Immunity: third life of defense

Third life of defense

adaptive immunity acquired over time

smart system

memory allows it recognize and respond rapidly to a second encounter with pathogen defending us against distinct invaders and their products

Antigens

includes components of bacterial cell wall, capsules, pili, flagella, proteins of viruses, fungi, protozoa may by found in food and dust, trigger B and T lymphocyte response

Antigens enter body via

breaks in the skin and mucous membrane

direct infection: bite or needle 

organ transplats and skin grafts 

B lymphocytes 

major function is the secretion of antibodies 

B lymphocytes origin

arise in red bone marrow

B lymphocytes primary location

spleen, lymph nodes, mucosal associate lymphoid tissues, small percentage circular in the blood 

B cell receptor (BCR)

an antibody attached to the B lymphocyte

BCR, each B lymphocyte

has multiple copes of a single type of BCR

BCR, each BCR

is complementary to only on antigenic determinant

BCR, antigen binding site

identical to that of the secreted antibody for that particular cell

BCR, randomly generate antibody variable region

determines the BCR (not found in response to antigens)

BCR, BCR on all of individuals B cells

capable of recognizing millions of different antigenic determinants

Antibodies 

soluble proteins that bind antigen: immunoglobulins (Ig), 5 different classes (1 not adequete)

Antibodies origin

secreted by plasma cells: B cells actively fighting exogenous antigen

Antibodies location

part of humoral immune response (bodily fluids such as lymph and blood were once called humors)

Antibody structure epitopes

antigen binding sites are complementary to antigenic determinants

Antibody structure close match

can form strong non-covalent interaction: hydrogen bonding etc

Antibody structure function

activation of complement

inflammation

neutralization

agglutination

opsonization

Antibody structure alternative splicing 

variation in antigen structure → diversity 

Neutralization

block sites on bacteria and viruses that they use to enter host cell with adhesion proteins

Opsonization

marks pathogen for destruction with opsonins

Agglutination

multiple antibodies bind to multiple pathogen cells → aggregation

Humoral immune response

production of antibodies

Lymphocyte editing 

clonal deletion vs. non self 

prevent immune response against autoantigens 

Body “edits” lymphocytes to eliminate only self-reactive cells 

Memory B cells 

Cells produced by B cell proliferation that don’t secrete antibodies

Memory B cells, cells that have BCR complementary to

the specific antigenic determinant that triggered their production

Memory B cells, long-lived cells that divide

only a few times and then persist to the lymphoid tissue

Memory B cells, available to initiate antibody production

if the same antigen is encountered again

T lymphocyte cell mediated immune response

act directly against various antigens, endogenous invaders, body’s cells that harbor intracellular pathogens, abnormal body cells such as cancer cells that produce abnormal cell surface proteins

T lymphocyte cell mediated immune response origin

produced in red bone marrow and mature under influence of thymus

T lymphocyte cell mediated immune response location

circulating in the lymph and blood and migrate to lymph nodes and speen

T lymphocyte cell mediated immune response types

cytotoxic T cells, TC

Helper T cells, TH, TH2

Cytotoxic T cells (TC cells) 

distinguished by the CD8 cell-surface glycoprotein

Cytotoxic T cells (TC cells) directly kill

cells infected with viruses and other intracellular pathogens

abnormal cells (cancer cells) 

Helper T cells

distinguished by CD4 cell-surface glycoproteins

Helper T cells help

regulate the activities of B cells (humoral) and cytotoxic T cells (cell-mediated) immune response

Helper T cells Secrete

various soluble protein messengers, cytokines that determine which immune response will be activated 

Type 1 helper T cell (TH1)

assist cytotoxic T cels and express cytokine receptor CCR 5

Type 2 helper T cells (TH2)

assist B cells, have cytokine receptors CCR3 and CCR4

Cell-mediated immunity

triggered when antigenic determinants of pathogen are displayed on host cell’s surface (MCH I)

Cytokines

soluble regulatory proteins that act as an intercellular signals when released from certain body cells 

Cytokines: interleukins (ILF) 

Signal among leukocytes 

Cytokines: Interferons (IFNs)

antiviral proteins that may act as cytokines

Cytokines: Growth factors

proteins that stimulate stem cells to divide, maintaining adequate supply of leukocytes

Cytokines: Tumor necrosis factor (TNF)

Secreted by macrophage and T cells to kill tumor cells and regulate immune response and regulation

Cytokines: chemokines

signal leukocytes to go to site of inflammation or infection and stimulate other leukocytes

Host cell protection

from destruction by phagocytes, major histocompatibility complex

Host cell protection, some phagocytes 

have receptors for bacterial surface components such as flagellar proteins or cell wall components that are lack on the body’s cells 

Host cell protection, opsonins

Complment nad antibody provide a singla to phagocyte

Graft rejection

perceived as foreign by a recipient and rejected

Normal immune response against foreign major histocompatibility complex (MHC) protein on surface of graft cells 

Likelihood depends on degree to which the graft foreign to recipient  

Isograft

transplant from genetically identical individuals (sibling, clone) 

Allograft

transplant from genetically different member of same species 

Xenograft

transplant from one species to another

MHC class I

endogenous pathway (viruses)

all nucleated cells

displays only protein produced within the cell

Immune system monitors health of cell; is it infected? yes → then kill by T-cells

MHC class II

exogenous pathway (e.g. bacteria)

only on APCs displays antigens

cell is kill by T cells

Adaptive

B-cells secrete antibodies that destroy or mark for attack by others

T cells recognize antigens displayed on APC. Some T cells help to active B-cells and other T-cells directly attack infected cells

T- and B- cells spawn memory cells that elimated invaders encountered before