MB: Ch 16

adaptive immunity is the body’s ability to

recognize and defend itself against distinct invaders and their products

5 attributes of adaptive immunity

1. specificity

2. inducibility

3. clonality

4. unresponsiveness to self

5. memory

inducibility of adaptive immunity

• need a cell = can be activated

• no need for a cell = doesn’t have to be activated

unneeded cell becomes activated = autoimmune disease

clonality of adaptive immunity

when a cell activates, it divides

unresponsiveness to self of adaptive immunity

• if you don’t this = autoimmune disease

  • genetic basis

memory of adaptive immunity

• MMR or TDAP vaccine

• if exposed = no need to go through steps bcuz the immune system already knows what’s happening

  • however viruses can change/multiply faster

  • most mutations are on spike proteins

• immune system will activate the T & B cells that were supposed to be activated

what is involved in the activity of lymphocytes?

the whole immune system starts in red bone marrow (stem cells) → hematopoiesis

two main types of lymphocytes

• B lymphocytes (B cells)

• T lymphocytes (T cells)

B lymphocytes

• matures in the bone marrow = immature B-cell

  • doesn’t produce antibodies

  • becomes a plasma cell → antibodies

  • hides in spleen & secrete antibodies there

• mature b-cell = if the cells sees an antigen or smth foreign

T lymphocytes (T cells)

• mature in the thymus (above the heart)

• thymus is used until puberty— by then you’d have produced all t-cells in life

• atrophies after puberty become nonfunctional & replaced with adipose tissue (fat)

• thymus cancer: thymoma

2 types of adaptive immune responses

1. cell-mediated immune responses (T-cells)

2. antibody immune responses (B-cells → plasma)

cell-mediated immune response (adaptive)

• best way to get rid of viruses (evict it)

• CV4 & CV8 T-cells directly kills it

  • identifies abnormal cells (cancer/virally infected)

antibody immune response (adaptive)

• identifies pathogens & neutralizes them

  • binds to lock & key fit (adherence)

  • pathogens/toxins can bind to targets

  • opsonization (coating/binding) can lead to neutralization = prevents adhesion

elements of adaptive immunity: tissues/organs of lymphatic system

• lymphatic capillaries, vessels, ducts, lymphatic cells. tissues. & organs

• screen the tissues of the body for foreign antigens

• flow of lymph

• lymphoid organs

flow of lymph

• serum (lymphatic fluid) → interstitial fluid → lymph

• leaked fluid in tissues → picked up by lymphatic vessels → back in circulatory system (left/right subclavian arteries in neck)

lymph (serum)

• liquid w/ composition similar to blood plasma

• arises from fluid leaked from blood vessels into surrounding tissues (capillaries are leaky)

lymphatic vessels

• fluid gets picked up here

• 1 way system that conducts lymph from tissues & returns it to the circulatory system

  • if fluid can’t get picked up = tissues swell

  • no pump = can’t go up p

  • muscles also pinch lymphatic vessels to move the fluid

lymphoid organs (primary & secondary)

primary: red bone marrow & thymus

secondary: lymph nodes, spleen, tonsils, mucosa-associated lymphoid tissue (MALT)

what do lymph nodes do?

memory cells stay here

what does the spleen do?

• filters blood (graveyard of RBC — dead cells are engulfed/removed)

• red pulp = RBC

• white pulp = immune system part

mucosa-associated lymphoid tissue (MALT)?

• below mucosal layers

GALT (Peyer’s patches) = gut (GI tract)

• patrols invaders & normal flora

BALT = bronchial (respiratory) = in airways

tertiary lymphoid organ

• immune system structures in the body where they don’t normally exist

• found in areas of chronic inflammation; constant infiltration of T and B cells

properties of antigens

• molecules that the body recognizes as foreign

  • regions within antigens = epitopes (antigen determinant)

  • what immune response is made against *

  • each epitope can produce an immune response (spike protein, membrane)

  • diff geometric shape - immune system can make multiple antibodies against that specific antigen

• bacterial components, proteins of viruses, fungi, & protozoa

• food, pollen, dust

• activates B & T cell to find epitope & neutralize/kill it

Prep of Adaptive Response: Major Histocompatibility Complex (MHC)

• group of antigens 1st identified in graft patients (og used for organ transplant)

• important in determining compatibility of tissues for tissue grafting

• MHC are glycoproteins found in the membranes of most cells of vertebrae animals

  • heterogeneous protein- similar to ppl (5-10%)

  • has peptide-binding or antigen groove = epitope (determined through crystallization studies)

  • displays normal proteins (actin)

