Adaptive immunity

Adaptive immune system

Adaptive Immune System

• Defining Key Terms

• Cell Mediated Immunity

• Humoral Immunity

• Immunological Memory

• Types of Immunity

innate vs adaptive immune system

Innate Immune System

• PRRs recognize broadly-conserved

PAMPs

• PAMPs are molecules that are essential for

pathogen survival

• Limited specificity

• Broad cross-reactivity across many

pathogens

• Perfect self:non-self discrimination

• Common to many lifeforms

• Immediate response

• No memory

Adaptive Immune System

• B cells and T cells have receptors that can recognize

specific antigens

• Antigens can be any kind of molecule

• protein/lipid/carb

• Receptors are generated by recombining a few genes

• Almost unlimited repertoire of specificities

• Extremely narrow cross-reactivity

• Very specific

• Mistakes are uncommon

• REALLY Good, but not perfect self:non-self discrimination

• Sometimes, mistakes happen!

• Restricted to jawed vertebrates

• Initial Responses are Slow

• (3-5 days to initiate)

• Memory

what if we dont have innate immune response

we also wont have adaptive

3 key features of adaptive immune system

1. It is specific

• Directed against particular pathogens or foreign substances that initiated an

innate, non-specific response

2. It is systemic

• Not restricted to the initial infection site

3. It has memory

• After an initial exposure (where the system is “primed”) subsequent responses are

faster and stronger

• Antigen recognition is required for these features to occur

cells of the adaptive immune system

B and T cells (lymphocytes)

Both derived from the common lymphoid progenitor in the red bone

marrow

• B cells stay and develop in the Bone marrow

• T cells go and develop / mature in the Thymus

devellop immunocompetence + self - tolerance (not kill healthy cells)

Naive B&T cells travel to lymph nodes to await antigen exposure

Why are these cells special?

• Some have a very long life-span (plasma cells/memory T cells)

• Can divide/regenerate rapidly

• Each cell has a unique receptor to recognize antigen

B cell receptor

2 antigen recognition sites

• Can be membrane bound

(i.e., be the BCR) or

released as antibody (Ab)

• Variable regions make up

the binding sites

• Stays on top of the cell

• Sometimes secreted

T cell receptor

1 antigen recognition site

• Membrane bound

• Variable regions make up

the binding site → bind to and recognize antigen

How are these receptors so specific

By rearranging and

recombining a few (3) genes!

• Almost unlimited number

of combinations!

CD4+ and CD8 T cells

• named by type of molecule that pairs with the T cell receptor

CD4:

• Helper T cell

  • The TCR recognizes antigens presented

  on MHCII

  • Help activate B cells

CD8:

• Cytotoxic T cell

• TCR recognizes antigens presented on

MHCI

• Kill infected/altered cells

Antigen (Ag)

• any molecule that can bind specifically to an antibody

May be a pathogen or a toxin, also can be non-toxic foreign molecules (e.g. food

antigens) or self-molecules presented at the wrong time/place

• E.g., bacterial structures, bacterial toxins, pollens, dust, egg albumin, incompatible blood or

tissue cells

• May be proteins, polysaccharides or (sometimes) lipi

Epitope

• A small defined structure on an antigen that can induce an immune response by

binding an antibody or receptor on a B or T cell

• i.e., “the part that does the binding”

• Most antigens will have several epitopes

• Also called antigenic determinants 14

Professional Antigen Presenting Cells (APCs)

• Both types of MHC (class 1 and class 2)

• Process and display antigenic peptides on cell-surface molecules

• Activate T Cells

• Dendritic cells (DCs) are the best at being APCs

• Macrophages can be APCs too, but they’re better phagocyt

Major histocompatibility comples (MHC)

• Glycoproteins found in the plasma membrane

• Your “self-antigens”

• Mark your cells as yours – strongly antigenic to other individuals

• Every person has unique MHC on all nucleated cells

• Function to help T cells recognize self from non-self

• 2 Types:

• MHC Class I

• In the plasma membrane of all nucleated cells

• MHC Class II

• On professional antigen-presenting cel

when looking at organ transplants, we look for MHC.

Antigen processing and presentation

• How a pathogen enters a cell determines whether it is presented on MHC

I or MHC II

• T cells can only “see” antigens if they’re presented on an MHC molecule

MHC Class I

• Binds to and presents cytosolic peptides

• Endogenous antigens

• i.e., present inside the cell

• E.g., viruses or intracellular bacteria

• Presents antigen to CD8+ T cell

Antigen processing and presentation (MHC class II)

• binds peptides from intracellular vescicles

• • These are exogenous antigens that have been brought into the cell

  from outside

  • E.g., through phagocytosis or specific binding

  • E.g., bacteria or viruses that have been phagocytosed

  • Presents antigen to CD4+ T cells

Adaptive Immune System DIVISIONS

Humoral:

• antibody mediated

• Made by B cells

• bind to things

• • Functions of Antibodies:

  • Opsonization, neutralization,

  activation of complement

  • “marked for destruction

Cell - mediated

• Mediated by living cells and has

cellular targets

• “cell on cell violence”

