Microbiology Chapter 17: Adaptive Immunity

Adaptive Immunity

consists of two parts:

humoral immunity

cellular immunity

Humoral immunity

antibody-mediated immune system

controls freely circulating pathogens

depends on B cells

Definition of cellular immunity

cell-mediated immune system

controls intracellular pathogens

depends on T cells

Lymphocytes origin

source is liver + bone marrow (stem cells)

stem cells differentiate into B cells from red bone marrow

differentiate into T cells in thymus

Function of B cells

recognizes antigens and makes antibodies in response

B cell + T cell differentiation

B cells in red bone marrow

T cells in thymus

Function of T cells

responds to antigens via receptors (TCR) and secretes cytokines

Antigen name

Antibody generators

aka immunogens

Role of antigens in immune system

provoke very specific immune response

results in antibody production

What are antigens typically composed of?

proteins or large polysaccharides

can be part of a capsule, cell wall, flagella, toxin, viral coat

Epitope

an antigenic determinant (specific binding site)

specific region on antigen that antibodies recognize and interact with

microbe can have multiple different ones

Antibodies

globular proteins (made up of diff subunits)

aka immunoglobulins (Ig)

produced in response to antigens

interact very specifically with epitope

Factors influencing interaction between antibodies and epitopes

size, shape, and chemistry of the binding site

How many identical binding sites do antibodies have?

two identical binding sites

(at least, most human Abs have 2)

Basic antibody structure

4 polypeptide chains (two identical light + two identical heavy chains)

Variable (V) region

Constant (C) region

Bonds holding chains of an antibody together?

covalent disulfide bridges

Variable region

part binding epitopes

top halves of Ab arms

Constant region

portion of the antibody that is the same for particular class of immunoglobulins (Ig)

lower part of arms and stem

Antibodies of same Ig class

Differing V region

Same C region

IgG

80% of all Ab in serum

protects against circulating bacteria + viruses

by neutralizing toxins + enhancing phagocytosis (when bound to Abs)

IgM

pentamer structure

appears first in response to infection

and effective at agglutination of antigens (bc 10 binding sites)

IgA

most common Ab found in mucous membranes + body secretions

(tears, saliva, breastmilk)

IgE

involved in allergic reactions

works against parasitic worm (helminths) infections

IgD

found in blood and surfaces of B cells

no well-defined function

B cell Activation

occurs when membrane-bound Igs bind to epitope of an Ag

can be with T-dependent or T-independent Ags

T-dependent antigen

antigen requiring T helper cell for antibody production

T-dependent antigen process

Ig binds to Ag, antigen processed (internalized + broken down)

Ag fragments displaced by MHC II protein recognized by T_H cell

T cell produces cytokines which activate B cell to proliferate and secrete Abs

T-independent antigen

antigen that stimulates B cells without T cells

characterized by repeating subunits (polysaccs or LPS molecules that can be portion of capsule)

provoke weaker immune response (than dependent)

no memory cells produced

Clonal selection + proliferation

B cell “selected” by antigen

activated B cell proliferates (multiplies over and over)

into large clone of cells

can be plasma or memory cells

Plasma cells

clonal cells acting as factories for antibody production

(secrete produced Abs)

all made to recognize specific Ag and produce specific Ab

Memory cells

long-lived cells

subset of activated B cells

responsible for enhanced secondary response to an antigen

basis of vaccines

Flow of B cell activation

B cells “selected” activate and proliferate into plasma + memory cells

Non selected B cells die off

Antigen - antibody binding methods

agglutination

opsonization

neutralization

antibody-dependent cell-mediated cytotoxicity

Agglutination

antibody causes antigens to clump together

(Ag binding sites can bind epitopes on 2 diff cells / molecules)

easier for phagocytes to ingest

Opsonization

antigen is coated with antibodies

which enhances phagocytosis + lysis

(more “red flags” for phagocytes to recognize)

Neutralization

IgG inactivates microbes or toxins

by blocking their attachment to host cells

(“physical barrier”)

Antibody-dependent cell-mediated cytotoxicity (ADCC)

use of Abs to target large organisms (ex protozoans + helminths) that cannot be phagocytized

target coated with Abs, variety of immune system cells bind to Abs (+ thus target cell)

Those cells secrete enzymes that result in lysis

Why did T cells evolve

to respond to intracellular pathogens B cells cannot

allows immune system to recognize non-self (ex cancer) cells from self cells

Age and adaptive immunity

Ability to make new T cells decrease with age

T cells in thymus less active

Fewer B cells produced in red bone marrow

So immune system weaker in older adults

T cell function

essential for cellular immunity

interacts directly with Ag (but not contributing to Ab production)

T cell classes

T helper cells (T_H)

T cytotoxic cells (T_C)

T cell type differentiation

By glycoproteins on cell surface

Clusters of differentiation (CDs)

(ex T_H cells have CD CD4+)

T_H cells

CD4⁺ cells

bind to MHC class II protein on APC

MHC, TCR, APC

Major Histo Compatibility (region presenting proteins)

Toll cell receptor (or T cell receptor)

Antigen presenting cell

T_H cells action

TCR recognizes Ag presented by MHC class II protein on APC

TCR binds to APC

T_H cell can stimulate Ab production, phagocytosis, opsonization

T_c cells

CD8⁺ cells

precursors to CTL (cytotoxic T lymphocytes)

developed into CTL if receptor recognizes Ag on MHC class I protein

CTL

Cytotoxic T Lymphocytes (activated form of CD8⁺ cells)

recognizes + kills non-self cells (ex cancer cells, cell infected with virus)

releases perforin + granzyme

Cytokines

cell + move

soluble proteins/glycoproteins

function as chemical messengers of immune cells

produced in response to a stimulus and are receptor-specific

Types of cytokines

Interleukins (IL)

Chemokines

Interferons (IFN)

Tumor Necrosis Factors (TNF)

Interleukins (IL)

cytokines occurring between WBCs

(inter = between; leukin = leukocytes)

Chemokines

induce migration of leukocytes into infected areas

important for inflammation

(named based on chemotaxis)

Interferons (IFN)

interfere with viral replication

Tumor Necrosis Factors (TNF)

strong factor in inflammatory reactions of autoimmune disorders

Primary response

initial contact with Ag

no Abs detectable for 4-7 days

slow rise in Ab titer

raise first of IgM, then IgG

Secondary response

occurs after a second exposure

Ab-mediated immune response is intensified

(is faster, longer, more intense)

Adaptive immunity types

Actively or passively acquired

Both can be either naturally or artificially obtained

Actively acquired immunity

exposure to foreign substance elicits immune system response

Passively acquired immunity

transfer of antibodies from one person to another

only lasts as long as Ab are present (weeks)

Naturally acquired active immunity

occurs through exposure to an antigen

via illness and recovery

Naturally acquired passive immunity

natural transfer of Ab from mother to infant

transplacental or through breastmilk

lasts only as long as Ab is present (weeks to months)

Artificially acquired active immunity

occurs from exposure to antigens as killed or inactivated microbes or toxoids

(ex through vaccines)

Artificially acquired passive immunity

injection of antibodies into the body (not antigens)

taken from organism already immune to the disease

half life of Ab usually ~3 weeks

Active vs passive immunity?

active relies on the individual to create their own antibodies

passive provides the individual with antibodies

Natural vs artificial immunity

natural is developed by the body

artificial is acquired through medical treatments