Immunology: Immune Response & Genetics

Introduction to Immunohematology

• Immunohematology requires understanding blood banking, blood group genetics, and pathogen testing to ensure blood supply safety
• Population genetics and inheritance patterns are central to genetics role in blood banking

Genetics: Cellular vs. Molecular

• Cellular genetics relates to the organization of genetic material inside cells
• Molecular genetics relates to the biochemistry of genes and supportive structures
• Modern genetic techniques analyze blood donor/recipient profiles, formerly done via serology

Genetic Terminologies

• Chromosomes are thread-like structures in cell nuclei containing genetic information, essentially condensed DNA
• Chromosomes consist of protein and a DNA molecule.
• Genes, units coding for inherited genetic information, are DNA areas controlling traits and characteristics
• Genes code for proteins specific to traits.
• Loci/locus indicate specific gene locations on chromosomes
• Alleles refer to alternate gene forms at loci, accounting for gene variations

Genetic Traits

• Dominant traits are always expressed over other traits due to dominant genes
• Recessive traits are only expressed in homozygous states with identical recessive genes
• Recessive traits are not expressed with dominant genes
• Codominant traits involve two inherited, and equally expressed alleles

Genetic Definitions

• An amorph describes a gene not expressing detectable products, resulting in a null phenotype
• Homozygous describes identical alleles for a trait
• Heterozygous describes different alleles for a trait
• Genotype represents the genetic makeup of an organism, and comprises inherited genes
• Phenotype is the physical or observable trait manifestation
• Homologous chromosomes are similar in size/structure, and have genes coding for the same traits

Patterns of Inheritance

• Autosomal Dominant: expressed when the allele is present, same frequency, occurs in every generation if person has affected parent
• Autosomal Recessive: expressed in homozygous state only, parents carriers, not in every generation
• Sex-linked Dominant: inherited from father to daughter, more frequently in females
• Sex-linked Recessive: mainly in males via mother, frequently in males, in each generation
• Autosomal inheritance occurs on autosomal chromosomes
• Sex-linked inheritance occurs on the X chromosomes

Genetic Similarities

• Zygosity describes gene likeness at allelic positions on homologous chromosomes
• Homozygous = identical alleles
• Heterozygous involves different alleles
• Dosage is related to antigen strength
• Dosage involves higher expressions of homozygous genes

Genotype versus Phenotype

• Genotype is RR, CC, RC, R, or c
• Phenotype is R, C, or RC

Mendel's Contributions

• Gregor Mendel, Austrian monk, is considered the Father of Genetics
• He studied physical trait inheritances by experimenting with pea plants
• "Law of Independent Assortment" relates to independence of allele inheritance
• "Law of Independent Segregation" dictates random parental gene separation into gametes

Immunology Overview

• Immunohematology embodies blood group antigen/antibody studies
• It involves immune responses: body mechanisms recognizing/defending against foreign entities

Antigen Characteristics

• Antigens are large molecules (proteins/polysaccharides) binding to antibodies or T-cell receptors
• Antigens are located: cell membranes surface
• Antigens are located in viruses, bacteria, fungi, protozoa, blood cells, organs, and tissues
• Antigen & antibody complexes may occur: in vivo versus in vitro

Types of Antigens

• Allogeneic antigens do not come from the individual being transfused
• Allogeneic antigens come from the same species from donor to recipient
• In transfusions, allogeneic antigens expose individuals to antigens differing from their own
• Autologous antigens refers to self-antigens originating from the same individual
• The immune system tolerates self-antigens but failure causes immune responses and autoimmune diseases
• In transfusions, autologous antigens originate from recipient

Immune System Terms

• Immunogens are antigens eliciting immune responses
• Antigens distinguishes from immunogens by their capacity to bind lymphocytes/antibodies
• Immunogens can elicit immune responses, antigens cannot
• Immune system can respond/recognize and immune system's ability varies among individuals

