Physiology Lecture Week 5

cells/proteins

can be active or inactive

can be innate or adaptive

• body does this so cells/proteins don’t act when not needed

adaptive immune system

specific

recognizes antigens

B & T cells

• identifies specific target

• makes specific antibodies

• provides immune memory

innate immune system

general, nonspecific defense

attacks things recognized as foreign/damaged

• helps destroy marked target

antigen

target that the immune system recognizes and may attack

• part of a larger molecule/pathogen

• can be found on:

  • pathogens

  • cancer cells

  • foreign material

antibody

body’s weapon against antigens

• made by B cells/plasma cells

• specifically binds to an antigen, circulates freely in bodily fluid for defense

B lymphocytes function

humoral (antibody-mediated) immunity

• each B cell has a specific receptor on its surface

  • the antibody attaches to this receptor on cell membrane & gives body thousands of possible antigen-recognition patterns

  • antibody has 2 recognition sites

when pathogen enters:

1) different B cells encounter pathogen

2) 1 B cells receptor might fit the antigen

3) B cell is activated

4) makes copies of itself

5) some become plasma cells

T lymphocytes function

cellular (cell-mediated) immunity

• has surface receptor (1 recognition site)

• acts against target cell

• has other cells help them

  • antigen-presenting cells: infected or immune cells can take pieces of pathogens & present the antigen on their surface

either:

• directly kills infected cell

  • by using T cell receptor which acts like B cell surface antibodies

• indirectly attacks by releasing chemicals that

  • enhance inflammatory response

  • activates other lymphocytes/macrophages

B Lymphocyte Types

plasma cells: make and release antibodies when exposed to foreign antigen

memory cells: some B cells remain & remember antigen

• if similar pathogen enters again response is faster

*mature in red bone marrow

T Lymphocyte Types

Cytotoxic T cells: recognize infected body cells & presents pieces of virus

• cell recognizes & attacks

Helper T cells: coordinate immune response (communicate w/ immune cells)

• help activate B and T cells

  • Ex.: HIV (human immunodeficiency virus)

    • infects/damages helper T cells…weakens immune system

  • Ex.: AIDS (acquired immunodeficiency virus)

    • severe immune system damage after HIV

Regulatory T cells: control immune response

• immune system gets too active sometimes

• prevents autoimmune diseases

Memory T cells: remembers cells after infection…body responds faster/defeats antigen

first immune response takes time

body must:

• recognize the antigen

• activate correct B-cell

• make copies

• produce enough antibodies

by second exposure…body can use memory cells

antibody/immunoglobins

immunoglobin G, E, D: have 2 identical antigen binding sites

immunoglobin G: “good immunoglobin”, small, can cross placenta, allows fetus to receive antibodies from mom

immunoglobin A: has 4 antigen binding sites, “secreted immunoglobin”, found in saliva/mucous/breast milk, protection at body surfaces

immunoglobin M: has 10 antigen binding sites, large, binds multiple antigens together, important in agglutination, blood typing

antibodies…

• tag or inactivate antigens

• don’t destroy antigens

• prepare for destruction by innate defense

Antibody Functions: Agglutination

clumping things together

• antibody has multiple binding sites:

  • 1 antibody binds antigens on different cells

  • causes pathogens to be stuck together

  • large clumps are easier for immune cells to deal with “stuck in 1 place”

  • innate immune cells can attack group

Antibody Functions: Neutralization

if pathogens attach to cell…infection

• antibody:

  • binds to virus/pathogen

  • covers the part it needs to attach to cell

  • prevents it from entering/infecting cell

  • coats pathogen…prevents infection

Antibody Functions: Precipitation

leaves solution

soluble molecules

Antibody Functions: Identification (opsonization)

antibody stuck on cell…signals cells to come phagocytize antigen

• “marked for death”

Tissue Typing

Ex.: pig transplant

• anything introduced outside your body can be recognized as foreign

Blood Typing

surface of RBCs: 30 types of glycoprotein antigens

RBCs carry gases…O2

if someone loses blood might need blood transfusion (compatible RBCs)

• if incompatible:

