3.1

Question 1

Immunodeficiency diseases

Answer 1

Inherited diseases: Pathogens evade and subvert the immune system

Question 2

Type of Immunodeficiency disease: Streptococcus pneumoniae (90 Serotypes)

Answer 2

Numerous different strains
Antigen variability
Long-term immunity decreased

Question 3

Antigenic Drift

Answer 3

Process by which point mutations in influenza virus genes causes alterations in the structure of viral surface antigens causes year-to-year antigenic variation

Common in influenza and avian viruses

Question 4

Mutation and recombination

Answer 4

Generation of new viral strains that avoid immunity

Question 5

RNA viruses more prone to errors

Answer 5

Influenza, HIV and Covid

Question 6

Antigenic Shift

Answer 6

Process by which influenza viruses reassort their segmented genomes and change their surface antigens radically - shifts are usually the cause of influenza pandemics

Question 7

Epidemic versus Pandemic

Answer 7

Mutation and antigenic drift (epidemic) versus recombination and antigenic shift (pandemic)

Question 8

Trypanosoma brucei

Answer 8

protozoan
Africa - cattle and humans

Insect and animal host - genome encodes for 1000 genes encoding for variable surface glycoproteins (VSGs)

Gene conversion - gene in the expression site is excised and replaced by a copy of a different homologous gene

Host makes defense to dominant VSG form not the new minority VSG selection for minority

Question 9

Salmonella typhimurium and Neisseria gonorrhoeae

Answer 9

Dramatic cycling in the number of parasites in the individual - causes inflammation and neuro damage
leads to coma

Question 10

Viruses cleared by

Answer 10

cytotoxic CD8 T-cells

Question 11

HSV

Answer 11

latent
Infects epithelial cells then sensory neurons
cleared from epithelial cells but latent in neurons
Reactivation and it travels down the sensory neuron (trigeminal) to the epithelium

Question 12

why are neurons a good site for latent viruses?

Answer 12

express small numbers of MHC class I molecules 
do not recognize they are infected

Question 13

Latent viruses in neurons

Answer 13

Herpesvirus varicella-zoster (chicken pox/shingles) and Epstein-Barr Virus (EBV)

Question 14

Mycobacterium tuberculosis

Answer 14

Prevents the fusion of phagosome with lysosome in macrophages - flourishes in the vesicles

Question 15

Toxoplasma gondii

Answer 15

encloses itself in an impenetrable membrane-enclosed vesicle that does not fuse with other vesicles - prevents antigen processing

Question 16

Treponema pallidum (syphilis)

Answer 16

coats itself with human proteins to evade antibody binding

Question 17

Virus info

Answer 17

Greatest ability to evade human immune system
replication and life cycle depend on metabolic and biosynthetic processes of human cells
Capture of cellular genes encoding for cytokines or their receptors
synthesis of proteins that prevent complement fixation or antibody processing and presentation to CD8 T cells
Need host to survive and replicate

Question 18

Cytomegalovirus (CMV)

Answer 18

Latent
10 proteins to diminish MHC I from stimulating NK cells and CD8 T cells
158 million people infected - few initial symptoms remains latent
life-threatening to immunocompromised people

Question 19

Bacterial Superantigen

Answer 19

Small bacterial protein - toxin
Can crosslink MHC II on APC with TCR on CD4 T cell
Non-specific activation of CD4 T cells (2-20%) and excessive production of Il-2 INF-y and TNF-a confuse innate immune response
Lots of resources for a less specific response

Question 20

What uses bacteria superantigens to confuse the body?

Answer 20

Streptococcus aureus and streptococcus pyogenes

Question 21

S. Aureus

Answer 21

Staphylococcal superantigen-like proteins (SSLPs)
SSLP7 - prevents monomeric IgA from delivering bacteria to phagocytes
Contains binding sites for Fc region of IgA and C5 complement

Question 22

Primary immunodeficiency disease

Answer 22

Inherited defects

enhanced susceptibility to infection or autoimmunity

Question 23

Secondary immunodeficiency disease

Answer 23

Due to environmental factors (Immunosuppressive drugs)

Question 24

IFN-y

Answer 24

Dimer complex
only wild-wild signals
activates macs
Made by NK cells (innate) and Th1 CD4 and CD8 t cells (adaptive)

Question 25

Antibody deficiency

Answer 25

Poor clearing of extracellular bacteria

Question 26

Encapsulated bacteria

Answer 26

S. aureus S. pneumoniae P. aeruginosa - often evade innate immunity

Question 27

X-linked agammaglobulinemia (XLA) - Bruton's tyrosine kinase (BTK) defect

Answer 27

required for B-cell activation and pre-B cell development and differentiation Antibiotic treatable - successive treatments can lead to tissue damage (excessive release of proteases from bacteria and phagocytes) - airways- bronchiectasis There is an absense of mature B cels and all immunoglobulins Recessive x link pattern (on x) Treatable with monthly injections of immunoglobulin - antibodies against common pathogens (passive immunity)

