Week 8 - Immunotherapy + Infections and Deficiencies Flashcards
Mortality rate of unvaccinated Rabies Patient ?
100%
What is unique about the Vaccination of Rabies?
Requires in some instances active and passive immunization at once
Shorting of thee recommended timing of booster injection is _______ .
Why?
Contraindicated.
NO proper memory response possible.
(Also too long will have removed the memory cells)
In theory, when should every childhood Vaccination be repeated? why?
Every 10 years
Memory cells eventually die out - Reason for boosting.
Vaccination during fever is contraindicated . Why?
Leads to less memory cells formation.
Should to after fever is gone.
What are the difficulties in approach to vacination in Infants and Elderly?
How to solve?
Infants - High amount of naive B cells.
Elderly - High amount of Plasma and Memory cells.
For both - Boosters, more adjuvant, and Increased antigen dose could help form a higher response
Two reasons for variability in the efficiency of the vaccines for Flu?
1 - Different strains remain unchecked in regular doctor appointments (Resources).
2 - Incorrect estimation of the development of the virulence factor in each seasons.
Mechanism of herd immunity ?
Allows immunized people to protect the unimmunized people by not transferring the infection and not giving the causative agent links to spread through.
What are examples for infectious diseases that don’t have highly effective vaccines? (Still considered experimental.. )
Malaria
Schistosomiassis
TBC
HIV
Biological therapeutics
examples for given entities-
- Ab or its fragments
- Cytokines and Immune ligands
- IVIG
Main fields of application of Immunotherapy
Malignancies, Autoimmunity, Immunodeficiencies, Allergy and other Chronic Inflammatory disorder
Effector functions of the Antibodies given in immunotherapies
Neutralization by Antibodies
Induction of Apoptosis by Fragments of Antibodies
What are the possible conjugated materials to Antibodies given in Monoclonal Antibodies therapy ?
Toxins, Radioactive isotopes, Drug, Cytokines, enzymes, Lippoomes, effector cells.
Adverse effects of mAb treatment ?
Prevention and possible solutions?
Hypersensitivity and possible Anaphylactic shock, HAMA (Humen anti mouse antibodies).
Manufacturing of Ab in eukaryotic - Even humen recombinant Ab or usage of fragments of Antibodies
Endings of Humanized monoclonal Abs names? (4)
___omab - Mouse Ig
___umab - Human Ig
___ximab - Chimeric Ig
___zumab - CDR grafted humanized Ig
CD20
Where are they found?
B cells
LPS TLR
TLR4
Lipoproteins, Peptidoglycan, Flagellin - TLR
TLR1,2,5,6
TLR1,24,5,6 and IL1R converage their pathways to?
MyD88 - IRAK4
ssRNA, dsRNA and DNA in Extracellular matrix - TLR
After digestion in Endosome
TLR3,7,8,9
Intracellular bacterial receptors
NLR
NET releasing cells
Eosinophils and Neutrophils
Which Ig is strongly responding Bcterial polysaccharides?
IgM
Strategies of Extracellular bacteria to escape immunity (4)
1 - Genetic variation of surface antigen
2 - Capsules containing Salic acid - Complement inhibition
3 - Decoy Extracellular vesicles
4 - IgA Degrading protease
Neutrophillia - Meaning for infection type
Granulocytosis -Left shift
Bacterial (Extracellular)
Procalcitonin - Elevation signifies …
Systemic Bacterial Infection (Sepsis)- Stimulates its production
Intracellular bacteria - 2 options for how they reside in cells
Cytoplasmic or Vesicular
What are the cells aiding in the detection and destruction of intracellular bacteria? How?(3 cells)
NK cells by MHCI or IL12 from Macrophages or Neutrophils.
TH1 by IFNgamma release and Macrophages attack.
CTL - MHCI mediated Apoptosis
TIssue Injury mediated by the Immune system (in bacterial infection)
By activated macrophages, acculomation leads to Granuloma and healing
Strategies of ICM Bacteria escape from Immune system
Inhibition of Phagolysosome formation
Hemolysin formation - Inhibition Macrophages destruction
Lymphocytosis and Monocytosis signifies
Intracellular bacterial infection - TB for example
What is the role of Eosinophils role in the Parasite attack?
