Innate Immunity

Question 1

Paradoxically, cell death is needed to initiatie ____.

Answer 1

Paradoxically, cell death is needed to initiatie tissue repair.

Question 2

The two principal types of reactions of the innate immune system are ____ and ____.

Answer 2

The two principal types of reactions of the innate immune system are inflammation and antiviral defense

Question 3

high mobility group box protein 1

Answer 3

Histone protein released from necrotic cells and in NETs. Used as a DAMP.

Question 4

PRR Families

Answer 4

Question 5

The TLRs

Answer 5

Question 6

NOD-like Receptors

Answer 6

Sense DAMPs and PAMPs in the cytosol of cells and initiate signaling events that promote inflammation.

Question 7

NOD2 in Paneth Cells

Answer 7

NOD2 is expressed highly in Paneth cells and, when stimulated, triggers production of antimicrobial defensins and activates NFκB. NOD2 polymorphisms are associated with IBD.

Question 8

Inflammasomes are composed of. . .

Answer 8

An oligomerized sensor, a signaling platform, and caspase-1.

Most sensors belong to the NLR family, but AIM sensors and pyrin may also oligomerize to activate an inflammasome,

Question 9

Caspase-1 substrates

Answer 9

pro-IL-1

pro-IL-18

pro-GasderminD

Question 10

The RIG-like receptors

Answer 10

Cytosolic proteins that sense viral RNA and induce the production of the antiviral type I IFNs.

RLRs recognize features of viral RNAs not typical of mammalian RNA, such as dsRNA and 5’-triphosphate RNA.

Question 11

Cytosolic DNA sensors

Answer 11

Include several structurally related proteins that recognize microbial double-stranded DNA in the cytosol and activate signaling pathways that initiate antimicrobial responses, including type 1 IFN production and autophagy

Question 12

Most innate cytosolic DNA sensors engage the ____ pathway

Answer 12

Most innate cytosolic DNA sensors engage the STING (stimulator of interferon genes) pathway. This induces Type I IFN production. STING also stimulates autophagy.

Question 13

defensins and cathelicidins

Answer 13

Antimicrobial peptides produced by epithelial cells.

Kill bacteria and some viruses by disrupting their outer membranes.

Question 14

Intraepithelial lymphocytes

Answer 14

Belong to the T cell lineage but express antigen receptors of limited diversity. Made up of αβ and δγ T cells. Often recognize microbial lipids and other structures.

Presumably react against infectious agents that attempt to breach the epithelia, but the specificity and functions of these cells are poorly understood.

Question 15

Macrophages in adults and during development

Answer 15

Question 16

Innate lymphoid cells

Answer 16

Tissue-resident cells that produce cytokines similar to those secreted by helper T lymphocytes but do not express T cell antigen receptors (TCRs). The responses of ILCs are often stimulated by cytokines produced by damaged epithelial and other cells at sites of infection. ILCs likely provide early defense against infections in tissues, but their essential roles in host defense or immunological diseases, especially in humans, are not clear.

Question 17

NK Cell - Macrophage Interaction

Answer 17

Macrophages ingest microbes and produce IL-12, IL-12 activates NK cells to secrete IFN-γ, and IFN-γ in turn activates the macrophages to kill the ingested microbes.

Question 18

How DCs regulate NK cell activity

Answer 18

Dendritic cells that have encountered microbes enhance the ability of NK cells to protect against infections. These include Type I IFNs, IL-15, and IL-12. IL-15 is important for the development and maturation of NK cells, and type I IFNs and IL-12 enhance the killing functions of NK cells.

Question 19

antibody-dependent cellular cytotoxicity

Answer 19

The recognition of antibody-coated cells results in killing of these cells

Question 20

NK Cell Inhibitory Receptors

Answer 20

immunoglobulin-like receptors (KIRs), CD94, and the lectin NKG2. All contain ITIMs.

Question 21

NK-T cells

Answer 21

Express TCRs with limited diversity and surface molecules typically found on NK cells. They are present in epithelia and lymphoid organs. They recognize microbial lipids bound to a class I MHC–related molecule called CD1.

Question 22

Mucosal associated invariant T (MAIT) cells

Answer 22

Express TCRs with limited diversity but do not express CD4 or CD8. They are present in mucosal tissues and are most abundant in the human liver, accounting for 20% to 40% of all T cells in that organ. Many MAIT cells are specific for bacterial vitamin B metabolites and likely contribute to innate defense against intestinal bacteria that transgress the mucosal barrier and enter the portal circulation.

Question 23

B-1 cells

Answer 23

Population of B lymphocytes that are found mostly in the peritoneal cavity and mucosal tissues, where they produce antibodies in response to microbes and microbial toxins that pass through the walls of the intestine. Circulating IgM antibodies found in the blood of normal individuals, even without specific immunization, are called natural antibodies. They are the products of B-1 cells, and many of these antibodies are specific for carbohydrates that are present in the cell walls of many bacteria and for ABO blood group antigens found on red blood cells

Question 24

marginal-zone B cells

Answer 24

Present at the edges of lymphoid follicles in the spleen and other organs and also is involved in rapid antibody responses to blood-borne polysaccharide-rich microbes.

Question 25

Complement

Answer 25

Question 26

collectin family

Answer 26

Includes mannose-binding lectin (in the blood, binds mannose) and C reactive protein (in surfactant, binds phosphorylcholine).

May activate the complement pathway or serve as an opsonin. Circulating collectins increase dramatically following infection as part of the acute-phase response.

Question 27

Table of some of the most common cytokines

Answer 27

Question 28

TNF and IL-1 effects on endocrine organs

Answer 28

Induce fever by acting on the hypothalamus, stimuilate synthesis of antimicrobial proteins in the liver (such as CRP and fibrinogen)

Question 29

Septic Shock

Answer 29

Characterized by low blood pressure (the defining feature of shock), disseminated intravascular coagulation, and metabolic disturbances.

The main culprit is high TNF, among many other cytokines.

Question 30

Type I IFN Actions

Answer 30

Question 31

“Second signal” for T vs B cells

Answer 31

T cells: B7 and pro-inflammatory cytokines

B cells: C3d recognition

Question 32

Treatment for gout

Answer 32

Anakinra (recombinant IL1Ra)

Question 33

Plasmacytoid dendritic cell

Answer 33

In viral infections, pump tons of Type I IFN into the blood to engage systemic antiviral immunity

Question 34

While performing an autopsy on a 99 year old man who died of complications of dementia after several years in a nursing home, you discover a mass in his left hip. An X-ray reveals the “mass” to be a bullet. You call your senior attending (who happens to be a World War II history buff), who tells you that the bullet looks consistent with what might have been used by the German army circa 1944. If you were to take a section of the tissue around the bullet and perform an H&E stain, what would you be most likely to see?

Answer 34

Aggregates of macrophages surrounded by lymphocytes and occasional giant cells.

Aka, granulomatous inflammation