Immune Responses

• B lymphocytes (B cells)

  • Reside/mature in bone marrow
  • Become antibody-producing plasma cells when exposed to antigens
  • Identify foreign red cell antigens via receptors
  • Present antigens to T cells
  • Respond during antigen re-exposure by transforming into an antibody factory faster

• T lymphocytes

  • Reside/mature in thymus
  • Produce cytokines to activate immune cells
  • B cells recognize foreign blood antigens, primarily through humoral immunity
  • B cells uses receptors to recognize the antigens
  • Antigen presentation to the T cells which produce cytokines which signals to transform the B cell into plasma cells
  • Antibodies produced have same specificity as original B cell receptor B cells transformed into memeory cells to respond more quickly at reexposure

• Memory B cells allow immediate responses by not requiring presentation of t cells for activation -- important principle of vaccination

Antibodies

• Antibodies are proteins known as immunoglobulins
• Antibodies are 2 common functions in both antigen combination, and mediating biogical effects
  • IgG, IgM IgA, IgD, IgE
  • An antibody has contains 2 fragments:
• • Fab Fragment --The portion of protein that binds to the antigenic deteminant, also known as antigen-binding site
• -Fc fragment --Mediates bining to host issue and immune cells If the antibody attaches to a antigen, the immune cells will recognize this binding and attach to the Fc region of the to the assist in the removal of mechanisms

How the host removes antigens

• In transfusion medicine. the antibodies that are attached to red ceil attached they signal clearance in the lives and spleen leading to extravascular hemolysis.
• Immunoglobulins in banking - IgC. IgAA
  • IgC - clinically significant. react at 37 degrees clinically significant == IgC isotypes can destroy trans used antigens.

IgM

• Naturally occuring, reacts at 22°C
• Naturally occuring antigens are produce during intestinal flora and pollen grains
• Polyclonal antibodies are caused by response to a single antigen with multiple epitope

Cell preparation

• Involve in cell culture with hybridoma
• Uniform and Well characterize the immune

Immunity

• Naturally - found in serum of people previously not exposed to RBC antigens. IgM Cold agglutins; ABH. Hhil
  • Immune Antibodies: Found in Serum exposees

Important blood groups

• ABO, Rh, Kell, Duffy, Kid, and SS

Immunity is determined by?

• Nutritional status
• Hormoes
• Agemrace Sex
• Physical activity level
• Enviroemnr exposure
• Ocorrence of disease or injury.

Developments and contributions

• First Blood ransfusion, -Circulation of Blood
• Micro injection into veins
• Dog transfusions
• Aniamal to human transfusion

Impotant figures in Medicine History

• Anonie Mauory
• Antoine. 34 year old man- madman
• 1795 philip syng physick

The 19th century figures

• John Henry Peacoack
• James bundell
• Emil ponfick 1818 – Emel warning of physician
  • Introducel soclium iphosphate with the early times
• Karl land Karl disocovered the ABO blood groups, and determined the minimum mount

Dr. Charles Drew

• 1949
• Directed Amedrican Red cress at presbyrian hospital

Red Blood Cell: Biology and Preservation

• Need the normal chemical composition of the RBC membrane
• The membrane is to carry oxygen throughout body
• Since mature erythrocytes do not have a nucleus and no mitochondria that process uses energy, the process by the are generate that it can delivery oxygen, its through breakdown og lucose - anaherobic

The most inportance of function

• Represents a semipermiable lipid billayerspported by meshlike proetin cytskoskeletion structure
• External outer Layer = Lipidis and glycolipids
• Internal Layers - amino phospholipids.
• Proteins in the cell membrane - intergral membrane proteins - extend from the outer suface and span the entired membrane -Peripherial membrane proteins
• Peripheral protein= proteins beneaththe lipid bilayer

Most imporatnce Characteristics

• It is critical for he cells proeprites to be viable
• • Readosn that can affect those properties
• Loss of ATP - Decreate in phosphorylation of spectrom
• Membrane stability- Accumulation/ Increase in deposition of membrane calcium - the cell are at a marked disadvantage by spleein.

