adaptive immune response

Capsules

Resist phagocytosis

exoenzymes

Allow pathogens to get to endothelial layers

Adaptive immunity

Second line of defense. Acquired ability to recognize and destroy a specific pathogen or its products.

B cells

Mature in the bone marrow and confer humoral immunity

T cells

Mature first and bone marrow, and then in thymus and confer cell mediated immunity

Lymphoid precursor also differentiate into

Natural killer cells but are part of innate immune system

T cell clonal deletion

In the thymus they are tested for their ability to react with MHC molecules and destroyed if they don’t, and self antigens and destroyed if they do

Where do surviving T cells migrate to?

Lymph nodes, spleen, MALT

B cells are tested for their ability to react with

Self antigens and destroyed if they do

Where do surviving B cells migrate to?

Lymph nodes, MALT, spleen

If you get a paper cut

Pathogen first encounters macrophage and dendritic cells. PAMPs bind to PRRs and pathogen is phagocytosed. Antigens are processed and presented on MHC2 cell surface receptors.

What happens to genetic cells after pathogen exposure?

Enter the lymphatic system and move to a nearby lymph node

What happens to macrophages after pathogen exposure?

Stay in the area and casually continue to consume the pathogen

MHC2 Antigen presentation

Only found on antigen presenting cells like macrophages, B cells, dendritic cells

How many versions of MHC2 Does everyone have?

Six

How do helper T cells recognize pathogens?

Antigens found to MHC2 displayed on antigen presenting cell surface

Is one kind of helper T cell enough for all antigens?

No, there is a unique one for every Epitope

What co-receptor do helper T cells have that bind to MHC2 to strengthen the association?

CD4

What happens when helper T cells are activated?

Undergo clonal expansion and replicate to form multiple copies of the Epitope specific cell.

What do activated helper T cells differentiate into?

Th1, Th2, memory T cells

Th1 cells

Enter circulation and migrate to infection sites and release cytokines that activate macrophage

Th2 cells

Stay in lymphoid tissue and release cytokines that activate B cells

positive feedback loop in TH one cells

Release cytokines to activate phagocytes that improve phagocytosis And released their own cytokines

Superantigens

Excreted toxin proteins that inducing massive immune response that damage the host by indiscriminately activate Th cells

Naïve B cells have

Membrane bound antibodies that function on B cell receptors

Like macrophages and genetic cells, B cells are

Antigen presenting cells on MHC2

How do B cells get activated?

If a Th2 cell binds the MHC2 Epitope complex the Th2 cell releases cytokines

When a B cell is activated it undergoes

Clonal expansion into multiple copies of Epitope specific plasma cells and memory B cells

Plasma B cells

Produce and release antibodies specific to the antigen that was recognized by the TH2 cell

Antibody structure

Two identical light chains and two identical heavy chains arranged in a Y shape

Fab region

One light chain and one heavy chain interact to form antigen binding site

How many antigen binding sites do antibodies have

Two – bivalent

Why is the antigen finding site highly variable?

Each unique plasma cell produces one specific combination

Fc region

This region allows them to interact with other immune effectors

IgM

Functions as a B cell receptor and secreted by B cells during initial exposure and forms a pentamer

IgG

Secreted by B cells during subsequent exposure and is a monomer. Most abundant

IgA

Monomer in serum and dimeric when secreted at mucosal surfaces. found in anything fluid outside of the body

IgD

Monomer and functions as a B cell receptor

IgE

Displayed on basophils and mast cell. triggers release of histamine and pro-inflammatory cytokines. involved in allergies

Opsonization

Marks pathogens for phagocytosis, complement activation, or antibody dependent cell mediated cytotoxicity

In addition to PRR phagocytes have both

C3b and Fc receptors

Agglutination

Clumps foreign particles together for phagocytosis

neutralization

Prevents toxins, viruses, microbial adhesins from interacting with target

Memory B cells upon subsequent exposure

Rapidly differentiate into plasma cells with no assistance from TH2

Antibody response in subsequent exposure

Faster and more intense, releasing a lot more antibodies

Antibody class switching

IgM In serum and IgA In mucosal surfaces

vaccination

Deliberate antigen exposure to elicit a primary immune response to develop memory B and T cells

Vaccines from live attenuated pathogens

MMR

Vaccine from heat/chemically kill the pathogens

Polio/influenza

Vaccine from altered toxins

DTaP

Vaccine from subunit vaccines

HepB

Vaccine from viral vector or lipid nano particle

DNA or mRNA

Vaccines must be

Safe and effective – produce memory, T and B cells

MHC1

Found on all nucleated cells, including antigen presenting cells

Antigens bound to MHC1 are recognized by

Cytotoxic T cells

Can cytotoxicity cells recognize multiple antigens?

No, they can only recognize one specific Epitope

What co-receptor do cytotoxic T cells have that bind to MHC1 to strengthen the association?

CD8

How are cytotoxic T cells activated?

MHC1– Epitope – TCR – CD8 Interaction plus B7 on the APC must bind with CD28 on cytotoxicity cells. this prevents destruction of healthy cells

What do activated cytotoxic T cells do?

Form pores in the target membrane to induce apoptosis in the target cell. Release cytokines, and undergo clonal expansion to make memory T cells.

What forms pores in target membrane from cytotoxic T cell?

Perforins

What induces apoptosis in target cell from cytotoxic T cell?

Granzyme

Compliment proteins are activated when they bind

Antibodies coding a pathogen or the pathogen directly

Activation of complement proteins result in

Complement cascade

MAC attack 1

C1 complex binds to Fc portion of antibody

MAC attack 2

C1 recruits and activates C2 and C4

MAC attack 3

C2 Splits into C2a and C2b

C4 splits into C4a and C4b

MAC attack 4

C2a and C4b bind to the cell surface

C2b & C4a float away

MAC attack 5

C2a/C4b recruits and activate C3 and C5 that both split

MAC attack 6

C3b and C5b find to the cell surface

MAC attack 7

C3b/C5b recruits C6, C7, C8 and multiple C9 that forms membrane attack complex in the pathogen membrane causing cell lysis

Enhanced opsonization

C3b can opsonize pathogens Amplifying phagocytosis 10 times

Natural killer cell

MHC1 cell surface receptor on host cell. Many infected/cancer cells do not display MHC1 Instead of stress protein that activates natural killer cells.

What do natural killer cells release when activated?

Perforin in granzyme

Antibody dependent cell mediated cytotoxicity

Antibodies coating infected/cancerous host cells can bind to Fc receptor on natural killer cells, triggering release of messengers that induce apoptosis