Med I: Adaptive Immunity

T Cells vs B Cells (differences)

Antigen receptors on surface

• T Cells: Yes

• B Cells: Yes

Antigen receptor recognizes only processed peptides in association with MHC protein

• T Cells: Yes

• B Cells: No

Antigen receptor recognizes whole, unprocessed proteins and has no requirement for presentation by MHC protein

• T Cells: No

• B Cells: Yes

IgM on surface

• T Cells: No

• B Cells: Yes

CD3 proteins on surface

• T Cells: Yes

• B Cells: No

Clonal expansion after contact with specific antigen

• T Cells: Yes

• B Cells: Yes

Immunoglobulin synthesis

• T Cells: No

• B Cells: Yes

Regulator of antibody synthesis

• T Cells: Yes

• B Cells: No

IL‑2, IL‑4, IL‑5, and gamma interferon synthesis

• T Cells: Yes

• B Cells: No

Effector of cell‑mediated immunity

• T Cells: Yes

• B Cells: No

Maturation in thymus

• T Cells: Yes

• B Cells: No

Maturation in bone marrow

• T Cells: No

• B Cells: Yes

B cells

2 major functions

• differentiate into plasma cells that produce antibodies (aka immunoglobulins or Igs)

• become long-lived memory B cells that can rapidly respond to a reinfection

matures in bone marrow

Ig on the B-cell surface is its antigen receptor (B-cell receptor or BCR) and the ability of a B-cell precursor to make this antigen receptor determines whether it is allowed to develop into a mature B cell.

T cell

Matures in the thymus (prior to reaching thymus, considered “naive” (bc they havent seen foreign antigens))

Secondary Lymphoid organs include the spleen, MALT (mucous associated lymph tissue), lymph nodes

Named by markers/identifiers detected on their cell surface

• CD markers- cluster of differentiation

Antibodies

5 classes:

1. IgG

Mom to baby. fixes the complement. neutralizes bacterial toxins/viruses. highest titers (test to see past infections)

2. IgA (dimer only)

Found in mucous membranes. Secretory IgA prevents attachment of bacteria and viruses to mucous membranes

3. IgM

Early in Ab 1degree IR pentamer. Fixes complement. Antigen receptor on the surface of B cells

4. IgD

Function UNKNOWN. found on the surface of many B cells.

5. IgE

Allergic Ab. Release mediators from mast cells/basophils upon exposure to allergen. Defense against worm (parasites) infections by degranulation of eosinophils (CBC).

CD4 and CD8

Cluster of differentiation (CD) markers:

helper T cells are CD4-positive (CD4+); only bind w/o MHC2 (4×2=8)

cytotoxic T cells are CD8-positive (CD8+); MHCI (C8xD=8)

CD4 and CD8 proteins are coreceptors for the TCR

sit in the T-cell membrane and bind to nonpolymorphic regions on MHC (class II and class I, respectively)

cytoplasmic domains of CD4 and CD8 amplify the TCR signal transmission

T-cell receptor (TCR)

Maturation of T cells in the thymus → t cell is then marked with a unique antigen receptor (TCR)

TCR relies on CD3 to signal

• Purpose of CD3 s to transmit TCR peptide signal from the surface to the inside of the cell

goal is to recognize antigen via binding with MHC

Receptors on Tcells take part in the ability to recognize millions of antigens

T cell types

T cells proliferate and then differentiate into 4 different cell types.

CD4+ cells become:

1. follicular helper cells (Tfh) - they enter the B cell follicle and help B cells

2. CD4+ effector/helper T (Th) cells - leave the lymphoid organ and coordinate immune responses in inflamed tissue

3. CD4+ regulatory (Treg) cells - suppress inflammation

CD8+ cells become

4. CD8+ cells become cytotoxic T cells (CTLs) - kill virally infected cells

T cell activation

Relationship between CD4/CD8 and MHC1/MHC2

Rule of 8s

If CD4 cell binds to MHC2, cd expression turns off

If CD8 cell binds to MHC1, CD4 expression turns off

Negative and positive selection to provide optimal cells only

primary and secondary lymphoid organs

Primary lymphoid organs

• Thymus (T cell maturation)

• Bone marrow (B cell maturation)

Secondary lymphoid organs

• Lymph nodes (drain the tissue capillary beds through afferent lymphatics)

• Spleen (filters bloodstream)

• mucosa-associated lymphoid tissues (MALT) (filters the blood from the mucosal barrier)

Concentrate and filter antigenic material so that immune cells can sample it and remove it if necessary

Cytokines in cell-mediated immunity

control how immune cells talk to each other, grow, move, and act against infected or abnormal cells

T-cell functions

4 main categories

CD4-pos cells become:

1. Effector/helper (Teff or Th) cells, leave the lymph node, migrate to inflamed tissues in the body, and produce cytokines. must produce the appropriate cytokines for the appropriate organisms.

2. Follicular helper (Tfh) cells, which move into the B-cell follicle of the lymphoid organ and help the B cells. positioning of Tfh cells within the lymphoid tissue dictates which cells they will encounter.

3. Regulatory T (Treg) cells, which suppress inflammation. responsible for limiting immune responses and maintaining tolerance of self-antigens and harmless commensal antigens

CD8-positive cells become:

4. Cytotoxic T cells (or cytotoxic T lymphocytes, CTL), which kill virus-infected cells and tumor cells.

Memory T cells

ability to respond rapidly and vigorously for many years after the initial exposure to a microbe or other foreign material.

ex. CD4:Th (helper cells), Tfh (follicular helper cells), Treg (regulatory cells) and CD8: cytotoxic cells.

primary vs secondary B-cell response

Primary response occurs the first time that an antigen is encountered

• usually involves T-cell–dependent activation of B cell

Secondary response occurs when there is a second encounter with the same or closely related antigen, months or years after the primary response, the secondary response is both more rapid and generates higher levels of antibody than did the primary response

• bind antigen with higher affinity

• memory B cells

Antibodies protect against infectious agents.

1. Activating complement to lyse cell membranes and drive inflammation (see Chapter 63)

2. Opsonize bacteria, with or without complement

3. Stimulate immune cells’ Fc receptors to kill a target cell, also called antibody-dependent cellular cytotoxicity (ADCC)

4. Bind and neutralize toxins and viruses