1 - Cytotoxic cationic proteins like Esinophils peroxidase (EPO)
2 - Cytokines
3 - Lipid mediators
4 - Neuromediators
Tissue injury in liver by parasites (BY Immune sys)
CD4+ activation of Macrophages and DTH with Granuloma
NeMac
Helminth activated macrophages, which is similar to alternatively activated M2 macrophages (suppression)
IgE elevation
Parasitic infection
Soluble molecules produced by Helminths for attack
MIF and TGF for Macrophages
PS, Lysosome-PS,Glycans for DC
Cytotatins for APCs
Innate immunity for fungi
Neutrophills - ROS and Phagocytosis
TLR2,4 dependent
IL23
Released by Macrophages on Fungal infection
To support the TH17 and ILC3
Adaptive Immunity for Fungi
Dependent on TH1 and TH17 (Like in intracellular bacteria)
Fungal strategies to escape immunity
Not well known, Irrelevant .
Easier handling by Immune system
Interferon type 1 formation in Viral Infection
IFN alpha - by WBC
IFN Beta - by Fibroblasts
Type 2 Interferon (Gamma) formation in Viral infection
NK cells (ILC1) form them
IFN function
VIrus resistancy in uninflected cells
Adaptive immunity against viruses
CD8+ cytotoxicity mostly
TH1 and TH2 as well
Tissue Injury caused by viral infection
Cytopathic or Immune mediated dependent on virus type
Escape immunity strategies of VIruses
1 - Modification of Antigens
2 - Causing Generalized Immunosuppression
Antigenic Variants in VIruses
Structural Plasticity - Tolerable changes are high occurring in them, a lot of Mutation
(Some do not have this options)
Antigen shift
New gene in viruses by gene exchanges between two or more viruse
Like in Human Influenza virus with Avian Influenza Virus
Antigen Drift
Passage to host leads slight viral changes
HIV Nef
Rapid interlization of CD4 and MHCI and MHCII
EBV BZLF2
Physical blocking of MHCII molecules
HIV-1
Increases FasL expression of the Infected cells
CMV
Infected cells causes continues discharge of viruses in the glands
Lymphocytosis signefies
Viral infection
Hepatitis for example
Primary Immunodeficiency - percentage in Deficiencies and Causes
Genetic, 10%
Missing Enzyme like in ADA
Missing cell type like in CD40 def.
Secondary Immunodeficiency - Percentage and Causes
Acquired, 90%
Malignancies, HIV, Drugs, Malnutration,
Hyper-IgM Syndrome
No Isotype switch because of Lack of CD40 and CD40L
X linked
SIGAD
IgA deficiency - Infections of Mucosal surfaces are more common
CGD - Chronic Granulomatous
NADPH oxidase Def, Inability for Phagocytosis
(No ROS - Supraoxide)
X or Autosomal
C5-9 deficiency
No MAC, Neisseria recurrent infections
Which tumors could cause Secondary Immunodeficiencies?
Leukemia, Lymphoma or Multiple Myeloma
What are the Iatrogenic factors that cause Secondary Immunodeficiencies?
Immunosuprussive drugs
DMARDs (Disease-modifying antirheumatic drugs)
Chemo or Radiotherapy
Three glycoproteins of HIV
gp160, gp120, gp41
Target cells of HIV
CD4+ T cells
Where does the membrane of the HIV comes from?
Host cells
Gp41 of HIV
Transmembrane protein of HIV related to binding to Host
Gp120 of HIV
Ectoprotein associated to the membrane non covelantly.
Causes the Invasion to the Host
What are the other cells attacked by the HIV?
Macrophages and Monocytes that also have CD4 (Some of them have that)
Which cell releases these proteins and what are they for?
EPO,ECP,EDN,MBP
Eosinophils peroxidase,Eosinophil cationic protein,Eosinophils-derived neurotoxin, Major basic protein.
All against Parasites and released in Allergies
CTLA4 - Function?
Located on Helper T cells, Blocks interaction with B7 by CD28, leading to no second signal and inhibition of Antigen presentation by APC.
What is the most specific Acute phase protein for Inflammation of Infectious origin?
Procalcitonin
CRP is the most important but it rises in malignancy and Autoimmune as well
