Chapter 17

Adaptive Immunity

defenses that target a specific pathogen

acquired through infection or vaccination

Primary response

first time the immune system combats a particular foreign substance

Secondary response

later interactions with the same foreign substance, faster and more effective due to memory

Humoral (antibody-mediated) immunity

control of freely circulating pathogens

fights invaders outside cells

Cellular (cell-mediated) immunity

control of intracellular pathogens

attacks antigens found inside cells (viruses, some fungi, and parasites)

Humoral Immunity steps

1. A B cell binds to its antigen(need to get activated by T helper cell)

2. B cell, with stimulation from T h cell differentiates into a plasma cell, some will become memory cells

3. Plasma cells proliferate and produce antibodies against the antigen

Where are intracellular antigens expressed

on the surface of an APC, a cell infected by a virus, bacteria, or parasite

Cellular Immunity Steps

1. T cell binds to MHC-antigen complexes on the surface of the infected cell, activating cytokine receptors

2. Cytokines activate macrophage and T h cells

3. CTLP becomes an activated cytotoxic T lymphocyte, able to induce apoptosis of the target cell, some T cells become memory cells

Differentiation of T and B cells

stem cell diverges into 2 cell lines

1. differentiation to B cells in adult red bone marrow

2. differentiation to T cells in thymus

3. BOTH: migrate to lymphoid tissue such as spleen, but especially lymph nodes

T-lymphocytes

recognize antigenic peptides processed by phagocytic cells

mature in the thymus

T cell receptors

on the T cell surface

contact antigens causing the T cells to secrete cytokines instead of antibodies

Cytokines

small, bc cells produce large amounts to travel quickly

chemical messengers produced in response to a stimulus

Interleukins

cytokines between leukocytes

Chemokines

induce migration of leukocytes, help macrophages come to site of infection

Hematopoietic cytokines

control stem cells that develop into red and white blood cells

Cytokine storm

overproduction of cytokines

leads to septic shock

Antigens

foreign molecules that cause the production of antibodies, produced by humoral immunity

have to be foreign enough and big enough!

Epitopes

different binding sites for the antibodies on the antigen

antigenic determinants

Haptens

antigens too small to provoke immune response, attach to carrier molecules and cover it, so now its big enough to cause antibody production

Ex. penicillin

Immunoglobulins

globular proteins, AKA ANTIBODIES

Valence

number of antigen-binding sites on an antibody

Bivalent antibodies

most common antibody, has 2 binding sites

Shape of Ig

4 protein chains form a Y-shape

2 identical light chains and 2 heavy chains

What are light and dark chains joined by

disulfide links at the hinge region

Variable (v) regions

at the ends of the arms, bind epitopes

this is what is different between antibodies

has the antigen binding site

Constant (Fc) region

the stem, which is identical for a particular Ig class

5 classes of Ig

IgG, IgM, IgA (covers mucus membrane), IgD, IgE

IgG

monomer

80% of serum

most common in vaccines (bc half life is 23 days, its the longest)

located in blood, lymph, intestine

enhances phagocytosis, neutralizes toxins &viruses, protects fetus

IgM

Pentamer joined by J chain with disulfide bonds

6% of serum

heaviest class

located in blood, lymph, B cell surface (as monomers)

half life of 5 days

effective against microorganisms and agglutinating antigens

What antibodies are first ones produced

IgM, in repose to initial infection, then IgG

IgA

dimer (with secretory component)

located in secretions(mommy milk, tears, saliva), and blood and lymph

half life of 6 days

localized protection on mucosal surfaces

IgE

monomer

0.002%

located bound to mast and basophil cells throughout body, blood

half life of 2 days

allergic reactions, possible lysis of worms?

