Immunology Exam Study Notes

Antigens and Receptors

• T cells and B cells need receptors to see antigens before mounting an antigen response.
• Genetic rearrangement for these receptors occurs in the bone marrow for both cell types.
• T cells then mature.

Chemokines

• CCL19 and CCL20 are chemokines that facilitate the movement of T cells and B cells out of lymph node zones.
• This movement requires chemokine receptors.

T Cell Memory

• Memory T cells develop after antigen encounter and activation, resulting in a faster response compared to naive T cells.
• T cell memory does not require germinal center reactions or persistent antigen presence.
• Memory T cells reside in the bone marrow, providing long-term immunity.

Immune Cell Interactions

• LFA-1 (integrin) binds to ICAM-1, aiding in signal integration into cells.
• C9 forms the membrane attack complex, creating holes in target cells.
• Perforin, from CD8 T cells, also creates holes in the target cell membrane.

MHC Class II Deficiency

• MHC class II deficiency leads to decreased CD4 T cells and decreased antibody production.
• Class switching is impaired; patients primarily produce IgM and IgD.
• CD4 T cells recognize MHC class II.

T Cell Recognition

• T cells must have antigens chopped into peptide sequences to recognize them.
• Cytokines help activate T cells.
• Co-stimulation involves CD28 on T cells binding to CD80/86 (B7) on dendritic cells.
• TCR must bind with MHC for T cell activation.
• CD40 ligand on activated T cells interacts with CD40 on B cells.
• ITAMs (immunoreceptor tyrosine-based activation motifs) are critical for signaling.
• MHC class I restricted T cells are CD8 T cells.
• T cells cannot directly recognize antibodies.
• CD40 expression on B cells and CD40 ligand on T cells facilitate interaction.
• CD28 is a co-stimulatory molecule on T cells, and E-selectin is on the epithelium.

Dendritic Cells (DCs)

• DCs are professional antigen-presenting cells, presenting via both MHC class I and class II.
• DCs activate various cell types and produce numerous cytokines.

T Cell Activation Steps

• First step: Antigen recognition involving MHC presenting a peptide to the TCR.
• Second step: Signaling through CD3 and zeta chains, activating adaptive proteins.
• Third step: Adhesion molecules (e.g., LFA-1 on T cells binding to ICAM-1 on dendritic cells) to stabilize interactions.
• Fourth step: Co-stimulation via B7 (CD80/86) to change phosphorylation events of the adaptive proteins.

Antibody Types

• IgM antibodies neutralize polysaccharide antigens without T cell help (T cell-independent).
• IgA, IgE, and IgG require T cell help (T cell-dependent).

Transcription Factors

• Phosphorylation of LAT leads to activation of NF-κB (Nuclear Factor kappa B).
• Other transcription factors include NFAT (Nuclear Factor of Activated T-cells).
• T-bet is important for CD4 differentiation but not primary T cell activation.

T Helper Cell Differentiation

• Dendritic cells producing IL-12 and IFN-γ skew CD4 T cells to differentiate into TH1 cells.
• This response is crucial for bacterial infections.

CD4 T Cell Function

• CD4 T cells kill via cytokines that activate macrophages.
• Interferon-gamma (IFN-γ) activates macrophages and B cells.
• Antibodies opsonize and neutralize, especially against endotoxins and venoms.
• Macrophages have Fcγ receptors for IgG.
• The complement system is activated to help clear infections.

Vaccine Response

• A TH2 response to a vaccine against an intracellular bacterial infection is not ideal.
• Vaccinated individuals might experience enhanced disease due to the wrong type of immune response, which should be TH1.

T Regulatory Cells (Tregs)

• Tregs regulate T cells to prevent unwanted reactions against self-cells.
• IL-10 dampens down the immune system.
• IL-2 supports T cell proliferation; Tregs suppress IL-2 by expressing CD25 (high-affinity IL-2 receptor).
• CTLA-4 on Tregs binds to CD80/86, turning off transcription factors in activated T cells.
• Tregs also produce TGF-β.

