prevents infection of CNS, which could lead to often fatal inflammation

Keeps cerebrospinal fluid sterile

Chemical barriers

Cytokines

Antimicrobial substances

Antimicrobial peptides (AMPs)

Cytokines

Chemical barrier

Chemical messengers made by WBCs

Lysozyme

Chemical barrier

Antimicrobial substance

Degrades peptidoglycan

Lactoferrin and transferrin

Chemical barrier

Antimicrobial substance

Starves microbes of iron for growth

AMPs

Chemical barrier

Produced naturally by the body or in response to microbial invasion

Defensins

AMP

Form pores in microbial membranes

Secreted by macrophages and neutrophils

Mechanical barriers

Peristalsis of intestines

Mucociliary escalator of respiratory tract - remove microbes

Shedding of skin cells

Flushing action of urine - keeps kidneys, ureter and bladder sterile

Tears and flushing action - keep microbes from colonizing eyes

Hematopoietic cells

Where all blood cells originate from

Found in bone marrow

Acted on by CSFs to differentiate into different cell types

Neutrophils

Granulocyte

55-65% - most common leukocyte

Phagocytic - engulf and destroy bacteria

Circulate around the body in blood - few in tissue except when inflamed

Granules contain enzymes, antimicrobials

Increase in number during infection

Eosinophils

Granulocyte

2-4%

Fight parasitic worms

Involved in allergic reactions

Few in tissue except when there’s inflammation or an allergic reaction

Granules contain antimicrobials and histaminase

Basophils

Granulocytes

0-1%

Involved in allergic reactions and inflammation

Granules contain inflammatory histamine and anti-coagulant heparin

Circulate in blood

Mast cells are similar but are confined to tissues

Monocytes

Mononuclear

3-8%

Circulate in the blood

Mature into dendritic cells and macrophages

Phagocytize and digest engulfed materials

Macrophages

Mononuclear

Matured from monocyte

Found nearly in all tissue

Resident and recruiting in lymph nodes

Move through the body and scavenge bacteria, fungi, spores, dust, and dead body cells

Fixed stay within defined area or organ

Dendritic cells

Mononuclear

Matured from monocytes

Phagocytic

Function as scouts - engulf material in tissues and brings it to cells of adaptive immune system for inspection

Present in tissues that are in contact with the body’s external environment and mucous membrane - skin, inner lining of nose, lungs, stomach, and intestines

Migrate to lymph nodes after activation

Perform diapedesis

Stimulated by PAMPs

Lymphocytes

25-35%

In lymphoid organs, lymph nodes, spleen, thymus, appendix, tonsils

Also in circulation

Responsible for adaptive immunity

B cells

Lymphocyte

Mature in the bone marrow

Highly specific in recognition of antigen

Generally reside in lymph nodes and lymphatic tissues

T cells

Lymphocyte

Mature in the thymus

Highly specific in recognition of antigen

Generally reside in lymph nodes and lymphatic tissues

Innate lymphoid cells

Lymphocyte

Lack specificity

Can promote inflammatory response

NK cells

Lymphocyte

Destroy certain types of cells

PAMPs

Structures or molecules common to many groups of pathogens - not part of human

Peptidoglycan, flagellin, LPS, lipopeptides, and nucleic acids

TLRs

Recognize PAMPs

On WBCs

Signal danger

Cell often stimulated to produce substances with antimicrobial properties

PRRs

See signs of microbial invasion

Lead to cytokine secretion

Present on cells that are part of innate immunity

Located on every level within the cells

Cytokines

Chemical messengers of WBCs

Produced in response to an antigen

Regulate innate and adaptive immune systems

Stimulate hematopoiesis

Produced by almost all cells involved with immunity

Chemokines

Cytokine

Attract WBCs to site of infection, tissue damage, and inflammation

CSFs

Cytokine

Multiplication and differentiation of WBCs

Interferons

Cytokine

Control of viral infections

Regulation of immune responses

Released by virally infected cells

Type I interferons

Interferon-alpha and interferon-beta are produced and released by virally infected cells

Stimulate nearby cells to stop transcription and protein synthesis - inhibits viral replication

Promotes apoptosis in cells infected with viruses

Type II interferons

Interferon-gamma activates immune cells

Made by lymphocytes

Interleukins

Cytokine

Produced by leukocytes

Important in innate and adaptive immunity

Modulate immune functions but role isn’t restricted to just immune system

TNFs

Cytokine

Inflammation and apoptosis

Complement regulatory protein

Prevents host cells from activating complement system

Bind to C3b to prevent opsonization or triggering of alternative pathway

What are the three ways the complement system is activated?

Alternative pathway

Lectin pathway

Classical pathway

Alternative pathway

C3b binds to foreign cell surfaces

Lectin pathway

Inflammation triggers liver cells to create MBLs which bind to mannose on microbial cells

Classical pathway

Specific antibody binds to antigen

What are the outcomes of complement activation?

Opsonization

Inflammatory response

Lysis of foreign cells

All of these lead to complement cascade

Opsonization

C3b binds to bacterial cells and foreign particles

Enhances phagocytosis by allowing phagocytes to bind to opsonin

Inflammatory response

C5a attracts phagocytes to area

C3a and C5a increase permeability of blood vessels - C5a is a chemoattractant for neutrophils and WBCs

Induce mast cells to release cytokines

Lysis of foreign cells

C5b, C6, C7, C8, and C9 form MAC and punches whole into bacterial cell

Phagocytosis

Chemotaxis → recognition and attachment → engulfment → phagosome maturation and phagolysosome formation → destruction and digestion → exocytosis

Inflammatory response

Increased vascular permeability - caused by histamine and bradykinin

Greater blood flow and leakage of fluids

Migration of leukocytes from bloodstream to injured/infected tissues

Clotting factors wall off site of infection

Dead neutrophils, tissue debris, and lymph accumulate as pus

Five signs of of inflammation

Redness, swelling, heat, pain, altered function

Bradykinin

Binds to receptors on capillary walls

Causes dilation and leakage of fluids and WBCs out of the bloodstream into tissues

Leukotrienes

Potent proinflammatory mediators

Induce coughing, vomiting, diarrhea

Histamine

Proinflammatory chemicals

Induces bronchoconstriction, smooth muscle contraction, vasodilation, airway mucus production, and vascular permeability

Prostaglandins

Made at the site of tissue damage or infection

Cause inflammation, pain, and fever

Control processes like inflammation, blood flow, and formation of blood clots

Why are inflammation and fever considered first line defense mechanisms?

Are in response to wide array of targets

When is inflammation harmful?

Happens for an extended period of time

Prevents spread of infection but damages body

Enzymes and toxic compounds from phagocytic cells are released and damages tissues

Can be harmful in a delicate system like in the brain and spinal cord

Excessive inflammation may result in local tissue damage and may become deadly

Acute inflammation

Short-term

Mainly neutrophils

Macrophages clean up damage by ingesting dead cells and debris

Chronic inflammation

Macrophages and giant cells accumulate

Granulomas form

Happens because infectious agent can’t be removed

When is fever harmful?

Body temperature increases in response to pyrogens

Increase in temperature enhances immune response and many bacteria are inhibited from growing as well

Becomes too dangerous when temperatures get too high