Immunology Part II Flashcards
(47 cards)
What are five common deficiencies related to Innate Immunity?
- Congenital Neutropenia
- Chronic Granulomatous disease
- Leukocyte Adhesion Deficiency (LAD)
- Complement Defects (various)
- Chediak-Higashi Syndrome
What happens in Congenital Neutropenia?
(still have some innate immunity protection due to NK cells)
- Lack of GM-CSF
- Frequent bacterial infections
What happens in Chronic Granulomatous Disease?
- Inability to produce hydrogen peroxide and hypochlorus acid
- Inability to kill phagocytosed bacteria
What is Leukocyte Adhesion Deficiency (LAD)?
- Lack of intern subunit, the common beta chain
- Inability to recruit innate immune cells to site of inflammation
- Increased susceptibility to bacterial, fungal and viral infections
What are Complement Defects (various)?
- Increased susceptibility to bacterial infections
- Reduced ability to remove immunocomplexes (bound to surface of bacterial cells)
What is Chediak-Higashi Syndrome?
- Defect in gene LYST (CHS1), a lysosomal trafficking gene that affects lysosomes and melanosomes
- Increased susceptibility to bacterial infections
What are Defensins and Cathelicidins?
- Major families of antimicrobial peptides
- Widely expressed in a variety of epithelial cells and sometimes in leukocytes
What do Defensins and Cathelicidins do?
- Role in innate immunity through antimicrobial, chemotactic and regulatory activities
- Protect against bacteria, fungi, viruses and parasites
- 100s of defensin proteins have been identified in nature!
- Interact with microbial cell membrane components to increase cellular permeability resulting in cell death
- They also act to modulate the inflammatory response
What are Cathelicidins?
(CATionic HELIcal bacteriCIDal proteIN) are alpha-helical peptides
-Human cathelicidin LL37 is highly expressed by PMNs and numerous mucosal and epithelial cell types
What are Defensins?
Beta-strand peptides connected by disulfide bonds
How is the acute inflammatory response activated?
- Pathogen crosses or causes damage to physical barrier
- PAMPs and/or DAMPs get released
- TLR on resident macrophage gets stimulated (reprogrammed)
- Macrophage releases chemokines (IL-1 and TNF-alpha)
- TNF-alpha from macrophage stimulates endothelial cell to express E-selectin on its surface.
- If E-selectin is expressed and there is an inflammatory response, leukocyte will slow down in blood vessel and bind the E-selectins!
- Leukocyte migration occurs!
How does Leukocyte migration occur?
a. Rolling
b. Tethering to E-selectins –> mediated by CD15 and E-selectin
c. Adhesion (more stable interaction between leukocyte and surface of the cell)
d. Migration
How does a leukocyte get “pulled into” the cell?
- Th1 supplies interferon (IFN-gamma) to induce M1 (angry, phagocytosing) state in Macrophage.
- Endothelial cells make ICAM-1
- Lymphocytes make CR3 & CFA1 [These bind ICAM-1 and make a more permanent interaction] - Cell can move ICAM-1 into the tissue, bringing the cell in with it! [can also alter vascular permeability to Inc. migration]
What should you know about MHC I?
- Antigen synthesized in cell/from cell infections
- Recognized by CD8 cells
- Expressed on all cells except RBCs (may play role in malaria persistence)
- CD8 Surveys every cell in body and makes suits doing what it should be & if pathogen present will induce phagocytosis
What should you know about MHC II?
- Antigens are products of phagocytosis
- Recognized by CD4+ cells
- Expressed on monocytes/macrophages, DC, B cells and epithelial cells of thymus
What are the T cell markers?
- TCR (alpha-beta & gamma-delta) [antigen receptor]
- CD3 [part of TCR complex]
- Some have CD4, CD8, CD23
What are the B cell markers?
- BCR = Ig (Immunoglobulin) antigen receptor
- CD1, CD19, CD20, CD23, CD40, CD79a (part of BCR complex), CD79b (part of BCR complex)
What are Th1 cells?
-Recognize antigen and make lymphokine that attracts thousands of macrophages (the heavy-duty phagocytes) to the area where antigen has been recognized. This intense inflammation can wipe out serious infection (or a transplanted kidney!)
What are Th2 cells?
- Stimulate macrophages to become ‘alternately activated’, able to function in walling-off pathogens and promoting healing, a process that usually takes place after the pathogen-killing Th1 response
- They are very important in parasite immunity
What are Th17 cells?
- Similar to Th1 in that their main role is to cause focused inflammation, although they are more powerful than Th1
- They have been implicated in many serious forms of autoimmunity
What are Tfh cells?
Stimulated by antigen and migrate from T cell areas of lymph nodes into the B cell follicles, where they help B cells get activated and make the IgM, IgG, IgE and IgA antibody subclasses.
What are Treg cells?
Make cytokines that suppress the activation and function of Th1, Th17 and Th2 cells, so they keep the immune response in check. They are part of the Th family.
What do CTLs do?
Destroy any body cell they identify as bearing a foreign or abnormal antigen on its surface.
What do Cytotoxic T cells do?
Examine surfaces of incoming dendritic cells for presenting antigenic fragments. They are looking for fragments on a different class of antigen-presenting molecule, called MHC Class I which is on all cells (except RBC)
