Humoral/Cellular Immunity (MT1)

Define: Extracellular

Site of infection is outside of cells (blood, lymph, epithelial surfaces)

Define: Intracellular

Site of infection inside of cells (cytoplasmic or vesicular)

Define: Humoral Immunity

Related to the earliest efforts to understand immunity, belief that health is controlled by fluids, if the fluids are out of balance it less to disease.

Modern definition: Immunity mediated by soluble molecules

What were the four humors?

Blood, Phlegm, Bile (yellow bile), Stool (black bile)

Explain von Behring's contributions to Humoral immunity

He observed that fluids transferred from one inoculated animal could provide protection to another, even to a lethal dose of bacteria.

Explain Jules Bordet's contributions to Humoral immunity

Demonstrated two components of humoral immunity:
1. Heat stable, and specific for whatever the animal was immunized to
2. Heat-liable, non-specific anti-microbial activity

Explain Paul Ehrlich's contributions to humoral immunity

Define the components discovered by Bordet:

Component 1 were proteins produced by cells, expressed on cell surface and released into blood (antibodies - adaptive)

Component 2 was non-specific blood component that complemented the antibodies (complement - innate)

What mediates humoral immunity?

B cells (antibodies) and Complement. Pathogens are covered in antibodies so that they cannot replicate, then complement pokes holes in bacteria and lyses them.

Define: Complement

Approximately 40 soluble proteins that can bind to and activate in the presence of microbial cell surfaces. Activation leads to proteolytic cascade that results in the generation of the MAC (membrane attack complex), which creates pores and lyses the target.

Explain the characteristics of complement

- Little specificity and no memory (one complement protein the same as the next, secondary responses do not improve)
- NOT responsible for protective immunity observed in serum transfers

Define: Antibodies

Highly pathogen-specific side-chains produced by B-cells

How are humoral and cellular immunity related? Give an example that involves antibodies

Antibodies (humoral) are made by B-cells (cellular). Additionally B-cells often need help from T-cells (cellular) to make antibodies.

Name three functions of antibodies

Neutralization
Opsonization
Complement activation

What is Humoral Memory comprised of?

Long-lived circulating antibodies
Long-lived plasma-cells (B-cells) that continue to secrete antibodies
or memory B-cells

Explain Metchnikoff's contributions to our understandings of cellular immunity

Observed that cells from sea urchins were able to absorb and internalized particulate matter, first described phagocytosis (cells eating bacteria). Birth of cell-mediated immunity

Explain Miller's contributions to our understandings of cellular immunity

Proposed subsets of lymphocytes, named antibody producing cells in bone marrow B-cells and lymphocytes from the thymus T-cells

Which lymphocytes are produced in bone marrow?

B-cells

Where are T-cells created, do they mature in the same place?

T-cells are created in bone marrow, however unlike B-cells they mature in the thymus

Explain Pross's contributions to our understandings of cellular immunity

Identified Natural Killer cells (NK cells) from the spleen that can kill cells without prior exposure. These cells maintained their killing even after the depletion of B and T cells.

Define: Cellular immunity, name components of cellular immunity

Cell-mediated immune response, responsible for clearance of virally infected cells, intracellular bacteria and tumors.
Consists of involves phagocytes, granulocytes, T-cells, B-cells, and NK cells

How does cellular immunity kill targets?

Phagocytosis
Neutrophil degranulation
Modulation of cellular activity
Direct killing of infected cells

How do T-cells and Natural Killer cells differ?

T-cells can't recognize a pathogen directly, they rely on innate immune cells to present the pathogens to the T-cell. Only after activation are T-cells able to kill the target.

NK cells don't need to do this, they kill without aid from the innate immune system.

Define: Neutralization

Antibodies prevent bacterial adherence by coating pathogen

Define: Opsonization

Antibodies promote phagocytosis by coating pathogen with specific antibodies for phagocytes to target

Define: Complement activation

Antibodies activate complement, which enhances opsonization and lyses some bacteria (very efficient)

True or False: Antibodies are effective against all forms of bacteria

False, antibodies are ineffective against intracellular bacteria as antibodies cannot perform their functions within cells.

Define: Phagocytosis

Neutrophils or macrophages consume pathogen (extracellular)

Define: Neutrophil Degranulation

Neutrophils release toxins around pathogen (extracellular)

Define: Modulation of Cellular Activity

TH1 cells signal infected cells to increase levels of digestive enzymes to consume pathogen within, does not kill cell.(intracellular)

Define: Death Receptors

CD8+, T-cells, and NK cells signal death receptors, cell self-lyses. (intracellular)

Define: Cytotoxic Granules

CD8+, T-cells, and NK cells release toxins directly on affected cell, killing cell and pathogen within. (intracellular)