MMI 188A M3/Final

anti-ACE-2 blocks

SARS-COV-2 from binding to ACE-2 receptor and entering human cells

Dengue vax

live attenuated vax that is recomb of yellow fever vax

Hemagglutinin & Neuraminidase

flu genes H&N

antigenic drift

point mutaxns in H/N

antigenic shift

reassortment of H/N while within secondary host (i.e. pig or avian) and therefore is susceptible by primary host b/c doesn’t have ABs against new strain

trypanosome

protists causing sleeping sickness

genes ∆ b/c variable surface glycoproteins (VSGs) that make AB targeting easier

VSG

variable surface glycoprotesins that are dangerous b/c they’re always changing to evade host immune response.

but also allow ABs to target the protists

chaga

trypanosome disease that enters muscle and escapes the cytoplasm

- replicates within host and avoids targeting by host ABs b/c no VSG on surface to be recognized

trypanosoma brucei

parasite transmission via bug bites (by Tsetse fly) that cause aggressive CNS damage that cause changes to cytokine networks

within spinal cord, eye, brain <— important organs

streptococcus pneumonia

bacterial pneumonia, meningitis, otitis media

ABs opsonize capsular polysacc

type specific ABs so not protective against other serotypes of polysacc

HHV 1

oral cold sores

HHV 2

genital sores

HHV 3

varicella for chicken pox of shingles (VZV)

HHV 4

Epstein-Barr that causes mononucleosis (does not offer a long-term, complete immunity)

HHV 5

cytomegalovirus (causing birth defects and immunosuppression in newborns)

HHV 6a, 6b, 7

Roseolovirus

HHV 8

Kaposi’s Syndrome (one of the only cancers caused by a virus)

Staphylococcus Aurem

avoids IgA and stops complement
- SSLP7 (Staphylococcus superAg like protein 7) binds to C5 and Fc region of IgA

prevents phagocytosis of bac and t cells continue producing cytokines

X-linked agammaglobulinemia

defective Bruton’s Kinase (random X chromo inactivation) causes a lack of B cell development maturing beyond pre-B cell stage leading to increased susceptibility to infections

immu complex disease types

C1, C2, and C4 complement disease

C3 complement disease

increases susc to encapsulated bac

DAF and CD59 complement disease

autoimmu condition such as paroxysmal nocturnal hemoglobinuria

C1INH complement disease

inhib C1r and C1s

pseudosubs that inhib proteases and cause hereditary angioedema (swelling beneath the skin)

what are the four to-know SCIDs?

Xlinked SCID

Wiskott-Aldrich Syndrome

Omenn syndrome

Adenosine deaminase deficiency

x linked SCID

SCID; mutation in gamma chain so deficient in IL2 and IL4 which need gamma chain =

SCID

sever combines immune deficiencies of T cells

wiskott-aldrich syndrome

SCID

X-linked deficiency of T cell activation

defect in the gene for a protein needed for cytoskeletal reorganization (cell interactions)

poor antibody responses.

omenn syndrom

SCID

RAG defect (bad rearrange/reassortment of genes)

deficient V, D, and J

no functional T or B cells

Adenosine deaminase deficiency

SCID

purine degradation

nucleotide metabs accumulate and toxic to T and B cells

autosomal rec

IL-12 recept deficiency

needed for bac infections

no mutual activation of IFN-γ

IFN-γ receptor deficiency

needed for bac infections

no mutual activation of IL-12

HIV key features

single stranded (ss) mRNA — reverse transcriptase encoded within to convert to ssDNA and complementary © DNA

integrase: integrate cDNA into host genome

protease: cleaves viral proteins

HIV timeline

flu-like —> asymp —> sympto —> AIDS

after infection, CD4 T cells decrase while viral load increases

main impacts of HIV

1. suppression of T cell immu by killing CD4 T cell

2. less IL-2

3. less resp triggered by CD4 = less NK cells, CTL, macrophages, neutrophils

4. immu supress = opportunistic infection and cancer

5. AB prod decreased

6. non-specific polyclonal AB activation by B cells

allergic rhinitis

hay fever

allergen enters resp track and blood borne eosinophils enter via mucus, they then release their inflamm mediators and are later removed

allergic asthma

T_h2 mediated chronic asthma

inflamm of airways, bronchoconstriction, mast cells produce ag specific IgE in mucus

skin mast cell

Histamine from mast cells cause vasodilation = swelling and redness

ie. bed bug bites

food allergy

ie. NVD

ie urticaria = ag in blood and is carried to skin

atopic dermatitis

many genes associated with innate immu

tryptase is produced by… and does…

produced by mucosal mast cells, does

chymotryptase is produced by… and does …

produced by connective tissue mast cells, does degradation of proteins b/c it’s a protease

describe chronic asthma key feature

mucus plugs! = reduced r and therefore reduced o2 x∆

what are the four main allergy “treatments”/”fixes”

1. desensitization

• acute (small increments = less mast cells = no anaphylactic rxn)

• chronic = weekly injections, IgG blocks immu response

2. antihistamines

3. corticosteroids

   • anti inflam and immu suppression

4. inhibit Ca2+ influx = block mast cell mediator release (i.e Inhaler!)

