Immune and Lymphatic Systems

Opsonin defined & 3 types

any molecule that enchase phagocytosis by marking a pathogen for destruction; prominent opsonins include:

1. Antibodies

2. Complement proteins

3. C-reactive protein (C-RP)

The process by which a pathogen is marked for destruction is….

Opsonization

Difference between MHC-1 and MHC-II receptors?

MHC-1 → Found on all nucleated cells & used to identify peptides from viruses that have invaded the cell; also identifies “mutated” proteins related to cancer

• Trigger Cytotoxic cells (NK & cytotoxic T-Cells)

MHC-2 →Found mainly on antigen-presenting cells (APCs) to include macrophages, dentritic cells, & B Cells

• Used by leukocytes to communicate with each other

• Activate leukocytes & specifically trigger phagocytic cells

Major functions of Immune System (3)

1. Defend against pathogens (= antigen = antibody generator))

2. Remove cell debris & waste, damaged cells, & dead cells

3. Recognize “self” & remove abnormal (mutated) cells

Antigen vs Antibody

Antigen → A substance the immune system recognizes; can trigger an immune response

• the TARGET

Antibody → A protein made by B cells; helps fight infections (specific antigens)

• the DEFENDER

6 Common Human Pathogens

1. Viruses

2. Bacteria

3. Fungi

4. Protozoa

5. Parasites

6. Protein

Virus defined

Multi-celled but can only reproduce inside a pant, animal, or person (1)

Bacteria defined

tiny one-celled creatures that can live inside or outside the body

Fungi defined

Multi-celled but plant-lime similar to tree fungus; takes nutrition from a plant, tree, or animal

Protozoa defined

One-celled creatures; usually spread through water

Parasites defined

Actual complex living organism; can live in intestine tract or blood stream

Protein defined

Multi-celled but can only reproduce inside a plant, animal, or person

6 sites of the immune system

1. thymus

2. spleen

3. tonsils and adenoids

4. lymph nodes

5. Peyer’s paths and appendix

6. Bone marrow

Why is bone morrow important?

Contains stem cells for B lymphocytes, which mature and become antibody-producing plasma cells that react to many bacteria, viruses, and other antigens

• controls Humoral immunity

4 major functions of the lymphatic system

1. Store & transport leukocytes & lymph

2. Remove & transport cellular waste & pathogens

3. Remove excess ISF (around 3 liters a day)

4. Absorb chylomicrons from the small intestine & transport to central circulation

3 Layers of Immune Response defense

1. External (Surface) Immunity

• physical barriers to invasion

2. Innate Immunity (non-specific responses)

• Phagocytosis (dendritic cells, neutrophils, macrophages)

• Inflammation (mast cells, basophils, etc.)

• Fever (pyrogens, eicosanoids / prostaglandins)

3. Adaptive / Acquired Immunity (specific responses)

• cell-mediated immunity (T- & B-lymphocytes)

• Humoral-mediated immunity [immunoglobulins (Ig)]

Most endocrine secretions contain…

lysozyme & immunoglobulins

Flushing action of tears, saliva, & urine contain…

lysozyme & immunoglobulins

What is lysozyme?

is an enzyme that helps protect your body from bacteria by breaking down their cell walls

What is a tonsil?

a mass of lymphoid follicles supported on a connective tissue framework; tonsils are coated in non-keratinizing stratified squamous epithelium

What is Protease and a protease inhibitor??

protease → an enzyme that breaks down proteins into polypeptides or single amino acids; pathogens often use proteases to attack healthy cells

protease inhibitor → is a substance that breaks down protease; thereby inhibiting the replication of certain cells & pathogens (bacteria & viruses)

Lymphoid tissues are comprised of …

connective tissues w/ various leukocytes stored w/ in it; comprised of lymphocytes (T-cells & B-cells)

Primary lymphoid tissues produce… and include …

1. leukocytes from immature progenitor cells

2. includes bone marrow & thymus gland

Secondary lymphoid tissues store… and initiate …

they include…

1. Leukocytes & initiate the adaptive immune response

2. lymph nodes, spleen, tonsils, etc.

Multipotential hematopmietic stem cells split into…

Either:

• Common myeloid progenitor

• Common lymphoid progenitor

What 4 cells does common myeloid progenitor split into?

• Megakaryocyte

• Erythrocyte

• Mast cell

• Myeloblast

What two cells does common lymphoid progenitor split into?

• Natural killer cell (Large granular lymphocyte)

• small lymphocyte

What does Megakaryocytes produce?

thromocytes

What 4 cells are derived from Myeloblasts?

