ADAPTIVE IMMUNITY SYSTEM

OpenStax Ch 18

adaptive immunity

third line defense
specificity and memory

specific immunity

targets specific pathogens

memory

remembering how to fight pathogens quickly

First exposure to pathogen takes long because

primary response takes longer for antibodies to develop

Second exposure to pathogen

already antibodies so faster specific response

antigen

pathogen-specific structure that stimulate a specific immune response

epitope

smaller surface region of the antigen that the antibodies, b and t cells can recognize and respond to

why do you need antigens?

allow antibodies and t cells to attach to kill
triggers immune response

Antibodies (immunoglobulins)

glycoproteins in blood and tissue fluids that bind to epitopes on an antigen

antigen vs antibody

antigen bad antibody good

antibody structure

four protein chains with disulfide bonds
Y shape
2 heavy chains 2 light chains
Fab and Fc region

Fab region of antibody

fragment of antigen binding
has epitopes for binding

Fab region binding

neutralization, agglutination, aggregation, or cytotoxicity of pathogens

Fc region of antibody

fragment of crystallization
trunk of the Y
where complement factor and phagocytic cells bind

antibody 5 major classes

IgG, IgM, IgA, IgD, IgE

IgG monomer

Most abundant and versatile
cross placental barrier
penetrates into tissue

IgM pentameter

6 percent of serum
First antibody produced and secreted by B cells
primary and secondary

IgA dimer

13 percent of serum
mucus secretions, breast milk, tears, saliva
has secretory component

IgD membrane bound monomer

1 percent of serum
antigen-binding receptor of B cell surface

IgD is NOT ________

secreted

IgD are from degradation of

old B cells
release of IgD molecules from cytoplasmic membranes

IgE monomer

least abundant
secreted
anti parasitic defenses
allergic and inflammatory reactions

How do antibodies kill pathogens?

neutralization, opsonization, agglutination/aggregation, complement cascade, antibody dependent cell mediated cytotoxicity

Neutralization

binding of antibodies to epitopes to prevent pathogen attaching to cells

Antibodies that can neutralize

IgG, IgM, IgA

Opsonization

coats pathogen with molecules to help phagocytosis

Best antibody for opsonization

IgG

Agglutination/Aggregation

cross linking pathogens to create large clumps

Best agglutination/aggregation antibodies

IgM, IgG
(IgM best)

Complement cascade

recruit phagocytes to infection site, enhance opsonization, kills gram negative pathogens with MAC, promote inflammatory response

Most efficient complement cascade type

classical pathway

classical pathway

initial binding of IgG or IgM

Antibody-dependent cell-mediated cytotoxicity (ADCC)

enhances pathogen killing for pathogens that are too big

who can do ADCC?

Nk, macrophages, eosinophils

what antibody triggers ADCC?

IgG

MHC stands for?

major histocompatibility complex (molecules)

What is MHC?

collection of genes coding for MHC molecules on surface of nucleated cell

MHC genes AKA

human leukocyte antigen genes

what are the only cells that don't express MHC?

erythrocytes
(no nucleus)

what do MHC molecules do?

bind peptide fragments from pathogens and present on surface for T cells to recognize

MHC structure

transmembrane glycoproteins in dimer formation

where are MHC in the cells?

cytoplasmic membrane

MHC I presents:

normal self-antigens and abnormal/nonself pathogens

MHC II on what type of cells?

only on macrophages, dendritic cells B cells

MHC I on what types of cells?

all nucleated cells

MHC II presents:

present only bad antigens

MHC I structure

longer protein chain with smaller b2 microgobulin proteins
only a chain spans cytoplasmic membrane
a1, a2, a3

MHC II structure

a and b protein same length, two domains
both chain span membrane

where is antigen-binding site for MHC?

cleft on top of dimer

MHC I cleft formed between

a1 and a2 domains

MHC II cleft formed between

a1 and b1 domains

MHC I antigen presentation

signals that cell is normal

MHC I antigen presentation process

1. normal proteins degraded
2. processed into self-antigen epitopes
3. epitopes bind in cleft and present on surface

If cell is infected, what happens to MHC I molecules?

MHC I is destroyed

MHC II antigen presentation

only on surface of APCs
need proteases for presentation

MHC II presentation process

1. dendritic cell recognize and attach to pathogen
2. pathogen eaten and then phagosome
3. lysosome fuse for phagolysosome
4. degradation of pathogen for antigen processing

APC stand for?

antigen presenting cells

APCs role?

present antigens to activate T cells

Cell types that are APCs?

macrophages, B cells, dendritic cells

B cell main role

production and secretino of antibodies
use IgD and IgM

cross presentation

antigens brought into APC by mechanisms that are normally used for MHC II presentation but use CD8 T cells and MHC I

why use cross presentation?

when intracellular pathogen does not directly infect APCs

humoral immunity

fight pathogens in extracellular spaces
before toxins attach and enter host cells

cellular immunity

targets and eliminates intracellular pathogens with T cells
in the cell

T cell origin

multipoitent hematopoietic stem cells in bone marrow

Primary host for T cell development

red bone marrow and thymus

T cell development red bone marrow role

first steps of differentiation

T cell development thymus role

final steps of maturation
thymic selection

Thymic selection steps

Cortex, positive, negative

Cortex thymic selection

receptor develops

Positive thymic selection

positive stimulation means they move on
bad don't get the stimulation and are eliminated

Negative thymic selection

remove self-reacting thymocytes
medulla and cortex

negative selection aka

central tolerance
prevents self reacting T cells from reaching bloodstream

Peripheral tolerance

destroys self reactive T cells that escape and enter bloodstream

Peripheral tolerance mechanism

anergy and inhibition of self reactive T cells by regulatory T cells

anergy

state of nonresponsiveness to antigen stimulation

how does peripheral tolerance/anergy occur?

lacks an essential co stimulatory signal required for activation

about how many thymocytes survive thymic selection?

2%

Secondary lymphoid places

lymph nodes, spleen, tonsils, malt

secondary lymphoid place purpose

mature naive T cells wait to be activated by APCs

T cell receptor

first step of epitope recognition for activation

TCR structure

variable antigen binding site
constant region

Genetic rearrangement

process during thymic selection
adds diversity

lymph nodes function

guards lymphatic system
antigens filtered out here
has T and B cells, dendritic, macrophages

Spleen function

filters antigens from the blood
B and T cells, macrophages, dendritic, NK, RBCs

Tonsils function

part of GALT
stops pathogens from entering through mouth or nose

MALT stands for

mucosa associated lymphoid tissue

MALT function

clusters of T, B plasma cells, Th cells, macrophages
system of lymphoid tissues

How are T cells differentiated?

expression of surface molecules, mode of activation, roles in immunity

Most important CD molecules

CD4 and Cd8

CD stands for

cluster of differentiation (molecules)

T cell types

Helper, regulatory, cytotoxic

Helper T cells

CD4
activates macrophages and NK cells
only activated by APCs presenting MHC II antigens

Regulatory T cells

CD4
activated by MHC II antigens
prevent bad immune response and autoimmune disorders

Cytotoxic T cells

CD8
recognize MHC I antigens
primary effector cells and destroy infected cells

Activation for helper T cells

1. TCR recognition of specific epitope
2. CD4 interact with MHC II
3. APC and T cell secrete cytokine to activate helper T

Helper T cells differentiate into

TH1, Th2, Th17 cells

Th1 cells

autocrine
orchestrators for adaptive and innate immunity

Th2 cells

orchestrate humoral response
activate and differentiate B cells and antibodies

Th17 cells

specific to chronic mucocutaneous infections
(bacteremia and gi)