superantigen

after prez to T cell, cytokine “storm” leads to septic shock

how are HHV reactivated?

stress after initial exposure b/c remains dormant after initial symptoms/sickness is active

granuloma

aggregation of macrophages to isolate foreign substrates that immu sys cant eliminate

HIV

kills CD4 Tcells and therefore no IL2 to attract leukocytes

HIV 1 more deadly than HIV 2

acquired immunodeficieny syndrome (AIDS)

CNS degradation

CCR5 and CXCR4 (chemokine receptors crucial for T cell migration and activation) function as coreceptors for HIV-1 entry into CD4+ cells

CCR5 deletion

rare

makes individuals HIV resistent

how does HIV evade immu resp?

glycan shield! = glycoprotein encapsulated

Type 1 hypersensitivity

anaphylactic, IgE-mediated

soluble ag binds to IgE:FceRI complex on mast cell, triggering degranulation of mast cell

degranulation releases: histamines, prostaglandins, thromboxanes, leukotrienes, eosinophil chemo factor (ECF-A = attracts eosinophils to site)

IgG1 vs IgG4

IgG1 = activates receptors

IgG4 = inhibits receptors

IgG4 mechanism

IgG4 = anti inflam bc inhibits ab binding receptors so no histamine secretion

• binds to 2 ag’s at once

• doesn’t trigger complement

• binds to FcγRIIB

  • FcγRIIB inhibits FcγRIIA, which stim hist secretion

IgE mechanism

IgE binds FceRII or RceRI depending on cell

• FceRI = mast, eosin, baso = only one binding site

• FceRII = B cells = trimer

signals for histamine secretion and allergy response via mast cell degradation

Type II hypersensitivity rxn

cytotoxic

IgG or IgM abs against new epitopes from chemical modifications

Ie. penicillin causing chem mod of ag

• IgG binds to new epitope

• tiggers comp fixation (via C3b and CR1) and phagocytosis

type III hypersenstivity rxn

immu complexes that deposit in tissues, causing inflammation and tissue damage such as in blood vessels, kidneys, and joints.

type IV hypersensitivity rxns

cell-mediated! “delayed hypersens”

CD4 and CD8 T cells resp to foreign or new epitopes (i.e. metal piercings)

penicillin and hypersens rxns

chemical mod proteins into new epitopes which triggers all 4 typers of hypersens rxns

Atopy

genetic predisposition for hypersens/allergy

assoc with high IgE

• more IL4 by T cells = more IgE synth

• alpha chain of IL4 mutated to increase IL4 effectiveness and IgE synth

• uptake and prez of envir ags (allergy)

genes include:

• TIM and ADAM33

sensitization mech

induces T_FH2 resp

mech:

• inhale ag (i.e. pollen)

• binds mucus, APC engulf, and take ag to lymph

• APC prez and activate TH that secrete IL4

• IL4 binds B cells, maturing it to plasma cell to prod IgE

• at 2nd exposure, IgE already primed, binding to/”arms” mast cell

  • IgE binds to ag, triggering degranulation of mast cell adn hist secr

hay fever

hist and other mediators released to activate mast cells and increase perm and mucus prod

treatment of systemic anaphylaxis

epinephrine

• increases BP, HR, and vasodilation in skele musc

  • counteracts hist (decreases BP and airway constriction)

universal blood donor

O Rh-

universal blood recipient

AB Rh+

diff btwn O, A and B blood types structurally

O is in both A and B

A’s last sacc is Gal-NAc

B’s last sacc is Gal

result of mismatched blood types for transfuss

intravascular coagulation, comp fixaxn, and RBC hemolysis

Rh factor

no AB prod against naturally

Rh- cannot receieve Rh+ b/c foregin and will produce anti-Rh+ abs

what are the three types of organ rejection

hyperacute
acute

chronic

hyperacute organ rejecxn

ab mediate

immeidate

rate

ABs bind to graft vascular endothelium

against ABO/HLA-1 ags

comp activation and clotting

acute organ reject

t cell mediated

days to weeks

direct allorecognition = donor APCs has ag and decrease overtime

i.e. dendrites of donor (with donor ags prez on it) snitches on itself by going to spleen and activating alloreactive T cells

chronic organ rejection

mediated by anti-HLA I alloABs adn t cells

months to years

bind epithelial cells = fibrosis

recuits inflam cells (granulocytes, monocytes, and neutrophils)

indirect = own APCs have ag and increase over time

what are the two compativitlity assays

1. cell lysis

2. glutination

cell lysis compat assay

recipient serum wiht donor lymph

+ = lysing b/c anti-donor HLA ABs in recipient

- = low [anti-donor’s HLA ABs] = compat!

gluntination compat assay

recipeients serum with donor’s RBCs

+ = gluntination = incomp = jaundice and anemia

- = compat!

alloreactions (also direct vs indirect)

autoreactive T cells that bind to MHC too strongly b/c weren’t exposed/removed during negative selection

direct = ag from donors APC, donor APCs decrease over time and signal acute rejection

indirect = ag prez by own APC, recip APCs increase over time and signal chronic reject