Clonal Selection

inactive B cells contain surface Ig that bind to antigen

B cell internalizes and processes antigen

antigen fragments are displayed on MHC class 2 molecules (like sacrifice to T cells)

T helper cells contacts antigen fragment and releases cytokines to activate B cell

B cell undergo proliferation

Proliferation

clonal expansion

Major histocompatibility complex (MHC) genes

encode molecules on the cell surface

identify “self”

except for twins, everyone has different MHCs

MHC I

on the membrane of nucleated animal cells

MHC II

on the surface of antigen-presenting cells (APCs), like B cells, macrophage, and dendritic cells

What do activated B cells go into?

antibody producing plasma cells and memory cells

Percentage of B cells

95% become plasma cells and make antibodies

3?% stay silent to be memory cells, if antigen comes back

What does your body recognize as foreign

M protein

Antigen-antibody complex

forms when antibodies bind to antigens

protects the host by tagging foreign molecules or cells for destruction

What is the strength of the AA complex

the bond is strengthen by affinity

Protective mechanism of binding antibodies to antigens

agglutination, opsonization, antibody-dependent cell mediated cytotoxicity, neutralization, activation of the complement system

Agglutination

reduces number of infectious units to be dealt with,

antibodies have 2 binding sites, so 2 will hold 3 bacteria, binding them together

Activation of complement

C1 recruited bc they have stem antibody binding, and lysis causes big hole

ADCC

antibodies attached to target cell case destruction by macrophages, eosinophils, and NK cells

recognize a large target cell (parasite) as foreign, and dump enzymes to lyse target membrane to attack externally

immune system cells attach to the Fc regions of anitbodies

What needs to be ADCC

protozoans and helminths, because they are too large to be eaten

Opsonization

coating antigen with antibody to enhance phagocytosis

Neutralization

blocks adhesion of bacteria and viruses to mucosa

blocks attachment of toxin (cant bind to host cell, no AB toxin)

Thymic selection

eliminates immature T cells

T cells migrate from the thymus to lymphoid tissues

Microfold cells (M cells)

pathogens entering the GI tract pass through these, they control the flow of traffic

located over Peyer’s patches

transfer antigens to lymphocytes and antigen presenting cells

CD8+

Tc (cytotoxic) cells

Killer cells, bind MHC class I molecules

CD4+

T helper cells

see what’s happening and determine what signals/cytokines to send with B cells

interact directly w antigens

cell-mediated immunity because cells talk a lot

bind MHC class II molecules on B cells and APCS

Antigen presenting cells

Dendritic cells and macrophages

Dendritic cells

engulf and degrade microbes, display them to T cells

found in the skin, genital tract, lymph nodes, spleen, thymus, and blood

Macrophages

activated by cytokines or the ingestion of antigenic material

migrate to the lymph tissue, presenting antigen to T cells

Activation of CD4+ cells

TCR on the Th cell recognize and bind to the antigen fragment and MHC II class on APC

APC or Th secrete a costimulatory molecule, activating the Th cell

Th cells produces cytokines and differentiate, activated ones proliferate

Costimulatory molecule

required to activate T cells that have not previously encountered antigen

Apoptosis

programmed cell death

prevents the spread of viruses to other cells

cells cut their genome into fragments, so the membrane bulge outward, via BLEBBING

quiet killing, bc inflammation would explode the cell and get toxic particles everywhere

NK cells killing

granular leukocytes destroy cells that don’t express MHC I antigens

kill virus-infected and tumor cells, and attack parasites

not always stimulated by antigen (not always specific killing)

form pores in the target cell

Secondary (memory or anamnestic) response

occurs after 2nd exposure to antigen

more rapid, lasts many days, greater in magnitude

memory cells produced by first exposure activated with no delay

no higher IgM production, but its quicker

more IgG in your serum and stays longer (bigger curve)

Antibody titer

relative amount of antibody in the serum

reflects intensity of the humoral response

Naturally acquired active immunity

resulting from infection

antibodies enter body naturally, body induces antibodies

Naturally acquired passive immunity

transplacental or via colostrum(mothers milk), mother gives to baby (IgA)

Artificially acquired active immunity

injection of vaccination (immunization)

body produces antibodies

Artificially acquired passive immunity

injection of antibodies

with vaccine at same time (rabies)

Antibodies and..

B cells

Cytokines and..

T cells