Human Physiology Exam 2

Eight physical barriers that make up the first line of immune defense

skin, mucus, hair, cilia, sebum, lysozyme, gastric juice, vaginal secretions

Four functions of the second line of immune defense

IMMUNITY:

• defend against invading pathogens

• remove damaged or worn-out cells

• immune surveilance: identify and destroy abnormal cells

• disorder can be in the form of allergies or autoimmune disease

The seven cells of the immune system and their categories

Leukocytes: neutrophil, eosinophil, basophil, monocyte, lymphocyte

Non-leukocytes: mast cell, dendritic cell

Leukocytes can be broken up into two categories

polymorphonuclear granulocytes, mononuclear agranulocytes

Polymorphonuclear granulocytes

Nucleus appears to be lobed or segmented

• neutrophil

• eosinophil

• basophil

Mononuclear agranulocytes

One nucleus that is not segmented, lack prominent granules

• monocyte

• lymphocyte

Describe how the number of neutrophils in the blood serves as an indicator of infection or inflammation.

Infections, injury, and inflammatory disorders can all cause an increase in the number of neutrophils in the blood. Drugs such as corticosteroids can also lead to an increase.

Neutrophils

Highly mobile phagocytes that engulf and destroy unwanted materials

• release neutrophil extracellular traps (NETs) that contain bacteria-killing chemicals

• can destroy bacteria by phagocytosis

• inflammatory response

• scavenge and clean up debris

First recruited defenders on scene of bacterial invasion

neutrophils

Eosinophils

Secrete chemicals that fight parasites, involved in allergic reactions

• Examples: asthma and hay fever; worms

Basophils

Release histamine and heparin, involved in allergic reactions

• least numerous, not very well understood

• structurally similar (and therefore functionally) to mast cells

Histamine

Induces local vasodilation, increases capillary permeability

• participates in allergic reactions

Heparin

Speeds up removal of fat particles from blood after fatty meal, anticoagulant

Monocytes

Mature into macrophages, emerge from bone marrow while immature

• Life span ranges from months to years

Lymphocytes (two categories) are mainly produced from

(B&T) lymphoid colonies in lymphoid tissues

Hematopoiesis

Blood cell production

B lymphocytes

Transformed into plasma cells that secrete antibodies

T lymphocytes

Responsible for cell-mediated immunity

8 types of lymphoid tissues

Produce, store, or process lymphocytes

• bone marrow

• lymph nodes

• spleen

• thymus

• tonsils

• adenoids

• appendix

• Peyer’s patches (GAIT)

Two types of lymphoid organs

Primary: sites where stem cells divide and develop into B and T cells

Secondary: site of most immune responses

Two primary lymphoid organs

• bone marrow: produces mature B and T cells

• thymus: where T cells mature, above the heart, contains T cells, scattered dendritic cells, epithelial cells, and macrophages

  • atrophies after maturity

Three secondary lymphoid organs

• lymph nodes: scattered throughout lymphatic vessels of the body, filter microbes

  • contains macrophages and lymphocytes that destroy filtered microbes

• spleen: largest lymphoid organ, removes microbes and aged/defective erythrocytes (RBCs)

• lymphoid nodules: tonsils, Peyer’s patches, appendix

Two types of immune responses

innate and adaptive

Innate immune system

• nonspecfic, immediate response but limited

• important players: neutrophils, macrophages, several plasma proteins

Adaptive (acquired) immune system

• specific, targets material to which body has already been exposed

• body has taken time to prepare to attack

• ultimate weapon against most pathogens

• important players: B and T lymphocytes, memory cells

Four innate defenses

• inflammation (phagocytosis by neutrophils and macrophages)

• interferon: antiviral proteins

• natural killer cells: lyse and destroy virus-infected host cells and cancer cells

• complement system: plasma proteins that are activated to destroy foreign cells by attacking their plasma membranes

Functions of inflammation (innate immunity)

