TCELLS

T-cells: they are of 2 types:

CD4 &CD8 T cells

CD4: they are generally helper cells and are involved in:

• Producing cytokines

• Direct immune response

• Activate other cells

• Activated by antigen presenting cells (dendritic cells, B-cells and macrophages) & MHC class 2 (binds t cell receptor and CD4 and is expressed only on antigen presenting cells)

• For CD4 cells to get activated B7 on APCs and CD28 on CD4 must bind

• After getting activated they stimulate B-cells to produce antibodies more effectively, and also for class switching them to produce other components, stimulate CD8 T-cells and also activate macrophages.

CD4 cells have 2 subtypes:

• Th1 & Th2

• Th1: they are involved in cell mediated immunity

• Activate CD8 T-cells & macrophages

• Produces IgG antibodies

• It has two major types of cytokines:

• A) IL-2: it stimulates the production of CD4 & CD8 T-cells & also activates NK cells and B-cells & is a T-cell growth factor.

• B) Inf gamma: it suppresses the production of Th2 cytokines & and activates Th1 cells, activates macrophages & more MHC1 & MHC2 expression.

• Th2: they are involved in humoral immunity and are involved in the production of IgE & IgA.

• It has 3 major types:

• A) IL4: It is the major type and it inhibits the production of Th1& promotes the production of IgE antibodies (parasites)

• B) IL5: it is responsible for the production of IgA antibodies (GI infections)

• C) IL10: Inhibits Th1 production & is anti-inflammatory cytokine.

Th1 is important for intracellular infections as Th2 cannot identify the MO within the cells.

Children having deficiencies of receptors of IL12 or Inf gamma are susceptible to disseminated mycobacterial diseases.

CD8: they are cytotoxic cells and are involved in:

• Killing virus infected cells and also tumor cells.

• They react to MHC class 1 (found on all nucleated cells) instead of MHC class 2

• Their main role is to detect & kill virus infected cells

• They bind to T-cell receptor and CD8

• They kill the infected cells by inserting perforins or by inserting granzymes or by inserting granulysin or by producing Fas ligand ( by inducing extrinsic apoptosis without any inflammation)

There is another type called as regulatory T-cells: they are known to suppress the functions of both CD4 & CD8 cells and they all have CD25 on their surfaces which is a classical marker for them and have CD4 & CD3 molecules on their surfaces & are also known to produce anti-inflammatory substances. They ae not completely understood.

Another group are Th17 which are a subset of CD4 cells different from Th1 & 2. They are very imp for mucosal immunity in GI tract. They produce IL17, recruit neutrophils & macrophages, and have a role in autoimmune diseases too.

Memory T-cells: some die quickly and some stay for years.

Super antigens can cause toxic shock syndrome and are of 2 types:

1. Toxic shock syndrome toxin-1 (TSST-1),

2. Pyrogenic exotoxin A or C.

B-cells: they are part of the adaptive immunity of the body. They are part of the lymphocytes. B-cell receptors are made of IgM antibodies. B-cell receptor is a monomer of IgM antibodies. The interface between the second and the third constant regions of the heavy chain is where macrophages and protein A bind. There are more unique B-cell receptors than genes in our body. B-cells generate lots of receptors by the rearrangement of VDJ genes.

There are two types of B-cell activations:

1. T-cell dependent (only for protein antigens) [crosslinking of receptors bound to antigens], [T-cell binding].

2. T-cell independent (non-proteins)

1) T-cell dependent activation: It is the most powerful way of activating the B-cells. B-cell can present the antigen to T-cell via MHC class 2 proteins, simultaneously other B-cell and T-cell interactions also occur, one of those is the binding of CD40 (B-cells to CD40 ligands(T-cells) which is pthe binding of B7 (B-cell) to CD28 (T-cell) and is required for T-cell stimulation to produce cytokine. Only in this pathway, memory is generated.

2) T-cell independent activation: it is relatively weak. Mostly IgM, and no memory is produced. But if the polysaccharide is conjugated with peptide then memory is produced and stronger response is produced.

B-cell surface proteins:

• Proteins for binding with T-cells:

1. CD40 (binding with T-cell CD40 ligand)

2. MHC class 2

3. B7 (binds with CD28 on T-cells)

• Other surface markers:

1. CD19 (all B-cells)

2. CD20 (most B-cells, not plasma cells)

3. CD21 ( complement pathway, EB Virus)

Types of antibodies: antibody class is determined by the Fc portion of the antibodies, there are three types:

1. Monomer (IgD, IgE, IgG)

2. Dimer (IgA)

3. Pentamer (IgM)

Protein A: it is present in staphylococcus aureus, it prevents opsonization by making the Fc portion unavailable for binding to the macrophages, it is present in peptidoglycan wall, and also prevents complement activation.

The triggers for class switching mechanism of B-cells are:

1. Binding of CD40 to CD40 Ligands (T-cells).

2. Cytokine production (e.g: IL-4 & IL-5 in Th2 response)

IgM: It is the first antibody secreted during infection and is an excellent activator of complement system. It is the strongest binding of all antibodies. Prevents attachment of pathogens, cannot cross placenta, and is a weal opsonin because the Fc end is not free. However, it can activate complement and use C3b as an opsonin.

IgG: it has 2 binding sites and has 4 subclasses. It is the major antibody of secondary response. It is the only antibody that crosses the placenta (most abundant antibody in newborns). Excellent opsonin (IG1& IG3 are the best), they’re the longest lived of all antibodies (several weeks), and are the most abundant class in plasma. It is very imp for encapsulated bacteria.

IgA: It is the main type found in the mucosal membranes & mucosal secretions, it is originally a monomer in plasma but becomes a dimer by getting linked by the secretory components from epithelial cells while undergoing transcytosis. But because it is linked by the secretory component it doesn’t fix complement, however, is excellent at coating mucosal pathogens. It is ideal for mucosal secretions because it doesn’t fix complement so there’s no inflammation.

IgE: bind to mast cells and eosinophils, defends against parasites, are low in conc. In plasma, it doesn’t activate complement and mediates allergic reactions. When a parasite binds to the Fab portion, mast cell degranulates into the tissues.

After activation B-cells become either plasma cells or memory cells.

• Plasma cells: they move to the spleen or bone marrow and secrete 1000s of antibodies per second and die after a few days.

• B-cells: they are produced only in T-cell dependent activation.

Vaccines: there are 4 types of vaccines:

• Live attenuated: they induce a strong cell mediated immune response. Eg: MMR vaccine, BCG, influenza (intranasal), oral rotavirus, oral polio, yellow fever, oral typhoid.

• Killed: they induce strong humoral response, weaker immune response than the live attenuated vaccine. Eg: rabies, hepatitis A, Influenza (intramuscular).

• (Oral: stimulate GI mucosal immunity, largely IgA antibodies. Eg: oral polio vaccine and rotavirus. Intramuscular: stimulate tissue response, largely IgG.)

• Toxoids: tetanus, diphtheria, pertussis.