Aims

• Describe the innate immune system.

• Compare and contrast the innate immune system with the adaptive immune system.

• Readings: Abbas & Lichtman, Chapters 1 & 2

Innate Immune System

• Physical barriers to infection– Epithelial barrier (skin)– Mucus, saliva, tears

• Phagocytic cells– Macrophages– Neutrophils

• Natural Killer (NK) cells– Cytotoxicity

Abbas & Lichtman’s Basic Immunology 1-3

Innate Immune System

• Complement system– Membrane attack complex

• Cytokines and plasma proteins– Interferons– C-reactive protein (CRP)

• Fever

Abbas & Lichtman’s Basic Immunology 1-3

Role of Normal Flora in Innate Immunity

• Occupy receptor sites

• Compete for nutrients

• Produce substances which are toxic for some pathogens

• Stimulate cross-protective immunity– A foreign molecule found on NF may be similar to

that found on a pathogen – resulting in an immune response against the pathogen

Properties of the Innate Immune System

• Fast– Responds within minutes of infection.

• Non-specific– Molecules react to shared microbial structures.

• Limited diversity– Molecules are encoded in germline (no somatic recombination)

• No Memory– Responds the same way to repeat encounters with a microbe.

• Primitive– Seen in all members of the animal kingdom.

• Reliable– Will not recognize host cells.

Epithelial Barriers • Skin

– Continuous epithelial layer provides barrier.

– Dense outer layer of dead cells (keratin).

– Epithelial cells secrete peptide antibiotics.

– Keratinocytes secrete cytokines and chemokines if damaged.

– Lymphocyte killing of infected cells.

– Langerhans cells (migrate to lymph node and present antigen to T cells)

Adapted from Abbas & Lichtman’s Basic Immunology 2-2

Epithelial Barriers

• Respiratory tract– Same as skin.– Mucociliary escalator– Surfactants contain microorganism binding collectins which target them

for phagocytosis and/or complement.

• Gastrointestinal tract– Same as skin.– pH (Acidic stomach kills microorganisms)

Adapted from Roitt’s Immunology 1-2

Corneal Epithelial Barrier

• Corneal resistance to infection is thought to result primarily from components of innate immunity.

• Epithelial Barrier– tight junctions between corneal epithelial cells

provides a formidable barrier to microorganisms.

• Tear flow – tear flow flush microorganisms down lacrimal duct.

Phagocytic Cells

• Neutrophils

• Macrophages

• Resident cells all across the body– Derived from

monocytes

Adapted from Roitt’s Immunology 1-5

Phagocytic Cell Receptors• Phagocytic cells recognize bacteria through receptors

which bind molecules not found on mammalian cells.• Toll-like receptors

– Different Toll-like receptors bind to different components of microbes.

– TLR-4 binds LPS (endotoxin).

• _Mannose receptor– Bacterial glycoproteins end in a terminal mannose residue.

Abbas & Lichtman’s Basic Immunology 2-1

Natural Killer Cell

• Large granular lymphocytes– Compose ~10% of

lymphocytes in the blood and peripheral lymphoid organs.

• Function to eliminate cellular reservoirs of viral infection.

Adapted from Abbas & Lichtman’s Basic Immunology 2-9A

NK Cell Cytotoxicity

• NK cells are activated by IL-12 secreted by Macrophages.

• NK cells in turn secrete IFN which stimulates macrophages to be better at killing phagocytosed microbes.

Adapted from Abbas & Lichtman’s Basic Immunology 2-9B

NK Cell Cytotoxicity

• NK cells recognize cells without MHC class I molecules as targets for killing.– MHC class I acts as an _inhibitor to NK cytotoxicity – MHC class I molecules are down regulated in virally

infected cells and cancer cells.