Permeability of permeable properites

• Volume of RBC cell membrane is freely permeable to waater cCl and Bio carbonate.
• Calcium is activeley pumpes from the inteior-

Calmoduling

Cytopolasomic bindging proetin witch is specilates control and prevent execessive internal uptakes .

• Lead to increased of calcuim and lead to the decerase of potascicuam and water compartment

RBC metabolism

• Main goal provide patients requireing hemothereaphy with vuable -Maintain optimal viabiloty, blood are stores

Important of processes

• Anarheobiklytic PATHWAY -90 ATP is supplied by that
• defects generatic -low app
• Supplies NADH - keeps gutathione in reduced status.
• Methemofuluik
• Matunatu=ain ition state
• Leuerbring -

Hemoglobulin: Function

• Oxygen delivery Carbon dioxide
• Bood balancing is at balanced of pH

Hemoglonbin discossiation curge

• 23 bi phos

2 forms of Hemoglobin

1. Tenso form - lower affinity
2. Realexed for - H

• It allows us to deiver more oxygen

Red Blood cell perestation

• Maintain to to 4 celll
• FDA states at least 24 to survice past 75 cell must sun

Storage conditions

The more amount ot ATP can be can survive can hence CPDA# as m 3d5 amount of suruc.

Additive Solution The additive solution increases by 44% in amount

Behnefits extend shelfe of cell additiong -

• Extend shelfe for 44 to cell
• Production of RBC concentrate of less volume and easy inject

Manteitolel

Citoatte are to protect

Freeezing

Rejuvenation= allows for are

current trends:

devlopment

1. New method
2. platelets

Plates

• Cell frage
• Do 30% is squarated the sleen

Initial Arrest : Pllugging fromation;

• stabilizaton of fribin formmration

preservaotion storage

• major concer

current:

• Methods for platelets = that would platelets stored

platelets is not enuf

ABO Blood Group System

• Most Important Human Blooof Group STstem in transfusion Practise
• Discovered the ABO blood systems'
• Karl Landsteiner disovered abo blood group system
  • He was Able To identify 3 deiffetn pattersr if ecatubotu
• He drw blood from himeself

1902 Alref

• Routinte bood groupings was develpoed from banks
• Most importan of all bloos group.
• Recipinet and doner phpenotypes are importact of

Inheriancec

• One gene must inherit frorm each perants
• ABO gense semmed to for m simpel Mendelilan gena
• genese are in codomianat
• Example ABO gene - whart if 0gene the offesprin inherited what will be

formation of antigens

• Genes code prodeutcion gylsylsteratse or and

what if O geene in the inidvdi the more AFT ANEIAG.
and AB are in the serume, the

Antigens

A and B anitngens

a2b are not there A and Ab not there

• Direct aggtuintation in soil e=enboronment Optimal

ABO Sub Grooups More commons and B ubgtoups 8 a2 phenome

suvgouods different in number surtace

REactions

charachteristicts

• Direct Aggulitation
• Able to connect to the REcell if there recognize the aintgens Due to abiloty cause hemorolysis- clincialy sigaifncant-ahtir.

Antii-a is sersu

Aises of agests as B eople is serumm- agtulintahte rbcs and people. mofst is IagM Igaa- be present.

• anti A1 – readtns with A! not atall

reacts with A! nd A cells" a2 from a B presd

reagent-

reagent from planta called delocjhoss It is ah phenotyi8pe wich is a abndd

How to group o

• You c

we be with the all with the H leti what will hapen.

• Para boumar =

low levels treanstaeer

ab will is be

. All red be tested in TPMEB is at low volume A

Explore the intricacies of humoral immunity, B and T cells, and genetics. Understand the roles of plasma and memory cells in the immune response. Learn about the relationship between antigens and immunogens.