• bring phagocytes and plasma proteins to affected area

• isolate, destroy, or inactivate invaders

• remove debris

• prepare for subsequent healing and repair

Three stages of inflammation

• vasodilation

• emigration of phagocytes

• tissue repair

Inflammatory response is similar no matter what the triggering event. The nine characteristics of inflammation include…

• defense by resident tissue macrophages

• localized vasodilation

• increased capillary permeability

• localized edema (swelling due to fluid buildup)

• walling-off the inflamed area

• emigration of leukocytes (from bloodstream to inflamed tissue)

• leukocyte proliferation

• marking of bacteria for destruction by opsonins

• leukocytic destruction of bacteria

Inflammation: selectins from endothelial cells

Slow down neutrophils/monocytes

Inflammation: integrins from endothelial cells

Cause neutrophils/monocytes to bind to endothelial cells

Inflammation: margination

Process of leukocytes (WBCs) move from the center of a blood vessel to the outer edges near the vessel wall (endothelium)

5 steps producing inflammation

1. Macrophages engulf pathogens at the site of a wound. Cytokines and chemotaxins are released.

2. Activated mast cells release histamine.

3. Histamine and cytokines cause vasodilation and widen capillary pores. Cytokines make the vessel wall sticky, causing neutrophils and monocytes to attach.

4. Chemotaxins attract neutrophils and monocytes, which squeeze out between cells of the blood vessel wall (diapedesis) and migrate to the infection site.

5. Monocytes enlarge into macrophages. Newly arriving macrophages and neutrophils engulf the pathogens.

Inflammation: mast cells v.s. basophils

Mast cells are fixed in the tissues while basophils circulate in the blood. Thus, mast cells are the main players in the early phase of inflammation.

Inflammation: Which leukocytes are emigrated from the bloodstream first?

1. neutrophils

2. monocytes

Opsonins

An antibody or other substance that binds to foreign microorganisms or cells, making them more susceptible to phagocytosis

Phagocytes (four main steps of phagocytosis)

1. Adherence

2. Ingestion

3. Digestion

4. Killing

phagocytosis has yet to be fully understood

Phagocyte-secreted chemicals: Nitric oxide (NO)

Secreted by macrophages, toxic to nearby microorganisms

Phagocyte-secreted chemicals: Lactoferrin

Secreted by neutrophils, protein that binds with iron, making it unavailable for use by invading bacteria

Phagocyte-secreted chemicals: Histamine

Secreted by mast cells, induces local vasodilation and increases capillary permeability

Phagocyte-secreted chemicals: interleukin 1 (IL-1)

Secreted by macrophages, enhances proliferation and differentiation of B and T lymphocytes

Innate immunity includes tissue repair. Two kinds of tissue repair:

• Cell division can replace lost cells with the same kind of cells → perfect

• Nonregenerative tissue (muscle and nerve) → scar tissue

Two classes of drugs that suppress the inflammatory process

Nonsteroidal anti-inflammatory drugs (NSAIDs)

• aspirin (decrease histamine release), ibuprofen

Glucocorticoids

• immunosuppressant

Innate immunity: Six steps of interferon mechanism (preventing viral replication)

First cell invaded by a virus:

1. Virus enters a cell.

2. Cell releases interferon

3. Interferon binds with receptors on uninvaded cells.

4. Uninvaded cells produce inactive enzymes capable of breaking down viral mRNA and inhibiting protein synthesis.

Subsequent cells invaded:

4. Virus-blocking enzymes activated.

5. Virus unable to multiply in newly invaded cells.

Innate immunity: 5 functions of interferons

• proteins that inhibit viral multiplication, defense until more specific, slower mechanisms can begin

• triggers production of virus-blocking enzymes

• released nonspecifically by infected cells

• enhances macrophage phagocytic activity, stimulates production of antibodies, boosts killer cell power

• exerts anticancer effects

Innate immunity: natural killer cells

Naturally occuring lymphocyte-like cells, nonspecifically destroy virus-infected cells and cancer cells via direct lysis

