Immunology Flashcards
Organs of the Immune System
Primary Organs
- Stem cells from the yolk sac and Fetal Liver
- Bone Marrow
- thymus gland
Secondary Organ
- lymph nodes
- spleen
- mucosa-Associated Lymphoid Tissue (MALT)
Types of Antigens
- Immunogen
- Hapten (+carrier = immunogen)
- Allergen
- Tolerogen
- Ligand
The three lines of Host Defenses
- The covering of the body (skin and mucous membranes)
- The innate immune response
- The adaptive (aquired) immune response
What the skin and Mucous membranes provide the body
-unpleasant living conditions for microorganisms
via epidermis, Mucus, pH, enzymes
Mode of transmission for airway
- inhaled droplet
- spores
Mode of transmission for GIT
Contaminated water or food.
Microbial Recognition strategies
Recognition of microbial non-self
-detection of unique, conserved structures that are essential to microbial physiology (Molecular signatures of infection)
Pathogen-associated molecular patterns (PAMPs)
- lipopolysaccharide (LPS) of gram negative bacteria
- Peptidoglycan (PGN) of gram-positive bacteria
PAMPs are recognized by immune system receptors called Pattern Recognition Receptors (RRR) including toll-like receptors.
Toll-like Receptors (TLRs)
- a family of highly conserved type 1 transmembrane receptors
- essential for microbial recognition via PAMPs
N-terminal extracellular leucine-rich repect (LRR)
- This domain consists of 19-25 tandem LRR
- Each LRR is 24-29 amino acids in length
- LRRs form a horseshoe shape for ligand recognition
C-terminal intracellular signaling domain with homology to the interleukin-1 receptor (Toll/IL-1R= TIR domain)
-Protein-protein interaction module
Innate(natural, “Nonspecific”) Immunity
- cellular and humoral factors
- no memory
- early in evolution, danger signals
Cellular Factors
- Phagocytic cells (neutrophils, macrophages, interdigitating dendritic cells)
- Cells with inflammatory mediators (basophils, mast cells, eosinophils)
Humoral Factors
- acute phase reactants (e.g. C-reactive Protein, Complement, Interleukin)
- Cytokinins (interferon-alpha)
Normal Blood Cell Types
Erythrocytes
Leukocytes
- Neutrophils
- Eosinphils
- Basophils
- Monocytes
- Lymphocytes
Platelets
Innate Immune Response
Results in inflammation
Cellular Sequence:
- The tissue macrophage
- The neutrophil
Adaptive(acquired, specific)
- humoral (immunoglobulin/antibody mediated)
- cell-mediated (T cell/lymphocyte effector)
Limb’s of the Immune Response
- Afferent Limb
- Efferent Limb
Efferent ‘Limb’
- the effector or ‘killing’ aspect
- in the humoral immune response, this is antibody molecules (that will engage the complement)
- in the cellular immune response this will be T-cytotoxic (Tc) CD8+ lymphocytes
Afferent ‘limb’
-made up of the events that initiate the immune response. (Innate immunity to the interaction with T-helper (Th) CD4+ lymphocyte. This limb will have both humoral and cellular components in both the humoral and cellular immune response mechanisms.
Adaptive Immune Response 1
Antigen (and epitope) specific Antigen presenting cells (APC) -(MHC +peptide) -interdigitating dendritic cell -macrophage -B lymphocyte (B cell)
Major Histocompatibility Complex (MHC)
Makes two kinds of molecules in cells:
- class I (HLA-A, HLA-B, HLA-C)
- class II(HLA-DP, HLA-DQ, HLA-DR)
Class I MHC molecules
- the chains are of markedly different masses: a large alpha chain and a small beta-2 and microglobulin chain
- can hold only short peptides because the binding site is closed off
Class II MHC molecules
- the alpha and beta chains are almost of the same size
- can bind to peptides of different lengths, because the binding site is open at both ends.
Antibodies
- humoral immunity
- immunoglobin
- basic structure of monomeric antibody molecule:
- Four chains: two identical light chains (Kappa or Lambda) determine immunoglobulin TYPE
Immunoglobulin (Ig) molecules
- five classes: determined by the Heavy (H) chain ( delta, mu, gamma, alpha, epsilon)
- two types: determined by the light chain kappa, lambda
- Interchain and intrachain disulfide bonds are present between and within all chain.
Classes: IgM - complement binding IgG - placental transer, complement binding IgA - secretory properties (MALT) IgE - Mastocytophilic properties
The complement Cascade (Classic)
- Constant regions of 2 antibody molecules in the Antigen-antibody complex bind C1 - C4-C2-C3 (breaks down to C3a +C3b)
- products of C3 and C5 enhance neutrophil phagocytosis
- later molecules in the sequence, particulary C9 punch a hole in the bacterial membrane.
Alternative Pathway (more primitive)
- can be activated by other factors such as LPS (a PAMP)
- turns on the innate Immune response; and Complement plays a role here e.g. enhances phagocytosis (C3 and C5)
Other types of T-cells
- Regulatory T cells
- T helper 17 cells
- TH3 cells
- Natural Killer T cells
- Follicular B Helper T cells
Regulatory T cells (Treg)
-formerly know as suppressor T cells, are subpopulation of T cells which down regulated the immune system, maintains tolerance to self-antigens, and down regulates autoimmune disease.
T Helper 17 cells (Th17)
- subset of T helper cells producing interleukin 17 (IL-17). They are considered developmentally distinct from Th1 and Th2 cells and excessive amount of the cell are thought to play a key role in autoimmune disease such as Mulitple sclerosis.
TH3 cells
- involved in mucosal immunity and protecting mucosal surfaces in the gut from nonpathogenic non-self antigens. They mediate this non-infammatory environment by secreting TGF-beta and IL-10.
