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Immunology & Genetics Flashcards

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1
Q

Immunity

A

Body’s defense against pathogens, foreign materials, and malfunctioning self-cells

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2
Q

Type 1 Hypersensitivity

A

Allergic reactions mediated by IgE antibodies and mast cells or basophils, causing histamine release

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3
Q

Type 2 Hypersensitivity

A

Antibody-dependent reactions involving IgG, IgM, complement, and phagocytic cells
- Antibodies attack own self cells

Ex: Hemolytic disease of newborn (HDN), autoimmune hemolytic anemia, transfusion reaction

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4
Q

Type 3 Hypersensitivity

A

Tissue damaging reactions due to immune complex deposition

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5
Q

Type 4 Hypersensitivity

A

Mediated by T-cells without antibody involvement, causing graft vs. host responses

  • Th1 cells activated and release cytokines —> recruit macrophages and neutrophils —> inflammatory response
  • Tc cells —> tissue destruction
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6
Q

Immune mediated diseases

A
  • Immune deficiencies: can lead to false-negative reactions
  • Monoclonal gammopathies/polyclonal gammopathies (multiple myloma) and autoimmune diseases: increase serum proteins and interfere with alloantibody detection.
    > Ex: Rouleaux formation and panagglutination
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7
Q

Major Histocompatibility Complex (MHC) aka Human Leukocyte Antigen (HLA)

A

Surface markers that allow immune cells/WBCs to distinguish “self” vs “nonself”

Found on membrane of nucleated cells

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8
Q

MHC Class I coded by what genes?

A

HLA-A
HLA-B
HLA-C

*Remember ABC

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9
Q

MHC Class II coded by what genes?

A

HLA-DR
HLA-DQ
HLA-DP

*Remember: PQR in alphabet

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10
Q

MHC Class III coded by what gene?

A

Not associated with surface membrane

Codes for complement and cytokines like TNF (Tumor Necrosis Factor)

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11
Q

Antigen Binding Groove

A

On MHC Class I and II

So endogenous and exogenous antigens can bind for WBCs to make antibodies or cytokines

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12
Q

Exogenous vs Endogenous

A

Exogenous: outside of the cell

Endogenous: inside a cell that has already invaded or tumor cells

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13
Q

MHC Class I

A

Binds endogenous antigens (tumors, viruses, intracellular bacteria - produced within the cell)

When NK cell finds a cell that lacks MHC Class I, it releases perforin and granzymes to induce cell death/apoptosis

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14
Q

MHC Class II

A

On APCs (monocytes, macrophages, dendritic cells, B lymphocytes)

Bind exogenous antigens (fragments of bacteria, virus or parasites ingested by APCs)

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15
Q

Opsonization

A

Promotes phagocytosis

C4b or C3b

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16
Q

Anaphylatoxins

A

Increase vascular permeability, contract smooth muscle, release histamine from basophils and mast cells

C3a, C4a, C5a

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17
Q

C5a

A

Chemotaxin - signals WBCs to migrate to affected area

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18
Q

C5b67

A

Promotes monocyte and neutrophil adherence to blood vessel and WBC migration to tissue

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19
Q

Classical Pathway

A

C1 = recognition unit, stabilized by Ca2+. Binds to IgM. Recruits C1q, C1r, C1s
- Cleaves C4 + C2 —> C4b2a —> C3 convertase
- C4b2a3b —> C5 convertase

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20
Q

Membrane Attack Complex (MAC)

A

C5-C9

Allows influx of water, causing cell to swell and lyse

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21
Q

Alternative Pathway

A

C3 —> C3a + C3b

C3b and Factor B require Mg+ to combine
Factor D unbinds Factor B from C3b

Properdin (Factor P) stabilizes the C3bBb complex

C3bBbP = C5 convertase

Formation of MAC

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22
Q

Mannose Binding Lectin Pathway

A

MBL = equivalent to C1q in Classical Pathway

MASP-1 and MASP-2 = function similarly to C1r and C1s

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23
Q

Innate Humoral Immunity

A

Complement Proteins

Components formed in the liver
C1 formed in intestinal epithelial cells
Factor D forms in adipose tissues

Plasma - components in inactive form
Once activated, components split into 2 fragments:
- smaller “a” - stimulates immune system
- larger “b” - activates cascade

