Intro to Immunology 3&4 (B,T cells)

B lymphocytes

Defence against extracellular pathogens

CD8+ T cells

Regulating the immune system

Using membrane-bound antibodies as receptors

50,000 copies

Two light chains and two heavy chains

Antigens

Hyper variable region

Express peptide antigens

Thousands

Bind to MHC molecules

HLA molecules

Peptide antigens

Bind to peptide antigens

Form the antigen binding site

Hyper variable region

MHC molecules present peptide antigens to T cells.

TCRs bind to peptide antigens presented by MHC molecules.

T cells can recognize peptide antigens.

B cells produce antibodies and mediate humoral immune responses.

The hyper variable region formed by the tips of the alpha and beta TCR chains is unique to each T cell.

Antibodies bind to antigens.

CD4+ T cells help coordinate immune responses and activate other immune cells.

MHC molecules are also referred to as HLA (Human Leukocyte Antigens).

B lymphocytes have an important function in the adaptive immune system. They are responsible for humoral immune responses which are mediated by antibody molecules secreted by plasma cells.

T lymphocytes are responsible for cellular immune responses and thus have a key role in defence against intracellular pathogens.

The two types of T lymphocytes are CD4+ T cells (Helper T cells) and CD8+ T cells (Cytotoxic T cells). CD4+ T cells are the key regulators of the entire immune system, sending signals for cytokines to perform their functions. CD8+ T cells kill virally infected body cells.

B and T cells mature to distinguish self from non-self through a process called acquired immune tolerance. If they react to self antigens, they are usually destroyed or inactivated.

Acquired immune cells use specific recognition to detect invading pathogens. The pathogens have unique structures called antigens that are recognized by the adaptive leukocytes.

Antibodies are proteins that bind to one specific antigen. They are a complex of four polypeptide chains, which include 2 light chains and 2 heavy chains.

B cells use membrane-bound antibodies as receptors to recognize and bind to membrane-associated or soluble antigens.

IgG and IgA

Bone marrow

B and T cells normally circulate around their primary lymphoid tissue (site of development - bone marrow/thymus) in their inactive form

Antigen presentation activates the B cells and T cells in secondary lymphoid tissue (e.g. lymph nodes, spleen, MALT)

B cell activation and the eventual production of high affinity antibodies.

1. Membrane-bound antibodies on the B cells bind to target antigen IgM (or IgD) within the B cell zone of lymph nodes
2. B cells require 2 signals to become fully active and begin proliferation - the antigen and ‘helper signals’ e.g. from TH cells, PRR and PAMPs or from multiple antigens
3. Once activated, they clonally proliferate and become either a plasma cell (antibodies) or a memory B cell - germinal centre response
4. High affinity antibodies are generated - IgM (produced by plasma cells) → IgG (produced by B cells responding to certain antigens), assisted by TH cells

Signal 1- BCR and antigen complex Signal 2- T cell independent reaction therefore it requires PRR+PAMP complex. This produces low affinity antibodies and short lived plasma cells. Without the help of T cell response, it only provides a short lived response and no Memory cells.

Signal 1- BCR binding to antigen Signal 2- For T-dependent antigens, which are typically proteins, an additional co-stimulatory signal is required for full B cell activation. After BCR engagement with the antigen, the B cell presents processed antigenic peptides on its surface using (MHC II) molecules. Interaction between the B cell and a CD4+ helper T cell occurs when the T cell recognizes the antigen-MHC II complex on the B cell surface. This interaction provides the second signal.

1)Recognition function- Binding to antigen mediated by variable region sites. 2)Effector function- Clearance mechanisms mediated interaction of the heavy chain constant region with effector molecules.

