MEDL234 Immunology Ch. 1-2 (incomplete)

Introduction to immune system & Innate immunity

Non-self vs Self

• non-self: markers not recognized by immune system as self

  • antigen: any marker that can be recognized by immune system (ex: proteins, carbohydrates, lipids, nucleic acids)

• self: each cell carries specific molecular markers that ID as self

Extracellular pathogens (3)

• spread by lymphatics & blood

• accessible to soluble molecules & cells

• spread by lymphatics and blood; host maintains several innate immune defenses within these extracellular spaces

Intracellular pathogens

• spread by cell to cell

• release from cell into extracellular fluids to infect cell at a distance

• require cell-mediated cytoxicity

• innate immune response uses Natural Killer cells and macrophages which release mediators

Roles of Immune system (5)

• defense against infection

• defense against tumors

• injured cells & induce pathogenic inflammation

• control of tissue regeneration & scarring

• recognizes & responds to tissue grafts

Innate immunity: Expression at birth, PAMPS, defense, limiting infection, recruit, memory

• Defense mechanisms exist from birth: anatomic, physiologic, phagocytic, and inflammatory barriers

• PAMPS (pathogen-associated molecular patterns): Recognize structures shared by microbes

• Provides an immediate first-line of defense

• Powerful at limiting infection, but may not eradicate infectious agent

• Recruit immune cells to the site of infection & triggers the adaptive immune response

• No memory of prior exposure

Adaptive immunity: Lymphocyte receptors, lymphocyte interaction, lymphocyte memory

• lymphocytes express diverse & variable receptors for recognition of pathogen-specific molecules

• produces of lymphocytes interact with cells & molecules of innate to eliminate foreign substances

• lymphocytes generate immunological memory (allows faster recognition of previous pathogens)

Epithelial cells (5 functions)

• prevent infection

• physiological barrier

• secrete antimicrobial substances & biochemical mediators

• tissue remodeling

• immune cell recruitment

Mast Cells (location & 4 functions)

• reside in connective tissue at mucus membrane

• release mediators that modulate innate immune responses

• wound healing & defense against microbes

• allergic reactions

Neutrophils: Recruitment, life-span, pus

• recruited from blood & BM to site of infection

• short-lived

• Pus = dead neutrophils, bacteria, & skin cells

Macrophages: Secretion, aid in, and T cells

• release cytokines to induce inflammation at site of infection

• aid in repairing tissue damage

• APCs & interact with effector T cells

Dendritic cells: In tissue, immune responses, T cells, transportation, initate

• sentinel in tissue

• provide link between innate & adaptive immune responses

• APCs & interact with naive T cells

• move from site of infection to draining lymph node

• initiate adaptive immune response

Natural killer cells: Function & Secretion

• can recognize & kill abnormal cells (stressed, virus-infected, tumor)

• produce cytokines

Innate lymphoid cells (ILCs): Receptors & Signals

• don’t express specific antigen receptors like T cells

• act promptly to signals from infected/injured cells to produce cytokines that direct immune response

Complement

system of plasma & cell surface protein that interact with other molecules of the immune system to generate effectors of innate & adaptive immunity

Cells of Innate immunity

Epithelial cells, mast cells, neutrophils, macrophages, dendritic cells, NK cells, innate lymphoid cells (ILCs), and complement

Lymphocytes: Type of molecules, types of cells, circulation, receptors

• effector molecules of adaptive immunity

• T & B cells

• circulate through lymphoid & non-lymphoid tissues

• express receptors that specifically recognize foreign antigens

Benefits of having both Innate & Adaptive immunity (2)

• provides a multi-layered defense system that is more effective than either system alone

• ensures the body can handle immediate threats while preparing a specialized, long-term response for complex or recurring pathogen

Humoral immunity (HMI): Secretion, type of immunity, cell can recognize, T cells

• B lymphocytes secrete antibodies that eliminate extracellular microbes

• antibody-mediated immunity; mediated by B cells derived from BM

• B cells & antibodies can recognize different types of molecules (proteins, carbohydrates, nucleic acids, lipids)

• some T lymphocytes secrete soluble proteins (cytokines) that recruit & activate phagocytes & other T cells (CTLs, Cytotoxic T cells)

Cell-Mediated immunity (CMI): Mediated by, function, types of cells used

• mediated by T cells that express receptors that bind with antigens

• used to eliminate intracellular pathogens

• helper cells (Th) & T cytotoxic cells (Tc)

Helper cells (Th): Cues, both immune systems, help which type of cells

• provide cues (cytokines) to moderate immune responses (both CMI & HMI)

• provide receptor-ligand interactions to cells of both innate & adaptive immune system