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24
Q

Humoral Innate Immunity

A

Plasma proteins

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25
Cell Mediated Adaptive Immunity
APCs, T lymphocytes, B lymphocytes Phagocytize foreign antigen
26
TH cells
CD4 MHC II Stimulate TC lymphocytes and B-cell activation
27
TC cells
CD8 MHC I Produce perforin to destroy virus infected cells, tumor cells, tissue grafts TNF (tumor necrosis factor) and interferons are released to prevent spread of virus
28
Humoral Adaptive Immunity
B lymphocytes secrete membrane bound antibodies, react with exogenous antigens B cells produce specific antibodies (plasma cell) TH dependent clonal proliferation - B cell acts as an APC to the T cell: produce memory cells TH independent clonal proliferation - BCR are IgD that recognize polysaccharides and lipopolysaccharides: does not produce memory cells
29
Immunoglobulin
Glycoprotein with 2 heavy chains and 2 light chains, held together by disulfide bonds Fab region: binds to antigen Fc region: binds to complement and receptors on macrophages, determines Ig class
30
IgG
Only Ig that crosses placenta IgG1 and IgG3 interact with macrophages through Fc receptors — bind complement and promote phagocytosis 37°C - body temp Non-agglutinating antibodies — require AHG for hemagglutination
31
IgM
Pentamer, first antibody produced Indicates active infection Binds complement and cause intravascular hemolysis Reacts at RT - 4°C ABO antibodies
32
Primary Humoral Response
First exposure to antigen T and B lymphocytes 4-7 days of lag phase (time it takes antibody to reach detectable level) IgM Antibody level declines quickly
33
Secondary Humoral Response
Repeat exposure to same antigen Memory cells (anamnestic response) 1-4 days of lag phase IgG Greater antibody titer and level remains for a while
34
Convalescent Plasma Treatment
Isolating plasma from infected COVID patients (with antibodies), give plasma to sick patients to try to neutralize the virus
35
Rhogam
Antibody against Rh D antigen for prenatal testing
36
Immunogen
Chemical substance capable of eliciting an immune response
37
Epitope
Portion of the antigen that reacts with the antibody A single antigen can have multiple epitopes
38
Polyclonal antibody
Different epitopes on a single antigen, inducing B cell clones —> results in heterogeneous population of serum antibodies
39
Monoclonal antibody
Single clone proliferation to produce IDENTICAL antibodies
40
Hapten
Small molecule that requires a carrier molecule to stimulate antibody production
41
Immunogenicity
Antigen’s ability to elicit an immune response Factors: age, race, genetics
42
Dosage
Quantitative expression of specific antigen on the RBC surface based on gene inheritance
43
Tolerance
Lack of immune response or active immunosuppressive response
44
Sensitivity
Ability to detect antigen at a low titer
45
Antigenicity
Antigen’s ability to bind with its antibody Affected by antigen’s: location, size, shape, charge, solubility, digestibility
46
Avidity
Overall strength of binding between antigens and antibodies Influenced by valence of antibody and antigen
47
Affinity vs Avidity
Affinity: strength of a single antibody-antigen interaction - IgG has a high affinity to antigen Avidity: strength of ALL INTERACTIONS combined - IgM has a low AFFINITY antigen binding sites, but since there are 10 binding sites, the AVIDITY is high
48
Neutralization
Bound antibody inactivates antigen
49
Precipitation
Antigen-antibody complex can become insoluble
50
Opsonization
Bound antibody stimulates phagocytosis
51
Hemagglutination
Antibodies cross-link between RBCs, RBCs clump together Primary testing method for RBC typing, antibody screen, ID and crossmatch
52
Factors that affect Antigen-Antibody binding
- Ionic strength (IgM > IgG) - pH (6.5-7.5 optimal) - Temperature - Number of epitopes
53
Stages of hemagglutination
Stage 1: Sensitization - antibody attaches to epitope on RBC membrane Stage 2: Lattice Formation (agglutination) - antibodies crosslink RBCs, shows visible clumping
54
Direct Antiglobulin Test (Direct Coombs Test)
Detects non-agglutinating antibodies or complements coating RBCs in vivo Antihuman globulin (AHG) reacts with human globulins bound to RBCs, causing agglutination of sensitized cells (IgG)
55
Possible causes of in-vivo RBC sensitization
Autoimmune disease: Warm AIHA, CAD (cold autoimmune disease) Alloimmune hemolytic anemia: HTN, HDFN Drug induced immune hemolytic anemia
56
WAIHA
IgG, C3
57
CAD
C3 only IgM Specificity: anti-I
58
Indirect Antiglobulin Test (IAT)
Detects non-agglutinating IgG antibodies in plasma (so due to previous exposure of foreign red cell antigen) Used for antibody screens, antibody ID, crossmatch, and prenatal antibody titration
59
Alternative Testing Methods
Gel System - Utilizes microtubes with gel containing anti-IgG and Dextran microbeads - High sensitivity, no need for washing, and automation capability - Detects low antibody titers and provides precise results - (+) = agglutination in the gel column at some level, (-) = cell button at bottom of column Solid Phase Testing - Red cell antigens coated on microtiter plate wells for antibody detection - Indicator RBCs with AHG used for positive reactions. - Differentiates positive and negative reactions efficiently - (+) = diffuse adherence of indicator cells, (-) = solid button