• Largely mediated by T cells

• Infected cells, cancer cells, foreign

cells are killed

• Can be either direct or indirec

Generation of Effector T cell pt 1

A naïve T Cell gets activated by a specific antigen

• Once the T-cell is activated, it proliferates and differentiates

• Now capable of “doing its job” & is called an effector T cell

• Attack or help mount a response

• There are different types of mature, effector T cells:

• Cytotoxic T cells (CD8+)

• Helper T Cells (CD4+)

• TH1, TH2

• Memory T Cells

• Regulatory T Cells

Generation of Effector T cell pt 2

• T Cells cannot “see” antigens directly

• Must have antigen “presented” to them on MHC

• Naïve T cells need 2 signals to become activated

• “2-step” hypothesis of T Cell activation

• Presents immune responses from happening accidentally

• In the absence of co-stimulation the T cell becomes inactivated

• Activated APCs present antigen to T cells in the lymph nodes

• This event elicits the primary cell-mediated response

• T cells differentiate and proliferate become effectors

• Some of those will become memory T cells

• Protect against subsequent challenges

T cell activation

• Signals 1 & 2 are required

to activate a naïve T cell

• Signal 3 tells that T Cell

what it’s supposed to do

• Often a chemical signal from

the microenvironment

• In the form of cytokines

• E.g., what kind of THELPER cell

am I supposed to be? TH1?

TH2?

25

Cytotoxic T cell s

• Also called “killer” T Cells

• Activation of naïve T cells:

• T cell receptor binds to Antigen presented on MHC I

• Co-stimulatory signal required

• Activated T cells now proliferate and differentiate

• Also called clonal selection

• Activated cytotoxic T cells

• Kill via perforin and granzyme

• Do not require co-stimulatory signal to act

• Memory T cells

• Do not require co-stimulation for activatio

Cytotoxic T cells

• Activated CTL leave the lymph nodes and travel to the site of infection

• Recognize pathogenic epitopes in the context of MHCI on infected

cells

• Kill them via perforin/granzyme (remember NK cells?!)

• Also produce IFN-γ which can activate tissue macrophage

Helper T cells

• CD4+

• Activation of naïve T cells:

• T cell receptor binds to Antigen presented on MHC II

• Co-stimulatory signal also required

• 3rd, cytokine signal to “give the cell instructions”

• Activated T cells now proliferate and differentiate

• Activated helper T cells secrete cytokines

• Help stimulate immune responses, enhance proliferation of T cells, B cells and NK

cells

• Memory T cells

• Do not require co-stimulation for activatio

Memory T cells

• Remain after cell mediated response is over

• Long lived (we dont know → some maybe your whole life)

• if they get exposed to the same antigen, faster and more vigorous response.

• do not require co-signal.

• more vigurous response.

Humoral immunity

• We have millions of different B cells

• Each bear unique BCRs and can recognize and respond to different Ag

• Once activated they proliferate and differentiate into:

• Plasma cells that secrete antibodies

• Memory B cells that await subsequent exposure

• Antibodies circulate in lymph and blood to recognize specific A

B cell activation

• can see antigen through BCR

• require costimulated

• T cell independent activation

  • less common

  • other microbial constituents provide secondary signal

T cell dependent activation

more common

• B cell recognizes antigen, bring antigen inside, process, then presents to T cell, T cell does what ut needs to do.

once B cell is activated

• clonal expansion → clone and clone and clone

• matire antibody producing cells cells are called plasma cells

• plasma cells make 1 millions Abs per day (live 4-5 days)

• some B cells become memory cells

Antibodies structure

• Core structure consists of:

• 2 identical heavy chains

• 5 types

• 2 identical light chains

• 2 types

• Each chain consists of:

• A variable region

• Responsible for Ag recognition

• A constant region

• Structural stability

• In the heavy chain – determines the effector function

• The different heavy chains determine what KIND of antibody you get

• Called isotypes, or classes

• IgM, IgD, IgG, IgA, IgE

• Different isotypes have different roles/functions

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hi

immunological memory

Primary Immune Response

• First response is steady, slow

• Response begins 3-6 days following exposure

• Memory cells may remain for decades

• Ab titres usually fall within 28 day

immunological memory (seconday immune response)

• Occurs following re-exposure

• Faster, stronger, and more prolonged than 1st response

• Onset within hours

• Ab titre remains elevated for weeks to months

• Pathogen can be destroyed before they can even multiply – may be

no symptoms

• Memory cells can result in lifetime immunity to some antigen

types of immunity - Natural

Active Immunity

• Adaptive immune responses

• B & T cell responses

• Production of memory cells

• Long-term protection

• E.g., in response to an infection

Passive Immunity

• No memory cells produced

• Short-term protection

• Antibodies “mop up” antigens before they can cause a problem

• E.g., Transfer of antibodies across the placenta or through lactatio

Types of immunity - artificially required

• What we’re doing with vaccination or administration of immunoglobulin

Artificially-Acquired Active Immunity

• Delivery of a pathogen (or part of one) that stimulates an adaptive immune

response

• Antigens are immunogenic but not pathogenic

• Production of memory cells

• Long-term protection

• E.g., vaccine containing a weakened virus

Artificially-Acquired Passive Immunity

• Antibodies are injected into the body to confer immediate protection

• No memory produced

• Short-term protection (until used up or degraded, ≈2-3 weeks)

• E.g., WinRho (anti-RhD Ig), IVIG