CD8 T Cell Activation

• Activation of CD8 T cells leads to upregulation (increased production) of enzymes and perforins.
• Upregulation of integrins and selectins facilitates movement out of lymph nodes.

TH17 Cells

• TH17 cells produce IL-17 and IL-22.
• IL-22 is important for maintaining tissue homeostasis.

Extracellular Bacteria

• Extracellular bacteria replicate outside of host cells and produce endotoxins.
• Gram-negative bacteria produce LPS (lipopolysaccharide), leading to sepsis in high amounts.
• Gram-positive bacteria also release toxins.

Immune Response to Extracellular Bacteria

• Sentinel cells sense bacteria breaching barriers and secrete cytokines to initiate inflammation.
• Leukocytes and granulocytes are recruited to the blood.
• The complement system is activated.
• B cells produce IgG to opsonize bacteria and activate the complement system.
• Neutrophils are also recruited.

Immune Response to Open Wounds

• In the first few minutes, mast cells in the tissue secrete cytokines.
• Granulocytes phagocytose and undergo NETosis, releasing chromatin DNA to trap bacteria.
• DNA fragments act as damage-associated molecular patterns (DAMPs).
• DAMPs, such as mitochondrial DNA and ATP, activate innate immune cells.
• After one week, exudate and pus indicate an ongoing immune response.
• Depending on the pathogen (bacteria, parasites, viruses), different immune cells respond.

Complement Cascade

• The complement system involves floating proteins, with C3 being the most abundant.
• The classical pathway is activated by antibody-coated bacteria.
• The lectin pathway binds to lectins and mannans on the surface.
• The alternative pathway is activated by C3 tick-over, where C3 spontaneously breaks down into C3a and C3b.
• C3b binds to bacteria, activating the pathway.

Outcomes of Complement Pathways

• All three complement pathways lead to the production of C3a, C3b, C5a, C5b, and the membrane attack complex (MAC).
• MAC causes cell lysis.
• C3b opsonizes bacteria, enhancing phagocytosis.
• C3a and C5a contribute to inflammation by recruiting leukocytes.

Complement Activation by IgM

• IgM antibodies activate the classical pathway.
• IgG1 and IgG3 also activate the classical pathway.

C3 Deficiency

• C3 deficiency results in the inability to activate any complement pathway.
• This leads to decreased opsonization, less macrophage activation, and increased susceptibility to infections.

Cytokine Groups

• Five simplified groups: chemokines, interferons, tumor necrosis factors (TNFs), interleukins, and growth factors.
• Chemokines are involved in cell movement.
• Interferons interfere with viral replication.
• TNFs are involved in cellular proliferation, survival, and apoptosis.
• Interleukins are a broad group involved in various immune functions.
• Growth factors promote cell growth and differentiation.

Pathogen Recognition

• Immune cells recognize pathogen-associated molecular patterns (PAMPs) on pathogens.
• Examples include LPS.
• Toll-like receptors (TLRs) are on the cell surface or in endosomes.
• Nod-like receptors (NLRs) are in the cytoplasm.

Innate Immune System Hallmarks

• Hallmarks include rapid response, repetitiveness, and short duration. It is not reactive to host.

Neutrophil and Mast Cell Features

• Both can perform extracellular traps.

Leukocyte Migration

• Cytokines induce the expression of adhesion molecules on endothelial cells.
• Integrins arrest lymphocytes.

Dendritic Cell Function

• Inflammatory cytokines increase the expression of adhesion molecules on human endothelial cells.

Somatic Hypermutation

• Increases the affinity for the antigen occurs after antigen exposure.

T Cell-Independent Activation

• IgM antibodies can bind and neutralize antigens that contain polysaccharides without additional T cell help.

Complement Regulation

• C1 inhibitor is an example of a complement regulator.

Blood Filtration

• Macrophages in the spleen filter the blood.

T Cell Egress

• S1PR1 on T cells interacts with S1P to facilitate egress.