  • cell-surfaced-bound glycoproteins

  hold and position antigens for presentation to T cells *

Prep of Adaptive Response: Antigen-Presenting Cells

• antigens bind in the antigen-binding groove of MHC molecules

• 2 classes of MHC proteins: 1 and 2

MHC class I

• present on all nucleated cells on the body except RBC

  • RBCs has no nucleus & is concave shape

• Antigens are processed in the endoplasmic reticulum & then loaded onto MHC I → goes to cell’s surface

MHC class II

• present on antigen-presenting cells (APCs)

  • needs an antigen to get activated to produce an antibody

  • inside the groove, it displays normal proteins

    includes B cells, macrophages, & dendritic cells

what are macrophages?

step #5 of phagocytosis (killing), where the antigen is presented

• whole bacterium is phagocytosed from the outside

  • fused w/ lysosome = phagolysosome

  • piece of the bacteria is taken out in a vehicle

  • put onto MHC I → cell’s surface

what are dendritic cells

• part of the immune system

• phagocytic cell in the nervous system

• can increase surface area & contact multiple pathogens through TLR (PAMPs) by binding and engulfing

antigen processing

• antigens processed & loaded onto MHC proteins

  • MHC I →ENDOgenous antigens (INTRAceullular) → viruses

  • MHC II →EXOgenous antigens (EXTRAcellular) → bacteria

• take antigens from the outside, brings it inside, & then processes it

cytokines (selected secretions)

language of the immune system

• trained to prevent

• like estrogen, secreted by the ovaries, binds to adipose tissue receptor = get a response

• produced by 1 cell & binds to another cell = response

immune response cytokines

soluble regulatory proteins that act as intercellular signals

cytokines secreted by various leukocytes

• t-cells

• b-cells

• macrophages

• dendritic cells

cytokine network

complex web of signals among cells of the immune system

paracrine

produce something and it acts on another cell

autocrine

produce something & it acts on another cell

• Th1 → IL-2 → CD8 → cloning

• CD8 →IL-2 →autocrine (acts on itself)

  • You need more IL-2 to make CD8 to kill a virally infected or cancerous cell

  • When it becomes active, make more IL-2

T-lymphocytes prep for an Adaptive immune response

• T cells act against cells that have intracellular pathogens & abnormal cell (cancer)

• Circulate in the lymph & blood

• T cells have a T receptor (TCR) on their cytoplasmic membrane

Specificity of the T cell receptor (TCR)

• each cell’s TCR has a specific antigen-binding site

  • DNA recombination

  • groove on cell’s surface glycoprotein recognized antigen on MHC = cells activates = immune response generates

• antigen must be presented by an antigen-presenting cell/epithelial cell

  • TCRs don’t recognize epitopes directly

  • TCRs bind only to epitopes associated w/ an MHC protein

• never binds to an antigen that’s free-floating

[MHC + T Cell = signal]

what’s cell signaling?

gives T cells instructions

• cloning

• target & kills intracellular pathogens & abnormal cell (cancer)

subsets of T-Lymphocytes (based on glycoproteins/functions)

1. cytotoxic T lymphocyte (CTL, Tc) CD8

2. helper T lymphocyte (Th1 & Th2) CD4

3. regulatory T lymphocyte (Treg) CD4

cytotoxic T lymphocyte (CTL, Tc) CD8

• directly kills other cells (abnormal = virally infected/cancerous)

• act against intracellular pathogens

• cell surface proteins → how the targeted cell is killed

• secretes perforin & granzyme (initiates apoptosis)

• produces IL-10 (initiates Treg & immunomodulating proteins)

helper T lymphocyte (Th1 & Th2) CD4

• helps regulate cytotoxic T cells/macrophages & B cells

• includes Type 1 and Type 2 helper T cells

• cell-surface proteins

• helps other cells to become activated

Th1 (T Helper 1) produces?

IL-2 → CD8 T cell

• binds/helps activate CD8/CTL

• activates the CD8 T cell

  • binds to the cell coating of T cell

  • clones

  • memory

  • can make more IL-2

  • CD8 → IL-2 → autocrine (acts on itself)

    • need more IL-2 to make CD8 to kill a virally infected/cancerous cell

    • active = more IL-2

TNF-alpha → macrophages (inflammation)

Gamma-interferon (helps activate macrophages; inc phagocytosis)

Th2 (T Helper 2) will produce?