• basophil

• neutrophil

• eosinophil

• monocyte

What does monocytes produce?

macrophage

What 2 cells are derived from small lymphocytes?

• T lymphocytes

• B lymphocytes

Cells involved in the Innate Immune System

1. Dendritic cells

2. Mast cells

3. Basophils

4. Neutrophils

5. Eosinophils

6. Monocytes

7. Macrophages

8. Natural Killer Cells

Cells involved in the Acquired Immune System

1. Helper T-cells

2. Cytotoxic (“Killer”) T-cells

3. Regulatory T-cells (“Tregs”)

4. Plasma B-cells

5. Memory B-cells

What cells are currently being used to fight cancer?

Cytotoxic T cells

Cytotoxic T cells use _____ to…

Perforins → to punches hole, then injects in granzymes in the hole which then produces apoptosis

B-Cells produce…

Antibodies!

Basophils and Mast Cells

• are RARE

• Release Histamines

• phagocytic

Neutrophils

• 50-70%

• “First-Responder” to tissue damage & inflammation

• Neutrophils migrate toward chemotactic agents

• Are prominent in inflammation

• Release cytokines

• Ingest and destroy invaders

• phagocytic

Eosinophils

• About 1 to 3%

• Destroy invaders, particularly parasites

• Phagocytic and cytotoxic

Monocytes and macrophages

• About 1 to 6%

• Ingest and destroy invaders; Antigen presentation → displayed like trophy on MHC class 2 receptor → for T-cells to see

• Phagocytic & Antigen-presenting cells

Lymphocytes and Plasma Cells

• 20-35%

• Specific responses to invaders, including antibody production

• Cytotoxic cells (some types) & Antigen-presenting cells

Dendritic Cells

• Not found in blood (unless there is an infection)

• Recognize pathogens and activate other immune cells by antigen presentation

• Antigen-presenting cells

What Opsonization?

an immune repose where protein coat pathogens or dead cells to mark them for destruction by immune cells

What is the primary lymphoid organ?

thymus gland

thymocytes are produced in…

& stored & mature in the …

1. bone marrow

2. cortex of the thymus gland

Thymus hormones are produced in…

reticular epithelial cells in the medulla

What are the parts of the Thymus gland? (from top to bottom)

• capsule

• Cortex

• Medulla

What are Hassall’s corpuscles?

structures found in the medulla of the thymus

• function is currently unclear

Thymopoietin & Thymosin

Type: peptide

From: thymus gland

Targets: thymus gland

Mechanism: stimulates T-lymphocytes to mature and differentiate

What is a lymph node and what do they do?

Is a kidney-shaped organ of the lymphatic system & adaptive immune system; they are linked by lymphatic vessels

• site for B-cell antibody production

Function of Spleen in secondary lymphoid process

1. Large garrison for RBCs & WBCs

2. Removes old RBCs and WBCs from circulating blood

3. Detects & filters foreign substances from the blood via phagocytic cells

4. Site for B-cell antibody production

What is the spleen made up of?

white and red pulp

Function of Tonsils in secondary lymphoid process

1. Trap pathogens

2. contains B-cells and T-cells

3. Site of antibody production

4. T-cells (Helpers and Killers)

• “sound the alarm” & help activate immune response

What is Waldeyer’s Ring?

Is a ring of lymphatic tissue (tonsils) in the back of your nose and throat that helps protect body from infections

• pharyngeal

• tubal tonsils

• two palatine tonsils

• the lingual tonsil

Define Innate immune system

comprises the cells & proteins that defend the body from infections in a generic manner

• does not confer long-lasting immunity

4 Main functions of innate immunity

1. Provide a physical & chemical barrier to pathogens

2. Recruit cells to a site of infection or damage through the production of cytokines (chemical messengers)

3. Identify & remove foreign substances

4. Activate the adaptive immune system through the process of antigen presenting to the lymphocytes (T-cells & B-cells)

(1)

“Natural killer” cells are named this because…

and they kill _____-

1. they do not require activation by T-cells

2. any cell that is missing MHC-1 “self” markers

What are Interferons and their function?

Are a type of cytokine (signaling protein) that is released by host cells in response to infection by viruses, bacteria, and parasites

• Think of them as alarm system that warns nearby cells about a viral infection

Mast Cells

• “sentry cell” (Tissues)

• releases histamine => vasodilation & hyperemia => inflammation

• releases heparin, cytokines, proteases

Basophils

Circulating leukocytes that contain granules (BLOOD):

• release histamine => vasodilation & hyperemia => inflammation

• Releases heparin (anticoagulant), cytokines, proteases

• Not phagocytic!

