Immunology II

antigen

a foreign molecule that stimulates a specific immune response

epitope

• regions of the antigen that are specifically recognized by antibodies or antigen receptors

• a large molecule may have more than one

antibody (B-cell receptor)

• complex of proteins that recognize and bind to a specific antigen

• also called immunoglobulin (Ig)

• made by immature B cells and plasma cells (mature B cells)

• may bind to free antigen or antigen on a pathogen cell

• can detect protein and carbohydrate antigens

T-cell receptor

• also called non-antibody antigen receptor

• only made by T lymphocytes

• only bind to antigen shown on a host cell surface

• only detect protein antigens

• require coreceptor CD4 or CD8

IgD

• B cell receptor on surface of immature B cells

• every B cell has a different one

IgM

• main secreted anitbody on primary exposure

• detectable around one week

IgG

• main secreted antibody on subsequent exposure

• detectable around two weeks after first exposure

IgA

in external secretions (ex: saliva, mucus)

IgE

responsible for allergic symptoms (immediate hypersensitivity)

antibody: structure

• Y-shaped with four proteins (two heavy chains and two light chains held together by disulfide bonds)

• dual function → Fab and Fc

antigen-binding/variable region (Fab)

recognizes and binds specific antigen

constant region (Fc)

interacts with other components of immune system

antigen-independent diversification

• during B cell development in bone marrow, extensive genetic recombination occurs in variable regions of light and heavy chain genes, plus different combinations of light and heavy chains

• occurs before any pathogen exposure

antigen-dependent diversification

1. B cells with Ab Fab/BCR/IgD recognize antigen → become activated

2. activated B cell proliferates in secondary lymphoid organ → somatic hypermutation during B cell division creates new Fab diversity

3. clonal selection → cells with Ab Fab best for binding the antigen get selected and proliferate to a clone

4. B cells from clone mature to:

   • plasma cells → secrete Ab/IgM for primary response

   • memory cells → retained in secondary lymphoid organs and activated quickly to secrete Ab/IgG on subsequent exposure

direct action

• antibody neutralizes free circulating virus particles or bacterial toxins

• blocks binding and entry into host cells

indirect action

• labels bacteria for immune attack by non-specific immune process

• opsonization of bacteria for phagocytosis

• activation of classic complement pathway (Ab-induced)

classic complement pathway

• non-specific defense that is targeted to specific pathogens by Ab

• 9 complement proteins (C1-C9)

classic complement pathway: mechanism

1. Ab Fab region binds to antigen on pathogen surface

2. Ab Fc region recognized by C1 and then C4

3. C4 is hydrolyzed by C1 into C4a and C4b → C4b attaches to pathogen membrane

4. C4b activates cascade to make C3b → C3b activates cascade to insert complement C5-C9 (membrane attack complex (MAC)) into pathogen cell membrane

5. complement fixation → MAC creates a large pore in membrane, killing the pathogen by osmotic disruption

activated complement proteins

• C4a → acts as chemokine to induce chemotaxis → attracts phagocytic cells to site

• C3b-induced opsonization promotes phagocytosis (phagocytic cells have C3b receptors)

• C3a and C5a stimulate degranulation of mast cells and basophils → histamine release → vasodilation and vascular permeability increases → blood flow increases → causes swelling and redness → recruits more phagocytic cells to site

alternative complement pathway

• non-specific defense against pathogens via PAMPs

• antibody-independent

• less efficient than classic pathway

• can work early in infection against new pathogen

alternative complement pathway: mechanism

1. low-level activation of C3b in circulation

2. C3b can bind PAMPs on pathogen if present

3. activates C5 (different cascade)

4. MAC formation from C5-C9

local inflammation: non-specific

1. break in skin → bacteria enters

2. resident phagocytic cells use PRRs to detect PAMPs → phagocytosis

3. activates alternative complement pathway

local inflammation: specific

1. B cells secrete Ab

2. Ab bind bacteria → opsonization

3. Ab activate classic complement pathway:

   • C3b → opsonization

   • C4a → chemotaxis

   • C3a and C5a → mast cell degranulation to release histamine

   • MAC (C5-C9) → cell lysis

4. extravasation of new phagocytic cells

local inflammation

• histamine causes vasodilation → redness and warmth

• increases vascular permeability and edema → swelling

• neutrophils liquefy surrounding tissues while killing pathogens → produce viscous fluid containing dead neutrophils, dead pathogens, and tissues → pus

• certain factors released activate nerve endings → pain

systemic inflammation

• same as local symptoms plus…

  • more neutrophils are released from bone marrow

  • pyrogens are produced → fever to reduce pathogen replication

  • widespread increased histamine-induced vascular permeability allows more edema → fluid loss from circulation into tissues

    • may lead to hypovolumetric shock if fluid loss is severe → heart is unable to pump blood through body → organs stop working

acquired immunity

immunity that develops during an individual’s lifetime

active immunity

• develops in response to an infection or vaccination

• memory retained → long-lasting

natural active immunity

antibodies developed in response to an infection

artificial active immunity

antibodies developed in response to a vaccination

passive immunity

• develops after an individual receives antibodies from someone or somewhere else

• faster than waiting for immune system to produce antibodies

• short-lasting

natural passive immunity

antibodies received from mother (ex: IgA → breast milk, IgG → placenta)

artificial passive immunity

antibodies received from a medicine (ex: gamma globulin injection, infusion)

vaccination

• administers some form of pathogen that activates a specific immune response but does not cause disease

• vaccination exposure creates immune memory

• if later exposed to pathogen → immune system mounts secondary response immediately

  • faster, more efficient response → less severe infection/disease

inoculation

• attenuated/destroyed pathogen (ex: heat inactivated anthrax bacteria)

• closely related, less virulent strain (ex: cowpox for smallpox)

• component of pathogen (ex: recombinant viral proteins → hepatitis B vaccine, RNA vaccine → COVID-19 vaccine)