The complement system is composed of

~30 plasma proteins in blood tha are produced by the liver and circulate in inactive form

When activated, form membrane attack complexes that punch holes in victim cells

The complement system is activated by

Antibodies to kill foreign cells

Exposure to carbohydrate chains present on surfaces of microorganisms but not on human cells

Complement system: cascade sequence of events

1. C1 activated → C2 activated… → C5

2. Components C5 through C9 assemble into membrane attack complexes 🍩

3. MAC embeds itself into surface membrane of nearby microorganisms, victim cell swells and bursts. (indirect killing)

Complement system: two types of complement pathways

• INNATE - alternative: binding directly and nonspecifically to a foreign invader → cascade activated

• ADAPTIVE - classical: binding to antibodies produced against and attached to a specific foreign invader → cascade activated

Two classes of adaptive immunity

• antibody-mediated (humoral): B lymphocyte derivatives (plasma cells) produce antibodies

• cell-mediated: production of activated T lymphocytes, which directly attack unwanted cells

Origins of B and T lymphocytes

B cells: matured and differentiated in the bone marrow (think: B is for bone marrow)

T cells: originated from bone marrow, matured and differentiated in the thymus (think: T is for thymus)

Thymosin

hormone released by thymus (located centrally in the chest between lungs and heart), enhanced T cell proliferation and augments immune capabilities of existing T cells

Thymus and aging

• The majority of the T lymphocytes produced in a human being’s entire lifetime are already made during early childhood/fetal development

• The thymus decreases in size during development

• Levels of thymosin decrease after ages 30–40 (naturally, decreases immunity against viruses and cancer)

Antigens v.s. antibody

• antigen: a foreign substance that induces an immune response in the body, especially the production of antibodies

antigen = antibody generator

Two important charcteristics of antigens

• immunogenicity: provoke immune response (i.e. specific antibody production)

• reactivity: antibody binds specifically to corresponding antigen

Typically small parts of a large antigen provoke a response. This is called the

Epitope (the part of an antigen molecule to which an antibody attaches itself

Antibody-mediated immunity involves the use of

B cell receptors (BCRs) and T cell receptors (TCRs) that can only bind to one specific type of antigen

Antigens stimulate B cells to convert into

plasma cells that produce antibodies

Upon binding by processed and presented antigen, B cells

mostly differentiate into active plasma cells, others become dormant (memory) cells

Antibodies, also called immunoglobulins, are

large Y-shaped proteins which function to identify and help remove foreign antigens. They each recognize a specific foreign antigen.

Anatomy of an antibody

• Y-shaped

• four interlinked polypeptide chains: two long/heavy, two short/light

• specific antigen-binding Fab fragment at tip of each arm

• tail (constant regions) within each subclass are identical

Antibody (gamma globulins or immunoglobulins) subclasses: IgM

B cell surface receptor for antigen attachment (think M for attachMent), secreted in early stages of plasma cell response

Antibody (gamma globulins or immunoglobulins) subclasses: IgG

Most abundant, produced in large amounts when body is exposed to same antigen

Antibody (gamma globulins or immunoglobulins) subclasses: IgE

Helps protect against parasitic worms (think: eosinophil also protects against parasites, also starts with E), antibody mediator for common allergic reponses (think: eosinophil also participates in allergic reactions)

Antibody (gamma globulins or immunoglobulins) subclasses: IgA

Found in secretions of digestive, respiratory, and genitourinary systems; also in breastmilk and tears

Antibody (gamma globulins or immunoglobulins) subclasses: IgD

Present on surface of many B cells, function is uncertain (think: D is for dunno)

Three antibody mechanisms

• neutralization: physically blocking by binding

• aggultination: aggregate antigens

• amplification: activation of complement system, enhance phagocytosis, stimulation of NK cells

Clonal selection theory

Through genetic recombination, lymphocytes develop distinct antigen receptors before ever encountering an antigen. The clone specific to the antigen proliferates and differentiates into plasma cells and memory cells.

