Lecture 22: Intro to Immunology

Question 1

Major components of innate immunity

Answer 1

1. Complement
2. Neutrophils
3. Macrophages
4. Innate Lymphoid Cells (e.g. NKs)

Question 2

Activation pathways for complement

Answer 2

1. Classical
2. Alternative
3. Lectin (mannose-binding)

Question 3

Classical activation of complement

Answer 3

Mediated by antigen recognition via antibodies produced by B cells

Question 4

Alternative activation of complement

Answer 4

Auto-destruction of anything that doesn’t inactivate C3

Question 5

Lectin (mannose-binding) activation of complement

Answer 5

Recognition of foreign sugars on cell membranes

Question 6

Opsonization

Answer 6

Tagging of pathogens by opsonins, allowing easy recognition + phagocytosis by mφ’s. Opsonin e.g. Abs, C3b, C4b

Question 7

Neutrophils

Answer 7

• Innate immune cells born/stored as “marginal pools” in marrow.
• Released in circulation as adult and band cells.
• Enter CT via rolling adhesion/diapedesis, die after use.
• Utilize Pattern Recognition Receptors to recognize PAMPs/DAMPs.
• Capable of NETosis.

Question 8

Macrophages

Answer 8

• Form as monocytes in marrow, then differentiate to mφ’s after diapedesis.
• Resident versions in peripheral tissues; mononuclear phagocyte system.
• Secondary roles in APCs, cell signaling.

Question 9

Macrophage activation

Answer 9

Activated by inflammatory cytokines, can by hyperactivated by T cell cytokines. 2 activation modes:
1. Classical (M1)
2. Alternative (M2)

Question 10

Classical activation of macrophages

Answer 10

Aka M1 macrophages, Type 1 inflammation, Th1 response. Phagocytic response.

Question 11

Alternative activation of macrophages

Answer 11

Aka M2, Type II inflammation, Th2 response, immunoregulation response. Primarily used for tissue remodeling/repair; many varieties of a more subtle immune response.

Question 12

Innate Lymphoid Cell groups

Answer 12

Group I: e.g. NK cells, IC pathogens
Group II: parasites, enriched in lung, skin, adipose
Group III: bacteria, fungi

Question 13

Antibodies

Answer 13

• Aka Ag receptors/Ig/γ globulins.
• Can be soluble or membrane bound.
• Have variable Fab and constant Fc domains.
• 5 classes: IgG, IgD, IgA, IgM, IgE

Question 14

Antibody structure

Answer 14

Variable Fab = heavy + light chain, antigen binding site, gives specificity (VDJ recombination)
Constant Fc = heavy chains, interacts with other immune components, defines antibody class/type.

Question 15

Class switching

Answer 15

IgM is the default B cell antibody; upon activation, class switching can occur to other Ab types.

Question 16

IgG

Answer 16

Most common Ab in blood/CT; readily diffusible. Triggers complement w/ sufficient Ag presence and can cross blood-placenta barrier for passive fetal immunity.

Question 17

IgD

Answer 17

Not much known. Marker for mature naive B cells.

Question 18

IgE

Answer 18

Mast cell surface receptor. Mediates parasite/allergy response by triggering degranulation.

Question 19

IgM

Answer 19

IgG pentamer/hexamer; default Ab due to low immunogenicity. Multimeric structure requires more Ag density for activation but can bring multiple C1 proteins to activate complement; roles in early infection response.

Question 20

IgA

Answer 20

Found in mucosal surfaces, breast milk. Dimer + “clip” structure gives acid resistance and can’t bind complement (clip blocks Fc); thus is important for Ag tolerance, esp. w/ food from gut.

Question 21

B cell

Answer 21

EC pathogen response; expresses BCRs (Igs) which recognize Ags. Activates at critical Ag density; also req. B cell coreceptor complex/T cell signals/C3d to facilitate activation.

Question 22

B cell life cycle

Answer 22

1. Immature B cell leaves marrow.
2. IgD/IgM expression defines mature naive B cell.
3. Ag-dependent activation -> differentiation + clonal expansion to plasma cell.
4. Potential class switching occurs + Ab secretion.
5. Small Bmem population persists with Ab specificity.

