Immunity: Adaptive Responses

What are the three lines of defenses in order?

1. Barrier defenses

2. Cellular & Molecular

3. Adaptive

What are the two responses of Adaptive immunity?

• Humeral

• Cellular

What are the two branches/cell types of adaptive immunity?

T and B cell

T-Cells

cell-mediated immunity cells effective against antigen within cells

T Cells require

an antigen-presenting cell

B-Cells

antibody mediated immunity, effective against antigen outside cells

T-Cells form:

• Cytotoxic cell

• Helper T-Cell

• Regulatory T Cells

• Memory T Cells

T-Cells are essentially responsible for:

destroying cells through apoptosis

B Cells form:

plasma cells

B Cells are essentially responsible for:

producing antibodies

Antigen

molecule the body recognizes as foreign/worthy of attacking

Hapten

incomplete antigens that bond to carrier molecules to be affective

Immunogenicity

ability to trigger immune response

Immunogen

antigen that triggers immune response

Foreign Antigen

differs from the body’s molecules & triggers immune response

Exogenous Antigens (bacteria)

toxins of extracellular antigens (microbial walls, flagella, etc) that activate b-cell response

Endogenous Antigens (virus)

produced by microbes that reproduce inside body’s cells & activate T-Cell response

Autoantigens (Self Antigens)

Made by the body & do not initiate immune response only with exception of auto-immune diseases

Example of autoantigens

erythrocyte antigens

Antigen Determinant Site (Epitope)

site on antigen that is recognized by immune system

Where do antibodies bind to

epitope: antigen determinant site

What are the three classes of lymophocytes?

• T Cells

• B Cells

• Natural Killer Cells

What are the two receptor complexes of lymphocytes

• TCR

• BCR

MHC

group of membrane proteins (histocompatibility complexes)

MHC I

genetically determined structure (unique to individual) on all nucleated cells

MHC II

on antigen presenting cells in exogenous pathways

Antigen-presenting cells

• Dendritic cells

• macrophages

• B-cells

If self-antigen attachment on MHC I

will ignore it

If foreign attachment on MHC I

activates cytotoxic T-Cell to destroy it

MHC II processes and presents

exogenous antigens that activate helper t-cell

How many CD markers exist

350+

Antigen Recognition happens depending on

CD markers and recogniztion of appropriate target cells

What are the two CD markers that are importnt?

CD4

CD8

CD8

on cytotoxic cells & recognizes antigens presented by MHC I

CD4

on helper t cells & recognizes antigens presented by MHC II

Clonal Selection

process by which the immune system selects specific B cells or T cells that recognize a pathogen & proliferates these cells to produce number of identical cells.

Where does clonal selection occur?

secondary lymphatic organs

What two classes of cells are produced in clonal selection?

• Memory Cells

• Effector Cells

Thymocyte

immature T cell containing CD4 & CD8

Positive T Cell Selection

selects ability to bind MHC molecules to thymocytes

If a thymocyte binds to MHC molecules

survives & goes to negative selection

If a thymocyte does not bind to MHC

destroyed by apoptosis

Negative T Cell Selection

T cell survives depending on recognition of self antigens, ensures that T Cells that react to self antigens are destroyed

If binding MHC-Thymocyte recognize self antigen

destroyed by apoptosis

If MHC-Thymocyte does not recognize self antigen

Survives

Naive T-Cell

cell that has not been exposed to antigens yet

What percentage of cells survive selection process in the thymus?

2%

Helper T-Lymphocyte

retains only CD4 protein

Cytotoxic T Lymphocyte

Retains only CD8 protein

Co-Stimulation

physical-chemical signal that stimulates a T Cell

What is the first signal in T-Cell Activation

Direct contact w/ APC where TCR binds to antigen presented by MHC I or II occurring in secondary lymphatic organs

Second signal in TCell Activation

Co-stimulation

Physical Co-Stimulation

Via Surface Molecules

Chemical Co-Stimulation

Via Cytokines

First Signal in Activation of T-Helper Cells

CD4 binds to antigen presented by MHC II

Second Signal in activation of TH-Cells

TH releases interleukin 2 which stimulates itself and produces a chemical signal

Result of TH-Cell activtion

clonal selection occurs and TH cell triggers innate & adaptive responses

what do TH cells release in innate immunity?