60
- Clotted specimen - Blood from IV line with DEXTROSE - Septecemia/bacteria contaminated samples
False (+) DATs
61
- Presence of autoantibodies - Drug interaction - Increased serum protein (fibrinogen and globulins) - Over centrifugation - Positive DAT
False (+) IAT
62
- Inadequate cell washing, neutralizing anti-IgG - Low titer IgG - postzone - Deteriorating reagents
False (-) DAT and IAT
63
Antihuman globulin (AHG)
Reacts with human globulins bound to RBCs, causing agglutination of sensitized cells Used in both DAT and IAT to enhance agglutination of IgG
64
Check cell
RBC coated with antibody and is used to verify validity of negative reaction Basically double checks negative tests
65
3 levels of genetics
Molecular genetics: biochemistry of gene and structures Cellular genetics: cellular organization of genetic materials Population genetics: genetic traits in large numbers of individuals
66
DNA
4 nitrogenous bases: Adenine, Guanine, Cytosine, Thymine 5-carbon deoxyribose sugar - 1 nitrous base bonded to number 1 carbon of deoxyribose - phosphate group at 3 and 5 carbon of deoxyribose Double stranded - antiparallel
67
RNA
Transmits genetic info from nucleus to cytoplasm for protein synthesis Single stranded 5-carbon ribose sugar Uracil instead of Thymine OH instead of H (DNA structure)
68
4 types of RNA
- Ribosomal (rRNA): cytoplasmic reticulum, translation - Messenger (mRNA): nucleus, transported out to cytoplasm for translation - Transfer (tRNA): transport amino acids to ribosome bound to mRNA during translation - Small nuclear (snRNA): splicing for modification of mRNA, regulatory, cell development, defense
69
DNA transcription
One DNA strand is copied into mRNA for translation Nucleus —> cytoplasm - 5’ end (7-methyl guanosyl cap): recognition site - Poly A polymerase: stabilizes mRNA - Intron: part of gene that does not code for protein, RNA slicing removes it - Extron: remaining sequence in mRNA
70
Translation
RNA transcripts —> proteins using codons Codons = code for amino acids
71
Stop codons
UAA UAG UGA
72
Start codon
AUG
73
Silent mutation
Does not change protein, functions the same
74
Transition mutation
One purine replaced with another purine (A and G), or pyrimidine with another pyrimidine
75
Transversion mutation
purine substituted for pyrimidine (A with C) or vice versa
76
Missense point mutation
Change in codon, alters amino acid UGU - Cystine CGU - Arginine
77
Nonsense mutation
Point change in nucleotide of a DNA sequence, causing stop codon to form Terminates reading of DNA sequence Stop codons: UAA, UAG, UGA
78
Insertion/Deletion (Frameshift mutation)
Changes the triplet codon sequence by altering the reading frame of the codon, results in large change in amino acid sequence downstream of the mutation
79
Recombination/crossing over
Takes place in meiosis From material and paternal homologous chromosomes —> new DNA sequence different from parent strains
80
Chromatin
Macromolecule composed of nucleic acids and structural proteins (histones)
81
Heterochromatin
Highly condensed region where transcription is not active
82
Euchromatin
Region where transcription is more active
83
Chromosome
Compressed/condensed coiled chromatin In dividing cells
84
Gamete cells
Sex cells Haploids, half the number of chromosomes
85
Gene
Section on the chromosome that encodes for a particular protein
86
Locus
Specific location of a gene
87
Allele
Alternative forms of the gene Can be on the same chromosome or another homologous chromosome pair
88
Mitosis
2 identical diploid daughter cells Asexual reproduction
89
Meiosis
4 unique haploid cells Sexual reproduction
90
Population Genetic
Principle of independent segregation and independent assortment
91
Mendel’s first law of inheritance
Independent or random segregation Each gene is passed onto the next generation
92
Mendel’s second law of independent assortment
Genes for different traits are inherited separately from each other Ex: flower color gene and seed shape gene are separate
93
Linked Disquilibrium Phenomenon
Exception to Mendel’s second law of independent assortment Linked genes do not assort independently
94
Hardy Weinberg Principle
Formula that explains Mendel’s inheritance p + q = 1 p = frequency of dominant allele q = frequency of recessive allele p^2 + 2pq + q^2 = 1
95
Autosomal Dominance
Expressed when the allele is present Homozygous or heterozygous In males and females
96
Autosomal Recessive Inheritance
Expressed when individual is homozygous for the allele and inherited recessive allele from both parents
97
Polymerase Chain Reaction
DNA replicated in the test tube by cyclic changes in the reaction temperature Denature: double helix into single strands Anneal: binding of forward and reverse primer Extension: DNA polymerase extends primer
98
4 types of NGS (new generation sequencing)
- Pyrosequencing: measures light released by pyrophosphate - Sequencing by synthesis: fluorescence labeled dideoxynucleotide - Sequencing by ligation: uses oligonucleotide probes (not DNA polymerase) - Ion semiconductor sequencing: measures release of H+

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