Primary v.s. secondary antibody-mediated immune response magnitude and time

Primary: first ever encounter, slow onset

Secondary: fast onset, antibody amount 1000x higher

B lymphocytes: plasma cells v.s. memory cells (significance of vaccination)

Plasma cells:

• produce and secrete IgG

• initial contact: antibody response is delayed, peak reached, antibody concentration decreases

Memory cells:

• small amt B lymphocytes become dormant

• upon reexposure to antigen, more ready for immediate action than original lymphocytes of the clone

• thus, secondary response is quicker, more potent, and longer lasting

Active v.s. passive immunity

• active: “self-generated”, resulting from exposure to antigen

• passive: “borrowed”, results from transfer of preformed antibodies, can provide immediate protection or bolster resistance

  • ex: IgG transfer from mother to fetus

Four steps of a cytotoxic T cell lysing a virus-invaded cell

1. Virus invades host cell.

2. Viral antigen is displayed on surface of host cell alongside the cell’s Class I major histo-compatibility complex (self-antigen).

3. T-killer cell recognizes and binds specifically with viral antigen in association with the self-antigen.

4. Cytotoxic T cell releases chemicals that destroy attacked cell before virus can enter its nucleus and start to replicate.

T cells learn to recognize foreign antigens

only in combination with a person’s own tissue antigens (surface of the cell must carry both foreign and self antigens).

A few days are required before T cells are activated to launch a cell-mediated attack.

The seven steps of the kiss of death (killer cell)

1. Killer cell binds target.

2. Kiler cell’s perforin-containing granules fuse with plasma membrane

3. Granules disgorge their perforin by exocytosis into small pocket of intercellular space between killer cell and target.

4. On exposure to Ca²⁺ in this space, individual perforin molecules change from spherical to cylindrical shape.

5. Remodeled perforin molecules bind to target cell membrane and insert into it.

6. Individual perforin molecules group together like staves of a barrel to form pores.

7. Pores admit salt and water, causing target cell to swell and burst.

Three main types of T cells

• CD8 cells (cytotoxic, killer T-cells): destroy host cells harboring anything foreign

• CD4 cells (helper T-cells): most abundant of circulating T-lymphocytes, modulate activities of other immune cells, secrete cytokines

• CD4+CD25 cells (regulatory): least abundant, suppresors

Five steps of antigen presentation (can be done by macrophages, B-cells, or dendritic cells)

1. Dendritic cell engulfs a bacterium.

2. Lysozymes break down large molecules to produce antigenic peptides.

3. New Class II MHC (self-antigen) molecule has been synthesized by ER/Golgi.

4. Antigenic peptides bind newly formed MHC proteins.

5. Antigen-MHC complex is displayed on the cell surface. Cell is now an antigen-presenting cell (APC).

Class I v.s. Class II MHC molecules

Class I: found on surface of all cells, recognized only by cytotoxic T cells

Class II: found onthe surface of immune cells with which helper T cells interact (i.e. dendritic cells, macrophages, B cells), recognized only by helper T cells

Four steps of activation of helper T cells by antigen presentation

1. APC cell surface displays bacterial antigenic peptides bound to class II MHC proteins, which helper T cells recognize.

2. APC secretes interleukins, which activate the T cell.

3. Activated T cell secretes cytokines, which stimulate T cell to proliferate to expand clone of selected cells.

4. Cloned helper T cells are ready to activate B cells and enhance other immune activities.

Upon binding to a B cell via CD4 coreceptor, the helper T cell secretes

interleukins which stimulate B cell proliferation to produce clones of selected cells (which differentiate into plasma and memory cells)

Autoimmune diseases arise from

loss of tolerance to self-antigens, can be caused by

• exposure of normally inaccessible self-antigens

• normal self-antigens modified by certain actors so that they are no longer recognized and tolerated

• exposure of immune system to a foreign antigen structurally identical to a self-antigen