IL-3 which stimulates macrophages

Stimulated macrophages in innate immunity release?

IL-12 which stimulates release of more IL-3 which leads to more macrophage activation (pos. feedback)

First Signal of activation of Cytotoxin T Cell

CD8 binds to antigen presented by MHC I

Second signal of activation of Cytotoxin T Cell

TH releases IL-2 to stimulate Cytotoxin T Cell, leads to clonal selection

What is the first step to the effects of TC Cells?

TC binds to target

Second step of TC Cell effect

TC releases perforins

Third Step of TC effect?

TC releases enzymes to fragment DNA in target Cell

Fourth step of TC effect

TC releases lymphotoxins

Fifth step of TC effect

TC detaches, moves on, and repeats process (cn redo many times)

Sensitization

Antigen binds to antibody on B Cell (BCR) to internalize & process

Activation

Sensitized B Cell interacts with TH Cell and releases IL-4 to activate the B Cell

Once B cell is activated it undergoes

clonal selection

Active B Cells

differentiate to plasma cells to make antibodies

Memory B Cells

retain their BCR for next exposure

Antibodies (Immunoglobulins)

proteins produced against a particular antigen

Variable Region

Varies among antigens & contains antigen binding sites that vary in shape

Constant region

same in structure for antibodies of given class

what are the 5 classes of of antibodies in the constant region

IgG, IgM, IgD, IgE, IgA

Antibody Titer

circulating blood concentration of antibody against a specific antigen

Antigen-Antibody Binding Promotes

• Neutralization

• Agglutination

• Precipitation

Neutralization

antibody binds to antigenic determinant sites (epitopes)

Agglutionation

cross-links antigens of foreign cells forming clumps

Precipitation

cross-link circulating antigens that form antigen-antibody complexes that become insoluble & precipitate out of fluids

igM

1st antibody secreted in the blood with concentrations declining as IgG levels increase

IgM performs

• Neutralization

• Agglutination

• Activation of complements

Anti A & B antibodies in the blood are apart of

IgM

IgG (singular)

Most prevalent (75-80%) in the blood with resistance against many viruses by neutralizing them

IgG performs

• activation of complement and NK Cells

• crosses placenta/provides passive immunity to fetus

Anti-Rh antibodies made by RH- moms are in

IgG

IgE

in the blood attaching to mast cells & basophils in allergic reaction, also produced due to parasitic infections

IgA

in glandular secretions (mucus, tears, saliva, etc) attacking pathogens before they gain accross to internal tissues, protect against infections

IgD

On the B Cell Surface involved in B-Cell Sensitization

Primary Antibody Response

takes time to develop bc B cells must be sensitized and activated ( lag phase 4-5 days)

Secondary AntiBody Response

IgG: subsequent exposures with memory cells responding, peaks 3-5 days and lags 1-3 days

• doesnt get as sick as 1st time due to memory cells and antibody titers increase more rapidly

Vaccines

Contain weakened or dead microorganisms to stimulate immune system to form memory B Cells which triggers secondary response if re-exposed

Herd immunity

Resistance of members of the population of disease, # of susceptible people is low so disease is unable to proliferate.

Activate Immunity

Due to direct contact w/ pathogen & antibodies are produced

Naturally Acquired Active Immunity

Develops after antigen exposure in daily life, builds up immunity

Artificially acquired active immunity

antigen is administered and antibodies are produced in response

Passive Immunity

antibodies obtained from other individual

Natural Acquired Passive Immunity

antibodies transfer from mom to baby by breastfeeding or across placenta

Artificially acquired passive immunity

lab-made antibodies are transferred (rabies shot, snake antivenom) allowing you to make antibodies quicker

Acute Hypersensitivity

allergies