IL-4 → helps activate the B cells

• activated B-cells become plasma cells → produce antibodies

• plasma cells → antibody-producing factor

Dendritic cells → IL-12

• will tell T-helper to become Th1

• all T-helpers start out as a Th cell

  • to become Th1 or Th2

• professional antigen-presenting cell

  • neither macrophages nor B cells can do this

if you don’t have Th2 cells, you can’t produce?

anitbodies

if there is no Th1, it can kill?

normal, healthy cells in the body

regulatory T lymphocyte (Treg) CD4

• sub-population of CD4

• represses adaptive immune responses

  • represses cells

    • infection → activated adaptive immune response

    • T cells are activated

    • end of immune response = memory cells made

    • get rid of reactive T cells (don’t want them floating in body)

    • send Treg cells to turn off the immune system

immune system is trained to prevent

autoantigens

T-cell education & Clonal deletion

• 94%-95% of T cells are lost

• gotten rid of/deleted → apoptosis

• can’t recognize self MHC molecules → deleted

  • need to present antigen that is inside of MHC

• recognize self proteins deleted (autoimmune disease)

• remaining 5-6% will protect you from antigens

B-cells & Antibodies

• in spleen, lymph nodes, & MALT, circulation

• major function is the secretion of anitbodies

  • activated b-cells → plasma cells → antibody production

• B-cells become plasma cells

• B-cell is inside rough endoplasmic reticulum

  • secretes proteins (anitbodies)

  • increases in size, then it has rough ER

• B-cell surface receptor (BCR) recognizes antigen

When B-cell surface receptor (BCR) recognizes antigen…

an antibody has 2 arms (sites) that can recognize an epitope → binds to it → the bacteria is endocytosized → gets digested → piece is put onto MHC II → goes to cell’s surface → Th2 cells will recognize this + bind to it → activates B cell = secretes IL-4

Specificity of the B-cell receptor (BCR)

• each B lymphocyte has multiple copies of 1 B cell receptor

• each BCR recognizes 1 epitope

• BCR is an immunoglobulin antibody

• entire collection of a person’s BCRs is capable of recognizing millions of different epitopes

  • DNA recombination

only B cell receptors can do DNA recombination

• encoded by different pieces of DNA found on different chromosomes

• takes different bits of DNA & make an antibody

• able to make different antibodies that can recognize different epitopes

  • constantly change the antigen recognition

antibodies = immunoglobulin = b-cell

• can be cell surface bound

• always have a b cell receptor

• or it can be secreted

specificity & structure of antibodies

• Antibodies are immunoglobulins similar to BCRs

• Secreted by activated B cells = plasma cells

• Have antigen-binding sites and antigen specificity 

structure of antibody

• has 2 heavy chains & 2 light chains 

  • Make up each arm 

• Antibody has 2 arms (sites) called the Fab (Fraction Antigen Binding) region

  • Each arm can recognize an epitope or antigen 

  • Can bind to an epitope and neutralize it

    • Can bind to 1

    • The max is 2

• Fc region / Stem

  • Constant

• Most have these structures 

name the classes of antibodies (in context of disease, vaccine, booster)

1. IgM

2. IgG

3. IgA

4. IgE

5. IgD

IgM

• First antibody produced

• Pentamer (5 antibodies and 10 antibody binding sites)

IgG

• Second antibody produced

• Most abundant, common and longest-lasting antibody class 

  • Will be present on your serum at a particular band level 

  • levels rise at 14 days 

• Can cross the placenta (mother to fetus) 

  • Flu and covid 

  • until 3 months of age (decent amount from mother), then after it decreases

  • month 6: child makes their own antibodies

IgG of children between months 3-12, 6-12, & 12-15:

3-12: babies are vulnerable to infections

6-12: start to have a more mature immune system

12-15: MMR is given due to a better immune system

IgA

• associated with body secretions 

  • GI tract, respiratory tract

    • Secreted in the MALT and BALT areas & hangs in the mucous areas on top of the mucous membrane

    • IgA will bind to pathogen

  • Breast milk

• dimer

IgE

• Involved in response to parasitic infections 

  • eosinophils will increase 

  • IgE BRIDGES between the parasite and the eosinophil 

  • Bind to worm/fluke (parasite) 

    • Eosinophil will go there & bind to IgE = Degranulate 

• Allergies

  • Will bind to a mast cell → degranulation = histamine production

IgD

• exact function is not known

• Tends to be localized in the tonsil area (reaction with basophils)

• Basophil and IgD will control normal flora and pathogens in the upper respiratory tract 

actions of anitbodies

1. neutralization

2. opsonization

3. agglutination

4. antibody-dependent cytotoxicity

neutralization of antibodies

• Will bind to virus, bacteria or toxin 

  • Pathogen cannot bind to its receptor 

  • Blocked the lock and key fit (adhesion) 

opsonization of antibodies

• Antibody will bind to pathogen and COAT it 

  • Macrophage, dendritic cell or neutrophil will bind to it, internalize it, digest it, & get rid of it 

    • Need the receptor for the antibody 

agglutination of antibodies

• used in various diagnostic tests to detect and identify antigens and antibodies. 

