Innate/Adaptive Immunity (MT1)

Define: Innate Immunity

The immune system we have at birth, first and fastest response to pathogens, non-specific (recognizes self vs. non-self)

What does our innate immune system consist of?

• Barriers

• Anti-microbial peptides

• Complement

• Soluble mediators

• Phagocytes, and Granulocytes

Define: Adaptive Immunity

The immune system develop over time, specific but slow response to pathogens, recognizes/evolves over the course of an infection. Present only in vertebrates -Consists of B-Lymphocytes and T-Lymphocytes Very tightly regulated (mistakes can lead to autoimmunity/immunosuppression)

Define: Humoral Immunity

The aspect of immunity that is mediated by macromolecules located in extracellular fluids. Humoral immunity is named so because it involves substances found in the humors, or body fluids.

Define: Cellular Immunity

A protective immune process that involves the activation of cells to fight off pathogens.

What are examples of barriers?

All surfaces where the body interacts with the outside world: skin, lung surface, intestinal surface.

Define: Anti-microbial Peptides/Proteins

• Present in secretions (sweat, mucus, tears, salvia)

• Rich in positively charged amino acid residues

• Disrupt microbial membranes, activate lytic proteins, inhibit DNA/RNA/protein synthesis (inhibits reproduction of invasive pathogens) -Capable of target lysis in minutes

Define: Complement

• Soluble (humoral), preformed, inactive proteins that breakdown a microbial cell once it recognizes it

• Coats target cell with complement proteins resulting in lysis

• Binds directly to a microbial cell surface, or to antibodies which have coated the cell

Define: Soluble Mediators

• Cell level hormones, rapidly released by infected cells (warning sign)

• Control physiology/actions of host/nearby cells Includes: Acute proteins (complement), Interferons (induce fever/general antiviral state) Cytokines/Chemokines (how white blood cells communicate and work at infection)

Define: Phagocytes/Granulocytes

• Found throughout the body

• Non-clonal (all identical)

• Activates immediately after recognition of target (self vs. non self)

• Directly kills target (phagocytosis, release of toxic compounds)

• Activates adaptive immune response

Define: Non-Clonal

All progeny are identical (clones/replica of each other)

Which factors of the innate immune system are capable of target recognition?

Anti-microbial peptides, Complement, Soluble mediators, and Phagocytes + Granulocytes: Differentiate between self and not-self

Barriers have no target recognition, they keep everything out.

How does the innate immune system recognize pathogens?

Pathogen Associated Molecular Patterns(PAMP) which don't exist in our own cells.

Give examples of PAMPs

Unmethylated RNA/DNA Polysaccharides Lipids dsRNA (double stranded RNA) Flagella Formulated peptides (formal groups on protein)

Define: Opsonization

The process of making a foreign cell more susceptible to phagocytosis by coating the cell with specific antibodies that phagocytes to recognize and consume.

Why doesn't the innate immune system have memory?

Innate cells die after immune response, and no memory cells are formed. No advantage in keeping cells around since they aren't pathogen specific, and the immune response will never get any better or faster

Define: Autoimmunity

Adaptive immune system mistakes self for pathogen, body attacks itself.

Define: Immunosuppression

Adaptive immune system mistakes pathogen for self, pathogen flourishes in body without immune response.

Explain the target recognition of the adaptive immune system.

Incredibly exact/precise immunity, capable of killing/targeting a single infected cell without damaging surrounding cells.

Explain: Lymphocyte Specificity

• Adaptive immune system recognizes individual pathogens

• Capable of differentiating between similar pathogens (annual influenza)

• Recognizes specific residues on targets

• Targets the one cell without damaging neighbouring cells

Explain: Lymphocyte Diversity

The adaptive immune system's ability to generate diversity for identifying pathogens by rearranging small gene fragments to have an infinite amount of receptors to recognize pathogens

Explain: Lymphocyte Selection

Disposes of genetic shuffling that results in cells with receptors that recognize our own cells (attacks self) failure to eliminate auto-reactive cells results in autoimmunity

Explain how the adaptive immune system "learns" or reacts to many different pathogens

About 1 in every 10000 lymphocytes recognize any single pathogen, once one recognizes a pathogen we select these cells and expand/replicate them (cell proliferation) as these these cells proliferate, their receptors evolve to be the best at recognizing pathogens,

Define: Clonal Theory

A single cell gives rise to a variation of different lymphocytes, after the removal of self-reactive and immature lymphocytes, a single lymphocyte will recognize a single pathogen, that lymphocyte is then proliferated (activated/replicated)

What are the four postulates of clonal theory?

• Each lymphocyte is unique and bears a single unique receptor

• Interaction between a foreign particle and a lymphocyte receptor leads to lymphocyte activation

• Any lymphocyte that attacks self (self-reactive) is destroyed before it can mature

• An activated lymphocyte will proliferate resulting in daughter lymphocytes which bear receptors identical to that of the parent

Explain: Adaptive Immunity Memory

• During an immune response, some lymphocytes diversify into long-lived memory cells. These memory cells survive a lifetime (we'll always have them)

• Unlike the innate system, there is an advantage to keeping these cells around, they specifically recognize pathogens and are very efficient

• Capable of evolving/improving resulting in greater/faster responses when re-infected with a previous pathogen

Explain: Adaptive Modulation of Innate Immunity

Highly specific antibodies produced by B-lymphocytes bind to target cells resulting in: Complement activation and/or tagging targets for phagocytes (via soluble mediators)

Adaptive helps eliminate targets while minimizing collateral damage, modulating inflammation and down-regulating innate response.

Explain: Innate Modulation of Adaptive Immunity

Activation of T cells require phagocytosis and digestion of pathogen by cells of the innate system (macrophages/dendritic cells) Once the pathogen is digested it is presented to the lymphocyte to "see" and recognize. Innate immune system cells also send a second signal out to signal full lymphocyte activation after the lymphocyte has "seen" the pathogen.

Where are the majority of the body's immune resources directed?

Barriers, this massive interface is our first level of protection, and requires lots of maintenance

Define: Non-Clonal

Progeny are identical

Explain the difference between the response time of the innate and adaptive immune systems

Innate: Immediate response (Minutes/Hours) Adaptive: Days

Explain the difference between the specificity of the innate and adaptive immune systems

Innate: Recognizes general molecular patterns (PAMPs) self vs. non-self Adaptive: Highly specific recognition of particular pathogens

Explain the difference between the diversity of the innate and adaptive immune systems

Innate: Germline encoded, very limited diversity Adaptive: Capable of genetic rearrangement, highly diverse

Explain the difference between the memory of the innate and adaptive immune systems

Innate: None Adaptive: Persistent memory, faster and better secondary responses

Explain the difference between the soluble components of the innate and adaptive immune systems

Innate: Anti-microbial peptides/proteins, interferon complement Adaptive: antibodies

Explain the difference between the cellular components of the innate and adaptive immune systems

Innate: Phagocytes, granulocytes, natural killer cells, dendritic cells Adaptive: B and T lymphocytes

Explain the difference between the self/non-self discrimination of the innate and adaptive immune systems

Innate: Nearly perfect Adaptive: Good, but failures are very bad (autoimmune diseases)