  • antibodies bind to antigens on donor RBCs

  • causes agglutination

  • clumping of RBCs interfere with blood flow + O2 delivery

2 groups: ABO & Rh antigen groups

ABO blood group

Type A: A antigen, anti-B antibodies

Type B: B antigen, anti-A antibodies

Type AB: A + B antigens, no anti-A or anti-B antibodies

Type O: neither A or B antigen, anti-A & anti-B antibodies

Rh blood group

52 types of Rh antigens

Rh+ has D antigen

Rh- has no D antigen

• if exposed to Rh+ they will make antibody

  • only Rh- can carry the antibody

golden blood: extremely rare, no Rh antigens & can give blood to anyone

you carry the antibody

for the antigen you don’t have

agglutination means

you have that antigen

if you agglutinate for A & Rh… you have A+ blood

patient with type A blood

has anti-B antibody

• can receive from O

universal donor/recipient

O: universal donor (no A or B antigens)

AB: universal recipient (no anti-A or anti-B antibodies)

whole blood matching rule

if recipients antibodies CANNOT recognize (agglutinate) the donors antigens, then it is compatible!

Blood transfusions

mix recipients serum w/ donor RBCs

mix recipients RBCs w/ donor serum

(usually not performed in emergencies)

if they agglutinate…incompatible

rare/common blood types

B is rare

A & O are common

AB is most rare

• AB- is rarest blood group

Newborn/Mom (Erythroblastosis Fetalis)

mom is Rh- & baby is Rh+

• during birth, fetal blood may enter mom’s bloodstream

• mom may be exposed to & develop Rh antibody

Rh- mom carries the antibody

• can cross uterus & stick to RBCs in 2nd pregnancy…killing the baby in eutero due to agglutination

Rhogam: giving mom antibody Rh-

• given to all moms with Rh- blood group

Plasma Transfusions

promote clotting after surgery/hemophilia

• when giving plasma, compatibility rules are reversed w/ RBC transfusions

donor antibodies attack recipients RBC antigens

Plasma donor/recipient:

AB gives to A, B, AB, O

A gives to A, O

B gives to B, O

O gives to O

Rh+ gives to Rh-

• AB doesn’t have antibodies so it becomes the universal plasma donor

vaccination/immunity

vaccination: exposes immune system to something associated with pathogen so adaptive immune system can develop protection

• include:

  • weakened/inactivated pathogen

  • parts of pathogen

  • modified toxin

immunization: immunity to antigen

Active vs. Passive Immunization

active: introduce antigen, injection

• own immune system makes the response (vaccination)

passive: introduce specific antibodies, injected or acquired

• receive antibodies already made by someone/something else

active immunization

your own immune system is exposed to antigen + makes its own immune response (antibody)

(vaccines)
introduce antigen so immune system can

• recognize antigen, make antibodies, create immune memory, respond faster if exposed again

• some vaccines use modified virus with changed DNA

passive immunization

body receives antibody that was already made

(baby receives antibodys through mothers milk)

vaccines

prevents/reduces infection by preparing immune system

flu vaccine

• development takes months

• prediction, not always exact match

• effectiveness varies

• encouraged for old adults/young kids

covid vaccine

• covid caused by SARS-CoV-2

• this virus has spike proteins

• vaccine targets the spike proteins because immune system recognizes them

2 options for gaining immunity

1) weak virus carries sequence

• virus-based vaccine infects cells

• cells express spike protein

• immune system generates antibody against spike protein

modified virus, delivers genetic instructions, cells make spike proteins, immune system recognizes them, antibody + memory made

2) mRNA vaccine of the sequence is injected into body

• lipid nanoparticle carries mRNA across plasma membrane

• cells express spike protein

• immune system generates antibody against spike protein

lipid nanoparticle, enters cell, releases mRNA, cell makes spike protein, immune system recognizes antigen, antibody + memory made

mRNA needs delivery system because

RNA is large, highly charged, and hydrophilic

antiviral drugs

Ex.: Paxlovid

• inhibits SARS-CoV-2 replication

• must be taken early on in infection because virus replicates FAST!