What is a phagocyte?

is a type of cell that can ingest & digest foreign particles & remove dead cells & debris

• two main types:

1. Neutrophils

2. macrophages

What is opsonization?

the process by which a pathogen is marked for destruction

What is an opsonin?

any molecule that enhances phagocytosis by making a pathogen for destruction; includes 1. antibodies, 2. complement proteins, 3 C-reactive protein

What are opsonin receptors?

located on phagocytic cells

Humoral Immunity uses ____ & ____ to target …

Cellular Immunity uses ____ & ____ to destroy…

1. B cells & free-floating antibodies to target outside threats in body fluids

2. T cells to destroy host cells that are already infected or cancerous

T cells are produced in ____ and are stored in ____; where they …

1. Bone marrow

2. Thymus

3. mature in the cortex of the thymus

Define Innate Immunity

comprises the cells & proteins that defend the body from infection in a genetic manner; does not confer long-lasting immunity (1)

Main functions of innate immunity

1. Provide a physical & chemical barrier to pathogens

2. Recruit cells to a site of infection or damage through the production of cytokines (chemical messengers)

3. Identify & remove foreign substances

4. Activate the adaptive immune system through the process of antigen presenting tot he lymphocytes (T-cells & B-cells)

Innate Immunity: Non specific Responses

1. Interferons

• a type of cytokine released by host cells in response to infection by viruses, bacteria, & parasites; a virus-infected cell will release these causing adjacent cells to heighten their anti-viral defenses

2. Complement System

• enhances (complements) the ability of antibodies & phagocytic cells to clear microbes & damaged cells, promotes inflammation, & attacked the pathogen'‘s plasma membrane

3. Inflammatory Response

• Mast cells & Basophils are involved and release chemicals to: increase blood flow, activate phagocytes, increase capillary permeability, activate complement, initiation clotting reaction, increase regional temperature

4. Fever

• Pyrogens (endogenous & Exogenous) - body temperatures rises in response to these

In the complement system, protease cleave specific proteins to initiate ___________ and this does what

1. Complement activation - and this stimulates phagocytes to clear foreign substances & damaged cells; similar to antibodies, complement proteins also serve as opsonins

What is a phagocyte? What are the two main types?

a type of cell that can ingest & digest foreign particles & remove dead cells & debris

1. Neutrophils = First responders → Quickly

2. Macrophages = Cleanup crew → Eat pathogens, remove dead cells, and help activate T cells (more long-termdefendse)

(these two are considered primary “professional” phagocytes)

What is Antigen presentation?

Is an essential process where protein fragments from invaders or internal anomalies are displayed on the surface of cells using MHC molecules; this display allows T cells to recognize & trigger an adaptive immune response

What are Pattern recognition receptors?

play a crucial role in the innate immune system; are cell surface & intracellular sensors (proteins) which detect pathogens

• used to identify 2 classes of molecules: pathogen-associated molecular patterns (PAMPs) associated with pathogens & damaged-associated molecular patterns (DAMPs) associated with damaged or dead cells

Monocytes / Macrophages

• Produced in bone marrow, stored in spleen, circulate for about 3 days , then migrate into tissue to replenish resident macrophages

• Respond to tissue damage & inflammation, migrate toward chemotactic agents (Cytokines), & then are activated to become “Angry Macrophages”

• Phagocytic

Dendritic / Langerhan Cell

• “Sentry Cell”

• “Nibbler” phagocyte

• APC

• Usually found in epithelial tissues on contact w/ environment (i.e. skin, res. & GI tract)

Natural Killer Cells

a type of lymphocyte that contains granules of cytotoxic proteins (performs & granzymes) that can “punch holes” in their target cells & induce apoptosis

• Ability to recognize stressed cells that do not display normal MHC I cell surface protein receptors

acute vs chronic inflammation

• Both are immune responses that help protect the body from injury or infection

Acute → “fast response”; neutrophils are usually the first major immune cells required; usually resolves once the problem is eliminated

Chronic → “Long-lasting response”; Macrophages and lymphocytes are the main immune cells involved; can cause ongoing damage and fibrosis (scarring)

What is inflammation?