Question 23

T cells

Answer 23

IC pathogen response (viral, phagocytosed material). TCRs recognize MHC complexed Ag. Primarily classed as Tc or Th.

Question 24

Tc cells

Answer 24

Cytotoxic T cells, CD8+. Self vs. non-self via MHC-1.

Question 25

Th cells

Answer 25

Helper T cells, CD4+. Recognize internalized Ags from APCs complexed with MHC-II.

Question 26

MHC-I

Answer 26

Expressed on almost all cells. Displays peptide fragments of produced proteins.

Question 27

MHC-II

Answer 27

Expressed on APCs only. Displays peptide fragments from internalized proteins.

Question 28

Other T cell types

Answer 28

Treg: CD4+ regulatory, immune suppression.
Tmem: CD4+ CD8+; central = self-renewing SCs, effector = CD8+ cytotoxic
γδ T cells: variant TCRs not MHC restricted; include intraepithelial lymphocytes.

Question 29

Th subsets

Answer 29

Based on immune recruitment.
Th1 -> IFN-γ, TNF-α/β to help Tc vs IC viruses
Th2 -> IL-4/-5/-13 for B cell response vs worms, allergy
Th17 -> IL-6/-17 for mφ, neutrophil vs EC bacteria
Treg -> TGF-β, IL-10; dampen immune response.

Question 30

Immune organ categories

Answer 30

Primary = generative (bone marrow, thymus)
Secondary = effector (peripheral MALT, lymph nodes, spleen, liver)

Question 31

Thymus

Answer 31

Trains immunocompetence of immature T cells (thymocytes. Involutes with age to adipocytes. Derived from 3rd pharyngeal pouch endoderm; induction by ectomesenchyme/ectoderm interactions.

Question 32

Blood-thymus barrier

Answer 32

ERCs physically block entrances to thymic medullar and reentry to circulation, keeping naive thymocytes trapped until immunocompetent.

Question 33

DiGeorge syndrome

Answer 33

No thymus development; results in no T cells, no adaptive immunity

Question 34

Thymic epithelial compartment

Answer 34

Cortex/medulla = epithelial-derived. Stroma formed by ERCs.

Question 35

Epithelioreticular cells

Answer 35

Nurse/teacher cells for thymocytes; physically let out good thymocytes and trap immature ones.

Question 36

Thymocyte pathway through spleen

Answer 36

1. From vascular circulation -> perivascular -> epithelial for education
2. Cortex -> medulla during education
3. Medulla -> perivascular compartment -> vascular after immunocompetence

Question 37

ERC classes

Answer 37

Type 1: cortical epithelioreticulum
Type 3: cortical/medullary border
Type 5: medullary
Type 6: assoc. w/ Hassall’s corpuscles

Question 38

Thymic selection

Answer 38

1. Positive selection (cortex; assure functional TCR that recognizes Ag; pre-req. for Th/Tc fate specification.
2. Negative selection (medulla; assure non-self-reactive TCR; req. for access to perivascular space)
   Non-immunocompetent cells are phagocytosed by thymic macrophages.

Question 39

TCR development

Answer 39

1. Naive: CD3- CD4- CD8-
2. Double positive (cortex): CD3+ CD4+ CD8+
3. Tc or Th (medulla): CD3+ CD4+/CD8+

Question 40

What are thymoma disorders classed as?

Answer 40

Primary autoimmune disorders; failure in central tolerance.

Question 41

B cell selection

Answer 41

Pos/neg selection of B cells occurs in marrow, preventing autoreactivity.

Question 42

T cell exhaustion

Answer 42

During chronic active immune responses, gradual senescence of T cells to Tex occurs esp. for Tc/Tmem. Critical to chronic diseases.

Question 43

Dendritic cell classes

Answer 43

1. Conventional (mucosal surfaces)
2. Plasmacytoid (blood, secondary immune organs; antiviral interferon secretion)