Abbas & Lichtman’s Basic Immunology 2-10

Mechanisms of Cell Cytotoxicity

• Direct cell-to-cell signaling using cell surface receptors

• Indirect cell-to-cell signaling using cytokines

• Granules containing proteins that damage target cells by poking holes in their membrane

• Cells kill by inducing _apoptosis

Cytokines

Adapted from Abbas & Lichtman’s Basic Immunology 2-11B

Plasma Proteins

• Plasma mannose-binding lectin– Recognizes microbial carbohydrates.– Coats microbes for phagocytosis or lysis by

complement via lectin pathway.

• C-reactive protein (CRP)– Binds to phorylcholine on microbes.– Coats microbe for phagocytosis by macrophages with

CRP receptor.

Antimicrobial Factor Secretion by Corneal Epithelial Cells

– Mucins • aggregate bacteria and inhibit epithelial

colonization.

-defensin • Cationic peptides which inhibit growth or viability

of many bacterial pathogens.

– Lysozyme• Hydrolytic enzyme against gram positive bacteria.

Recognition of “foreigness” via Innate Cells

• Recognize broad categories or patterns of foreign molecules via receptors that are “hardwired” into the DNA - e.g. Toll-like receptors on phagocytes. Thus, non-mutable.

• Recognize lack of self - e.g. Killer immunoglobulin-like receptors (KIRs) on natural killer cells – bind self molecules called MHC

Adaptive Immune System

• Antigen Recognition molecules– B-cell

• antibody or immunoglobulin (IgG)– T-cell

• T-cell receptor (TCR)– All cells

• Major Histocompatibility Complex (MHC)

Adaptive Immune System

• Slow– Response develops over days following infection.

• Genetic– Genetic recombination occurs to create diversity.

• Specific– Each cell responds to a specific antigen.

• Memory– Repeated exposure results in faster and stronger responses.

• Sophisticated– First found in early vertebrates.

Adaptive Immunity

Natural AcquiredActive: Patient acquires Patient is

disease then recovers vaccinated

Passive:Mother passes Patient receivesimmunity to child preformed immuneeither transplacentally components or through breast- (e.g. gamma

globulin)feeding.

Recognition of “foreignness” via Adaptive Immune System

• Recognize foreignness in highly specific manner via unique receptors that are randomly generated during ontogeny.

• This random rearrangement enables the body to generate lymphocytes capable of responding to an almost limitless number of foreign invaders

Recognition of “foreignness” via Adaptive Immune System

• T cells recognize only those foreign molecules (antigens) that have been previously “processed” by another cell

• B cells can recognized unprocessed antigens

• Receptors are not “hardwired” but are highly susceptible to random somatic mutations occurring during development (ontogeny) – prior to encountering a foreign molecule

Innate vs. Adaptive Immunity

• Cells of the innate immune system recognize pathogen-associated molecular patterns (PAMPs)

• Cells of the adaptive immune system specifically recognize and respond to particular foreign molecules through receptors

Innate vs. Adaptive Immunity

• Cells of the innate immune system recognize broad categories or patterns of foreignness

• Cells of the adaptive immune system specifically distinguish between self and non-self

Innate vs. Adaptive Immunity

• Innate immune response is pre-existing

• Adaptive immune response does not pre-exist, resulting in a “lag time” before the first response can be detected

– 7-10 days to detect the 1st response

– 3-4 days to detect the 2nd response

Innate vs. Adaptive Immunity

• Innate immune responses have no “memory”

• Adaptive immune response possesses an anamnestic (“memory”) response – not only is the anamnestic response quicker, but it is

more vigorous than the 1st response

KEY CONCEPT

• The innate and adaptive responses do not lead separate lives.

• They constantly interact with one another.

• The innate response initiating the adaptive response and the adaptive response will, in-turn, regulate the innate response.

Next Time

• Complement Cascade

• Characteristics of antigens and immunogens

• Readings: Abbas & Lichtman, Chapters 3 & 8

Objectives

1. Describe the components, functions, and properties of the innate immune system.

2. Describe the mechanisms of cell cytotoxicity.1. Cytokines, Plasma proteins, Antimicrobials

3. Describe the components, functions, and properties of the adaptive immune system.

4. Describe how innate and adaptive immune components recognize “foreigness”

5. Describe the differences between innate and adaptive immunity.