Antibody therapy (passive immunization)

receiving antibodies that were already made

antibodies are generated against antigens on:

• molecules involved w/ autoimmune diseases

• cancer cells

• bacteria

• viruses

Ex.: Cosentyx for plaque psoriasis (chronic skin inflammation)

• blocks molecules involved in inflammation

**patients receiving biological therapies need extra precautions + vaccines

• lower immune activity leads to higher susceptibility to infection

Antibodies + cancer cells

cancer cells display specific antigens

researchers develop antibodies that target particular molecules on cancer cells

cancer antigen…antibody recognizes target…immune system can attack targeted cell

innate immunity

present from birth

acts quick

less specific

doesn’t require previous exposure

adaptive immunity

develops after exposure

highly specific

produces immune memory

Major innate defenses (innate immunity is nonspecific)

1) Surface Barriers

• skin

• mucous (catches bacteria, slows virus down, cilia sweep out)

  • respiratory + GI tract

2) Cells

• granulocytes

• monocytes

  • antibodies help with opsonization (marking)

3) Inflammatory Response

• Redness (vasodilation…higher amounts of blood in area)

• Heat (vasodilation…higher amounts of blood in area)

• Swelling (basophils release histamine, moves fluid out of bv’s, enters surrounding tissue)

• Pain (swelling causes pressure & compresses nerves)

4) Antimicrobial Proteins (lytic)
5) Antimicrobial Proteins (markers, signaling molecules)

Phagocytosis

cells engulf particle/pathogen

• place pathogen in vesicle (endocytosis)

• lysosome fuses w/ vesicle

• hydrolytic enzymes break pathogen down

Chemotaxis

movement of cell toward chemical signal

• neutrophils can follow a chemical trail to a pathogen

pathogens hide in cells

Ex.: virus replicates inside host cell

makes it harder for antibodies to reach

Complement Proteins (innate immune system)

group of proteins already present in body that help defend against pathogens

• about 20 blood proteins circulating in inactive form)

function:

• agglutination (cluster + stick pathogens together)

• opsonization (enhances phagocytosis of antigens by marking for recognization)

• cell lysis (ruptures membranes of foreign cells)

• chemotaxis (attract neutrophils + macrophages)

these proteins

• mark/identify pathogens

• promote inflammation

• attract immune cells

• damage pathogen membranes

complement protein vs. antibody

complement protein

• marks pathogen + directly damages membranes

antibody

• binds to specific antigen

tattoo doesn’t blur

ink enters dermis (extracellular matrix)

ink is phagocytosed (macrophages)

lysosome can’t fuse w/ it & break down…sits in belly of macrophage

*nanoplastics remain in body)

Antimicrobial Proteins: Defensins

• in neutrophils

• form large pores in pathogen membranes

Antimicrobial Proteins: Dermcidin

• sweat

• form large channels/pores in membranes

Antimicrobial Proteins: Lysozyme

• tears/saliva

• chews up bacterial cell walls (lets other proteins do their job of forming pores in membranes)

Antimicrobial Proteins: Interferon

protein released by virus infected cells to ‘warn’ nearby cells about viral infection

• make nearby cells more resistant to viral replication

Leukocyte Disorders

Leukopenia = too few WBCs (caused by HIV…reduces helper T cells, aplastic anemia)

Leukocytosis = increased WBCs (can be good when fighting infection…bad in inflammation)

Leukemia = increased WBCs (cancer)

Leukemia

cancer involving blood-forming tissues that lead to abnormal production of white blood cells

• can crowd out normal blood cells

  • reduces RBC production…anemia

  • reduces platelet production…bleed out

  • immature WBC…can’t function right

treatment harms other components not only cancer cells

need platelets & plasma so clotting factors are involved

Types of leukemia

acute leukemia:

• comes in quick and fast

• derives from stem cells

• primarily affects children

chronic leukemia:

• progresses more slowly

• more prevalent in old people

myeloid leukemia:

• involves myeloblast descendants

• granulocytes + monocytes

lymphocytic leukemia:

• involves lymphocytes

infectious mononucleosis (kissing disease/epstein-barr virus)

highly contagious viral disease

• B lymphocytes infected with virus

• T lymphocytes attack infected B lymphocytes

• tired, achy, chronic sore throat, low fever

• treatment: rest