• helper T cells help B cells & macrophages

T Cytotoxic cells (Tc): Functions, secretion, interactions, granules

• immune defense against intracellular pathogens & tumor surveillance

• secretes cytokines

• use receptor-ligand interactions to signal a target cell to die

• releases cytotoxic granules onto target cells

Active immunity: Occurs, naturally vs artificially, provides

• occurs when exposure triggers immune system lymphocytes

• naturally = through infection

• artificially = through vaccination

• provides immune memory

Passive immunity: Define, naturally vs artificially, provides

• person given antibodies

• naturally = in utero

• artifically = antibody containing blood products (IVIG)

• provides immediate protection but no immune memory

Properties of Adaptive immune responses

• specificity: ensure response is directed against that microbe and not against others that are not infecting individual

• diversity

• memory

• non-reactivity to self (immunologic tolerance)

Clonal selection: Mature develop when, total collection, clones develop when

• Mature lymphocytes with receptors for antigens develop before encountering the antigens

• total collection of lymphocyte specificities (lymphocyte repertoire) is extremely diverse

• Clones of lymphocytes specific for different antigens develop before an encounter with these antigens

  • each antigen elicits an immune response by selecting & activating the lymphocytes of a specific clone

Clonal expansion

Phases of Adaptive immune responses

Primary immune response

Secondary immune response

BM: Site of Hematopoiesis

• HSC:

• myeloid vs lymphoid progenitor:

• further differentiation:

Lymphocyte receptors: T cell

Lymphocyte receptors: B cell

1 Main type of B lymphocyte

3 Main types of lymphocytes

Th, Tc, Treg

Cluster designation (CD)

CD4+ T helper lymphocyte

CD8+ Cytotoxic T lymphocyte

Regulatory T lymphocyte (Tr)

Maturation and Tissue Distribution of Lymphocytes

Generative (primary) lymphoid organs → blood → recirculation/lymph → peripheral (secondary) lymphoid organs

Maturation and Tissue Distribution of Lymphocytes: Primary vs Secondary Lymphoid organs

Maturation and Tissue Distribution of Lymphocytes: Blood vs Recirculation/lymph

Maturation and Tissue Distribution of Lymphocytes: Effector cells

Stages in the Life History of Lymphocytes: Cell type

Stages in the Life History of Lymphocytes: B lymphocytes

Stages in the Life History of Lymphocytes: T lymphocytes

Stages in the Life History of Lymphocytes: Memory

Antigen presenting cells (APCs): Steps 1-3

Antigen presenting cells (APCs): Steps 4-5

Primary vs Secondary Lymphoid organs

Lymphatic system

Lymph node: Capsule & Trabecula vs High endothelial venule (HEV)

Lymph node: Afferent vs Efferent lymphatic

Lymph node: Outer vs Inner Cortex

Lymph node: Germinal center vs Medulla

Spleen: Red vs White pulp

Mucosal immune system: General

Mucosal immune system: Mucosal lymphoid tissue vs Mucosal Epithelium

Mucosal immune system: Intestinal lumen vs Lamina propria

Mucosal immune system: Mesentery (small bowels)

Cutaneous immune system: General

Lymph node: HEV

Lymph node: T cell zone

Lymph node: B cell zone (follicles)

Lymph node: B cell zone (germinal center) vs Exiting node

Naive lymphocyte

Effector B vs T cells

Lymphocyte Recirculation and Migration into Tissues: Peripheral lymphoid tissues

Immune system: At site of infection vs Lymphatics

Immune system: Memory cells vs Effector cells

General features & specificity of Innate immune response

Inflammation & Antiviral defense: General

Inflammation & Antiviral defense: Macrophage vs Neutrophil vs Dendritic

Antiviral defense/infections

• NK cells:

Innate vs Adaptive immunity: Specificity

Innate vs Adaptive immunity: Receptors

Innate vs Adaptive immunity: Numbers & Types

Innate vs Adaptive immunity: Discrimination of self & non-self

Innate immunity series of reactions: At portal of entry for microbes vs In blood

Innate immunity series of reactions: In tissues

PRRs vs PAMPS

DAMPs

Major families of PRRs

Specificities of TLRs

Signaling functions of TLRs

NOD-Like receptors (NLRs): General

NOD-Like receptors (NLRs): NOD-1 & NOD-2

Inflammasome

Inflammasome: Autoimmune disorders

Cytosolic RNA and DNA Sensors: General

Cytosolic RNA and DNA Sensors: Cell death vs Microbial DNA

Cytosolic RNA and DNA Sensors: DNA sensors vs Viral RNA

Cytosolic RNA and DNA Sensors: RNA sensors vs MAVs

Components of Innate immunity: Barriers, cells, soluble plasma proteins

Epithelial barriers: General

Epithelial barriers: Keratin & mucus vs Antimicrobial peptides

Epithelial barriers: IELs

Neutrophils: Number/life span vs Production

Neutrophils: Receptors vs Clearing debris

Neutrophils: Acute inflammation

Monocytes: Innate immunity (general)