B cell activation, agglutination (immune complex formation - enhances phagocytosis), complement system activation through classical pathway

IgG

IgA

Produced in allergic response

• helps with neutralization of pathogens (membrane bound form)
• Dimer in secretory fluids (e.g. colostrum)
  • Neonatal defense - protects GI tract of neonates

IgG>IgA>IgM>IgD>IgE

It plays a role in B cell activation.

foetal immunity (placental transfer), complement activation, NK cell activation, neutralisation, opsonisation, agglutination

Innate immune response- Intracellular pathogens infect host cells. The PAMPs stimulate the secretion of Interferons alpha and beta (IFN alpha/beta). These interferons activate the natural killer cells which perform the killing of infected host cells and produce pro inflammatory mediators.

The antigen bound IgG is a good activator of natural killer cells which then performs the killing of infected host cells by apoptosis and produces pro inflammatory mediators.

CD4+ Helper T cells activate B cells and stimulate production of memory B cells.

CD8+ Killer T cells kill infected cells via perforin, granzymes, and granulysin.

Regulatory T cells suppress lymphocyte activity.

Class I MHC: expressed on all nucleated cells, present peptide antigens to CD8+ killer T cells; Class II MHC: expressed only on antigen presenting cells (e.g. dendrites, macrophages), present peptide antigens to CD4+ helper T cells

MHC molecules present peptide antigens to T cells, allowing T cells to recognize and respond to specific antigens

CD8+ killer T cells: recognize peptide antigens presented by Class I MHC molecules and destroy infected cells; CD4+ helper T cells: recognize peptide antigens presented by Class II MHC molecules and help coordinate immune responses

Class I MHC: presented to CD8+ killer T cells, Class II MHC: presented to CD4+ helper T cells

Expressed on all nucleated cells, present peptide antigens to CD8+ killer T cells

Expressed only on antigen presenting cells (e.g. dendritic cells, macrophages), present peptide antigens to CD4+ helper T cells

1. Dendritic cells recognise and phagocytose antigenic debris
2. In the presence of pro-inflammatory mediators (e.g. TNF⍺), the dendritic cells mature and increase expression of stimulatory molecules on their surface
3. Dendritic cells phagocytose the pathogenic antigens, break the antigens down into short peptides and load them onto MHC II molecules
4. MHC II molecules transported to cell surface
   1. At the same time, the maturing dendritic cells migrate into the lymph nodes via the afferent lymphatic vessels
5. Co-stimulatory molecules enable T cell to respond to antigen and fully differentiate

The dendritic cell expresses the MHC II peptide, it forms a complex with the antigen activated CD4+ T cell. The CD4+ T cell secretes T cell growth factors called IL-2 which are autocrine mediated. These IL-2 growth factors promote T cell proliferation and differentiation.

TH1 cells: secrete pro-inflammatory cytokines (IL2, IFN𝛾), which stimulates production of Reactive Oxygen Species (macrophage-mediated)-(switch on expression of NADPH oxidase genes). This allows the macrophages to kill the bacteria much more effectively.

TH2 cells: secrete mainly IL4, IL5 and IL6 which promote B cell proliferation and induces antibody production. Th2 cells stimulate and recruit specialized subsets of immune cells, such as eosinophils and basophils, to the site of infection or in response to allergens or toxins.

FH cells: stimulated by presented antigen peptides + MHC II molecules on B cell, then stimulate the B cells to proliferate and differentiate (plasma + memory) by secreting IL4 and IL21

IL-2 (provided by TH cells) promotes differentiation and proliferation of antigen activated (via MHC I) CD8+ cells into cytotoxic T lymphocytes (CTLs)

• CTLs migrate out of secondary nodes and enter site of infection (via transendothelial migration) and then kill virally infected host cells by recognizing pathogenic antigens attached to MHC class I
  • Also involved in killing cancer cells

There are proteins in lytic granules of cytotoxic T cells:-Perforin, Granzymes and Granulysin. These substances are secreted in order to kill in a similar mechanism to NK cells.

It is a cytotoxic granule secreted by the T cell polymerises to form a pore in the target membrane.

Granzymes are secreted by cytotoxic T cells. They are serine proteases, which activate apoptosis once in the cytoplasm of the target cell.

Granulysin is a substance secreted by the Cytotoxic T cells which induces apoptosis in infected host cells.