Immunology: Case Studies, Bonus, Cytokines, Specialize T Cells

TH1

defend intracellular pathogens, activate macrophages & CD8+ (IFN-y and IL-2)

TH2

defend extracellular pathogens like parasites, activate B cells to antibodies (IL-4, IL-5, and IL-13)

TFH

Assist B cells in germinal center, activate B cells to class switching, somatic hypermutation, affinity maturation (IL-21, IL-4, CD40L)

TH17

defend fungal/bacterial infection, recruit neutrophils (IL-17)

IL-1

inflammation, fever (act on hypothalamus/acute phase response proteins for systemic inflammation)

TNF-a

inflammation, vascular permeability, trigger apoptosis (infected cells) + acute phase

IL-6

activate liver cells to generate complement proteins (DCs)

CXCL8

recruit neutrophils, induce LFA-1 expression & gradient for neutrophil migration

IL-12

activate NK cells (DCs)

IFN (a/b)

antiviral (signal creation of antiviral proteins in cells = autocrine) & NK cell proliferation = paracrine

TGF-b

neutrophil response, suppress inflammation, promote tissue repair (DCs to extracellular response)

IL-2

T cell proliferation (mostly CD8+)

IL-21

B cell differentiation (TFH cells)

IL-4

TH2 differentiation, B cells to antibodies (TFH cells)

CD40L

B cell differentiation (TFH cells)

IL-5

activate B cell to antibodies (TH2)

IL-13

activate B cell to antibodies (TH2)

IL-17

recruit neutrophils, inflammation (TH17)

IL-1b

inflammation/fever (like IL-1)

IFN-y

activate macrophages, increase MHC, (TH1 cells) DCs too

How does ICP47 aid in HSV immune evasion?

ICP47 aids in HSV immune evasion by suppressing the presentation of viral antigens on MHC-I. It does this by embedding itself in the host cell’s phospholipid membrane and blocking the function of the Tap 1 and Tap 2 proteins. These proteins are responsible for transporting viral peptide fragments into the endoplasmic reticulum to load onto MHC-I molecules. Without this process, MHC-I molecules cannot present viral peptides on the cell surface making it difficult for cytotoxic T lymphocytes (CTLs) to recognize and eliminate infected cells.

How does gE/gI aid in HSV immune evasion

The gE/gl complex helps HSV evade the immune system by binding to the Fc region of antibodies, preventing them from triggering immune responses. This blocks macrophages from recognizing and phagocytosing infected cells. By finding the Fc region, the virus also disrupts important antibody functions, like opsonization and complement activation, which are key to fighting the virus. Additionally, the gE/gl complex acts as a decoy of sorts to prevent effective antibody binding thus reducing the immune system’s ability to fight the infection. Ultimately this helps HSV evade detection which prolongs the infection.

How does gC aid in HSV immune evasion?

The glycoproteins, gC-1 and gC-2, are produced by the virus. The gC1 prevents stabilization of C3 convertase by properdin binding to C3b; as gC1 has already bound to C3b. Thus, less C3 is cleaved into C3a and C3b. gC1 blocking C3b also prevents C5 binding to C3b, which is necessary in formation of the alternative convertase complex. This leads to less opsonization of pathogens and inhibition of the alternative complement pathway. C3b molecules also cannot bind to each other, so the C5 alternative convertase, the first step of MAC attack, cannot be initiated. The prevention of forming this convertase leads to inhibition of C5 cleavage into C5a and C5b, so the MAC attack is no longer effective.

Bonus: CAR T cells

(Chimeric Antigen Receptor - artificial TCR injected vector into patients own T cells) They recognize CD-19 on all B cells (killing all B cells in body) This aids in killing the cancer (B cell acute lymphocytic leukemia (B-ALL), immature B cells (lymphoblasts) proliferate uncontrollably, crowding out healthy blood cells in the bone marrow and impairing immune function.)

Patients have no antibodies from B cells and have an excess of cytokines released (cytokine storm) making them feel very ill. Also allowed for allo-HSCT treatement. Very rapid kinetics. Young girl = Jesse

MIC-A/MIC-B

expressed when a cell is stressed/infected (NK cells bind here to kill the cell)

NK Cells activated by

MIC-A/MIC-B (stressed/infected cells) or Lack of MHC-I on surface of cell (will target both

Extracellular response

MHC-II and IL-6, TGF-B (neutrophils)

Intracellular response

MHC-I and IL-12, IFN-y (macrophages)

Cytokines that trigger lectin and classical pathways

inflammatory (IL-1, IL-6, TNF-a)

macrophages release

IL-1, IL-6, IL-12, TNF-a, CXCL8