A general localized response to injury that is characterized by a rapid increase in blood flow (hyperemia) to the site of injury; involves the movement of plasma, leukocytes, & proteins from inside blood vessels into the extravascular compartment (can be acute or chronic)

Characteristics of Inflammation

1. Redness

2. heat

3. swelling

4. pain

5. loss of function

steps of development of inflammation

1. Recognize the offending agents by host cells (epithelial, dendritic, mast)

2. Recruit leukocytes to the site of damage (via chemotaxis)

3. Remove the offending agent by phagocytic &/or cytotoxic cells

4. Repair the damaged tissue

Causes of Inflammation

1. Infections (bacterial, viral, fungal, parasitic)

2. Tissue necrosis → ischemia, trauma, physical & chemical injury

3. Foreign bodies (splinters, dirt, sutures)

4. Immune reactions (also called hypersensitivity) → reactions in which the normally protective immune system damages tissues; the responses may be directed against self-antigens, causing autoimmune diseases, or may be inappropriate reactions against environmental substances, as in allergies

What are Fc receptors?

• Is an antibody receptor involved in antigen recognition; are located on the plasma membrane of certain leukocytes including neutrophils, macrophages, NK cells, B-cells, and mast cells

Recognizes the “tails” of immunoglobins (Igs) / antibodies; once the Fc receptors have been activated on the leukocyte, they promote phagocytosis & inflammation

What are Toll-Like receptors?

Are a class of protein membrane-spanning receptors on certain leukocytes that recognize microbes; once microbes have breached physical Barries such s skin or intestinal tract mucosa, they are recognized by TLRs, which activate immune cell responses

Process of recognizing Microbes & Cell injury via PAMPs & DAMPs

• When PRRs (like a TLR) identify a pathogen (virus, etc.) or a molecule associated w damage, they activate a complex called an inflammasome

• When activated, inflammasomes cause the infected / damaged cell to produce cytokines - which are used to recruit other leukocytes to the area of damage

Inflammasomes also contain a pro-caspase which can activate the cascade cascade leading to a type of apoptosis

What is the role of lymphatic Vessels?

• drain & filter extravascular fluids that has seeped out of capillaries

• During inflammation → lymph flow is increased and helps drain fluid that accumulates because of increased vascular permeability

The movement of the plasma & solutes across a capillary wall is done by…

bulk flow filtration

What are the factors that affect diffusion that affect filtration?

• surface area

• size & polarity of solutes

• thickness of wall

• capillary wall permeability

The rate of filtration is dependent on the…

“Starling Forces”

What are “Staring Forces”?

the direction of fluid exchange between blood (plasma) & ISF across the capillary wall is determined by a combination of the relative hydrostatic and oncotic pressures

• The rate of exchange is governed by the permeability of the capillary wall itself

Hydrostatic Pressures (2)

1. Capillary hydrostatic pressure → pressure exerted on the inside of the capillary wall by the blood

2. Interstitial fluid hydrostatic pressure → pressure exerted on the outside of the capillary wall by the interstitial fluid

Colloid Oncotic Pressures (2)

1. Plasma colloid oncotic pressure → pressure from concentrations of proteins inside the capillary

2. Interstitial fluid colloid oncotic pressure → pressure from concentration of proteins in ISF

Oncotic Pressure

“pulling” pressure generated by proteins

Osmotic pressure

passive “pulling” pressure generated by sodium and glucose

Transmigration and Chemotaxis

Both are processes that help white blood cells reach an area of infection or inflammation

Trans → White blood cells squeeze through blood vessel walls into tissues (diapedesis)

Chemotaxis → White blood cells move toward an infection by following chemical signals; guided by chemical attractants

What is reabsorption?

fluid being pulled back into the capillary

• is determined by plasma colloid osmotic (oncotic) pressure & ISF hydrostatic pressure

3 steps of phagocytosis

1. Recognition → attachment of the particle to be ingested by the leukocyte

2. Engulfment → with subsequent formation of a phagocytic vacuole

3. Killing or deflation of ingested material

Phagocytic receptors

mannose receptors, scavenger receptors, & receptors fro various opsonins bind & ingest microbes

Classification of chemical mediators of inflammation (2)

1. Cell-Derived Mediators

• Released from cells

• Either preformed in granules or newly synthesized on stimulation

Main members: Vasoactive amines, Arachidonic acid metabolites, cytokines, Neuropeptides, etc.

2. Plasma-Protein Derived Mediators

• Derived from plasma proteins

• Mainly synthesized in the liver

• released as inactive precursors which require activation

Main members: Kinin system, clotting system, complement system

Eicosanoids are derivative of …formed by _______ & _______ pathways

1. Arachidonic acid

2. cyclooxyrgenase (COX) & lipoxygenase (LOX) pathways

What is arachidonic acid?