L19- Adaptive Immunity and Immunization Pt.1

Innate and adaptive immunity work together…

to protect the host.

Innate is more…

generalized protection while adaptive is more specific and long lasting.

3 Functions of adaptive immunity:

1. Recognize foreign molecules

2. Defend the host

3. Remember the foreign molecules.

5 characteristics of Adpative Immunity

1. Discriminate

2. Specificity

3. Diversity

4. Timing

5. Memory

Discriminate-

Between self and non-self

Specificity-

Respond to specific antigens

Diversity-

Great diversity in the types of
antibodies generated.

Timing-

Adaptive immunity takes some time to kick in.

Memory-

Memory cells are generated to
protect against re-exposure.

Components of Adaptive Immunity

• Also known as acquired immunity against a specific agent.

• Adaptive immunity relies on the activity of T and B lymphocytes.

• This response will clear the foreign molecule from the body and develop memory.

• A later infection can trigger memory cells.

• Much fast response than the first encounter.

Adaptive immunity relies on the activity of…

T and B lymphocytes

Adaptive Immunity includes what 2 things?

1. Humoral

2. Cell-mediated Immunity

Humoral Response

B-cells producing antibodies against a pathogen

Cell-mediated immunity:

T-cell recognize abnormal antigens on host cells (from virus or tumors).

Antigens:

A substance that elicits an immune response.

Structure of Antigens

• Complex in structure.

• Polysaccharides /glycoproteins/nucleoproteins.

Valent

• Number of epitopes on an antigen (the specific small part of an antigen that an antibody or T-cell receptor recognizes and binds to)

• Antigens have several epitopes

• Multivalent is better because it means more than 1 kind of antibody can attach to the same antigen.

Where are antigens found?

• Found on the surface of bacteria (cell wall, membrane, flagella), viruses and determine by organism's genetic information.

2 types of acquired apdaptive immunity

1. Natural Immunity

2. Artificial immunity

Naturally acquired adaptive immunity

• Obtained by specific disease.

• Antibodies produced due to antigens on an invading infectious agent. Memory.

• Antibodies transferred to fetus: via placenta or colostrum.

Artificially acquired adaptive immunity

• Receiving an antigen via injection (vaccine)

• Immunization

Active Immunity

• The person’s own immune system activates lymphocytes and produces antibodies.

• Immunity can last for weeks to a lifetime.

• Antigen is remembered.

  • Naturally acquired active immunity: Person is exposed to infectious agent.

  • Artificially acquired active immunity: Person is exposed to a vaccine

Passive Immunity

• Antibodies are introduced to the body. Antibodies are not made by the person’s immune system.

  • Naturally acquired passive immunity: made by the mother's immune system and transferred to offspring

  • Artificially acquired passive immunity: antibodies made by another host are introduced into a new host.

    • Ex :snake antivenin injection.

Antibodies:

• also called immunoglobulin

• is a protein that is made to bind a specific antigen.

• Can bind to specific epitopes.

  • The body can recognize the foreign molecules as non-self using antibodies.

  • The body still needs a mechanism to recognize self as self.

    • The system in place to do this is called the Major Histocompatibility Complex.

The Major Histocompatibility Complex

• Composed of a collection of genes located on the human
  chromosome 6 called the Human Leukocyte Antigen (HLA)
  (polymorphic).

• There are 3 classes of MHC proteins

  • Class I

  • Class II

  • Class III

Class I MHC proteins:

• proteins expressed in nucleated body cells

Class II MHC proteins:

• Proteins expressed in antigen presenting cells such as macrophages, dendritic cells , and B cells.

Class III MHC proteins:

• secreted proteins that function in the immune process.

MHC Class I components

• Consists of a 2-protein complex.

  • Large alpha chain that spans the membrane, small beta chain.

  • Together they make a binding pocket that binds to
    antigens.

• Recognizes self and non-self.

  • If it binds a non-self antigen, it signals an immune response.

• Not present on RBC since they are anucleated.

• Many forms of Class I MHC exists.

• Class I typing is considered for organ transplant.

Class II MHC Components

• Class II MHC are only found on antigen presenting cells.

  • This plays a major role in antibody production.

• Generates a deeper binding pocket than MHC I.

• Can bind self and non-self.

  • Triggers a reaction when bound to non-self antigen.

Antigen processing

• refers to the process of processing and attaching the antigen to the MHC.

Endogenous antigen processing:

• Molecules in the cell (self or pathogen) are digested in a continuous process of recycling proteins in the cells.

• This process sends the digested fragments to the ER.

• The molecules binds to one of the many MHC class I receptors.
  

Exogenous antigen process

• bind molecules that enter the cell from outside (bacteria, viruses, toxins that come into the cells)

• MHC Class II

Antigen processing- Class I MHC

• Endogenous Antigen Processing ( digestion and recycling of proteins in cells. digested fragments sent to ER, and moplecules bind to MHC class I receptors)

• The MHC then presents that molecule to a type of T cell called CD8+ or cytotoxic T cell which determines if the molecule is self or non-self.

