Immunology Overview, Complement, Inflammation, Antibodies

What is innate immunity?

Born with, always present

What is adaptive immunity?

Acquired over time, depends on exposure

Examples of first line defenses?

Skin, mucus, normal flora, cilia, acidic pH

Mechanism of second line defense?

Inflammation, phagocytosis, NK cells, antiviral cytokines

What are the sentinel cells in innate immunity?

Macrophages and mast cells

What are PAMPs?

Pathogen patterns activating sentinel cells

What are the phagocytic cells in innate immunity?

Neutrophils, macrophages

Effects of second line defense at distant sites?

Fever, acute phase proteins, WBC increase, catabolism of proteins, lipids, carbohydrates

Function of natural killer cells?

Lysis of virus-infected cells and tumor cells

Clonal selection theory?

Each lymphocyte can only recognize one antigen, when it does it activates & clones

What is receptor repertoire?

All receptors recognizing all antigens except self

B-lymphocytes develop into?

Plasma cells

T-lymphocytes develop into?

Cytotoxic T-cells, T-helper 1 cells, T-helper 2 cells

Third line of defense?

Adaptive immunity with memory

What happens in the primary lymphoid organs?

Development of lymphocytes

What happens in the secondary lymphoid organs?

Lymphocytes encounter antigens

Primary lymphoid organs?

Bone marrow, thymus

Secondary lymphoid organs?

Lymph nodes, spleen, MALT

Define affinity.

Binding strength at a single epitope

Define avidity.

Total strength of binding to all epitopes

Three major outcomes of complement activation?

Opsonization, inflammation, cell lysis

Which complement proteins are proinflammatory?

C5a, C3a

How does membrane attack complex (MAC) kill microbes?

Inserts pore into membrane, causes lysis

What is T-independent B-cell activation?

When B cells encounter antigen they recognize, internalize, and present on MHC class 2 as a linear peptide it can then become a plasma cell without the need of a T cell

What is T-dependent B-cell activation?

When B cells encounter antigen they recognize, internalize, and present on MHC class 2 as a linear peptide it cannot then become a plasma cell without T cell activation

Immunological function of neutrophils?

Phagocytosis and bactericidal activity

Immunological function of macrophages?

Phagocytosis, antigen presentation, cytokines

Humoral immunity components innate?

Acute Phase Proteins, Alternative Complement Pathway, MBlectin Complement Pathway

Humoral immunity components adaptive?

Antibodies, Classical Complement Pathway

How many complement proteins circulate in blood?

~20

What are zymogens in complement?

Inactive proenzymes needing cleavage to activate

Function of opsonization?

Coats targets for phagocytosis

Classical complement pathway trigger?

Antigen-antibody complex

Alternative complement pathway trigger?

Bacterial endotoxin

MBLectin pathway trigger?

Mannose-binding lectin protease

Sequence to C3 convertase (classical)?

C1 → C4 → C2 → C4b2a

Sequence to membrane attack complex?

C5b → C6 → C7 → C8 → C9

Complement amplification of acute inflammation?

C5a recruits phagocytes, enhances capillary dilation

Deficiency in complement causes?

Autoantibodies and bacterial infections

Regulators DAF and CR1 function?

Inhibit C2 binding to C4b, dissociate C2b from C4b

Regulators CR1 and MCP function?

Catabolize C4b via Factor 1

Four changes to blood vessels during inflammation?

Increased diameter, permeability, adhesion, clotting

Purpose of acute inflammation?

Leukocyte migration, create barriers in micro vessels, tissue repair

What triggers chemotaxis in inflammation?

Macrophages and neutrophils releasing chemokines

Late inflammation sustained by?

Antibodies and T-cells

Stimuli that induce inflammation?

Physical injury, chronic T-cell activation, antibody-antigen binding

C5a role in inflammation?

Stimulates oxidative burst, increases permeability and adhesion

TNF alpha role in inflammation?

Activates endothelial cells and macrophages

What are neutrophil extracellular traps (NETs)?

Neutrophil DNA/histone net to trap pathogens

Neutroses definition?

Special neutrophil death to extrude nucleus in NETs

C3b role?

Potent opsonization molecule

IFN gamma role?

Activates macrophages and MHC

Cytokines from T helper 1?

IFN gamma, TNF beta

Cytokines from T helper 2?

IL-4, IL-5

IL-2 function?

T-cell growth

IFN gamma function?

Activates MHC class 1 and 2

IL-4 function?

Activates B cells, IgG/IgE, increases MHC2, T-cell growth

IL-5 function?

Eosinophil growth

IL-10 function?

Increases MHC2, inhibits T helper 1

TNF alpha function?

Activates macrophages

General structure of an antibody?

Two heavy chains, two light chains, variable and constant regions

What is the B-cell receptor (BCR)?

Membrane-bound antibody on B-cell

IgM structure?

Pentamer in serum

IgG structure?

Monomer

IgA structure?

Dimer

IgE structure?

Monomer

BCR structure?

Membrane-bound IgM or IgD with signaling molecules

Function of antibodies?

Bind antigens, neutralize, opsonize, activate complement

Characteristics of IgM?

First produced, pentamer, efficient complement activator

Characteristics of IgG?

Most abundant, crosses placenta, long half-life

Characteristics of IgA?

Secretory in mucosa, dimer, protects surfaces

Characteristics of IgE?

Monomer, binds Fc receptors on mast cells and basophils

Essential antibody effector functions?

Neutralization, opsonization, complement activation, antibody-dependent cellular cytotoxicity

Difference between a BCR vs secreted antibody?

BCR membrane-bound, secreted antibody free in serum

Conditions of granuloma formation?

Chronic inflammation with persistent pathogen or foreign body

Functions of macrophages that enhance resolution of inflammation (wound healing)?

Phagocytosis of debris, secretion of growth factors, tissue repair