• can be related to pregnancy

Immune surveillance

Process by which T cells recognize and destroy newly arisen, potentially cancerous tumor cells

Two general forms of immune disease

immunodeficiency (ex: severe combined immunodeficiency, AIDS)

inappropriate immune attacks, i.e. autoimmune responses, immune complex diseases, allergies

Muscles comprise the largest group of tissues in the body. Types and classification of muscles

Three types

• skeletal muscle: muscular system

• cardiac muscle: heart

• smooth muscle: components of hollow organs and tubes

Classification of muscles:

• striated v.s. unstriated

• voluntary v.s. involuntary

Controlled muscle contraction allows

• purposeful movement of the whole body or parts of the body

• manipulation of external objects

• propulsion of contents through various hollow internal organs

• emptying of contents of certain organs to external environment

Structure of skeletal muscle

• parallel muscle fibers held together by connective tissue

• single skeletal muscle cell = muscle fiber

• multinucleated, large, elongated, cylindrical

• fibers usually extend entire length of muscle

Myofibrils (skeletal muscle)

• contractile elements of muscle fiber

• regular arrangement of thick (myosin) and thin (actin) filaments

• alternating dark (A) bands and light (I) bands, giving the appearance of striations

Sarcomere (skeletal muscle)

Basic functional and contractile unit of the myofibril, spanning from one Z-disc to the next

Titin (skeletal muscle)

• giant, highly elastic protein (acts like a spring)

• largest protein in the body

• along with M-line proteins, helps stabilize position of thick filaments in relation to thin filaments

Myosin

• component of thick filament

• consists of two identical subunits shaped somewhat like golf club: tail ends intertwined, globular head project out at one end

• tails oriented toward center of filament, globular heads protrude outward at regular intervals

• heads form cross bridges between thick and thin filaments

The two important sites of the myosin cross bridge (between thick and thin filaments)

• actin-binding site

• myosin ATPase (ATP-splitting) site

Composition of a thin filament

• actin: spherical, primary structural component

• tropomyosin and troponin

Each actin molecule has a special binding site for

attachment with myosin cross bridge. Binding results in contraction of muscle fiber.

T/F Actin and myosin are contractile proteins, so they contract.

False. Neither actually contracts.

Tropomyosin and troponin

• “regulatory proteins”

• tropomyosin: thread-like molecules that lie end to end alongside groove of actin spiral, covers actin sites → block interaction that leads to muscle contraction

• troponin: made of three polypeptide units, binding (1) tropomyosin, (2) actin, and (3) Ca²⁺

Sliding filament mechanism

• Initiation: Increase in Ca²⁺

• Stop: Decrease in Ca²⁺

• Thin filaments slide inward over stationary thick filaments toward center of A band (M line) → Z lines pulled closer together, sarcomeres throughout muscle length shorten

• Facilitated by cross-bridge interaction

Four steps of contraction cycle

1. Myosin head hydrolyzes ATP energized and oriented

2. Myosin head binds to actin, forming a crossbrdige

3. Myosin crossbridge pivots, pulling the thin filament toward center of the sarcomere (power stroke)

4. As myosin head binds ATP, the crossbridge detaches from actin

Power stroke

• activated cross bridge bends toward center of thick filament

• sarcoplasmic reticulum releases Ca²⁺ into sarcoplasm

• contraction continues if ATP is available and Ca²⁺ level in sarcoplasm is high

Transverse tubules

• run perpendicularly from surface of muscle cell membrane into central portions of the muscle

• membrane is continuous with surface membrane: action potential on surface membrane spreads down into T-tubule → triggers release of Ca²⁺ from sarcoplasmic reticulum into cytosol

Sarcoplasmic reticulum

• modified endoplasmic reticulum, consists of fine network of interconnected compartments that surround each myofibril

• not continuous, but encircles myofibril throughout its length

• segments wrapped around each A band and each I band

• ends of segments expand to form lateral sac-like regions (terminal cisternae)