  • rapid flu/covid/strep/RSV/pregnancy test or blood typing

• antibodies bind to specific antigens, causing them to clump together. immune response that helps to neutralize and eliminate pathogens.

  • visualization: red/blue line or binding (coagulation) and settling out of solution

antibody-dependent cellular cytotoxicity

• antibody bound to a pathogen + kills it (lysed/apoptosis)

  • Need only 1 antibody & a cell that has a receptor for it 

B-cells education and Clonal deletion 

• occurs in the bone marrow (produce B-cell w/ B Cell Receptor

• similar to deletion of T cells

• self-reactive B cells may become inactive/change their BCR

Self-reactive B cells should not be

autoreactive (not recognize self)

• if it recognizes a self-antigen → apoptosis

• if NOT → circulation, lymph, organs

if B-cells escape the bone marrow

• they are reactive to self

• cause an autoimmune disease

• Treg cell will secrete IL-10 to inhibit this

cell-mediated immune response

• effector cell: CD8 T-cell

  • Only T-cell can directly identify a virally infected or cancerous cell 

• Respond to intracellular pathogens and abnormal body cells

  • Put the players together 

Activation of Cytotoxic T Cell Clones and Their Functions

• Adaptive immune responses initiated in lymphoid organs (lymph nodes)

• Steps involved in activation of cytotoxic T cells 

  • Antigen presentation

  • Helper T cell differentiation (Th cell) 

  • Activation of CD8 T-cells and Clonal expansion

majority of immune reactions in lymphoid organs occur here:

• All the cells are here 

• Antigens are drained here

• Antigen-presenting cells will pick these up, process it, & bind to B-cells and T-cells 

• getting a vaccine = will be drained in the axillary lymph node 

Activation of a clone of cytotoxic T (Tc) cells:

• Dendritic cell 

  • IL-12 

• T-Helper cell 

  • Th1 → IL2 → CD8 → clonal expansion and memory cells

How Cytotoxic T-cells (CD8) will kill targets?

• activated CD8 T cells will receive instructions from dendritic cell & from MHC I

  • pick up pathogen, give it to T-helper, recieves IL-2 to undergo clonal expansion, cells recognize green epitope

• find where patho came from

  • go in blood, bind to it, release perforin-granzyme pathway

perforin helps cytotoxic t-cell (CD8) to kill its targets by?

creating a pore on the target cell

granzyme helps cytotoxic t-cell (CD8) to kill its targets by?

• going into the target cell & initiate apoptosis 

  • involves synthesis of killing proteins

antibody-mediated immune response

• mounted against exogenous pathogens and toxins

• activates only in response to specific pathogens

T-independent antigens =

= NO long-lived immunity

• in the fetus before its born & in the liver

T-dependent immunity =

= long lived immunity

• Require the assistance of helper T cells (Th2)

  • IL-4 secreted by TH2 cells activates B-cells

• Majority of the cells 

  • Long-lived memory 

B-cell will take in the antigen and then?

presents to Th2 → produce IL-4 (tell B cells to start clong)

• b cell → plasma cells → antibodies = memory B cells

B-cells & T-cells both like to? and they both have what kind of cells?

• circulate between the lymph fluid, blood and lymph nodes

• both also have memory cells 

plasma cells

• majority are produced during B cell proliferation

  • Only secrete antibody molecules that are complementary to the specific antigen

  • Short-lived cells that die within a few days of activation

    • Their antibodies and progeny can persist

majority of plasma cell’s cytoplasm is rough ER meaning

nucleus and organelles is pushed up to the side so it needs to start spitting out antibodies 

location of plasma cells

• some stay in lymph node\

• majority goes into bone marrow (where they produce antibodies)

Th1 (CD4) [H stands for helper] →

activates macrophages and cytotoxic T cells (Tc cells)

Th2 (CD4) [H stands for helper] →

activates B-cells

Tc cells (CD8) [C stands for cytotoxic] →

kills virally infected or abnormal cells 

Th1 and Th2 cells recognize antigen presented in the context…

MHCII (exogenous antigen)

Tc cells recognize antigen presented in the context of

MHC I (endogenous antigen)