Question 28

Autosomal Agammaglobulinemia's (non-Bruton type)

Answer 28

Can be caused by mutations in a large number of genes | Usually, autosomal recessive but there have been dominant cases in families

Question 29

Phagocytosis defects

Answer 29

enhanced susceptibility to bacterial infection

Question 30

Leukocyte adhesion deficiency (LAD-1)

Answer 30

Autosomal recessive Phagocytic disfunction Defect in the LFA-1 integrin proteins on phagocytes which prevents their adherence and migration out of the blood vessels Presents with recurrent bacterial infections, absent pus formation, poor wound healing and delayed separation of the umbilical cord Neutrophilia will be observed on a blood smear

Question 31

Chediak-Higashi Syndrome (CHS)

Answer 31

Characterized by recurrent staph/strep infections, partial albinism, and peripheral neuropathy (nystagmus) Caused by defect in LYST (lysosomal trafficking regulator) gene which leads to microtubule dysfunction in phagocytes Autosomal recessive 3 Ps Pyogenic infections (strep/staph) Partial albinism Peripheral neuropathy Giant granules in neutrophils on blood smear

Question 32

Chronic Granulomatous disease (CGD)

Answer 32

Deficiency of neutrophil NADPH oxidase - cannot make hydrogen peroxide Neutrophils are dysfunctional susceptibility to infection by catalase-producing organisms highly susceptible to bacteria that break down hydrogen peroxide (catalase-positive organisms) ex: S. Aureus; E. coli; Psudomonas; and Aspergillus treatment is lifelong regimens of antibiotics and antifungals to prevent infections interferon-gamma treatment and hematopoietic stem cell transplant

Question 33

C1-C4

Answer 33

Classical pathway is required for elimination of immune complexes - CR1 binds C4b and C3b attached to the complex and transports to RBCs. Accumulation of immune complexes in blood and deposition of immune complexes in tissue activates phagocytes increasing inflammation and tissue damage

Question 34

C3

Answer 34

Opsonin that promotes the efficient elimination of bacteria by phagocytes Susceptibility to encapsulated bacteria

Question 35

C4-C9

Answer 35

Terminal complement components of the membrane-attack complex increased susceptibility to Neisseria infections

Question 36

Hereditary Angioedema

Answer 36

Deficiency in the C1 esterase inhibitor (C1NH) Autosomal dominat Eyelids, lips, genitals, hands and feet Localized edema, puffy skin and swelling Treatment involves Danazol (a synthetic androgen and partial agonist at the androgen receptor; promotes C4 synthesis and increase in C1-NH replacement therapy with C1NH

Question 37

T cell dependent antibody response and cell-mediated immune response deficiency

Answer 37

SCIF - severe combined immune deficiency

Question 38

SCID (severe combined immunodeficiency)

Answer 38

X-linked defect leading to an impaired common gamma chain on cytokine receptors - mainly an absence of t cells or cellular absence of adenosine deaminase (ADA) or purine nucleoside phosphorylase (PNP) - auto recessive - absence of B, t and NK cells

Question 39

DiGeorge Syndrome

Answer 39

Spontaneous deletion of part of chromosome 22 No proper formation of the thymus - decreased/ absent t-cell mediated immune response ``` treatments antibiotics calcium supplements ear tubes or hearing aids occupational therapy physical therapy replacement of missing hormones surgery ```

Question 40

Wiskott-aldrich syndrome

Answer 40

x-linked recessive presents early in childhood in males with recurrent bacterial infections, eczema, purpura, epistaxis (nosebleed) and splenomegaly IgM low IgE and IgA are high WASp is the mutated x gene - WASp is expressed only in hematopoietic cells

Question 41

Hyper-IgM Syndrome

Answer 41

Absence of other immunoglobulins Deficiency in CD40 Ligand require immunoglobulin replacement therapy

Question 42

AIDS

Answer 42

Massive reduction in CD4 t cells and severe infection from pathogens that rarely cause trouble in healthy individuals (opportunistic infection)

Question 43

HIV 1

Answer 43

Chimps

Question 44

HIV 2

Answer 44

Monkey

Question 45

HIV

Answer 45

Exogenous retrovirus | spike protein

Question 46

CCR5 deficiency

Answer 46

White population - 10% heterozygous 1% homo | deletion mutant resistant to HIV infection

Question 47

HAART

Answer 47

highly active anti-retroviral therapy 1997