Lecture 4: The Immune System (Part 1) PubHlth 80

Three layers of immunity

Physical barriers (skin, mucosal tissues), innate immunity (non-specific, rapid, no memory) and adaptive immunity (tailored, slower, remembers).

Ports of entry

Ways pathogens gain entry: inhalation, ingestion, broken skin, sex, mother to child, and the eyes.

Non-self

Foreign material the immune system fights: viruses, bacteria, fungi and parasites.

Altered self

The body's own cells that have changed, such as cancer cells (and infected cells). Killed by T-killer cells.

Plasma

The fluid portion of blood. Carries sugars, clotting factors, and antibodies and other proteins that fight infection.

White blood cells

The immune defense cells in blood. Replenished from stem cells in the bone marrow.

Lymphatic system

Lymph channels drain tissue (interstitial) fluid into lymph nodes and return it toward the heart to rejoin the blood.

Lymph node

Site containing immune cells that can respond to infection. Where antigen-presenting cells meet matching lymphocytes ('Tinder for lymphocytes').

Innate immunity

Pre-programmed first line of defense. Fast, non-specific, no memory, same every time. Like the local police.

Adaptive immunity

Specific to an individual infection, slower, and remembers re-exposure. Like the military. Uses lymphocytes (T and B cells).

Lymphocytes

White blood cells of adaptive immunity: T cells and B cells.

PAMP

Pathogen Associated Molecular Pattern: a component of pathogens that doesn't exist in humans (non-self).

PRR

Pattern Recognition Receptor: receptor on innate immune cells that detects PAMPs, telling the cell a pathogen is near.

Inflammation

Innate weapon that calls other innate immune cells to the site of infection.

Phagocytosis

Engulfing ('eating', from Greek phagein) foreign cells or bacteria. Pathogens are then killed by toxic chemicals inside the phagocyte.

Killing by toxins

Innate weapon against pathogens too big to eat (e.g. worms). Mast cells, basophils and eosinophils secrete toxic compounds, causing collateral damage.

Antigen

A small part of a non-self protein. 'Antibody generator'.

APC

Antigen Presenting Cell: a phagocyte that grabs pieces of pathogen (antigens) and presents them to CD4 T-cells.

T-cell receptor

Unique receptor on each T-cell that recognizes only one specific pathogen antigen.

Thymus

Butterfly-shaped gland over the heart where T cells mature. Removes T cells that recognize 'self' antigens to prevent attacks on the body.

CD4 T-cell (T-helper, Th)

Coordinates the adaptive response. When activated it divides and activates CD8 T-cells and B-cells specific to the same pathogen. HIV's target.

CD8 T-cell (T-killer, CTL)

Kills non-self cells (infected or cancerous). Needs two signals: one from an activated CD4 cell and recognition of its antigen on the target cell.

Memory T-cell

Long-lived T-cell that remains after infection is cleared, allowing a more rapid response on re-exposure.

CD4

Protein receptor important for T-helper cell function and the receptor HIV uses to enter cells. CD4 and CD8 are names of receptors.

What are the three layers of immunity?

Physical barriers (skin, mucosal tissues), innate immunity and adaptive immunity.

How do pathogens get into the body?

Inhalation, ingestion, broken skin, sex, mother to child, and the eyes.

What does the immune system fight?

'Non-self': viruses, bacteria, fungi, parasites. 'Altered self': cancer cells.

How do blood and the lymphatic system help immune surveillance?

Blood carries white blood cells through vessels and capillaries into tissues. Plasma seeps into tissues as interstitial fluid, which lymph channels drain into lymph nodes, where immune cells can respond to infection.

Where do white blood cells come from?

Stem cells in the bone marrow, which develop into committed precursors that divide or differentiate into mature blood cells.

Compare innate and adaptive immunity.

Innate: fast, not specific, no memory, recognizes common features of pathogens, phagocytes and others. Adaptive: slower, specific, has memory, recognizes specific pathogens, lymphocytes (T and B).

Why is innate immunity compared to the local police and adaptive to the military?

Innate is in place at all times, responds the same every time and is critical in the first hours to days. Adaptive specialists are called in for lasting threats and remember them.

How do immune cells communicate?

By secreting proteins. Some recruit more immune cells ('call for backup'). Infected cells secrete alarm proteins that make nearby cells express antiviral proteins ('raise the shield'). Th cells coordinate adaptive responses.

How does innate immunity recognize pathogens?

PRRs on immune cells bind PAMPs, components of pathogens absent in humans. Binding tells the cell a pathogen is nearby.

What are the four main weapons of innate immune cells?

1) Inflammation, 2) phagocytosis, 3) killing by toxins, 4) calling for backup by activating adaptive immune cells.

Why can't innate immunity cope with large parasites like worms by eating them?

They are too big to be eaten. Mast cells, basophils and eosinophils secrete toxic compounds instead, with collateral damage.

Why can't adaptive immunity use PRRs?

Humans have only ~20,000 genes but face an infinite number of potential pathogens, including ones that don't exist yet (like SARS-CoV-2).

What does each arm of adaptive immunity do?

Antibodies (B-cells) protect against infections outside your cells. T killer cells (CD8) kill cells infected by pathogens and cancer cells.

What are the other names for T-helper and T-killer cells?

T-helper = Th = CD4 T-cell. T-killer = CTL = CD8 T-cell.

Where do T cells mature, and why does it matter?

The thymus. It removes T cells with receptors that recognize 'self' antigens, preventing the immune system from attacking your body.

How does an APC find the matching CD4 T-cell in the whole body?

Antigens are carried to the lymph nodes, where immune cells gather and the APC can meet the one CD4 cell specific to that antigen.

What happens when a CD4 T-cell is activated?

It divides to make more CD4 cells specific to that antigen, and activates CD8 T-cells and B-cells specific to the same pathogen (hence 'helper').

What two signals does a CD8 T-cell need to become active?

1) A signal from an activated CD4 cell. 2) Specific recognition of its antigen on the infected cell.

What happens to T cells after an infection is cleared?

Most activated CD4 and CD8 cells die. A few remain as long-lived memory T-cells that respond faster next time.

Why does HIV damage the immune system?

HIV uses CD4 as its receptor, infecting T-helper cells. CD4 numbers fall, causing immune deficiency (AIDS). Like fighting a war without a communication network.

How are HIV-positive people monitored?

A simple blood test quantifies the number of CD4 cells.

Summarize immunology part 1.

3 layers of immunity. Innate immunity recognizes PAMPs with PRRs and uses inflammation, phagocytosis and toxins. Adaptive immunity is specific, with antibodies (B-cells) and killer cells (CD8). CD4 T-cells coordinate both and are HIV's target.