Lecture 2: Antigens and Cell Mediated Immunity

what is an antigen

macromolecule capable of reacting with Ab or T lymph (term for diagnosis)

what is an immunogen

macromolecule capable of inducing immune response (Ab or T lymphs)

what makes an immunogen successful (size)

minimum 10,000 Da

best when >100,000 Da

what makes an immunogen successful (foreign-ness)

more foreign is better! plant material is more foreign than other animal material

what makes an immunogen successful (chemical composition)

proteins are more complex than sugars so they stimulate a larger response

what makes an immunogen successful (processing)

processed and presented with MHC. stimulates adaptive immune response

what is an epitope

part of the immunogen that is recognized in immune response. B cell and T cell recognize

epitopes can be

linear or conformational

what are linear epitopes

amino acid on linear chain. No secondary structure

what are conformational epitopes

May be folded or contributory effect. More than one epitope

what is hapten

non immunologic material that doesn't create a response since it is so small.

when can hapten create an immune response

When associated with a carrier molecule

what makes a larger immune response?

2 Ab attached to the cell

1 Ab attached to the cell

2 separate antibodies attached to the antigen (crosslinking)

what is an autoantigen

Ag belongs to the host. Does not stimulate an immune response except in autoimmunity.

what is an alloantigen

antigen from other members of the host species. May happen due to transfusion/transplant

what is a heteroantigen

antigen from a non human

what is a heterophile antigen

subdivision of heteroantigen. Antigen exists in an unrelated plant/animal which is super close to something we have. (examples: EBV, mono)

what does MHC stand for

major histocompatibility complex

what is MHC

brings antigen to the surface of antigen presenting cells for recognition by T lymphocytes. pleomorphic

MHC class 1 is found on

Myeloid/lymphoid tissue: highest level of expression

Liver cells: low level of expression

MHC class 1 structure

alpha chain anchored to membrane (A1, A2, A3). 3 alpha sections

Peptide binding cleft between A1 and A2 (holds Ag 8-11 amino acids long)

Beta chain keeps confirmation of alpha chain

MHC class 1 is (endogenous/exogenous)

endogenous

mechanism for MHC class 1 (6)

Endogenous antigen within the cytoplasm

TAP move antigen peptides into the endoplasmic reticulum

Alpha chain of MHC binds beta microglobulin

Alpha chain of MHC binds antigen peptide

Peptide + MHC move into the golgi complex and then to the cell surface

Peptide + MHC bind to CD8 T cell

MHC class 2 is found on

antigen presenting cells, macrophages, dendritic cells

MHC class 2 structure

2 alpha sections

2 beta sections

Peptide binding cleft slightly larger (binds antigens 13-18 amino acids long)

MHC class 2 is (endogenous/exogenous)

exogenous

MHC class 2 mechanism (7)

MHC class 2 with invariant chain bound to peptide cleft

MHC complex is from the rough ER and moves to the golgi complex

Invariant chain is degraded leaving only the CLIP fragment

Exogenous antigen taken in and degraded. Sent to intracellular vesicle

CLIP fragment is exchanged for the antigenic peptide

Class 2 MHC transported to the cell surface

Complex binds to CD4 T cell

adaptive immunity definition

Highly evolved defense mechanism stimulated by immunogens. Increase in magnitude upon each exposure.

features of adaptive immunity

specificity

ability to remember and respond more vigorously

diversity in response

self limitation

non reactivity to self

components of adaptive immunity

lymphocytes and antibodies

two kinds of adaptive immune responses

cell mediated immunity

humoral mediated immunity

t lymphocytes relate to this kind of adaptive immune response

cell mediated

b lymphocytes relate to this kind of adaptive immune response

humoral

t lymphs are found

in the blood

b lymphs are found

in the lymph nodes, spleen, and bone marrow

t lymphocytes look like this

rosette formation with sheep RBC

b lymphocytes have this

surface immunoglobulins

t lymphocytes create this

cytokines

b lymphocytes create this

antibodies

t lymphocytes are related to these CD markers

CD2

CD3

CD4

CD8

b lymphocytes are related to these CD markers

CD19

CD20

CD21

CD40

t lymphocytes are made in the

Pericortical region of lymph nodes

b lymphocytes are made in the

Cortical region of lymph nodes

two modes of procuring adaptive immunity

active and passive

active immunity is _____________

induced by exposure to immunogen. Host activity plays a role in immunity

what are the methods of active immunity

infection

vaccination

passive immunity is _______________

transfer of immune content to the host. Specific immune response. Immune response without the exposure

what are methods of passive immunity

Breastfeeding (IgA)

Placenta (IgG)

Antitoxin administration

Gamma globulin bolus IgG injection

Rhogam

what is cell mediated immunity

promotes the destruction of pathogens residing in phagocytes. Viruses and bacteria

basic steps of t lymph differentiation

precursor cell

heads to thymus

t lymph gets activated

once the precursor cell reaches the thymus is is now called a

thymocyte

thymocyte development

T cell receptor construction

Make the beta chain and then the alpha chain

6 additional chains in the transmembrane protein

Double positive (cell has both CD4 and CD8)

now its mature

what is the beta chain called

VDJC

what is the alpha chain called

VJC

positive selection definition

thymocyte interacts with MHC. too loose or too tight means the cell undergoes apoptosis

negative selection definition

cells that survive are exposed to host antigen. If the cell reacts with the host antigen it undergoes apoptosis.

mature lymphs have either

CD4 or CD8

CD8 is this kind of lymph

cytotoxic

where does the CD8 develop

lymph node and spleen

what does CD8 need to activate

immunogen

information about CD8 activation

needs immunogen to activate.

Has to be 5-8 days of exposure to activate the cell. Once activated the cell is deployed to the site of infection.

CD8 method of killing

introduces granules to cell, induces apoptosis

CD4 is this kind of lymph

helper

CD4 development happens in the

lymph nodes and spleen

CD4 activation information

Immunogen exposure to activate. Takes 1-2 days to activate.

CD4 is called _________ when activated

blast cells

blast cells can become either

effector cells

memory cells

effector cell information

IFN gamma leads to TH1 cell (inflammation)

IL4 leads to TH2 cell (antibody)

memory cell information

Enhanced response upon second exposure. Better affinity at the second exposure.

what influences lymphocyte activation

cytokines (IFN gamma and IL4)

TH1 is related to this process

inflammation

TH1 activates

cytotoxic lymphocytes and interacts within the macrophage (IFN gamma, IL2, TNF beta)

TH2 is related to this

antibodies

TH2 activates

B cells to make antibodies against extracellular antigens

(IL4, IL5, IL6, IL9, IL10, IL13)