• If self, it leaves it alone. If non-self, the T cell with kill
  the host cell.

Antigen processing- Class II

• Exogenous Antigen Processing

  • Class II will only bind molecules that enter the cell from
    outside (bacteria, viruses, toxins that come into the cells) and undergo a process called exogenous antigen process.

• Antigen presenting cells (macrophages, DC) will ingest the
  invader.

• The digested foreign molecules are attached to the MHC I molecule.

• Those that fit the pocket will remain bound and this complex can recognize by T cells called CD4+ (helper cells).

• CD4+ do not kill the host cell like CD8+, rather they release
  cytokines that signal that an infection is present.

  • This results in a more global effect.

Differentiation of stem cells into…

• B cells and T cells.

• Occurs in the bone marrow and thymus, respectively.

Thymus in adult vs. children

Still active and differentiating T-cells, but at a lower rate.

T cell development in the thymus

• The thymus determines what kind of T-cell develops.

• Depends on the T-cell receptor and coreceptor.

  • Receptor alpha:Beta

  • Receptor Gamma:Delta

• Before leaving the thymus, all T cells are screened to determined if they can recognize self.

• If they can, they undergo apoptosis.

  • This results in nearly 98% of T cells dying.

  • Those that mature are still naïve since they have not responded to antigen by Antigen presenting cells.

Receptor alpha:Beta-

• The majority of T cells.

• Remain in the thymus where they receive a coreceptor.

• Countless possibilities of co-receptors determined by molecules called cluster of differentiation (CD).

  • The CD4+ coreceptor(T-helper cells) on the T cell will allow it to interact with MHC class II

  • The CD8+ coreceptor(Cytotoxic T-cells) on the T cell will allow it to interact with MHC class

Receptor Gamma:Delta-

• Migrate to the lymphoid tissue and do not receive a coreceptor.

• Found in skin/mucus membranes

T-cell receptor activation by antigen

• Receptor is made up of heterodimeric transmembrane receptor and 6 accessory polypeptides.

• Variability dictated by a series of unique genetic events.

• The T-cell is not naïve after it binds the antigen on the antigen presenting cell.

• Immune Synapse – signal transduction
  

T-cell activation Signal 2

• Signal 1: MHC binding to TCR.

• Signal 2: B7 receptor on APC binds to on of the T-cell accessory receptors.

• Signal 3: is not well understood but includes a chemical signal between the 2 cells.

Recognition of self: Clonal Deletion

• Takes place in the bone marrow and thymus during fetal development.

• Removes lymphocytes that have receptors for self antigens.

2 types of T-cells

• T-helper cells

• Cytotoxic T cells

T-helper cells:

• Known as CD4+ T cells.

• Interferon and interleukin can stimulate the differentiation of TH0 into TH1 or TH2 (most important 2).

  • TH1- Activates macrophages, inflammation, interleukins, interferons, tumor necrosis factor.
    Production of interleukins + interferons further amplifies the effect.

  • TH2- Activates antibody response (B-cells to generate antibodies). Activates IL-4-6, and IL 13
    which responses to worm infections.

  • TH17- Recruits neutrophils and inflammatory response.

  • Tregs- help decrease the immune response by producing the anti-inflammatory cytokine IL-
    10.

TH1-

• Activates macrophages, inflammation, interleukins, interferons, tumor necrosis factor.

• Production of interleukins + interferons further amplifies the effect.

TH2-

• Activates antibody response (B-cells to generate antibodies).

• Activates IL-4-6, and IL 13 which responses to worm infections.

TH17-

• Recruits neutrophils and inflammatory response.

Tregs-

• help decrease the immune response by producing the anti inflammatory cytokine IL- 10.

T-cells components

• Are found on helper T-cells:

  • Bind to MHCII

• Are found onvcytotoxic T- cells:

  • Bind to MHCI

1st step of Cell Mediated Immunity

• B-cells, dendritic cells or macrophages encounter pathogenic agent.

• They ingest and degrade the pathogen

2nd step of Cell Mediated Immunity

• Pieces of the pathogen/peptide are associate with MHC and form
  an MHC-antigen complex

3rd step of Cell Mediated Immunity

MHC-antigen complex is transported to the surface of the dendritic
cells, macrophages, B-cells.

4th step of Cell Mediated Immunity

• A T-cell that has the proper antigen receptor can recognize and
  bind the antigen on the antigen presenting cell.

  • T-helper cells: activated by MHC-II antigen presenting cells

  • Cytotoxic T cells: activated by MHC-I (virus, bacterial, cancer cells, organ transplant

5th step of Cell Mediated Immunity

Once activated, T cells can stimulate other T and B cells or destroy
the infected cell

Activation of cytotoxic t-cells

1. Toxins and bacterial or viral antigens enter cells

2. MHC Class I binds with antigen fragment

3. Pre Tc cell binds to the antigen fragment MHC Class I complex

4. Cell division occurs

5. Tc cell releases destructive enzymes against abnormal virus infected cell

T-cells can differentiate in different kinds of cells

• Helper T cell (Th)

• Cytotoxic T cells (Tc)

• Memory T cell